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Sample records for caspases evolutionary aspects

  1. Evolutionary Aspects of Depression, Stress and Subordination

    African Journals Online (AJOL)

    QuickSilver

    Evolutionary Aspects of Depression,. Stress and Subordination care, reciprocity, friendships and mothering in both sexes), that is, a utility harmonious with its previous function. We shall return later to the importance of self-nurturance, forgiveness and accep- tance. Peripherally, vasopressin produces water retention and ...

  2. EVOLUTIONARY ASPECTS OF THE GEORGIAN BANKING SYSTEM

    Directory of Open Access Journals (Sweden)

    Tamar ATANELISHVILI

    2016-08-01

    Full Text Available Georgian monetary relations have a centuries-old history. Credit associations were first founded in 11-13th centuries. Network of credit institutions became larger in the 19th century – independent commercial banks were established in the second half of the 19th century. Central State Bank of Georgia was established in the Democratic Republic of Georgia in the beginning of the 20th century. At the same time, there were efforts to create independent two-level banking system, although those efforts failed due to forceful sovietization of Georgia. But still, independent banking system was founded in Georgia after the collapse of the former Soviet Union. This work examines afore-mentioned evolutionary processes and some of peculiarities of modern banking system. The research shows that modern Georgian banking system is growing fast but it contains signs of oligopoly which contradicts the interests of vast masses of population and entrepreneurial development, while stimulating retaining of high interest rates and devaluation of national currency.

  3. Comparative and evolutionary aspects of macromolecular translocation across membranes.

    Science.gov (United States)

    Tartakoff, Alan M; Tao, Tao

    2010-02-01

    Membrane barriers preserve the integrity of organelles of eukaryotic cells, yet the genesis and ongoing functions of the same organelles requires that their limiting membranes allow import and export of selected macromolecules. Multiple distinct mechanisms are used for this purpose, only some of which have been traced to prokaryotes. Some can accommodate both monomeric and also large heterooligomeric cargoes. The best characterized of these is nucleocytoplasmic transport. This synthesis compares the unidirectional and bidirectional mechanisms of macromolecular transport of the endoplasmic reticulum, mitochondria, peroxisomes and the nucleus, calls attention to the powerful experimental approaches which have been used for their elucidation, discusses their regulation and evolutionary origins, and highlights relatively unexplored areas. Copyright (c) 2009 Elsevier Ltd. All rights reserved.

  4. Evolutionary aspects of growth hormones and prolactins and their receptors

    International Nuclear Information System (INIS)

    Tarpey, J.F.

    1986-01-01

    The interactions of GH's, PRL's and PL's with receptors for GH and PRL were examined from a comparative and evolutionary viewpoint. The binding of 125 I-bGH to membrane preparations from liver of representatives of the major classes of non-mammalian vertebrates was also studied. Only hepatic membranes from sturgeon and Gillichthys had significant bGH binding and were further characterized and compared with male rabbit liver membranes in terms of time, temperature, pH, and membrane concentration to optimize binding conditions. The binding of several members of the GH, PRL, PL family of hormones to GH receptors from liver of sturgeon, Gillichthys, rabbit, mouse and rat was investigated. in terms of hormonal specificity, the mammalian receptors and the sturgeon binding sites were similar, while Gillichthys receptors had a different pattern of hormonal specificity. The binding of 125 I-oPRL to renal membranes of the turtle, Pseudemys scripta elegans, was characterized and compared to PRL binding sites of kidney membranes of the bullfrog, Rana catesbeiana, and the tiger salamander, Ambystoma tigrinum

  5. Evolutionary dynamics on rugged fitness landscapes: exact dynamics and information theoretical aspects.

    Science.gov (United States)

    Saakian, David B; Fontanari, José F

    2009-10-01

    The parallel mutation-selection evolutionary dynamics, in which mutation and replication are independent events, is solved exactly in the case that the Malthusian fitnesses associated to the genomes are described by the random energy model (REM) and by a ferromagnetic version of the REM. The solution method uses the mapping of the evolutionary dynamics into a quantum Ising chain in a transverse field and the Suzuki-Trotter formalism to calculate the transition probabilities between configurations at different times. We find that in the case of the REM landscape the dynamics can exhibit three distinct regimes: pure diffusion or stasis for short times, depending on the fitness of the initial configuration, and a spin-glass regime for large times. The dynamic transition between these dynamical regimes is marked by discontinuities in the mean-fitness as well as in the overlap with the initial reference sequence. The relaxation to equilibrium is described by an inverse time decay. In the ferromagnetic REM, we find in addition to these three regimes, a ferromagnetic regime where the overlap and the mean-fitness are frozen. In this case, the system relaxes to equilibrium in a finite time. The relevance of our results to information processing aspects of evolution is discussed.

  6. Motivational and evolutionary aspects of a physical exercise training program: a longitudinal study.

    Directory of Open Access Journals (Sweden)

    João Paulo Pereira Rosa

    2015-05-01

    Full Text Available Several studies have indicated that motivational level and prior expectations are relevant aspects to increase commitment to physical activity. Moreover, these aspects are not properly described in terms of proximal (Self Determination Theory and distal (evolutionary explanations in the literature. This paper aims to verify if level of motivation (BREQ-2 and expectations regarding regular physical exercise (IMPRAF-54 before starting a one-year exercise program could determine likelihood of completion. Ninety-four volunteers (53 women included a completed protocol group (CPG n=21 and drop-out group (DG n=73. The IMPRAF-54 scale was used to assess six different expectations associated with physical activity, and the BREQ-2 inventory was used to assess the level of motivation in five steps (from amotivation to intrinsic motivation. Both questionnaires were assessed before the regular exercise program. The CPG group presented higher sociability and lower pleasure scores according to IMPRAF-54 domains. A logistic regression showed that a one-point increment on sociability score increased the chance of completing the program by 10%, and the same one-point increment on pleasure score reduced the chance of completing the protocol by 16%. ROC curves were also calculated to establish IMPRAF-54 cutoffs for adherence (Sociability - 18.5 points – 81% sensibility/50% specificity and dropout (Pleasure – 25.5 points – 86% sensibility/20% specificity of the exercise protocol. Our results indicate that an expectation of social interaction was a positive factor in predicting adherence to exercise. Grounded in SDT and its innate needs (competence, autonomy, relatedness, physical exercise is not an end; it is a means to achieve autonomy and self-cohesion. The association of physical activity with social practices, like in hunter-gathering groups, can engage people to be physically active and can provide better results in adherence exercise programs for the

  7. Evolutionary, kinetic and thermodynamic aspects on the bioenergetics of inorganic pyrophosphate (PPi) and adenosine triphosphate (ATP)

    International Nuclear Information System (INIS)

    Baltscheffsky, H.; Baltscheffsky, M.

    1995-01-01

    Energy barriers for energy carriers are of fundamental significance for the successful operation of the bioenergetic reactions in living cells. PPi and ATP are outstanding ''energy-rich'' examples of molecular ''energy currencies'' in biological systems, with kinetic barriers preventing excessively fast thermodynamically feasible hydrolysis from occurring. The barriers may be considered to facilitate the energy coupling roles of these phosphate compounds, which are to secure growth and maintain numerous other energy requiring functions. The enzymes involved in overcoming the energies of activation of the bioenergetic reactions have evolved to be very well tuned for their roles. Three aspects will be discussed in some detail. The first is the fact that ATP at neutral pH is considerably more energy-rich than PPi, which thus has been called a ''poor man's ATP''. This is exemplified by the kinetic and thermodynamic differences observed between the requirements for the photosynthetic formation of PPi and ATP in certain photobacterial chromatophores by varying levels of energy supply. At lower pH, PPi and ATP are equally energy-rich, which may be of significance for acidophiles. The second concerns the possible evolutionary significance of the finding that, in the dark, a pH gradient suffices to drive extensive PPi synthesis, whereas ATP synthesis requires both a pH gradient and a membrane potential (Strid et al, Biochim. Biophys. Acta 892 (1987) 236-244). Thirdly, PPi as the most plausible predecessor to ATP in the origin and early evolution of life, will be discussed. (author). Abstract only

  8. Motivational and evolutionary aspects of a physical exercise training program: a longitudinal study

    Science.gov (United States)

    Rosa, João P. P.; de Souza, Altay A. L.; de Lima, Giscard H. O.; Rodrigues, Dayane F.; de Aquino Lemos, Valdir; da Silva Alves, Eduardo; Tufik, Sergio; de Mello, Marco T.

    2015-01-01

    Several studies have indicated that motivational level and prior expectations influence one’s commitment to physical activity. Moreover, these aspects are not properly described in terms of proximal (SDT, Self Determination Theory) and distal (evolutionary) explanations in the literature. This paper aims to verify if level of motivation (BREQ-2, Behavioral Regulation in Exercise Questionnaire-2) and expectations regarding regular physical exercise (IMPRAF-54) before starting a 1-year exercise program could determine likelihood of completion. Ninety-four volunteers (53 women) included a completed protocol group (CPG; n = 21) and drop-out group (n = 73). The IMPRAF-54 scale was used to assess six different expectations associated with physical activity, and the BREQ-2 inventory was used to assess the level of motivation in five steps (from amotivation to intrinsic motivation). Both questionnaires were assessed before starting a regular exercise program. The CPG group presented higher sociability and lower pleasure scores according to IMPRAF-54 domains. A logistic regression analysis showed that a one-point increment on sociability score increased the chance of completing the program by 10%, and the same one-point increment on pleasure score reduced the chance of completing the protocol by 16%. ROC curves were also calculated to establish IMPRAF-54 cutoffs for adherence (Sociability – 18.5 points – 81% sensibility/50% specificity) and dropout (Pleasure – 25.5 points – 86% sensibility/20% specificity) of the exercise protocol. Our results indicate that an expectation of social interaction was a positive factor in predicting adherence to exercise. Grounded in SDT and its innate needs (competence, autonomy, relatedness), physical exercise is not an end; it is a means to achieve autonomy and self-cohesion. The association of physical activity with social practices, as occurs in hunter-gathering groups, can engage people to be physically active and can provide

  9. G protein-coupled time travel: evolutionary aspects of GPCR research.

    Science.gov (United States)

    Römpler, Holger; Stäubert, Claudia; Thor, Doreen; Schulz, Angela; Hofreiter, Michael; Schöneberg, Torsten

    2007-02-01

    The common seven-transmembrane-domain (TMD) architecture of G protein-coupled receptors (GPCRs) has been preserved over a vast period of time, and highly conserved amino acid motifs and residues have evolved to establish ligand and signal transduction specificities. The mining of evolutionary data from sequenced genomes and targeted retrieved orthologs has proven helpful for understanding the physiological relevance of individual GPCRs and for interpreting the clinical significance of GPCR mutations in structural terms. Sequence analysis of GPCR pseudogenes, which are considered as genomic traces of past functions, as well as recent success in sequence analysis of GPCR genes from extinct species, provide further information. This review discusses recent advances and approaches aimed at developing a better understanding of GPCR biology based on evolutionary data.

  10. Structural and evolutionary aspects of algal blue light receptors of the cryptochrome and aureochrome type.

    Science.gov (United States)

    Essen, Lars-Oliver; Franz, Sophie; Banerjee, Ankan

    2017-10-01

    Blue-light reception plays a pivotal role for algae to adapt to changing environmental conditions. In this review we summarize the current structural and mechanistic knowledge about flavin-dependent algal photoreceptors. We especially focus on the cryptochrome and aureochrome type photoreceptors in the context of their evolutionary divergence. Despite similar photochemical characteristics to orthologous photoreceptors from higher plants and animals the algal blue-light photoreceptors have developed a set of unique structural and mechanistic features that are summarized below. Copyright © 2017 Elsevier GmbH. All rights reserved.

  11. A computer lab exploring evolutionary aspects of chromatin structure and dynamics for an undergraduate chromatin course*.

    Science.gov (United States)

    Eirín-López, José M

    2013-01-01

    The study of chromatin constitutes one of the most active research fields in life sciences, being subject to constant revisions that continuously redefine the state of the art in its knowledge. As every other rapidly changing field, chromatin biology requires clear and straightforward educational strategies able to efficiently translate such a vast body of knowledge to the classroom. With this aim, the present work describes a multidisciplinary computer lab designed to introduce undergraduate students to the dynamic nature of chromatin, within the context of the one semester course "Chromatin: Structure, Function and Evolution." This exercise is organized in three parts including (a) molecular evolutionary biology of histone families (using the H1 family as example), (b) histone structure and variation across different animal groups, and (c) effect of histone diversity on nucleosome structure and chromatin dynamics. By using freely available bioinformatic tools that can be run on common computers, the concept of chromatin dynamics is interactively illustrated from a comparative/evolutionary perspective. At the end of this computer lab, students are able to translate the bioinformatic information into a biochemical context in which the relevance of histone primary structure on chromatin dynamics is exposed. During the last 8 years this exercise has proven to be a powerful approach for teaching chromatin structure and dynamics, allowing students a higher degree of independence during the processes of learning and self-assessment. Copyright © 2013 International Union of Biochemistry and Molecular Biology, Inc.

  12. Is perceived childlessness a cue for stereotyping? Evolutionary aspects of a social phenomenon.

    Science.gov (United States)

    Kemkes, Ariane

    2008-01-01

    The present research investigates the moderating role of the "child factor" in impression formation. 307 university students (148 males, 159 females) were asked to assess 14 traits related to physical attractiveness, resource accruing potential, and emotional stability. The stimulus person was either accompanied by a child or shown individually. As expected, targets depicted with children were believed to be more family-committed and to possess greater parenting skills. The child factor also favourably biased respondents' assessments in terms of honesty, faithfulness, and maturity. Women with children were assumed to be less ambitious, while men with children were believed to be more generous and possess higher status and financial security. All results are discussed within the greater evolutionary context of kin selection and the "good-parent process". It is hypothesized that the negative stereotyping of the voluntary childfree is a by-product of cues that infer prosocial behaviour--similar to those used in mate selection.

  13. Caspase-12 and the inflammatory response to Yersinia pestis.

    Science.gov (United States)

    Ferwerda, Bart; McCall, Matthew B B; de Vries, Maaike C; Hopman, Joost; Maiga, Boubacar; Dolo, Amagana; Doumbo, Ogobara; Daou, Modibo; de Jong, Dirk; Joosten, Leo A B; Tissingh, Rudi A; Reubsaet, Frans A G; Sauerwein, Robert; van der Meer, Jos W M; van der Ven, André J A M; Netea, Mihai G

    2009-09-01

    Caspase-12 functions as an antiinflammatory enzyme inhibiting caspase-1 and the NOD2/RIP2 pathways. Due to increased susceptibility to sepsis in individuals with functional caspase-12, an early-stop mutation leading to the loss of caspase-12 has replaced the ancient genotype in Eurasia and a significant proportion of individuals from African populations. In African-Americans, it has been shown that caspase-12 inhibits the pro-inflammatory cytokine production. We assessed whether similar mechanisms are present in African individuals, and whether evolutionary pressures due to plague may have led to the present caspase-12 genotype population frequencies. No difference in cytokine induction through the caspase-1 and/or NOD2/RIP2 pathways was observed in two independent African populations, among individuals with either an intact or absent caspase-12. In addition, stimulations with Yersinia pestis and two other species of Yersinia were preformed to investigate whether caspase-12 modulates the inflammatory reaction induced by Yersinia. We found that caspase-12 did not modulate cytokine production induced by Yersinia spp. Our experiments demonstrate for the first time the involvement of the NOD2/RIP2 pathway for recognition of Yersinia. However, caspase-12 does not modulate innate host defense against Y. pestis and alternative explanations for the geographical distribution of caspase-12 should be sought.

  14. Safety aspects of designs for future light water reactors (evolutionary reactors)

    International Nuclear Information System (INIS)

    1993-07-01

    The main purpose of this document is to describe the major innovations of proposed designs of future light water reactors, to describe specific safety characteristics and safety analysis methodologies, and to give a general overview of the most important safety aspects related to future reactors. The reactors considered in this report are limited to those intended for fixed station electrical power production, excluding most revolutionary concepts. More in depth discussion is devoted to those designs that are in a more advanced state of completion and have been more extensively described and analysed in the open literature. Other designs will be briefly described, as evidence of the large spectrum of new proposals. Some designs are similar; others implement unique features and require specific discussion (not all aspects of designs with unique features are fully discussed in this document). 131 refs, 22 figs

  15. Polyketides in insects: ecological role of these widespread chemicals and evolutionary aspects of their biogenesis.

    Science.gov (United States)

    Pankewitz, Florian; Hilker, Monika

    2008-05-01

    Polyketides are known to be used by insects for pheromone communication and defence against enemies. Although in microorganisms (fungi, bacteria) and plants polyketide biogenesis is known to be catalysed by polyketide synthases (PKS), no insect PKS involved in biosynthesis of pheromones or defensive compounds have yet been found. Polyketides detected in insects may also be biosynthesized by endosymbionts. From a chemical perspective, polyketide biogenesis involves the formation of a polyketide chain using carboxylic acids as precursors. Fatty acid biosynthesis also requires carboxylic acids as precursors, but utilizes fatty acid synthases (FAS) to catalyse this process. In the present review, studies of the biosynthesis of insect polyketides applying labelled carboxylic acids as precursors are outlined to exemplify chemical approaches used to elucidate insect polyketide formation. However, since compounds biosynthesised by FAS may use the same precursors, it still remains unclear whether the structures that are formed from e.g. acetate chains (acetogenins) or propanoate chains (propanogenins) are PKS or FAS products. A critical comparison of PKS and FAS architectures and activities supports the hypothesis of a common evolutionary origin of these enzyme complexes and highlights why PKS can catalyse the biosynthesis of much more complex products than can FAS. Finally, we summarise knowledge which might assist researchers in designing approaches for the detection of insect PKS genes.

  16. Evolutionary origins of pectin methylesterase genes associated with novel aspects of angiosperm pollen tube walls.

    Science.gov (United States)

    Wallace, Simon; Williams, Joseph H

    2017-06-03

    The early evolution of angiosperms was marked by a number of innovations of the reproductive cycle including an accelerated fertilization process involving faster transport of sperm to the egg via a pollen tube. Fast pollen tube growth rates in angiosperms are accompanied by a hard shank-soft tip pollen tube morphology. A critical actor in that morphology is the wall-embedded enzyme pectin methylesterase (PME), which in type II PMEs is accompanied by a co-transcribed inhibitor, PMEI. PMEs convert the esterified pectic tip wall to a stiffer state in the subapical flank by pectin de-esterification. It is hypothesized that rapid and precise targeting of PME activity was gained with the origin of type II genes, which are derived and have only expanded since the origin of vascular plants. Pollen-active PMEs have yet to be reported in early-divergent angiosperms or gymnosperms. Gene expression studies in Nymphaea odorata found transcripts from four type II VGD1-like and 16 type I AtPPME1-like homologs that were more abundant in pollen and pollen tubes than in vegetative tissues. The near full-length coding sequence of one type II PME (NoPMEII-1) included at least one PMEI domain. The identification of possible VGD1 homologs in an early-diverging angiosperm suggests that the refined control of PMEs that mediate de-esterification of pectins near pollen tube tips is a conserved feature across angiosperms. The recruitment of type II PMEs into a pollen tube elongation role in angiosperms may represent a key evolutionary step in the development of faster growing pollen tubes. Copyright © 2017 Elsevier Inc. All rights reserved.

  17. [Advantage of obsessive-compulsive symptoms from the aspect of individual selection and group selection: an evolutionary psychological approach to obsessive-compulsive disorder].

    Science.gov (United States)

    Gonda, Xénia; Jekkel, Eva; Varga, Anna; Miklósi, Mónika; Forintos, Dóra Perczel

    2008-10-01

    Psychiatric disorders are difficult to explain from an evolutionary aspect, since it is hard to reason how a characteristic carrying a reproductive disadvantage survives through natural selection. There are several evolution-based papers concerning obsessive-compulsive disorder (OCD), which aim at resolving this contradiction. Recent studies provided considerable evidence in support for the evolutionary theories of OCD. Research confirmed an important role for genetic factors in the background of OCD, and neuroanatomic studies supported that neuroanatomical structures playing a role in OCD are those areas which are activated during the processing of danger and threat. From the evolutionary aspect OCD can be explained both from the individual and group selection aspect. According to the theory of individual selection, OCD symptoms are based on such behaviors which are by themselves advantageous serving individual survival and reproduction and therefore carry on through natural selection. According to group selection theory, although OCD is disadvantageous for the individual, it is adaptive for the survival of the group. In our paper we review the individual and group selection theories of OCD, and we also outline the continuity and discontinuity theories which show a significant overlap with the evolutionary theories. We review characteristic age and gender differences related to OCD from this aspect. The evolutionary approach to OCD is important in understanding the background factors, development and symptoms of OCD, which mean new tools in the prevention and treatment of this disorder.

  18. Caspases: An apoptosis mediator

    Directory of Open Access Journals (Sweden)

    Tapan Kumar Palai

    2015-03-01

    Full Text Available The process of programmed cell death, or apoptosis, is generally characterized by distinct morphological characteristics and energy - dependent biochemical mechanisms. Apoptosis is a widely conserved phenomenon helping many processes, including normal cell turnover, proper development and functioning of the immune system, hormone dependent atrophy etc. Inappropriate apoptosis (either low level or high level leads to many developmental abnormalities like, neurodegenerative diseases, ischemic damage, autoimmune disorders and many types of cancer. To use cells for therapeutic purposes through generating cell lines, it is critical to study the cell cycle machinery and signalling pathways that controls cell death and apoptosis. Apoptotic pathways provide a fundamental protective mechanism that decreases cellular sensitivity to damaging events and allow proper developmental process in multi-cellular organisms. Major mediator of apoptosis is a family of proteins known as caspases. There are mainly fourteen types of caspases but out of them only ten caspasese have got essential role in controlling the process of apoptosis. These ten caspases have been categorized into either initiator caspases (caspase 2, 8, 9, 10 or executioner caspases (caspase 3, 6, 7. Although various types of caspases have been identified so far, the exact mechanisms of action of these groups of proteins is still to be fully understood. The aim of this review is to provide a detail overview of role of different caspases in regulating the process of apoptosis.

  19. Genomics and evolutionary aspect of calcium signaling event in calmodulin and calmodulin-like proteins in plants.

    Science.gov (United States)

    Mohanta, Tapan Kumar; Kumar, Pradeep; Bae, Hanhong

    2017-02-03

    Ca 2+ ion is a versatile second messenger that operate in a wide ranges of cellular processes that impact nearly every aspect of life. Ca 2+ regulates gene expression and biotic and abiotic stress responses in organisms ranging from unicellular algae to multi-cellular higher plants through the cascades of calcium signaling processes. In this study, we deciphered the genomics and evolutionary aspects of calcium signaling event of calmodulin (CaM) and calmodulin like- (CML) proteins. We studied the CaM and CML gene family of 41 different species across the plant lineages. Genomic analysis showed that plant encodes more calmodulin like-protein than calmodulins. Further analyses showed, the majority of CMLs were intronless, while CaMs were intron rich. Multiple sequence alignment showed, the EF-hand domain of CaM contains four conserved D-x-D motifs, one in each EF-hand while CMLs contain only one D-x-D-x-D motif in the fourth EF-hand. Phylogenetic analysis revealed that, the CMLs were evolved earlier than CaM and later diversified. Gene expression analysis demonstrated that different CaM and CMLs genes were express differentially in different tissues in a spatio-temporal manner. In this study we provided in detailed genome-wide identifications and characterization of CaM and CML protein family, phylogenetic relationships, and domain structure. Expression study of CaM and CML genes were conducted in Glycine max and Phaseolus vulgaris. Our study provides a strong foundation for future functional research in CaM and CML gene family in plant kingdom.

  20. Evolutionary Demography

    DEFF Research Database (Denmark)

    Levitis, Daniel

    2015-01-01

    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...... 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...

  1. Caspases : more than just killers?

    OpenAIRE

    Los, Marek Jan; Stroh, C.; Janicke, R. U.; Engels, I. H.; Schulze-Osthoff, K.

    2001-01-01

    Proteases of the caspase family constitute the central executioners of apoptosis, Several recent observations suggest that caspases and apoptosis-regulatory molecules exert important functions beyond that of cell death, including the control of T-cell proliferation and cell-cycle progression. Here, Los and colleagues propose a model that directly connects cell suicide mechanisms to the regulation of cell-cycle progression.

  2. Caspases: more than just killers?

    Science.gov (United States)

    Los, M; Stroh, C; Jänicke, R U; Engels, I H; Schulze-Osthoff, K

    2001-01-01

    Proteases of the caspase family constitute the central executioners of apoptosis. Several recent observations suggest that caspases and apoptosis-regulatory molecules exert important functions beyond that of cell death, including the control of T-cell proliferation and cell-cycle progression. Here, Los and colleagues propose a model that directly connects cell suicide mechanisms to the regulation of cell-cycle progression.

  3. Evolutionary history of the PER3 variable number of tandem repeats (VNTR): idiosyncratic aspect of primate molecular circadian clock.

    Science.gov (United States)

    Sabino, Flávia Cal; Ribeiro, Amanda Oliveira; Tufik, Sérgio; Torres, Laila Brito; Oliveira, José Américo; Mello, Luiz Eugênio Araújo Moraes; Cavalcante, Jeferson Souza; Pedrazzoli, Mario

    2014-01-01

    The PER3 gene is one of the clock genes, which function in the core mammalian molecular circadian system. A variable number of tandem repeats (VNTR) locus in the 18th exon of this gene has been strongly associated to circadian rhythm phenotypes and sleep organization in humans, but it has not been identified in other mammals except primates. To better understand the evolution and the placement of the PER3 VNTR in a phylogenetical context, the present study enlarges the investigation about the presence and the structure of this variable region in a large sample of primate species and other mammals. The analysis of the results has revealed that the PER3 VNTR occurs exclusively in simiiforme primates and that the number of copies of the primitive unit ranges from 2 to 11 across different primate species. Two transposable elements surrounding the 18th exon of PER3 were found in primates with published genome sequences, including the tarsiiforme Tarsius syrichta, which lacks the VNTR. These results suggest that this VNTR may have evolved in a common ancestor of the simiiforme branch and that the evolutionary copy number differentiation of this VNTR may be associated with primate simiiformes sleep and circadian phenotype patterns.

  4. Evolutionary history of the PER3 variable number of tandem repeats (VNTR: idiosyncratic aspect of primate molecular circadian clock.

    Directory of Open Access Journals (Sweden)

    Flávia Cal Sabino

    Full Text Available The PER3 gene is one of the clock genes, which function in the core mammalian molecular circadian system. A variable number of tandem repeats (VNTR locus in the 18th exon of this gene has been strongly associated to circadian rhythm phenotypes and sleep organization in humans, but it has not been identified in other mammals except primates. To better understand the evolution and the placement of the PER3 VNTR in a phylogenetical context, the present study enlarges the investigation about the presence and the structure of this variable region in a large sample of primate species and other mammals. The analysis of the results has revealed that the PER3 VNTR occurs exclusively in simiiforme primates and that the number of copies of the primitive unit ranges from 2 to 11 across different primate species. Two transposable elements surrounding the 18th exon of PER3 were found in primates with published genome sequences, including the tarsiiforme Tarsius syrichta, which lacks the VNTR. These results suggest that this VNTR may have evolved in a common ancestor of the simiiforme branch and that the evolutionary copy number differentiation of this VNTR may be associated with primate simiiformes sleep and circadian phenotype patterns.

  5. Roles of inflammatory caspases during processing of zebrafish interleukin-1β in Francisella noatunensis infection

    Science.gov (United States)

    Vojtech, Lucia N.; Scharping, Nichole; Woodson, James C.; Hansen, John D.

    2012-01-01

    The interleukin-1 family of cytokines are essential for the control of pathogenic microbes but are also responsible for devastating autoimmune pathologies. Consequently, tight regulation of inflammatory processes is essential for maintaining homeostasis. In mammals, interleukin-1 beta (IL-1β) is primarily regulated at two levels, transcription and processing. The main pathway for processing IL-1β is the inflammasome, a multiprotein complex that forms in the cytosol and which results in the activation of inflammatory caspase (caspase 1) and the subsequent cleavage and secretion of active IL-1β. Although zebrafish encode orthologs of IL-1β and inflammatory caspases, the processing of IL-1β by activated caspase(s) has never been examined. Here, we demonstrate that in response to infection with the fish-specific bacterial pathogen Francisella noatunensis, primary leukocytes from adult zebrafish display caspase-1-like activity that results in IL-1β processing. Addition of caspase 1 or pancaspase inhibitors considerably abrogates IL-1β processing. As in mammals, this processing event is concurrent with the secretion of cleaved IL-1β into the culture medium. Furthermore, two putative zebrafish inflammatory caspase orthologs, caspase A and caspase B, are both able to cleave IL-1β, but with different specificities. These results represent the first demonstration of processing and secretion of zebrafish IL-1β in response to a pathogen, contributing to our understanding of the evolutionary processes governing the regulation of inflammation.                   

  6. EVOLUTIONARY ASPECTS OF THE WELFARE OF THE RURAL POPULATION IN THE REPUBLIC OF MOLDOVA AND THEIR MOTIVATIONAL IMPLICATIONS

    Directory of Open Access Journals (Sweden)

    Veronica PRISACARU

    2013-12-01

    Full Text Available The paper is focused on the issue of rural population incomes, their evolution, and changes in their structure that occurred in the period 2006-2012. It was performed a comparative analysis of the ratio between the available income per capita and subsistence minimum in rural and urban areas, and based on this, it was highlighted the gap between the welfare of urban and rural population. The result of the study proved that despite positive tendencies in reducing rural poverty, rural population income is still very low, without reaching the subsistence minimum. This fact, along with other negative aspects (reduced share of income from employment, increased share of social allowances and remittances leads to the decrease of the motivational effects of work payment and income from agricultural activity. Thus, it is obvious, that along with government social programs, to have more effective state actions targeted to business development in rural areas and hence creating new workplaces.

  7. The highly leukotoxic JP2 clone of Aggregatibacter actinomycetemcomitans: evolutionary aspects, epidemiology and etiological role in aggressive periodontitis.

    Science.gov (United States)

    Haubek, Dorte

    2010-09-01

    For many years, attention has been given to the oral bacterium Aggregatibacter actinomycetemcomitans, as a species possibly implicated in the etiology of aggressive periodontitis in adolescents. One of the major virulence factors of A. actinomycetemcomitans is the leukotoxin which is able to kill important cells of the immune system. As demonstrated in population genetic analyses, the population structure of A. actinomycetemcomitans is mainly clonal with evolutionary lineages corresponding to the serotypes. A particular highly leukotoxic clone (JP2) of serotype b has been discovered. The JP2 clone, with an estimated origin some 2400 years ago, is found to be highly conserved, based on analyses of a collection of JP2 clone strains collected through more than 20 years from individuals of diverse origin and living geographically widespread. Despite demonstration of minor evolutionary changes within the genome of JP2 clone strains of A. actinomycetemcomitans, the JP2 clone strains constitute a unique clonal type, the characteristics of which include a 530 basepair deletion in the leukotoxin operon implicated in the enhanced leukotoxic activity of the clone. Mapping of the geographic occurrence of the JP2 clone of A. actinomycetemcomitans has revealed that its colonization is largely restricted to individuals of African descent. Characteristic mutations, which allow JP2 clone isolates from the Mediterranean region to be distinguished from isolates from West Africa, including the Cape Verde islands, suggest that the JP2 clone initially emerged as a distinct genotype in the Mediterranean region of Africa and subsequently spread to West Africa, from where it might have been transferred to the American continent during the transatlantic slave trade. The finding of a sustained selective colonization of individuals of African descent, despite geographical separation from the African continent for centuries, suggests that the JP2 clone might have a distinct host tropism

  8. Structural, functional, and evolutionary aspects of galectins in aquatic mollusks: From a sweet tooth to the Trojan horse.

    Science.gov (United States)

    Vasta, G R; Feng, C; Bianchet, M A; Bachvaroff, T R; Tasumi, S

    2015-09-01

    Galectins constitute a conserved and widely distributed lectin family characterized by their binding affinity for β-galactosides and a unique binding site sequence motif in the carbohydrate recognition domain (CRD). In spite of their structural conservation, galectins display a remarkable functional diversity, by participating in developmental processes, cell adhesion and motility, regulation of immune homeostasis, and recognition of glycans on the surface of viruses, bacteria and protozoan parasites. In contrast with mammals, and other vertebrate and invertebrate taxa, the identification and characterization of bona fide galectins in aquatic mollusks has been relatively recent. Most of the studies have focused on the identification and domain organization of galectin-like transcripts or proteins in diverse tissues and cell types, including hemocytes, and their expression upon environmental or infectious challenge. Lectins from the eastern oyster Crassostrea virginica, however, have been characterized in their molecular, structural and functional aspects and some notable features have become apparent in the galectin repertoire of aquatic mollusks. These including less diversified galectin repertoires and different domain organizations relative to those observed in vertebrates, carbohydrate specificity for blood group oligosaccharides, and up regulation of galectin expression by infectious challenge, a feature that supports their proposed role(s) in innate immune responses. Although galectins from some aquatic mollusks have been shown to recognize microbial pathogens and parasites and promote their phagocytosis, they can also selectively bind to phytoplankton components, suggesting that they also participate in uptake and intracellular digestion of microalgae. In addition, the experimental evidence suggests that the protozoan parasite Perkinsus marinus has co-evolved with the oyster host to be selectively recognized by the oyster hemocyte galectins over algal food

  9. The caspase-activated DNase

    DEFF Research Database (Denmark)

    Larsen, Brian D; Sørensen, Claus S

    2017-01-01

    CAD-induced DNA breaks. Furthermore, an apparent consequence of CAD activity is also emerging, as a potential source of oncogenic mutations. This review will discuss the mechanisms underlying CAD-induced DNA breaks and highlight how CAD activity promotes diverse cell fates....... and integral to this balance. Importantly, the view of apoptotic signal transduction has expanded over the previous decades. Subapoptotic caspase signaling has surfaced as mechanism that can promote the adoption of a range of cellular fates. An emerging mechanism of subapoptotic caspase signaling...... is the activation of the caspase-activated DNase (CAD) through controlled cleavage of the inhibitor of CAD (ICAD). CAD-induced DNA breaks incite a DNA damage response, frequently invoking p53 signaling, that transduces a change in cell fate. Cell differentiation and senescence are fates demonstrated to arise from...

  10. Structural Features of Caspase-Activating Complexes

    Directory of Open Access Journals (Sweden)

    Hyun Ho Park

    2012-04-01

    Full Text Available Apoptosis, also called programmed cell death, is an orderly cellular suicide program that is critical for the development, immune regulation and homeostasis of a multi-cellular organism. Failure to control this process can lead to serious human diseases, including many types of cancer, neurodegenerative diseases, and autoimmununity. The process of apoptosis is mediated by the sequential activation of caspases, which are cysteine proteases. Initiator caspases, such as caspase-2, -8, -9, and -10, are activated by formation of caspase-activating complexes, which function as a platform to recruit caspases, providing proximity for self-activation. Well-known initiator caspase-activating complexes include (1 DISC (Death Inducing Signaling Complex, which activates caspases-8 and 10; (2 Apoptosome, which activates caspase-9; and (3 PIDDosome, which activates caspase-2. Because of the fundamental biological importance of capases, many structural and biochemical studies to understand the molecular basis of assembly mechanism of caspase-activating complexes have been performed. In this review, we summarize previous studies that have examined the structural and biochemical features of caspase-activating complexes. By analyzing the structural basis for the assembly mechanism of the caspase-activating complex, we hope to provide a comprehensive understanding of caspase activation by these important oligomeric complexes.

  11. Pharmacological caspase inhibitors: research towards therapeutic perspectives.

    Science.gov (United States)

    Kudelova, J; Fleischmannova, J; Adamova, E; Matalova, E

    2015-08-01

    Caspases are key molecules of apoptosis and the inflammatory response. Up-regulation of the caspase cascade contributes to human pathologies such as neurodegenerative and immune disorders. Thus, blocking the excessive apoptosis by pharmacological inhibitors seems promising for therapeutic interventions in such diseases. Caspase inhibitors, both natural and artificial, have been used as research tools and have helped to define the role of the individual caspases in apoptosis and in non-apoptotic processes. Moreover, some caspase inhibitors have demonstrated their therapeutic efficiency in the reduction of cell death and inflammation in animal models of human diseases. However, no drug based on caspase inhibition has been approved on the market until now. Thus, the development of therapeutic approaches that specifically target caspases remains a great challenge and is now the focus of intense biological and clinical interest. Here, we provide a brief review of recent knowledge about pharmacological caspase inhibitors with special focus on their proposed clinical applications.

  12. Integrity of XIAP is essential for effective activity recovery of apoptosome and its downstream caspases by Smac/Diablo.

    Science.gov (United States)

    Attaran-Bandarabadi, Faezeh; Abhari, Behnaz Ahangarian; Neishabouri, Shima Hallaj; Davoodi, Jamshid

    2017-08-01

    Contribution of individual BIR domains to Smac antagonism is investigated. Ammonium citrate was used to activate caspase-9 and pro-caspase-9 (D315, D330/A). However, the presence of citrate resulted in autoproteolysis of pro-caspase-9 and its inhibition by XIAP BIR3, which was not observed for apoptosome activated pro-caspase-9 indicating abnormal behavior of pro-caspase-9 in kosmotropic citrate salt. Thus, we used Apaf-1(residues 1-591) to activate caspase-9 through the formation of mini-apoptosome instead. Inhibition of apoptosome by XIAP BIR-1-2-3 was observed to be similar to that of BIR3 indicating that the cleavage of XIAP does not affect its potency. However, BIR1-2-3 was more prone to Smac antagonism due to simultaneous interaction of two BIR domains from XIAP with two N-terminal binding sites of Smac. Therefore, despite the role in caspase-9 activation, Apaf-1 does not influence caspase-9 inhibition by XIAP. In addition, caspase-3, -7 and -9 activity recovery by Smac protein and peptide were more efficient for BIR1-2-3 than for BIR1-2. Consequently, it can be proposed that the presence of multiple BIR domains for XIAP among different species along with dimeric nature of Smac are evolutionary designed to strengthen the antagonistic activity of Smac culminating in efficient induction of cell death. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. Inflammasomes and inflammatory caspases in skin inflammation.

    Science.gov (United States)

    Iversen, Lars; Johansen, Claus

    2008-11-01

    The inflammatory caspases comprise a subclass of caspases associated with immune responses. Caspase-1 was the first identified member of this class, which also includes caspase-4, -5, -11 and -12. Caspase-1 was identified as the IL-1beta-converting enzyme and, more recently, it has also been shown to activate IL-18 and IL-33. Activation of the inflammatory caspases occurs upon assembly of multiprotein complexes, termed inflammasomes. The inflammasomes and inflammatory caspases are part of the innate immune system, which constitutes the first line of defense that detects pathogens, such as nonself antigens, bacterial and viral components, and other danger signals, and orchestrates the immune response. Inflammasomes and inflammatory caspases have also been suggested to bridge the innate immune responses to the adaptive immune system. More recently, the expression and role of inflammasomes and inflammatory caspases have been studied in both human and rodent skin, and findings have indicated a possible key role of these regulators of the immune system in the pathogenesis of inflammatory skin diseases. This article will review some of the most recent findings, identifying inflammasomes and inflammatory caspases as potential inducers and regulators of skin inflammation in contact hypersensitivity and psoriasis.

  14. Molecular cloning, immunohistochemical localization, characterization and expression analysis of caspase-9 from the purse red common carp (Cyprinus carpio) exposed to cadmium

    Energy Technology Data Exchange (ETDEWEB)

    Gao, Dian; Xu, Zhen’e [Medical College of Nanchang University, Nanchang 330006 (China); Institute of Immunotherapy, Nanchang University, Nanchang 330006 (China); Zhang, Xiaoyan [Medical College of Nanchang University, Nanchang 330006 (China); Wang, Hongmei [Medical College of Nanchang University, Nanchang 330006 (China); Institute of Immunotherapy, Nanchang University, Nanchang 330006 (China); Wang, Yannan [Medical College of Nanchang University, Nanchang 330006 (China); Min, Weiping, E-mail: weiping.min@gmail.com [Medical College of Nanchang University, Nanchang 330006 (China); Institute of Immunotherapy, Nanchang University, Nanchang 330006 (China); Jiangxi Academy of Medical Sciences, Nanchang 330006 (China)

    2013-10-15

    Highlights: •The cDNA of caspase-9 in common carp was cloned. •The evolutionary conservation including caspase recruitment domain, large and small subunits was clarified. •The mRNA level of caspase-9 cannot be used as a major marker at an earlier point in the apoptotic cascade. •Caspase-9 cleavage form was detected. •Immunopositive staining was limited to the cytoplasm of renal tubular epithelial cells. -- Abstract: Caspase-9, the essential initiator caspase is believed to play a central role in mitochondria-mediated apoptosis signaling. In this study, we isolated the caspase-9 gene from common carp, one of the most important industrial aquatic animals in China using rapid amplification of cDNA ends (RACE). The deduced amino acid sequence of caspase-9, composed of 436 amino acids, showed approximately 47.6% identity and 64.7% similarity to human caspase-9. It also possessed a conserved caspase-associated recruitment domain (CARD), a large subunit and a small subunit. Phylogenetic analysis clearly demonstrated that caspase-9 formed a clade with cyprinid fish caspase-9. Real-time quantitative PCR analysis revealed that caspase-9 transcripts were not significantly increased in kidney after exposure to cadmium (Cd). Whereas caspase-9 cleaved fragments were detected using Western blot analysis with the same Cd treatment condition. Furthermore, the result of immunohistochemical detection showed immunoreactivities were predominantly limited to the cytoplasm of renal tubular epithelial cells and no remarkable changes of immunopositive staining were observed after Cd treatment. Accordingly, the results signify that caspase-9 may play an essential role in Cd induced apoptosis.

  15. Interfaces in evolutionary games

    Science.gov (United States)

    Kolotev, Sergei; Malyutin, Aleksandr; Burovski, Evgeni; Shchur, Lev

    2018-01-01

    We investigate geometrical aspects of a spatial evolutionary game. The game is based on the Prisoner’s dilemma. We analyze the geometrical structure of the space distribution of cooperators and defectors in the steady-state regime of evolution. We develop algorithm for the identification of the interfaces between clusters of cooperators and defectors, and measure fractal properties of the interfaces.

  16. Pharmacological caspase inhibitors: Research towards therapeutic perspectives

    Czech Academy of Sciences Publication Activity Database

    Kudělová, J.; Fleischmannová, Jana; Adamová, Eva; Matalová, Eva

    2015-01-01

    Roč. 66, č. 4 (2015), s. 473-482 ISSN 0867-5910 R&D Projects: GA ČR GB14-37368G Institutional support: RVO:67985904 Keywords : caspase * caspase inhibitor * apoptosis Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.804, year: 2015

  17. Pharmacological caspase inhibitors: Research towards therapeutic perspectives

    Czech Academy of Sciences Publication Activity Database

    Kudělová, J.; Fleischmannová, J.; Adamová, E.; Matalová, Eva

    2015-01-01

    Roč. 66, č. 4 (2015), s. 473-482 ISSN 0867-5910 R&D Projects: GA ČR(CZ) GA14-28254S Institutional support: RVO:68081715 Keywords : caspase * caspase inhibitor * apoptosis Subject RIV: CB - Analytical Chemistry, Separation Impact factor: 2.804, year: 2015

  18. 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.

  19. 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...

  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. A novel tachykinin-related peptide receptor of Octopus vulgaris--evolutionary aspects of invertebrate tachykinin and tachykinin-related peptide.

    Science.gov (United States)

    Kanda, Atsuhiro; Takuwa-Kuroda, Kyoko; Aoyama, Masato; Satake, Honoo

    2007-05-01

    The tachykinin (TK) and tachykinin-related peptide (TKRP) family represent one of the largest peptide families in the animal kingdom and exert their actions via a subfamily of structurally related G-protein-coupled receptors. In this study, we have identified a novel TKRP receptor from the Octopus heart, oct-TKRPR. oct-TKRPR includes domains and motifs typical of G-protein-coupled receptors. Xenopus oocytes that expressed oct-TKRPR, like TK and TKRP receptors, elicited an induction of membrane chloride currents coupled to the inositol phosphate/calcium pathway in response to Octopus TKRPs (oct-TKRP I-VII) with moderate ligand selectivity. Substance P and Octopus salivary gland-specific TK, oct-TK-I, completely failed to activate oct-TKRPR, whereas a Substance P analog containing a C-terminal Arg-NH2 exhibited equipotent activation of oct-TKRPs. These functional analyses prove that oct-TKRPs, but not oct-TK-I, serve as endogenous functional ligands through oct-TKRPR, although both of the family peptides were identified in a single species, and the importance of C-terminal Arg-NH2 in the specific recognition of TKRPs by TKRPR is conserved through evolutionary lineages of Octopus. Southern blotting of RT-PCR products revealed that the oct-TKRPR mRNA was widely distributed in the central and peripheral nervous systems plus several peripheral tissues. These results suggest multiple physiologic functions of oct-TKRPs as neuropeptides both in the Octopus central nervous system and in peripheral tissues. This is the first report on functional discrimination between invertebrate TKRPs and salivary gland-specific TKs.

  2. Caspase-12 and the inflammatory response to Yersinia pestis.

    NARCIS (Netherlands)

    Ferwerda, B.; McCall, M.B.B.; Vries, M.C. de; Hopman, J.C.W.; Maiga, B.; Dolo, A.; Doumbo, O.; Daou, M.; Jong, D.J. de; Joosten, L.A.B.; Tissingh, R.A.; Reubsaet, F.A.; Sauerwein, R.W.; Meer, J.W.M. van der; Ven, A.J.A.M. van der; Netea, M.G.

    2009-01-01

    BACKGROUND: Caspase-12 functions as an antiinflammatory enzyme inhibiting caspase-1 and the NOD2/RIP2 pathways. Due to increased susceptibility to sepsis in individuals with functional caspase-12, an early-stop mutation leading to the loss of caspase-12 has replaced the ancient genotype in Eurasia

  3. 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.

  4. Evolutionary macroecology

    Directory of Open Access Journals (Sweden)

    José Alexandre F. Diniz-Filho

    2013-10-01

    Full Text Available Macroecology focuses on ecological questions at broad spatial and temporal scales, providing a statistical description of patterns in species abundance, distribution and diversity. More recently, historical components of these patterns have begun to be investigated more deeply. We tentatively refer to the practice of explicitly taking species history into account, both analytically and conceptually, as ‘evolutionary macroecology’. We discuss how the evolutionary dimension can be incorporated into macroecology through two orthogonal and complementary data types: fossils and phylogenies. Research traditions dealing with these data have developed more‐or‐less independently over the last 20–30 years, but merging them will help elucidate the historical components of diversity gradients and the evolutionary dynamics of species’ traits. Here we highlight conceptual and methodological advances in merging these two research traditions and review the viewpoints and toolboxes that can, in combination, help address patterns and unveil processes at temporal and spatial macro‐scales.

  5. 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......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...... 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...

  6. Evolutionary computation for trading systems

    OpenAIRE

    Kaucic, Massimiliano

    2008-01-01

    2007/2008 Evolutionary computations, also called evolutionary algorithms, consist of several heuristics, which are able to solve optimization tasks by imitating some aspects of natural evolution. They may use different levels of abstraction, but they are always working on populations of possible solutions for a given task. The basic idea is that if only those individuals of a population which meet a certain selection criteria reproduce, while the remaining individuals die, the ...

  7. 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 ...

  8. Sox11 Reduces Caspase-6 Cleavage and Activity.

    Directory of Open Access Journals (Sweden)

    Elaine Waldron-Roby

    Full Text Available The apoptotic cascade is an orchestrated event, whose final stages are mediated by effector caspases. Regulatory binding proteins have been identified for caspases such as caspase-3, -7, -8, and -9. Many of these proteins belong to the inhibitor of apoptosis (IAP family. By contrast, caspase-6 is not believed to be influenced by IAPs, and little is known about its regulation. We therefore performed a yeast-two-hybrid screen using a constitutively inactive form of caspase-6 for bait in order to identify novel regulators of caspase-6 activity. Sox11 was identified as a potential caspase-6 interacting protein. Sox11 was capable of dramatically reducing caspase-6 activity, as well as preventing caspase-6 self- cleavage. Several regions, including amino acids 117-214 and 362-395 within sox11 as well as a nuclear localization signal (NLS all contributed to the reduction in caspase-6 activity. Furthermore, sox11 was also capable of decreasing other effector caspase activity but not initiator caspases -8 and -9. The ability of sox11 to reduce effector caspase activity was also reflected in its capacity to reduce cell death following toxic insult. Interestingly, other sox proteins also had the ability to reduce caspase-6 activity but to a lesser extent than sox11.

  9. Krebs Cycle Moonlights in Caspase Regulation

    OpenAIRE

    Minis, Adi; Steller, Hermann

    2016-01-01

    In this issue of Developmental Cell, Aram et al. (2016) identify a mechanism that uses a Krebs cycle protein to control local activation of a ubiquitin ligase complex at the mitochondrial outer membrane for temporally and spatially restricted caspase activation during Drosophila sperm differentiation.

  10. Krebs Cycle Moonlights in Caspase Regulation.

    Science.gov (United States)

    Minis, Adi; Steller, Hermann

    2016-04-04

    In this issue of Developmental Cell, Aram et al. (2016) identify a mechanism that uses a Krebs cycle protein to control local activation of a ubiquitin ligase complex at the mitochondrial outer membrane for temporally and spatially restricted caspase activation during Drosophila sperm differentiation. Copyright © 2016 Elsevier Inc. All rights reserved.

  11. Evolutionary Finance

    OpenAIRE

    Igor V. Evstigneev; Thorsten Hens; Klaus Reiner Schenk-Hoppé

    2008-01-01

    Evolutionary finance studies the dynamic interaction of investment strategies in financial markets. This market interaction generates a stochastic wealth dynamics on a heterogenous population of traders through the fluctuation of asset prices and their random payoffs. Asset prices are endogenously determined through short-term market clearing. Investors' portfolio choices are characterized by investment strategies which provide a descriptive model of decision behavior. The mathematical framew...

  12. 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.

  13. Conformational similarity in the activation of caspase-3 and -7 revealed by the unliganded and inhibited structures of caspase-7

    Energy Technology Data Exchange (ETDEWEB)

    Agniswamy, Johnson; Fang, Bin; Weber, Irene T.; (GSU)

    2009-09-08

    Caspase-mediated apoptosis has important roles in normal cell differentiation and aging and in many diseases including cancer, neuromuscular disorders and neurodegenerative diseases. Therefore, modulation of caspase activity and conformational states is of therapeutic importance. We report crystal structures of a new unliganded conformation of caspase-7 and the inhibited caspase-7 with the tetrapeptide Ac-YVAD-Cho. Different conformational states and mechanisms for substrate recognition have been proposed based on unliganded structures of the redundant apoptotic executioner caspase-3 and -7. The current study shows that the executioner caspase-3 and -7 have similar conformations for the unliganded active site as well as the inhibitor-bound active site. The new unliganded caspase-7 structure exhibits the tyrosine flipping mechanism in which the Tyr230 has rotated to block entry to the S2 binding site similar to the active site conformation of unliganded caspase-3. The inhibited structure of caspase-7/YVAD shows that the P4 Tyr binds the S4 region specific to polar residues at the expense of a main chain hydrogen bond between the P4 amide and carbonyl oxygen of caspase-7 Gln 276, which is similar to the caspase-3 complex. This new knowledge of the structures and conformational states of unliganded and inhibited caspases will be important for the design of drugs to modulate caspase activity and apoptosis.

  14. Evolutionary Aspects of Depression, Stress and Subordination ...

    African Journals Online (AJOL)

    HPA- axis) as the final common pathway to depression. The key role of serotonin in these processes is explored. Finally this paper offers suggestions for therapeutic interventions, based on an understanding of these interactions. South African ...

  15. The impact of caspase-12 on susceptibility to candidemia.

    NARCIS (Netherlands)

    Rosentul, D.C.; Plantinga, T.S.; Scott, W.K.; Alexander, B.D.; Geer, N.M. van de; Perfect, J.R.; Kullberg, B.J.; Johnson, M.D.; Netea, M.G.

    2012-01-01

    Candida is one of the leading causes of sepsis, and an effective host immune response to Candida critically depends on the cytokines IL-1beta and IL-18, which need caspase-1 cleavage to become bioactive. Caspase-12 has been suggested to inhibit caspase-1 activation and has been implicated as a

  16. Evolutionary Biology in the Medical School Curriculum.

    Science.gov (United States)

    Neese, Randolph M.; Schiffman, Joshua D.

    2003-01-01

    Presents a study in which a questionnaire was given to deans at North American medical schools to determine which aspects of evolutionary biology are included in the curricula and the factors that influence this. Suggests that most future physicians should learn evolutionary biology as undergraduates if they are to learn it at all. (Author/NB)

  17. Comparative genomics reveals conservation of filaggrin and loss of caspase-14 in dolphins.

    Science.gov (United States)

    Strasser, Bettina; Mlitz, Veronika; Fischer, Heinz; Tschachler, Erwin; Eckhart, Leopold

    2015-05-01

    The expression of filaggrin and its stepwise proteolytic degradation are critical events in the terminal differentiation of epidermal keratinocytes and in the formation of the skin barrier to the environment. Here, we investigated whether the evolutionary transition from a terrestrial to a fully aquatic lifestyle of cetaceans, that is dolphins and whales, has been associated with changes in genes encoding filaggrin and proteins involved in the processing of filaggrin. We used comparative genomics, PCRs and re-sequencing of gene segments to screen for the presence and integrity of genes coding for filaggrin and proteases implicated in the maturation of (pro)filaggrin. Filaggrin has been conserved in dolphins (bottlenose dolphin, orca and baiji) but has been lost in whales (sperm whale and minke whale). All other S100 fused-type genes have been lost in cetaceans. Among filaggrin-processing proteases, aspartic peptidase retroviral-like 1 (ASPRV1), also known as saspase, has been conserved, whereas caspase-14 has been lost in all cetaceans investigated. In conclusion, our results suggest that filaggrin is dispensable for the acquisition of fully aquatic lifestyles of whales, whereas it appears to confer an evolutionary advantage to dolphins. The discordant evolution of filaggrin, saspase and caspase-14 in cetaceans indicates that the biological roles of these proteins are not strictly interdependent. © 2015 The Authors. Experimental Dermatology Published by John Wiley & Sons Ltd.

  18. A short caspase-3 isoform inhibits chemotherapy-induced apoptosis by blocking apoptosome assembly.

    Directory of Open Access Journals (Sweden)

    Frédérique Végran

    Full Text Available Alternative splicing of caspase-3 produces a short isoform caspase-3s that antagonizes caspase-3 apoptotic activity. However, the mechanism of apoptosis inhibition by caspase-3s remains unknown. Here we show that exogenous caspase-3 sensitizes MCF-7 and HBL100 breast cancers cells to chemotherapeutic treatments such as etoposide and methotrexate whereas co-transfection with caspase-3s strongly inhibits etoposide and methotrexate-induced apoptosis underlying thus the anti-apoptotic role of caspase-3s. In caspase-3 transfected cells, lamin-A and α-fodrin were cleaved when caspase-3 was activated by etoposide or methotrexate. When caspase-3s was co-transfected, this cleavage was strongly reduced. Depletion of caspase-3 by RNA interference in HBL100 containing endogenous caspase-3s caused reduction in etoposide and methotrexate-induced apoptosis, whereas the depletion of caspase-3s sensitized cells to chemotherapy. In the presence of caspase-3s, a lack of interaction between caspase-3 and caspase-9 was observed. Immunoprecipitation assays showed that caspase-3s binds the pro-forms of caspase-3. This result suggested that the absence of interaction with caspase-9 when both variants of caspase-3 are present contribute to block the apoptosome assembly and inhibit apoptosis. These data support that caspases-3s negatively interferes with caspase-3 activation and apoptosis in breast cancer, and that it can play key roles in the modulation of response to chemotherapeutic treatments.

  19. Inhibitor specificity of recombinant and endogenous caspase-9.

    Science.gov (United States)

    Ryan, Ciara A; Stennicke, Henning R; Nava, Victor E; Burch, Jennifer B; Hardwick, J Marie; Salvesen, Guy S

    2002-01-01

    Apoptosis triggered through the intrinsic pathway by radiation and anti-neoplastic drugs is initiated by the activation of caspase-9. To elucidate control mechanisms in this pathway we used a range of synthetic and natural reagents. The inhibitory potency of acetyl-Asp-Glu-Val-Asp-aldehyde ('Ac-DEVD-CHO'), benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone ('Z-VAD-FMK') and the endogenous caspase inhibitor X-chromosome-linked inhibitor of apoptosis protein ('XIAP') against recombinant caspase-9 were predictive of the efficacy of these compounds in a cell-free system. However, the viral proteins CrmA and p35, although potent inhibitors of recombinant caspase-9, had almost no ability to block caspase-9 in this system. These findings were also mirrored in cell expression studies. We hypothesize that the viral inhibitors CrmA and p35 are excluded from reacting productively with the natural form of active caspase-9 in vivo, making the potency of inhibitors highly context-dependent. This is supported by survival data from a mouse model of apoptosis driven by Sindbis virus expressing either p35 or a catalytic mutant of caspase-9. These results consolidate previous findings that CrmA is a potent inhibitor of caspase-9 in vitro, yet fails to block caspase-9-mediated cell death. PMID:12067274

  20. Prokaryotic caspase homologs: phylogenetic patterns and functional characteristics reveal considerable diversity.

    Directory of Open Access Journals (Sweden)

    Johannes Asplund-Samuelsson

    Full Text Available Caspases accomplish initiation and execution of apoptosis, a programmed cell death process specific to metazoans. The existence of prokaryotic caspase homologs, termed metacaspases, has been known for slightly more than a decade. Despite their potential connection to the evolution of programmed cell death in eukaryotes, the phylogenetic distribution and functions of these prokaryotic metacaspase sequences are largely uncharted, while a few experiments imply involvement in programmed cell death. Aiming at providing a more detailed picture of prokaryotic caspase homologs, we applied a computational approach based on Hidden Markov Model search profiles to identify and functionally characterize putative metacaspases in bacterial and archaeal genomes. Out of the total of 1463 analyzed genomes, merely 267 (18% were identified to contain putative metacaspases, but their taxonomic distribution included most prokaryotic phyla and a few archaea (Euryarchaeota. Metacaspases were particularly abundant in Alphaproteobacteria, Deltaproteobacteria and Cyanobacteria, which harbor many morphologically and developmentally complex organisms, and a distinct correlation was found between abundance and phenotypic complexity in Cyanobacteria. Notably, Bacillus subtilis and Escherichia coli, known to undergo genetically regulated autolysis, lacked metacaspases. Pfam domain architecture analysis combined with operon identification revealed rich and varied configurations among the metacaspase sequences. These imply roles in programmed cell death, but also e.g. in signaling, various enzymatic activities and protein modification. Together our data show a wide and scattered distribution of caspase homologs in prokaryotes with structurally and functionally diverse sub-groups, and with a potentially intriguing evolutionary role. These features will help delineate future characterizations of death pathways in prokaryotes.

  1. Caspase-10 Negatively Regulates Caspase-8-Mediated Cell Death, Switching the Response to CD95L in Favor of NF-κB Activation and Cell Survival

    Directory of Open Access Journals (Sweden)

    Sebastian Horn

    2017-04-01

    Full Text Available Formation of the death-inducing signaling complex (DISC initiates extrinsic apoptosis. Caspase-8 and its regulator cFLIP control death signaling by binding to death-receptor-bound FADD. By elucidating the function of the caspase-8 homolog, caspase-10, we discover that caspase-10 negatively regulates caspase-8-mediated cell death. Significantly, we reveal that caspase-10 reduces DISC association and activation of caspase-8. Furthermore, we extend our co-operative/hierarchical binding model of caspase-8/cFLIP and show that caspase-10 does not compete with caspase-8 for binding to FADD. Utilizing caspase-8-knockout cells, we demonstrate that caspase-8 is required upstream of both cFLIP and caspase-10 and that DISC formation critically depends on the scaffold function of caspase-8. We establish that caspase-10 rewires DISC signaling to NF-κB activation/cell survival and demonstrate that the catalytic activity of caspase-10, and caspase-8, is redundant in gene induction. Thus, our data are consistent with a model in which both caspase-10 and cFLIP coordinately regulate CD95L-mediated signaling for death or survival.

  2. Studies in evolutionary agroecology

    DEFF Research Database (Denmark)

    Wille, Wibke

    difference between optimal individual and optimal population performance increases with strong competition among individuals. Thus dense populations make ideal environments to exert forms of selection pressure deviating from natural selection. The first part of this study investigates the central hypothesis...... 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...... with each other, it will have a negative impact on the population performance. While high density results in strong competition, it also increases the potential for cooperation. The other aspect of this study has been to investigate the possibility of improving the yield and weed suppression potential...

  3. Caspases -2, -3, -6, and -9, but not caspase-1, are activated in sepsis-induced thymocyte apoptosis.

    Science.gov (United States)

    Tinsley, K W; Cheng, S L; Buchman, T G; Chang, K C; Hui, J J; Swanson, P E; Karl, I E; Hotchkiss, R S

    2000-01-01

    Sepsis induces extensive lymphocyte cell death that may contribute to immune depression and morbidity/mortality in the disorder. bcl-2 is a member of a new class of oncogenes that prevents cell death from an array of noxious stimuli. Transgenic mice that overexpress BCL-2 in T lymphocytes are resistant to sepsis-induced T cell apoptosis, and mortality was decreased in sepsis. The purpose of this study was to identify key initiator and executioner "caspases" involved in sepsis-induced lymphocyte apoptosis and to determine if BCL-2 acts prior to caspase activation. Thymi were removed 5-22 h post-cecal ligation and puncture (CLP) or sham surgery. Apoptosis was evaluated in thymocytes by annexin-V FITC labeling and flow cytometry. Caspase-1 activity was determined by western blot analysis of the procaspase protein and p20 subunit of the activated caspase; activities of caspases -2, -6, and -9 were determined by colorimetric assays using specific substrates conjugated to a color reporter molecule. Caspase-3 activity was determined both by western blot and by a fluorogenic assay in which a fluorescent compound was generated. Thymocytes from CLP mice had markedly increased apoptosis and activation of caspases -2, -3, -6, and -9 in comparison with thymocytes of sham-operated mice. Caspase-1 was not activated. BCL-2 prevented sepsis-induced thymocyte apoptosis and inhibited activation of all caspases. We conclude that sepsis causes activation of multiple caspases and that BCL-2 acts upstream as an inhibitor of caspase activation. The pattern of caspase activation suggests a mitochondrial mediated pathway.

  4. Caspase activation increases beta-amyloid generation independently of caspase cleavage of the beta-amyloid precursor protein (APP).

    Science.gov (United States)

    Tesco, Giuseppina; Koh, Young Ho; Tanzi, Rudolph E

    2003-11-14

    The amyloid precursor protein (APP) undergoes "alternative" proteolysis mediated by caspases. Three major caspase recognition sites have been identified in the APP, i.e. one at the C terminus (Asp720) and two at the N terminus (Asp197 and Asp219). Caspase cleavage at Asp720 has been suggested as leading to increased production of Abeta. Thus, we set out to determine which putative caspase sites in APP, if any, are cleaved in Chinese hamster ovary cell lines concurrently with the increased Abeta production that occurs during apoptosis. We found that cleavage at Asp720 occurred concurrently with caspase 3 activation and the increased production of total secreted Abeta and Abeta1-42 in association with staurosporine- and etoposide-induced apoptosis. To investigate the contribution of caspase cleavage of APP to Abeta generation, we expressed an APP mutant truncated at Asp720 that mimics APP caspase cleavage at the C-terminal site. This did not increase Abeta generation but, in contrast, dramatically decreased Abeta production in Chinese hamster ovary cells. Furthermore, the ablation of caspase-dependent cleavage at Asp720, Asp197, and Asp219 (by site-directed mutagenesis) did not prevent enhanced Abeta production following etoposide-induced apoptosis. These findings indicate that the enhanced Abeta generation associated with apoptosis does not require cleavage of APP at its C-terminal (Asp720) and/or N-terminal caspase sites.

  5. Passivity and Evolutionary Game Dynamics

    KAUST Repository

    Park, Shinkyu

    2018-03-21

    This paper investigates an energy conservation and dissipation -- passivity -- aspect of dynamic models in evolutionary game theory. We define a notion of passivity using the state-space representation of the models, and we devise systematic methods to examine passivity and to identify properties of passive dynamic models. Based on the methods, we describe how passivity is connected to stability in population games and illustrate stability of passive dynamic models using numerical simulations.

  6. A novel bicistronic sensor vector for detecting caspase-3 activation.

    Science.gov (United States)

    Vagner, Tatyana; Mouravlev, Alexandre; Young, Deborah

    2015-01-01

    Apoptosis is involved in pathological cell death of a wide range of human diseases. One of the most important biochemical markers of apoptosis is activation of caspase-3. Ability to detect caspase-3 activation early in the pathological process is important for determining the timing for interfering with apoptosis initiation and prevention of cell damage. Techniques allowing detection of caspase-3 activity at a single cell level show increased sensitivity, compared to biochemical assays; therefore, we developed a novel bicistronic caspase-3 sensor vector enabling detection of caspase-3 activity in individual cells. We employed green fluorescent protein (GFP) as a reporter for caspase-3 activation in our constructs and assessed the functionality of the generated constructs in transiently transfected Neuro2A and HEK293 cells under basal conditions and following application of okadaic acid (OA) or staurosporine (STS) to induce apoptosis. To ensure responsiveness of the new sensor vector to active caspase-3, we co-transfected the sensor with plasmid(s) overexpressing active caspase-3 and quantified GFP fluorescence using a plate reader. We observed an increase in GFP expression in cells transfected with the new bicistronic caspase-3 sensor in response to both OA and STS. We also showed a significant increase in GFP fluorescence intensity in cells co-expressing the sensor with the plasmid(s) encoding active caspase-3. We generated a novel bicistronic caspase-3 sensor vector which relies on a transcription factor/response element system. The obtained sensor combines high sensitivity of the single cell level detection with the possibility of automated quantification. Copyright © 2015 Elsevier Inc. All rights reserved.

  7. Divergent modulation of neuronal differentiation by caspase-2 and -9.

    Directory of Open Access Journals (Sweden)

    Giuseppa Pistritto

    Full Text Available Human Ntera2/cl.D1 (NT2 cells treated with retinoic acid (RA differentiate towards a well characterized neuronal phenotype sharing many features with human fetal neurons. In view of the emerging role of caspases in murine stem cell/neural precursor differentiation, caspases activity was evaluated during RA differentiation. Caspase-2, -3 and -9 activity was transiently and selectively increased in differentiating and non-apoptotic NT2-cells. SiRNA-mediated selective silencing of either caspase-2 (si-Casp2 or -9 (si-Casp9 was implemented in order to dissect the role of distinct caspases. The RA-induced expression of neuronal markers, i.e. neural cell adhesion molecule (NCAM, microtubule associated protein-2 (MAP2 and tyrosine hydroxylase (TH mRNAs and proteins, was decreased in si-Casp9, but markedly increased in si-Casp2 cells. During RA-induced NT2 differentiation, the class III histone deacetylase Sirt1, a putative caspase substrate implicated in the regulation of the proneural bHLH MASH1 gene expression, was cleaved to a ∼100 kDa fragment. Sirt1 cleavage was markedly reduced in si-Casp9 cells, even though caspase-3 was normally activated, but was not affected (still cleaved in si-Casp2 cells, despite a marked reduction of caspase-3 activity. The expression of MASH1 mRNA was higher and occurred earlier in si-Casp2 cells, while was reduced at early time points during differentiation in si-Casp9 cells. Thus, caspase-2 and -9 may perform opposite functions during RA-induced NT2 neuronal differentiation. While caspase-9 activation is relevant for proper neuronal differentiation, likely through the fine tuning of Sirt1 function, caspase-2 activation appears to hinder the RA-induced neuronal differentiation of NT2 cells.

  8. Caspase-like proteins: Acanthamoeba castellanii metacaspase and ...

    Indian Academy of Sciences (India)

    Caspases are cysteine proteases that are important regulators of programmed cell death in animals. Two novel relatives to members of the caspase families metacaspases and paracaspase have been discovered. Metacaspase type-1 was identified in Acanthamoeba castellanii, an opportunistic protozoan parasite that ...

  9. Endogenous money: the evolutionary versus revolutionary views

    OpenAIRE

    Louis-Philippe Rochon; Sergio Rossi

    2013-01-01

    The purpose of this paper is to shed light on the endogenous nature of money. Contrary to the established post-Keynesian, or evolutionary, view, this paper argues that money has always been endogenous, irrespective of the historical period. Instead of the evolutionary theory of money and banking that can be traced back to Chick (1986), this paper puts forward a revolutionary definition of endogenous money consistent with many aspects of post-Keynesian economics as well as with the monetary ci...

  10. Activation of caspase-9 is required for UV-induced apoptosis of human keratinocytes.

    Science.gov (United States)

    Sitailo, Leonid A; Tibudan, Shalini S; Denning, Mitchell F

    2002-05-31

    UV radiation from the sun activates both the membrane death receptor and the intrinsic or mitochondrial apoptotic signaling pathways in epidermal keratinocytes, triggering apoptosis and affording protection against skin cancer formation. We have investigated the involvement of caspase-9 in the UV death effector pathway in human keratinocytes, since this is the initiating caspase in the mitochondrial pathway required for UV-induced apoptosis in some, but not all, cell types. UV radiation triggered activation of caspase-3, caspase-9, and caspase-8 with similar kinetics, although the rank order of activation was caspase-3 > caspase-9 > caspase-8. Inhibition of caspase-9 with either the peptide inhibitor benzyloxycarbonyl-Leu-Glu(OCH(3))-His-Asp(OCH(3))-fluoromethyl ketone, or expression of a catalytically inactive caspase-9 by retroviral transduction, protected normal keratinocytes from UV-induced apoptosis. HaCaT keratinocytes harboring mutant p53 alleles were also protected from UV-induced apoptosis by the dominant negative caspase-9. The dominant negative caspase-9 blocked UV-induced activation of caspase-3, caspase-9, and caspase-8, and also protected cells from the loss of mitochondrial membrane potential. In contrast, the dominant negative caspase-9 did not protect from anti-Fas-induced apoptosis or caspase activation. These results identify caspase-9 as the critical upstream caspase initiating apoptosis by UV radiation in human keratinocytes, the relevant cell type for this important environmental carcinogen.

  11. 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.

  12. 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

  13. Zinc-mediated Allosteric Inhibition of Caspase-6*

    Science.gov (United States)

    Velázquez-Delgado, Elih M.; Hardy, Jeanne A.

    2012-01-01

    Zinc and caspase-6 have independently been implicated in several neurodegenerative disorders. Depletion of zinc intracellularly leads to apoptosis by an unknown mechanism. Zinc inhibits cysteine proteases, including the apoptotic caspases, leading to the hypothesis that zinc-mediated inhibition of caspase-6 might contribute to its regulation in a neurodegenerative context. Using inductively coupled plasma optical emission spectroscopy, we observed that caspase-6 binds one zinc per monomer, under the same conditions where the zinc leads to complete loss of enzymatic activity. To understand the molecular details of zinc binding and inhibition, we performed an anomalous diffraction experiment above the zinc edge. The anomalous difference maps showed strong 5σ peaks, indicating the presence of one zinc/monomer bound at an exosite distal from the active site. Zinc was not observed bound to the active site. The zinc in the exosite was liganded by Lys-36, Glu-244, and His-287 with a water molecule serving as the fourth ligand, forming a distorted tetrahedral ligation sphere. This exosite appears to be unique to caspase-6, as the residues involved in zinc binding were not conserved across the caspase family. Our data suggest that binding of zinc at the exosite is the primary route of inhibition, potentially locking caspase-6 into the inactive helical conformation. PMID:22891250

  14. Tau and Caspase 3 as Targets for Neuroprotection

    Directory of Open Access Journals (Sweden)

    Anat Idan-Feldman

    2012-01-01

    Full Text Available The peptide drug candidate NAP (davunetide has demonstrated protective effects in various in vivo and in vitro models of neurodegeneration. NAP was shown to reduce tau hyperphosphorylation as well as to prevent caspase-3 activation and cytochrome-3 release from mitochondria, both characteristic of apoptotic cell death. Recent studies suggest that caspases may play a role in tau pathology. The purpose of this study was to evaluate the effect of NAP on tau hyperphosphorylation and caspase activity in the same biological system. Our experimental setup used primary neuronal cultures subjected to oxygen-glucose deprivation (OGD, with and without NAP or caspase inhibitor. Cell viability was assessed by measuring mitochondrial activity (MTS assay, and immunoblots were used for analyzing protein level. It was shown that apoptosis was responsible for all cell death occurring following ischemia, and NAP treatment showed a concentration-dependent protection from cell death. Ischemia caused an increase in the levels of active caspase-3 and hyperphosphorylated tau, both of which were prevented by either NAP or caspase-inhibitor treatment. Our data suggest that, in this model system, caspase activation may be an upstream event to tau hyperphosphorylation, although additional studies will be required to fully elucidate the cascade of events.

  15. Intrinsic-mediated caspase activation is essential for cardiomyocyte hypertrophy

    Science.gov (United States)

    Putinski, Charis; Abdul-Ghani, Mohammad; Stiles, Rebecca; Brunette, Steve; Dick, Sarah A.; Fernando, Pasan; Megeney, Lynn A.

    2013-01-01

    Cardiomyocyte hypertrophy is the cellular response that mediates pathologic enlargement of the heart. This maladaptation is also characterized by cell behaviors that are typically associated with apoptosis, including cytoskeletal reorganization and disassembly, altered nuclear morphology, and enhanced protein synthesis/translation. Here, we investigated the requirement of apoptotic caspase pathways in mediating cardiomyocyte hypertrophy. Cardiomyocytes treated with hypertrophy agonists displayed rapid and transient activation of the intrinsic-mediated cell death pathway, characterized by elevated levels of caspase 9, followed by caspase 3 protease activity. Disruption of the intrinsic cell death pathway at multiple junctures led to a significant inhibition of cardiomyocyte hypertrophy during agonist stimulation, with a corresponding reduction in the expression of known hypertrophic markers (atrial natriuretic peptide) and transcription factor activity [myocyte enhancer factor-2, nuclear factor kappa B (NF-κB)]. Similarly, in vivo attenuation of caspase activity via adenoviral expression of the biologic effector caspase inhibitor p35 blunted cardiomyocyte hypertrophy in response to agonist stimulation. Treatment of cardiomyocytes with procaspase 3 activating compound 1, a small-molecule activator of caspase 3, resulted in a robust induction of the hypertrophy response in the absence of any agonist stimulation. These results suggest that caspase-dependent signaling is necessary and sufficient to promote cardiomyocyte hypertrophy. These results also confirm that cell death signal pathways behave as active remodeling agents in cardiomyocytes, independent of inducing an apoptosis response. PMID:24101493

  16. Evolutionary Biology Today

    Indian Academy of Sciences (India)

    Evolutionary Biology Today - The Domain of Evolutionary Biology ... Keywords. Evolution; natural selection; biodiversity; fitness; adaptation. Author Affiliations. Amitabh Joshi1. Evolutionary and Organismal Biology Unit Jawaharlal Nehru Centre for Advanced Scientific Research P.Box 6436, Jakkur Bangalore 560 065, India.

  17. Non-steroidal Anti-inflammatory Drugs Are Caspase Inhibitors.

    Science.gov (United States)

    Smith, Christina E; Soti, Subada; Jones, Torey A; Nakagawa, Akihisa; Xue, Ding; Yin, Hang

    2017-03-16

    Non-steroidal anti-inflammatory drugs (NSAIDs) are among the most commonly used drugs in the world. While the role of NSAIDs as cyclooxygenase (COX) inhibitors is well established, other targets may contribute to anti-inflammation. Here we report caspases as a new pharmacological target for NSAID family drugs such as ibuprofen, naproxen, and ketorolac at physiologic concentrations both in vitro and in vivo. We characterize caspase activity in both in vitro and in cell culture, and combine computational modeling and biophysical analysis to determine the mechanism of action. We observe that inhibition of caspase catalysis reduces cell death and the generation of pro-inflammatory cytokines. Further, NSAID inhibition of caspases is COX independent, representing a new anti-inflammatory mechanism. This finding expands upon existing NSAID anti-inflammatory behaviors, with implications for patient safety and next-generation drug design. Copyright © 2017 Elsevier Ltd. All rights reserved.

  18. Methylene Blue Inhibits Caspases by Oxidation of the Catalytic Cysteine.

    Science.gov (United States)

    Pakavathkumar, Prateep; Sharma, Gyanesh; Kaushal, Vikas; Foveau, Bénédicte; LeBlanc, Andrea C

    2015-09-24

    Methylene blue, currently in phase 3 clinical trials against Alzheimer Disease, disaggregates the Tau protein of neurofibrillary tangles by oxidizing specific cysteine residues. Here, we investigated if methylene blue can inhibit caspases via the oxidation of their active site cysteine. Methylene blue, and derivatives, azure A and azure B competitively inhibited recombinant Caspase-6 (Casp6), and inhibited Casp6 activity in transfected human colon carcinoma cells and in serum-deprived primary human neuron cultures. Methylene blue also inhibited recombinant Casp1 and Casp3. Furthermore, methylene blue inhibited Casp3 activity in an acute mouse model of liver toxicity. Mass spectrometry confirmed methylene blue and azure B oxidation of the catalytic Cys163 cysteine of Casp6. Together, these results show a novel inhibitory mechanism of caspases via sulfenation of the active site cysteine. These results indicate that methylene blue or its derivatives could (1) have an additional effect against Alzheimer Disease by inhibiting brain caspase activity, (2) be used as a drug to prevent caspase activation in other conditions, and (3) predispose chronically treated individuals to cancer via the inhibition of caspases.

  19. Suture compression induced midpalatal suture chondrocyte apoptosis with increased caspase-3, caspase-9, Bad, Bak, Bax and Bid expression.

    Science.gov (United States)

    Lan, Tingting; Zhao, Hanchi; Xiang, Bilu; Wang, Jun; Liu, Yang

    2017-07-22

    Previous studies found bone resorption and chondrocytes loss in mouse models of mid-palatal suture when given continuous compressive force, although chondrocytes response remained unknown. Herein, we design this study to determine how continuous compression force induces chondrocytes apoptosis. Thirty C57BL/6 male mice (aged 6 weeks) were randomly assigned into controls (not ligated to a spring), blank controls (ligated with no compression) and the compression group (ligated with 20-g compression). After 4 d, palatal tissues were sampled and stained by TB and safranin-O. Tunel staining measured the percentage of apoptotic chondrocytes, and immunohistochemistry was performed to label apoptosis-associated proteins (e.g., Bcl-2, Bcl-xl, Bax, Bak, Bid, Bad, caspase-3, caspase-8 and caspase-9). Intergroup comparison was made by the rank sum test, and P compression group was significantly decreased, while the control group remained largely unaltered. Tunel staining showed that apoptotic cell numbers in the mid-palatal suture were significantly higher than the control group. Immunohistochemistry showed that mice in the compression group had significantly increased expression of caspase-3, caspase-9, Bad, Bak, Bax and Bid; However, caspase-8 remained unaltered. No expression of Bcl-2 and Bcl-xl was detected. Continuous compression force induces chondrocytes apoptosis in the mid-palatal suture. This process might be associated with the mitochondrial pathway. Copyright © 2017 Elsevier Inc. All rights reserved.

  20. Making evolutionary biology a basic science for medicine

    Science.gov (United States)

    Nesse, Randolph M.; Bergstrom, Carl T.; Ellison, Peter T.; Flier, Jeffrey S.; Gluckman, Peter; Govindaraju, Diddahally R.; Niethammer, Dietrich; Omenn, Gilbert S.; Perlman, Robert L.; Schwartz, Mark D.; Thomas, Mark G.; Stearns, Stephen C.; Valle, David

    2010-01-01

    New applications of evolutionary biology in medicine are being discovered at an accelerating rate, but few physicians have sufficient educational background to use them fully. This article summarizes suggestions from several groups that have considered how evolutionary biology can be useful in medicine, what physicians should learn about it, and when and how they should learn it. Our general conclusion is that evolutionary biology is a crucial basic science for medicine. In addition to looking at established evolutionary methods and topics, such as population genetics and pathogen evolution, we highlight questions about why natural selection leaves bodies vulnerable to disease. Knowledge about evolution provides physicians with an integrative framework that links otherwise disparate bits of knowledge. It replaces the prevalent view of bodies as machines with a biological view of bodies shaped by evolutionary processes. Like other basic sciences, evolutionary biology needs to be taught both before and during medical school. Most introductory biology courses are insufficient to establish competency in evolutionary biology. Premedical students need evolution courses, possibly ones that emphasize medically relevant aspects. In medical school, evolutionary biology should be taught as one of the basic medical sciences. This will require a course that reviews basic principles and specific medical applications, followed by an integrated presentation of evolutionary aspects that apply to each disease and organ system. Evolutionary biology is not just another topic vying for inclusion in the curriculum; it is an essential foundation for a biological understanding of health and disease. PMID:19918069

  1. BID is cleaved by caspase-8 within a native complex on the mitochondrial membrane

    NARCIS (Netherlands)

    Schug, Z. T.; Gonzalvez, F.; Houtkooper, R. H.; Vaz, F. M.; Gottlieb, E.

    2011-01-01

    Caspase-8 stably inserts into the mitochondrial outer membrane during extrinsic apoptosis. Inhibition of caspase-8 enrichment on the mitochondria impairs caspase-8 activation and prevents apoptosis. However, the function of active caspase-8 on the mitochondrial membrane remains unknown. In this

  2. Caspase-14 Expression Impairs Retinal Pigment Epithelium Barrier Function: Potential Role in Diabetic Macular Edema

    Directory of Open Access Journals (Sweden)

    Selina Beasley

    2014-01-01

    Full Text Available We recently showed that caspase-14 is a novel molecule in retina with potential role in accelerated vascular cell death during diabetic retinopathy (DR. Here, we evaluated whether caspase-14 is implicated in retinal pigment epithelial cells (RPE dysfunction under hyperglycemia. The impact of high glucose (HG, 30 mM D-glucose on caspase-14 expression in human RPE (ARPE-19 cells was tested, which showed significant increase in caspase-14 expression compared with normal glucose (5 mM D-glucose + 25 mM L-glucose. We also evaluated the impact of modulating caspase-14 expression on RPE cells barrier function, phagocytosis, and activation of other caspases using ARPE-19 cells transfected with caspase-14 plasmid or caspase-14 siRNA. We used FITC-dextran flux assay and electric cell substrate impedance sensing (ECIS to test the changes in RPE cell barrier function. Similar to HG, caspase-14 expression in ARPE-19 cells increased FITC-dextran leakage through the confluent monolayer and decreased the transcellular electrical resistance (TER. These effects of HG were prevented by caspase-14 knockdown. Furthermore, caspase-14 knockdown prevented the HG-induced activation of caspase-1 and caspase-9, the only activated caspases by HG. Phagocytic activity was unaffected by caspase-14 expression. Our results suggest that caspase-14 contributes to RPE cell barrier disruption under hyperglycemic conditions and thus plays a role in the development of diabetic macular edema.

  3. Caspase-12 ablation preserves muscle function in the mdx mouse

    Science.gov (United States)

    Moorwood, Catherine; Barton, Elisabeth R.

    2014-01-01

    Duchenne muscular dystrophy (DMD) is a devastating muscle wasting disease caused by mutations in dystrophin. Several downstream consequences of dystrophin deficiency are triggers of endoplasmic reticulum (ER) stress, including loss of calcium homeostasis, hypoxia and oxidative stress. During ER stress, misfolded proteins accumulate in the ER lumen and the unfolded protein response (UPR) is triggered, leading to adaptation or apoptosis. We hypothesized that ER stress is heightened in dystrophic muscles and contributes to the pathology of DMD. We observed increases in the ER stress markers BiP and cleaved caspase-4 in DMD patient biopsies, compared with controls, and an increase in multiple UPR pathways in muscles of the dystrophin-deficient mdx mouse. We then crossed mdx mice with mice null for caspase-12, the murine equivalent of human caspase-4, which are resistant to ER stress. We found that deleting caspase-12 preserved mdx muscle function, resulting in a 75% recovery of both specific force generation and resistance to eccentric contractions. The compensatory hypertrophy normally found in mdx muscles was normalized in the absence of caspase-12; this was found to be due to decreased fibre sizes, and not to a fibre type shift or a decrease in fibrosis. Fibre central nucleation was not significantly altered in the absence of caspase-12, but muscle fibre degeneration found in the mdx mouse was reduced almost to wild-type levels. In conclusion, we have identified heightened ER stress and abnormal UPR signalling as novel contributors to the dystrophic phenotype. Caspase-4 is therefore a potential therapeutic target for DMD. PMID:24879640

  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. Testing evolutionary convergence on Europa

    International Nuclear Information System (INIS)

    Chela-Flores, Julian

    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)

  6. Cancer research meets evolutionary biology.

    Science.gov (United States)

    Pepper, John W; Scott Findlay, C; Kassen, Rees; Spencer, Sabrina L; Maley, Carlo C

    2009-02-01

    There is increasing evidence that Darwin's theory of evolution by natural selection provides insights into the etiology and treatment of cancer. On a microscopic scale, neoplastic cells meet the conditions for evolution by Darwinian selection: cell reproduction with heritable variability that affects cell survival and replication. This suggests that, like other areas of biological and biomedical research, Darwinian theory can provide a general framework for understanding many aspects of cancer, including problems of great clinical importance. With the availability of raw molecular data increasing rapidly, this theory may provide guidance in translating data into understanding and progress. Several conceptual and analytical tools from evolutionary biology can be applied to cancer biology. Two clinical problems may benefit most from the application of Darwinian theory: neoplastic progression and acquired therapeutic resistance. The Darwinian theory of cancer has especially profound implications for drug development, both in terms of explaining past difficulties, and pointing the way toward new approaches. Because cancer involves complex evolutionary processes, research should incorporate both tractable (simplified) experimental systems, and also longitudinal observational studies of the evolutionary dynamics of cancer in laboratory animals and in human patients. Cancer biology will require new tools to control the evolution of neoplastic cells.

  7. Blockade of processing/activation of caspase-3 by hypoxia

    International Nuclear Information System (INIS)

    Han, Sang Hee; Kim, Moonil; Park, Kyoungsook; Kim, Tae-Hyoung; Seol, Dai-Wu

    2008-01-01

    Tumor hypoxia, which is caused by the rapid proliferation of tumor cells and aberrant vasculature in tumors, results in inadequate supplies of oxygen and nutrients to tumor cells. Paradoxically, these unfavorable growth conditions benefit tumor cell survival, although the mechanism is poorly understood. We have demonstrated for the first time that hypoxia inhibits TRAIL-induced apoptosis by blocking translocation of Bax from cytosol to the mitochondria in tumor cells. However, it is largely unknown how hypoxia-inhibited Bax translocation attenuates TRAIL-induced apoptosis. Here, we demonstrate that despite its inhibitory activity in TRAIL-induced apoptosis, hypoxia does not affect TRAIL-triggered proximal apoptotic signaling events, including caspase-8 activation and Bid cleavage. Instead, hypoxia inhibited processing of caspase-3, leading to incomplete activation of the caspase. Importantly, hypoxia-blocked translocation of Bax to the mitochondria significantly inhibited releasing the mitochondrial factors, such as cytochrome c and Smac/DIABLO, to the cytosol in response to TRAIL. It is well-known that complete processing/activation of caspase-3 requires Smac/DIABLO released from mitochondria. Therefore, our data indicate that an engagement of the apoptotic mitochondrial events leading to caspase-3 activation is blocked by hypoxia. Our data shed new light on understanding of the apoptotic signal transduction and targets regulated by tumor hypoxia

  8. Saikosaponin d induces cell death through caspase-3-dependent, caspase-3-independent and mitochondrial pathways in mammalian hepatic stellate cells

    International Nuclear Information System (INIS)

    Chen, Ming-Feng; Huang, S. Joseph; Huang, Chao-Cheng; Liu, Pei-Shan; Lin, Kun-I; Liu, Ching-Wen; Hsieh, Wen-Chuan; Shiu, Li-Yen; Chen, Chang-Han

    2016-01-01

    Saikosaponin d (SSd) is one of the main active triterpene saponins in Bupleurum falcatum. It has a steroid-like structure, and is reported to have pharmacological activities, including liver protection in rat, cell cycle arrest and apoptosis induction in several cancer cell lines. However, the biological functions and molecular mechanisms of mammalian cells under SSd treatment are still unclear. The cytotoxicity and apoptosis of hepatic stellate cells (HSCs) upon SSd treatment were discovered by MTT assay, colony formation assay and flow cytometry. The collage I/III, caspase activity and apoptotic related genes were examined by quantitative PCR, Western blotting, immunofluorescence and ELISA. The mitochondrial functions were monitored by flow cytometry, MitoTracker staining, ATP production and XF24 bioenergetic assay. This study found that SSd triggers cell death via an apoptosis path. An example of this path might be typical apoptotic morphology, increased sub-G1 phase cell population, inhibition of cell proliferation and activation of caspase-3 and caspase-9. However, the apoptotic effects induced by SSd are partially blocked by the caspase-3 inhibitor, Z-DEVD-FMK, suggesting that SSd may trigger both HSC-T6 and LX-2 cell apoptosis through caspase-3-dependent and independent pathways. We also found that SSd can trigger BAX and BAK translocation from the cytosol to the mitochondria, resulting in mitochondrial function inhibition, membrane potential disruption. Finally, SSd also increases the release of apoptotic factors. The overall analytical data indicate that SSd-elicited cell death may occur through caspase-3-dependent, caspase-3-independent and mitochondrial pathways in mammalian HSCs, and thus can delay the formation of liver fibrosis by reducing the level of HSCs

  9. Evolutionary development of tensegrity structures.

    Science.gov (United States)

    Lobo, Daniel; Vico, Francisco J

    2010-09-01

    Contributions from the emerging fields of molecular genetics and evo-devo (evolutionary developmental biology) are greatly benefiting the field of evolutionary computation, initiating a promise of renewal in the traditional methodology. While direct encoding has constituted a dominant paradigm, indirect ways to encode the solutions have been reported, yet little attention has been paid to the benefits of the proposed methods to real problems. In this work, we study the biological properties that emerge by means of using indirect encodings in the context of form-finding problems. A novel indirect encoding model for artificial development has been defined and applied to an engineering structural-design problem, specifically to the discovery of tensegrity structures. This model has been compared with a direct encoding scheme. While the direct encoding performs similarly well to the proposed method, indirect-based results typically outperform the direct-based results in aspects not directly linked to the nature of the problem itself, but to the emergence of properties found in biological organisms, like organicity, generalization capacity, or modularity aspects which are highly valuable in engineering. Copyright 2010 Elsevier Ireland Ltd. All rights reserved.

  10. A Dimeric Smac/Diablo Peptide Directly Relieves Caspase-3 Inhibition by XIAP: Dynamic and Cooperative Regulation of XIAP by Smac/Diablo

    OpenAIRE

    Gao, Zhonghua; Tian, Yuan; Wang, Junru; Yin, Qian; Wu, Hao; Li, Yue-Ming; Jiang, Xuejun

    2007-01-01

    Caspase activation, the executing event of apoptosis, is under deliberate regulation. IAP proteins inhibit caspase activity whereas Smac/Diablo antagonizes IAP. XIAP, a ubiquitous IAP, can inhibit both caspase-9, the initiator caspase of the mitochondrial apoptotic pathway, and the downstream effector caspases, caspase-3 and caspase-7. Smac neutralizes XIAP inhibition of caspase-9 by competing for binding of the BIR3 domain of XIAP with caspase-9, whereas how Smac liberates effector caspases ...

  11. Evolutionary Biology Today

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education; Volume 8; Issue 2. Evolutionary Biology Today - What do Evolutionary Biologists do? Amitabh Joshi. Series Article Volume 8 Issue 2 February 2003 pp 6-18. Fulltext. Click here to view fulltext PDF. Permanent link:

  12. Evolutionary Stable Strategy

    Indian Academy of Sciences (India)

    2016-08-26

    Aug 26, 2016 ... Home; Journals; Resonance – Journal of Science Education; Volume 21; Issue 9. Evolutionary Stable Strategy: Application of Nash Equilibrium in Biology. General ... Using some examples of classical games, we show how evolutionary game theory can help understand behavioural decisions of animals.

  13. Evolutionary Biology Today

    Indian Academy of Sciences (India)

    Amitabh Joshi studies and teaches evolutionary genetics and population ecology at the Jawaharlal. Nehru Centre for Advanced. Scientific Research,. Bangalore. His current research interests are in life- history evolution, the evolutionary genetics of biological clocks, and small population and meta population dynamics.

  14. Methodological problems in evolutionary biology. XII. Against evolutionary ethics.

    NARCIS (Netherlands)

    vd Steen, W.J.

    1999-01-01

    Evolutionary ethics has recently become popular again. Some of its representatives elaborate new attempts to derive ethics from evolutionary biology. The attempts, like previous ones, fail because they commit the naturalistic fallacy. Premises from evolutionary biology together with normative

  15. Evolutionary cell biology: two origins, one objective.

    Science.gov (United States)

    Lynch, Michael; Field, Mark C; Goodson, Holly V; Malik, Harmit S; Pereira-Leal, José B; Roos, David S; Turkewitz, Aaron P; Sazer, Shelley

    2014-12-02

    All aspects of biological diversification ultimately trace to evolutionary modifications at the cellular level. This central role of cells frames the basic questions as to how cells work and how cells come to be the way they are. Although these two lines of inquiry lie respectively within the traditional provenance of cell biology and evolutionary biology, a comprehensive synthesis of evolutionary and cell-biological thinking is lacking. We define evolutionary cell biology as the fusion of these two eponymous fields with the theoretical and quantitative branches of biochemistry, biophysics, and population genetics. The key goals are to develop a mechanistic understanding of general evolutionary processes, while specifically infusing cell biology with an evolutionary perspective. The full development of this interdisciplinary field has the potential to solve numerous problems in diverse areas of biology, including the degree to which selection, effectively neutral processes, historical contingencies, and/or constraints at the chemical and biophysical levels dictate patterns of variation for intracellular features. These problems can now be examined at both the within- and among-species levels, with single-cell methodologies even allowing quantification of variation within genotypes. Some results from this emerging field have already had a substantial impact on cell biology, and future findings will significantly influence applications in agriculture, medicine, environmental science, and synthetic biology.

  16. Evolutionary change in continuous reaction norms

    DEFF Research Database (Denmark)

    Murren, Courtney J; Maclean, Heidi J; Diamond, Sarah E

    2014-01-01

    Understanding the evolution of reaction norms remains a major challenge in ecology and evolution. Investigating evolutionary divergence in reaction norm shapes between populations and closely related species is one approach to providing insights. Here we use a meta-analytic approach to compare...... or species. These results show that evolutionary divergence of curvature is common and should be considered an important aspect of plasticity, together with slope. Biological details about traits and environments, including cryptic variation expressed in novel environmental conditions, may be critical...

  17. 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

  18. Suppression of human T cell proliferation by the caspase inhibitors, z-VAD-FMK and z-IETD-FMK is independent of their caspase inhibition properties

    Energy Technology Data Exchange (ETDEWEB)

    Lawrence, C.P. [Medical Research Council Toxicology Unit, Hodgkin Building, Lancaster Road, University of Leicester, Leicester LE1 9HN (United Kingdom); Chow, S.C., E-mail: chow.sek.chuen@monash.edu [School of Science, Monash University Sunway Campus, Jalan Lagoon Selatan, Bandar Sunway, 46150 Selangor Darul Ehsan (Malaysia)

    2012-11-15

    The caspase inhibitors, benzyloxycarbony (Cbz)-l-Val-Ala-Asp (OMe)-fluoromethylketone (z-VAD-FMK) and benzyloxycarbonyl (Cbz)-Ile-Glu (OMe)-Thr-Asp (OMe)-FMK (z-IETD-FMK) at non-toxic doses were found to be immunosuppressive and inhibit human T cell proliferation induced by mitogens and IL-2 in vitro. Both caspase inhibitors were shown to block NF-κB in activated primary T cells, but have little inhibitory effect on the secretion of IL-2 and IFN-γ during T cell activation. However, the expression of IL-2 receptor α-chain (CD25) in activated T cells was inhibited by both z-VAD-FMK and z-IETD-FMK, whereas the expression of the early activated T cell marker, CD69 was unaffected. During primary T cell activation via the antigen receptor, both caspase-8 and caspase-3 were activated and processed to their respective subunits, but neither caspase inhibitors had any effect on the processing of these two caspases. In sharp contrast both caspase inhibitors readily blocked apoptosis and the activation of caspases during FasL-induced apoptosis in activated primary T cells and Jurkat T cells. Collectively, the results demonstrate that both z-VAD-FMK and z-IETD-FMK are immunosuppressive in vitro and inhibit T cell proliferation without blocking the processing of caspase-8 and caspase-3. -- Highlights: ► Caspase-8 and caspase-3 were activated during T cell activation and proliferation. ► T cell proliferation was blocked by caspase inhibitors. ► Caspase activation during T cell proliferation was not block by caspase inhibitors.

  19. 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...... evolutionary algorithms, such as memetic algorithms, which have emerged as a very promising tool for solving many real-world problems in a multitude of areas of science and technology. Moreover, parallel evolutionary combinatorial optimization has been presented. Search operators, which are crucial in all...

  20. Ethyl Alcohol Extract of Hizikia fusiforme Induces Caspase ...

    African Journals Online (AJOL)

    Ethyl Alcohol Extract of Hizikia fusiforme Induces Caspase-dependent Apoptosis in Human Leukemia U937 Cells by Generation of Reactive Oxygen Species. C-H Kang, S-H Kang, S-H Boo, S-Y Park, D-O Moon, G-Y Kim ...

  1. Active caspase-3 expression levels as bioindicator of individual radiosensitivity

    Directory of Open Access Journals (Sweden)

    NEYLIANE F.G. DOS SANTOS

    Full Text Available ABSTRACT Several molecules and events involved in cell response to radiation-induced damage have been investigated towards a personalized radiotherapy. Considering the importance of active caspase-3 in the proteolytic cascade that ensures radiation-induced apoptosis execution, this research was designed to evaluate the expression levels of this protein as a bioindicator of individual radiosensitivity. Peripheral blood samples of 10 healthy individuals were gamma-irradiated (cobalt-60 source with 1, 2 and 4 Gy (control: non-irradiated samples, and active caspase-3 expression levels were measured in lymphocytes, by flow cytometry, ex vivo and after different times of in vitro incubation (24, 48 and 72 hours. Short-term incubation of 24 h was the most adequate condition to evidence correlations between dose radiation and active caspase-3 expression. For each radiation dose, it was observed a significant inter-individual variation in active caspase-3 expression intensity, suggesting that this parameter may be suitable for evidence individual radiosensitivity. The methodology presented and discussed in this work may help to predict healthy tissues response to radiation exposure toward the better patient outcome.

  2. Inner ear dysfunction in caspase-3 deficient mice

    Directory of Open Access Journals (Sweden)

    Woo Minna

    2011-10-01

    Full Text Available Abstract Background Caspase-3 is one of the most downstream enzymes activated in the apoptotic pathway. In caspase-3 deficient mice, loss of cochlear hair cells and spiral ganglion cells coincide closely with hearing loss. In contrast with the auditory system, details of the vestibular phenotype have not been characterized. Here we report the vestibular phenotype and inner ear anatomy in the caspase-3 deficient (Casp3-/- mouse strain. Results Average ABR thresholds of Casp3-/- mice were significantly elevated (P Casp3+/- mice and Casp3+/+ mice at 3 months of age. In DPOAE testing, distortion product 2F1-F2 was significantly decreased (P Casp3-/- mice, whereas Casp3+/- and Casp3+/+ mice showed normal and comparable values to each other. Casp3-/- mice were hyperactive and exhibited circling behavior when excited. In lateral canal VOR testing, Casp3-/- mice had minimal response to any of the stimuli tested, whereas Casp3+/- mice had an intermediate response compared to Casp3+/+ mice. Inner ear anatomical and histological analysis revealed gross hypomorphism of the vestibular organs, in which the main site was the anterior semicircular canal. Hair cell numbers in the anterior- and lateral crista, and utricle were significantly smaller in Casp3-/- mice whereas the Casp3+/- and Casp3+/+ mice had normal hair cell numbers. Conclusions These results indicate that caspase-3 is essential for correct functioning of the cochlea as well as normal development and function of the vestibule.

  3. Programmed cell death in plants and caspase-like activities

    NARCIS (Netherlands)

    Gaussand, Gwénael Martial Daniel Jean-Marie

    2007-01-01

    The development of multicellular organisms involves an important balance between cell growth, cell division and cell death. In animals, programmed cell death (PCD) plays a key role by forming and deleting structures, controlling cell numbers and eliminating abnormal damaged cells. Caspases were

  4. Caspase-mediated apoptosis induction in zebrafish cerebellar Purkinje neurons.

    Science.gov (United States)

    Weber, Thomas; Namikawa, Kazuhiko; Winter, Barbara; Müller-Brown, Karina; Kühn, Ralf; Wurst, Wolfgang; Köster, Reinhard W

    2016-11-15

    The zebrafish is a well-established model organism in which to study in vivo mechanisms of cell communication, differentiation and function. Existing cell ablation methods are either invasive or they rely on the cellular expression of prokaryotic enzymes and the use of antibiotic drugs as cell death-inducing compounds. We have recently established a novel inducible genetic cell ablation system based on tamoxifen-inducible Caspase 8 activity, thereby exploiting mechanisms of cell death intrinsic to most cell types. Here, we prove its suitability in vivo by monitoring the ablation of cerebellar Purkinje cells (PCs) in transgenic zebrafish that co-express the inducible caspase and a fluorescent reporter. Incubation of larvae in tamoxifen for 8 h activated endogenous Caspase 3 and cell death, whereas incubation for 16 h led to the near-complete loss of PCs by apoptosis. We observed synchronous cell death autonomous to the PC population and phagocytosing microglia in the cerebellum, reminiscent of developmental apoptosis in the forebrain. Thus, induction of apoptosis through targeted activation of caspase by tamoxifen (ATTAC TM ) further expands the repertoire of genetic tools for conditional interrogation of cellular functions. © 2016. Published by The Company of Biologists Ltd.

  5. Computational intelligence synergies of fuzzy logic, neural networks and evolutionary computing

    CERN Document Server

    Siddique, Nazmul

    2013-01-01

    Computational Intelligence: Synergies of Fuzzy Logic, Neural Networks and Evolutionary Computing presents an introduction to some of the cutting edge technological paradigms under the umbrella of computational intelligence. Computational intelligence schemes are investigated with the development of a suitable framework for fuzzy logic, neural networks and evolutionary computing, neuro-fuzzy systems, evolutionary-fuzzy systems and evolutionary neural systems. Applications to linear and non-linear systems are discussed with examples. Key features: Covers all the aspect

  6. Evolutionary Mechanisms for Loneliness

    Science.gov (United States)

    Cacioppo, John T.; Cacioppo, Stephanie; Boomsma, Dorret I.

    2013-01-01

    Robert Weiss (1973) conceptualized loneliness as perceived social isolation, which he described as a gnawing, chronic disease without redeeming features. On the scale of everyday life, it is understandable how something as personally aversive as loneliness could be regarded as a blight on human existence. However, evolutionary time and evolutionary forces operate at such a different scale of organization than we experience in everyday life that personal experience is not sufficient to understand the role of loneliness in human existence. Research over the past decade suggests a very different view of loneliness than suggested by personal experience, one in which loneliness serves a variety of adaptive functions in specific habitats. We review evidence on the heritability of loneliness and outline an evolutionary theory of loneliness, with an emphasis on its potential adaptive value in an evolutionary timescale. PMID:24067110

  7. Eco-evolutionary feedbacks, adaptive dynamics and evolutionary rescue theory

    Science.gov (United States)

    Ferriere, Regis; Legendre, Stéphane

    2013-01-01

    Adaptive dynamics theory has been devised to account for feedbacks between ecological and evolutionary processes. Doing so opens new dimensions to and raises new challenges about evolutionary rescue. Adaptive dynamics theory predicts that successive trait substitutions driven by eco-evolutionary feedbacks can gradually erode population size or growth rate, thus potentially raising the extinction risk. Even a single trait substitution can suffice to degrade population viability drastically at once and cause ‘evolutionary suicide’. In a changing environment, a population may track a viable evolutionary attractor that leads to evolutionary suicide, a phenomenon called ‘evolutionary trapping’. Evolutionary trapping and suicide are commonly observed in adaptive dynamics models in which the smooth variation of traits causes catastrophic changes in ecological state. In the face of trapping and suicide, evolutionary rescue requires that the population overcome evolutionary threats generated by the adaptive process itself. Evolutionary repellors play an important role in determining how variation in environmental conditions correlates with the occurrence of evolutionary trapping and suicide, and what evolutionary pathways rescue may follow. In contrast with standard predictions of evolutionary rescue theory, low genetic variation may attenuate the threat of evolutionary suicide and small population sizes may facilitate escape from evolutionary traps. PMID:23209163

  8. Eco-evolutionary feedbacks, adaptive dynamics and evolutionary rescue theory.

    Science.gov (United States)

    Ferriere, Regis; Legendre, Stéphane

    2013-01-19

    Adaptive dynamics theory has been devised to account for feedbacks between ecological and evolutionary processes. Doing so opens new dimensions to and raises new challenges about evolutionary rescue. Adaptive dynamics theory predicts that successive trait substitutions driven by eco-evolutionary feedbacks can gradually erode population size or growth rate, thus potentially raising the extinction risk. Even a single trait substitution can suffice to degrade population viability drastically at once and cause 'evolutionary suicide'. In a changing environment, a population may track a viable evolutionary attractor that leads to evolutionary suicide, a phenomenon called 'evolutionary trapping'. Evolutionary trapping and suicide are commonly observed in adaptive dynamics models in which the smooth variation of traits causes catastrophic changes in ecological state. In the face of trapping and suicide, evolutionary rescue requires that the population overcome evolutionary threats generated by the adaptive process itself. Evolutionary repellors play an important role in determining how variation in environmental conditions correlates with the occurrence of evolutionary trapping and suicide, and what evolutionary pathways rescue may follow. In contrast with standard predictions of evolutionary rescue theory, low genetic variation may attenuate the threat of evolutionary suicide and small population sizes may facilitate escape from evolutionary traps.

  9. Activation of Pro-apoptotic Caspases in Non-apoptotic Cells During Odontogenesis and Related Osteogenesis

    Directory of Open Access Journals (Sweden)

    Eva Svandova

    2018-03-01

    Full Text Available Caspases are well known proteases in the context of inflammation and apoptosis. Recently, novel roles of pro-apoptotic caspases have been reported, including findings related to the development of hard tissues. To further investigate these emerging functions of pro-apoptotic caspases, the in vivo localisation of key pro-apoptotic caspases (-3,-6,-7,-8, and -9 was assessed, concentrating on the development of two neighbouring hard tissues, cells participating in odontogenesis (represented by the first mouse molar and intramembranous osteogenesis (mandibular/alveolar bone. The expression of the different caspases within the developing tissues was correlated with the apoptotic status of the cells, to produce a picture of whether different caspases have potentially distinct, or overlapping non-apoptotic functions. The in vivo investigation was additionally supported by examination of caspases in an osteoblast-like cell line in vitro. Caspases-3,-7, and -9 were activated in apoptotic cells of the primary enamel knot of the first molar; however, caspase-7 and -8 activation was also associated with the non-apoptotic enamel epithelium at the same stage and later with differentiating/differentiated odontoblasts and ameloblasts. In the adjacent bone, active caspases-7 and -8 were present abundantly in the prenatal period, while the appearance of caspases-3,-6, and -9 was marginal. Perinatally, caspases-3 and -7 were evident in some osteoclasts and osteoblastic cells, and caspase-8 was abundant mostly in osteoclasts. In addition, postnatal activation of caspases-7 and -8 was retained in osteocytes. The results provide a comprehensive temporo-spatial pattern of pro-apoptotic caspase activation, and demonstrate both unique and overlapping activation in non-apoptotic cells during development of the molar tooth and mandibular/alveolar bone. The importance of caspases in osteogenic pathways is highlighted by caspase inhibition in osteoblast-like cells, which

  10. Tyrosine Phosphorylation of Caspase-8 Abrogates Its Apoptotic Activity and Promotes Activation of c-Src

    Science.gov (United States)

    Tsang, Jennifer LY; Jia, Song Hui; Parodo, Jean; Plant, Pamela; Lodyga, Monika; Charbonney, Emmanuel; Szaszi, Katalin; Kapus, Andras; Marshall, John C.

    2016-01-01

    Src family tyrosine kinases (SFKs) phosphorylate caspase-8A at tyrosine (Y) 397 resulting in suppression of apoptosis. In addition, the phosphorylation of caspase-8A at other sites including Y465 has been implicated in the regulation of caspase-8 activity. However, the functional consequences of these modifications on caspase-8 processing/activity have not been elucidated. Moreover, various Src substrates are known to act as potent Src regulators, but no such role has been explored for caspase-8. We asked whether the newly identified caspase-8 phosphorylation sites might regulate caspase-8 activation and conversely, whether caspase-8 phosphorylation might affect Src activity. Here we show that Src phosphorylates caspase-8A at multiple tyrosine sites; of these, we have focused on Y397 within the linker region and Y465 within the p12 subunit of caspase-8A. We show that phosphomimetic mutation of caspase-8A at Y465 prevents its cleavage and the subsequent activation of caspase-3 and suppresses apoptosis. Furthermore, simultaneous phosphomimetic mutation of caspase-8A at Y397 and Y465 promotes the phosphorylation of c-Src at Y416 and increases c-Src activity. Finally, we demonstrate that caspase-8 activity prevents its own tyrosine phosphorylation by Src. Together these data reveal that dual phosphorylation converts caspase-8 from a pro-apoptotic to a pro-survival mediator. Specifically, tyrosine phosphorylation by Src renders caspase-8 uncleavable and thereby inactive, and at the same time converts it to a Src activator. This novel dynamic interplay between Src and caspase-8 likely acts as a potent signal-integrating switch directing the cell towards apoptosis or survival. PMID:27101103

  11. Caspase-1 cleavage of transcription factor GATA4 and regulation of cardiac cell fate.

    Science.gov (United States)

    Aries, A; Whitcomb, J; Shao, W; Komati, H; Saleh, M; Nemer, M

    2014-12-11

    Caspase-1 or interleukin-1β (IL-1β) converting enzyme is a pro-inflammatory member of the caspase family. An IL-1β-independent role for caspase-1 in cardiomyocyte cell death and heart failure has emerged but the mechanisms underlying these effects are incompletely understood. Here, we report that transcription factor GATA4, a key regulator of cardiomyocyte survival and adaptive stress response is an in vivo and in vitro substrate for caspase-1. Caspase-1 mediated cleavage of GATA4 generates a truncated protein that retains the ability to bind DNA but lacks transcriptional activation domains and acts as a dominant negative regulator of GATA4. We show that caspase-1 is rapidly activated in cardiomyocyte nuclei treated with the cell death inducing drug Doxorubicin. We also find that inhibition of caspase-1 alone is as effective as complete caspase inhibition at rescuing GATA4 degradation and myocyte cell death. Caspase-1 inhibition of GATA4 transcriptional activity is rescued by HSP70, which binds directly to GATA4 and masks the caspase recognition motif. The data identify a caspase-1 nuclear substrate and suggest a direct role for caspase-1 in transcriptional regulation. This mechanism may underlie the inflammation-independent action of caspase-1 in other organs.

  12. Caspase-3 Inhibition Attenuates the Cytopathic Effects of EV71 Infection

    Directory of Open Access Journals (Sweden)

    Fengmei Song

    2018-04-01

    Full Text Available Previous studies demonstrate that human enterovirus 71 (EV71, a primary causative agent for hand, foot, and mouth disease, activates caspase-3 through the non-structural viral 3C protein to induce host cell apoptosis; however, until now it was unclear how 3C activates caspase-3 and how caspase-3 activation affects viral production. Our results demonstrate that 3C binds caspase-8 and caspase-9 but does not directly bind caspase-3 to activate them, and that the proteolytic activity of 3C is required by the activation of caspase-8, caspase-9, and caspase-3. Inhibition of caspase-3 activity attenuates apoptosis in 3C-transfected cells. Furthermore, caspase-3 inhibitor protects host cells from the cytopathic effect of EV71 infection and prevents cell cycle arrest, which is known to be favored for EV71 viral replication. Inhibition of caspase-3 activity decreases EV71 viral protein expression and viral production, but has no effect on viral entry, replication, even polyprotein translation. Therefore, caspase-3 is exploited functionally by EV71 to facilitate its production, which suggests a novel therapeutic approach for the treatment and prevention of hand, foot, and mouth disease.

  13. The human papillomavirus (HPV) E6 oncoproteins promotes nuclear localization of active caspase 8

    Energy Technology Data Exchange (ETDEWEB)

    Manzo-Merino, Joaquin [Unidad de Investigación Biomédica en Cáncer, Instituto Nacional de Cancerología, México/Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México. Av. San Fernando No. 22, Col. Sección XVI, Tlalpan 14080 (Mexico); Massimi, Paola [International Centre for Genetic Engineering and Biotechnology, Padriciano 99, I-34149 Trieste (Italy); Lizano, Marcela, E-mail: lizanosoberon@gmail.com [Unidad de Investigación Biomédica en Cáncer, Instituto Nacional de Cancerología, México/Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México. Av. San Fernando No. 22, Col. Sección XVI, Tlalpan 14080 (Mexico); Banks, Lawrence, E-mail: banks@icgeb.org [International Centre for Genetic Engineering and Biotechnology, Padriciano 99, I-34149 Trieste (Italy)

    2014-02-15

    The HPV-16 E6 and E6{sup ⁎} proteins have been shown previously to be capable of regulating caspase 8 activity. We now show that the capacity of E6 to interact with caspase 8 is common to diverse HPV types, being also seen with HPV-11 E6, HPV-18 E6 and HPV-18 E6{sup ⁎}. Unlike most E6-interacting partners, caspase 8 does not appear to be a major proteasomal target of E6, but instead E6 appears able to stimulate caspase 8 activation, without affecting the overall apoptotic activity. This would appear to be mediated in part by the ability of the HPV E6 oncoproteins to recruit active caspase 8 to the nucleus. - Highlights: • Multiple HPV E6 oncoproteins interact with the caspase 8 DED domain. • HPV E6 stimulates activation of caspase 8. • HPV E6 promotes nuclear accumulation of caspase 8.

  14. Tree Contractions and Evolutionary Trees

    OpenAIRE

    Kao, Ming-Yang

    2001-01-01

    An evolutionary tree is a rooted tree where each internal vertex has at least two children and where the leaves are labeled with distinct symbols representing species. Evolutionary trees are useful for modeling the evolutionary history of species. An agreement subtree of two evolutionary trees is an evolutionary tree which is also a topological subtree of the two given trees. We give an algorithm to determine the largest possible number of leaves in any agreement subtree of two trees T_1 and ...

  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. Paleoanthropology and evolutionary theory.

    Science.gov (United States)

    Tattersall, Ian

    2012-01-01

    Paleoanthropologists of the first half of the twentieth century were little concerned either with evolutionary theory or with the technicalities and broader implications of zoological nomenclature. In consequence, the paleoanthropological literature of the period consisted largely of a series of descriptions accompanied by authoritative pronouncements, together with a huge excess of hominid genera and species. Given the intellectual flimsiness of the resulting paleoanthropological framework, it is hardly surprising that in 1950 the ornithologist Ernst Mayr met little resistance when he urged the new postwar generation of paleoanthropologists to accept not only the elegant reductionism of the Evolutionary Synthesis but a vast oversimplification of hominid phylogenetic history and nomenclature. Indeed, the impact of Mayr's onslaught was so great that even when developments in evolutionary biology during the last quarter of the century brought other paleontologists to the realization that much more has been involved in evolutionary histories than the simple action of natural selection within gradually transforming lineages, paleoanthropologists proved highly reluctant to follow. Even today, paleoanthropologists are struggling to reconcile an intuitive realization that the burgeoning hominid fossil record harbors a substantial diversity of species (bringing hominid evolutionary patterns into line with that of other successful mammalian families), with the desire to cram a huge variety of morphologies into an unrealistically minimalist systematic framework. As long as this theoretical ambivalence persists, our perception of events in hominid phylogeny will continue to be distorted.

  17. 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

  18. Bile Acid-induced Apoptosis in Hepatocytes Is Caspase-6-dependent

    NARCIS (Netherlands)

    Rust, Christian; Wild, Nadine; Bernt, Carina; Vennegeerts, Timo; Wimmer, Ralf; Beuers, Ulrich

    2009-01-01

    Apoptosis induced by hydrophobic bile acids is thought to contribute to liver injury during cholestasis. Caspase-6 is an executioner caspase that also appears to have regulatory functions in hematopoetic cell lines. We aimed to elucidate the role of caspase-6 in bile acid-induced apoptosis. The

  19. Prognostic value of inhibitors of apoptosis proteins (IAPs) and caspases in prostate cancer: caspase-3 forms and XIAP predict biochemical progression after radical prostatectomy

    International Nuclear Information System (INIS)

    Rodríguez-Berriguete, Gonzalo; Torrealba, Norelia; Ortega, Miguel Angel; Martínez-Onsurbe, Pilar; Olmedilla, Gabriel; Paniagua, Ricardo; Guil-Cid, Manuel; Fraile, Benito; Royuela, Mar

    2015-01-01

    The expression status of apoptotic regulators, such as caspases and inhibitors of apoptosis proteins (IAPs), could reflect the aggressiveness of tumors and, therefore, could be useful as prognostic markers. We explored the associations between tumor expression of caspases and IAPs and clinicopathological features of prostate cancer – clinical and pathological T stage, Gleason score, preoperative serum PSA levels, perineural invasion, lymph node involvement, surgical margin status and overall survival – and evaluated its capability to predict biochemical progression after radical prostatectomy. Protein expression of caspases (procaspase-8, cleaved caspase-8, procaspase-3, cleaved caspase-3, caspase-7 and procaspase-9) and IAPs (cIAP1/2, cIAP2, NAIP, Survivin and XIAP) was analyzed by immunohistochemistry in radical prostatectomy samples from 84 prostate cancer patients. Spearman’s test, Kaplan-Meier curves, and univariate and multivariate Cox proportional hazard regression analysis were performed. cIAP1/2, cIAP2, Survivin, procaspase-8, cleaved caspase-8, procaspase-3 and caspase-7 expression correlated with at least one clinicopathological feature of the disease. Patients negative for XIAP, procaspase-3 or cleaved caspase-3 had a significantly worse prognosis. Of note, XIAP, procaspase-3 and cleaved caspase-3 were predictors of biochemical progression independent of Gleason score and pathological T stage. Our results indicate that alterations in the expression of IAPs and caspases contribute to the malignant behavior of prostate tumors and suggest that tumor expression of XIAP, procaspase-3 and cleaved caspase-3 may help to identify prostate cancer patients at risk of progression

  20. Ecstasy-Induced Caspase Expression Alters Following Ginger Treatment

    Directory of Open Access Journals (Sweden)

    Sara Soleimani Asl

    2013-11-01

    Full Text Available Introduction: Exposure to 3-4, methylenedioxymethamphetamine (MDMA leads to cell death. Herein, we studied the protective effects of ginger on MDMA- induced apoptosis. Methods: 15 Sprague dawley male rats were administrated with 0, 10 mg/kg MDMA, or MDMA along with 100mg/kg ginger, IP for 7 days. Brains were removed to study the caspase 3, 8, and 9 expressions in the hippocampus by RT-PCR. Data was analyzed by SPSS 16 software using the one-way ANOVA test. Results: MDMA treatment resulted in a significant increase in caspase 3, 8, and 9 as compared to the sham group (p<0.001. Ginger administration however, appeared to significantly decrease the same (p<0.001. Discussion: Our findings suggest that ginger consumption may lead to the improvement of MDMA-induced neurotoxicity.

  1. Applications of evolutionary computation in image processing and pattern recognition

    CERN Document Server

    Cuevas, Erik; Perez-Cisneros, Marco

    2016-01-01

    This book presents the use of efficient Evolutionary Computation (EC) algorithms for solving diverse real-world image processing and pattern recognition problems. It provides an overview of the different aspects of evolutionary methods in order to enable the reader in reaching a global understanding of the field and, in conducting studies on specific evolutionary techniques that are related to applications in image processing and pattern recognition. It explains the basic ideas of the proposed applications in a way that can also be understood by readers outside of the field. Image processing and pattern recognition practitioners who are not evolutionary computation researchers will appreciate the discussed techniques beyond simple theoretical tools since they have been adapted to solve significant problems that commonly arise on such areas. On the other hand, members of the evolutionary computation community can learn the way in which image processing and pattern recognition problems can be translated into an...

  2. Caspases in yeast apoptosis-like death: facts and artefacts

    Czech Academy of Sciences Publication Activity Database

    Váchová, Libuše; Palková, Z.

    2007-01-01

    Roč. 7, - (2007), s. 12-21 ISSN 1567-1356 R&D Projects: GA ČR GA525/05/0297; GA MŠk(CZ) LC531 Institutional research plan: CEZ:AV0Z50200510 Keywords : caspases and metacaspases * apoptosis and programmed cell death in yeast * saccharomyces cerevisiae Subject RIV: EE - Microbiology, Virology Impact factor: 2.812, year: 2007

  3. Molar tooth development in caspase-3 deficient mice

    Czech Academy of Sciences Publication Activity Database

    Matalová, Eva; Sharpe, P. T.; Lakhani, S. A.; Roth, K. A.; Flavell, R. A.; Šetková, Jana; Míšek, Ivan; Tucker, A. S.

    2006-01-01

    Roč. 50, 5 (2006), s. 491-497 ISSN 0214-6282 R&D Projects: GA AV ČR KJB500450503; GA MŠk OC B23.001 Grant - others:European Molecular Biology Organization ASTF195.00-05; NIH NS41962 Institutional research plan: CEZ:AV0Z50450515 Keywords : tooth development * dental apoptosis * caspase-3 mutant Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.577, year: 2006

  4. Bioluminescence determination of active caspase-3 in single apoptotic cells

    Czech Academy of Sciences Publication Activity Database

    Lišková, Marcela; Klepárník, Karel; Matalová, Eva; Hegrová, Jitka; Přikryl, Jan; Švandová, Eva; Foret, František

    2013-01-01

    Roč. 34, č. 12 (2013), s. 1772-1777 ISSN 0173-0835 R&D Projects: GA ČR GAP206/11/2377 Grant - others:GA ČR(CZ) GAP502/12/1285 Program:GA Institutional support: RVO:68081715 ; RVO:67985904 Keywords : apoptosis * bioluminescence * caspase-3 Subject RIV: CB - Analytical Chemistry, Separation Impact factor: 3.161, year: 2013

  5. Phosphorylation of Smac by Akt promotes the caspase-3 activation during etoposide-induced apoptosis in HeLa cells.

    Science.gov (United States)

    Jeong, Chul-Ho; Chun, Kyung-Soo; Kundu, Juthika; Park, Byoungduck

    2015-02-01

    The Akt, family of serine/threonine protein kinases functions as key regulators of multiple aspects of cell behavior, such as survival, proliferation, migration, and carcinogenesis. Notably, Akt exerts its anti-apoptotic effects through the phosphorylation of numerous substrates related with cell cycle, genome stability, and cancer development. In this report, nevertheless, we focused our view on the novel role of Akt which involves in a pro-apoptotic action by phosphorylating second mitochondria derived activator of caspases (Smac) protein during etoposide-induced apoptotic processes. Our data reveals that Akt could bind to and phosphorylate Smac at serine residue 67, which enhances the ability of Smac to interact with the cytosolic X-chromosome linked IAP (XIAP) protein. The cellular interaction of wild-type Smac with XIAP was enhanced with similar activation kinetics of Akt activity, while this interaction was markedly attenuated in cells expressing the phosphorylation-defective mutant S67A-Smac during etoposide-induced apoptosis. Moreover, we provide the evidence indicating that the phosphorylation of Smac at ser-67 markedly upregulates the caspase-3 activity by promoting the interaction of Smac with XIAP. Taken together, we propose that the phosphorylation of Smac by Akt might be a novel mechanism that involves in amplification of caspase cascade pathway during etoposide-induced apoptosis in HeLa cells. © 2013 Wiley Periodicals, Inc.

  6. 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

  7. Hypocapnia induces caspase-3 activation and increases Abeta production.

    Science.gov (United States)

    Xie, Zhongcong; Moir, Robert D; Romano, Donna M; Tesco, Giuseppina; Kovacs, Dora M; Tanzi, Rudolph E

    2004-01-01

    At least half of all cases of early onset (<60) familial Alzheimer's disease (FAD) are caused by any of over 150 mutations in three genes: the amyloid precursor protein (APP), presenilin 1 (PS1), and presenilin 2 (PS2). Mutant forms of PS1 have been shown to sensitize cells to apoptotic cell death. We investigated the effects of hypocapnia, a risk factor for both cognitive and neurodevelopment deficits, on caspase-3 activation, apoptosis, and amyloid beta-protein (Abeta) production, and assessed the influence of the PS1Delta9 FAD mutation on these effects. For this purpose, we exposed stably transfected H4 human neuroglioma cells to conditions consistent with hypocapnia (PCO2<40 mm Hg) and hypocapnia plus hypoxia (PO2<21%). Hypocapnia (20 mm Hg CO2 for 6 h) induced caspase-3 activation and apoptosis; the PS1Delta9 FAD mutation significantly potentiated these effects. Moreover, the combination of hypocapnia (20 mm Hg CO2) and hypoxia (5%O2) induced caspase-3 activation and apoptosis in a synergistic manner. Hypocapnia (5 and 20 mm Hg CO2 for 6 h) also led to an increased Abeta production. The findings suggest that hypocapnia (e.g. during general anesthesia) could exacerbate AD neuropathogenesis. Copyright (c) 2004 S. Karger AG, Basel.

  8. Development of cell death-based method for the selectivity screening of caspase-1 inhibitors

    DEFF Research Database (Denmark)

    Chopra, Puneet; Gupta, Shashank; Dastidar, Sunanda G

    2009-01-01

    be used for the selectivity screening of multiple caspases in a biologically relevant context in a single assay. In this study, we have developed an assay in which DNA fragmentation, a hallmark of apoptosis, of Jurkat cell line was examined post induction with etoposide in the presence or absence...... belonging to caspase-1 family (1, 4 and 5) are not present in the Jurkat cells or might not be involved in the etoposide-induced DNA fragmentation. Since the inhibition of caspases 3, 8 and 9 is accompanied by the down regulation of the activity of a cascade of caspases (caspases 2, 6, 7, 9 and 10...

  9. Evolutionary psychology in the modern world: applications, perspectives, and strategies.

    Science.gov (United States)

    Roberts, S Craig; van Vugt, Mark; Dunbar, Robin I M

    2012-12-20

    An evolutionary approach is a powerful framework which can bring new perspectives on any aspect of human behavior, to inform and complement those from other disciplines, from psychology and anthropology to economics and politics. Here we argue that insights from evolutionary psychology may be increasingly applied to address practical issues and help alleviate social problems. We outline the promise of this endeavor, and some of the challenges it faces. In doing so, we draw parallels between an applied evolutionary psychology and recent developments in Darwinian medicine, which similarly has the potential to complement conventional approaches. Finally, we describe some promising new directions which are developed in the associated papers accompanying this article.

  10. From computers to cultivation: reconceptualizing evolutionary psychology

    Directory of Open Access Journals (Sweden)

    Louise eBarrett

    2014-08-01

    Full Text Available Does evolutionary theorizing have a role in psychology? This is a more contentious issue than one might imagine, given that as evolved creatures, the answer must surely be yes. The contested nature of evolutionary psychology lies not in our status as evolved beings, but in the extent to which evolutionary ideas add value to studies of human behaviour, and the rigour with which these ideas are tested. This, in turn, is linked to the framework in which particular evolutionary ideas are situated. While the framing of the current research topic places the brain-as-computer metaphor in opposition to evolutionary psychology, the most prominent school of thought in this field (born out of cognitive psychology, and often known as the Santa Barbara school is entirely wedded to the computational theory of mind as an explanatory framework. Its unique aspect is to argue that the mind consists of a large number of functionally specialized (i.e., domain-specific computational mechanisms, or modules (the massive modularity hypothesis. Far from offering an alternative to, or an improvement on, the current perspective, we argue that evolutionary psychology is a mainstream computational theory, and that its arguments for domain-specificity often rest on shaky premises. We then go on to suggest that the various forms of e-cognition (i.e., embodied, embedded, enactive represent a true alternative to standard computational approaches, with an emphasis on cognitive integration or the extended mind hypothesis in particular. We feel this offers the most promise for human psychology because it incorporates the social and historical processes that are crucial to human ‘mind-making’ within an evolutionarily-informed framework. In addition to linking to other research areas in psychology, this approach is more likely to form productive links to other disciplines within the social sciences, not least by encouraging a healthy pluralism in approach.

  11. A Novel Method for Imaging Apoptosis Using a Caspase-1 Near-Infrared Fluorescent Probe

    Directory of Open Access Journals (Sweden)

    Shanta M. Messerli

    2004-03-01

    Full Text Available Here we describe a novel method for imaging apoptosis in cells using a near-infrared fluorescent (NIRF probe selective for caspase-1 (interleukin β-converting enzyme, ICE. This biocompatible, optically quenched ICE-NIRF probe incorporates a peptide substrate, which can be selectively cleaved by caspase-1, resulting in the release of fluorescence signal. The specificity of this probe for caspase-1 is supported by various lines of evidence: 1 activation by purified caspase-1, but not another caspase in vitro; 2 activation of the probe by infection of cells with a herpes simplex virus amplicon vector (HGC-ICE-IacZ expressing a catalytically active caspase-1-IacZ fusion protein; 3 inhibition of HGC-ICE-IacZ vector-induced activation of the probe by coincubation with the caspase-1 inhibitor YVAD-cmk, but not with a caspase-3 inhibitor; and 4 activation of the probe following standard methods of inducing apoptosis with staurosporine, ganciclovir, or ionizing radiation in culture. These results indicate that this novel ICE-NIRF probe can be used in monitoring endogenous and vector-expressed caspase-1 activity in cells. Furthermore, tumor implant experiments indicate that this ICE-NIRF probe can be used to detect caspase-1 activity in living animals. This novel ICE-NIRF probe should prove useful in monitoring endogenous and vector-expressed caspase-1 activity, and potentially apoptosis in cell culture and in vivo.

  12. 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...

  13. Origins of evolutionary transitions

    Indian Academy of Sciences (India)

    An `evolutionary transition in individuality' or `major transition' is a transformation in the hierarchical level at which natural selection operates on a population. In this article I give an abstract (i.e. level-neutral and substrate-neutral) articulation of the transition process in order to precisely understand how such processes can ...

  14. Origins of evolutionary transitions

    Indian Academy of Sciences (India)

    2014-03-15

    Mar 15, 2014 ... collectivist life forms have spread through the population, the situation – the terms of the evolutionary game – have changed. Where initially there ...... Kerr B and Godfrey-Smith P 2002 Individualist and multi-level perspectives on selection in structured populations. Biol. Philos. 17 477–517. Kirk DL 1998 ...

  15. Evolutionary Stable Strategy

    Indian Academy of Sciences (India)

    IAS Admin

    After Maynard-Smith and Price [1] mathematically derived why a given behaviour or strategy was adopted by a certain proportion of the population at a given time, it was shown that a strategy which is currently stable in a population need not be stable in evolutionary time (across generations). Additionally it was sug-.

  16. 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,

  17. 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

  18. Origins of evolutionary transitions

    Indian Academy of Sciences (India)

    2014-03-15

    Mar 15, 2014 ... was to define a major transition by identifying a pattern that is common across an otherwise diverse set of ... been many major evolutionary events that this definition of a transition excludes. The evolution of ...... fragmentation periodic, or brings it under endogenous con- trol. So the mechanisms are far from ...

  19. 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.

  20. Evolutionary Developmental Psychology.

    Science.gov (United States)

    Geary, David C.; Bjorklund, David F.

    2000-01-01

    Describes evolutionary developmental psychology as the study of the genetic and ecological mechanisms that govern the development of social and cognitive competencies common to all human beings and the epigenetic (gene-environment interactions) processes that adapt these competencies to local conditions. Outlines basic assumptions and domains of…

  1. 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

  2. Caspase-10 Is the Key Initiator Caspase Involved in Tributyltin-Mediated Apoptosis in Human Immune Cells

    Directory of Open Access Journals (Sweden)

    Harald F. Krug

    2012-01-01

    Full Text Available Tributyltin (TBT is one of the most toxic compounds produced by man and distributed in the environment. A multitude of toxic activities have been described, for example, immunotoxic, neurotoxic, and endocrine disruptive effects. Moreover, it has been shown for many cell types that they undergo apoptosis after treatment with TBT and the cell death of immune cells could be the molecular background of its immunotoxic effect. As low as 200 nM up to 1 μM of TBT induces all signs of apoptosis in Jurkat T cells within 1 to 24 hrs of treatment. When compared to Fas-ligand control stimulation, the same sequence of events occurs: membrane blebbing, phosphatidylserine externalisation, the activation of the “death-inducing signalling complex,” and the following sequence of cleavage processes. In genetically modified caspase-8-deficient Jurkat cells, the apoptotic effects are only slightly reduced, whereas, in FADD-negative Jurkat cells, the TBT effect is significantly diminished. We could show that caspase-10 is recruited by the TRAIL-R2 receptor and apoptosis is totally prevented when caspase-10 is specifically inhibited in all three cell lines.

  3. A genetic screen for modifiers of Drosophila caspase Dcp-1 reveals caspase involvement in autophagy and novel caspase-related genes

    Directory of Open Access Journals (Sweden)

    Ahnn Joohong

    2010-01-01

    Full Text Available Abstract Background Caspases are cysteine proteases with essential functions in the apoptotic pathway; their proteolytic activity toward various substrates is associated with the morphological changes of cells. Recent reports have described non-apoptotic functions of caspases, including autophagy. In this report, we searched for novel modifiers of the phenotype of Dcp-1 gain-of-function (GF animals by screening promoter element- inserted Drosophila melanogaster lines (EP lines. Results We screened ~15,000 EP lines and identified 72 Dcp-1-interacting genes that were classified into 10 groups based on their functions and pathways: 4 apoptosis signaling genes, 10 autophagy genes, 5 insulin/IGF and TOR signaling pathway genes, 6 MAP kinase and JNK signaling pathway genes, 4 ecdysone signaling genes, 6 ubiquitination genes, 11 various developmental signaling genes, 12 transcription factors, 3 translation factors, and 11 other unclassified genes including 5 functionally undefined genes. Among them, insulin/IGF and TOR signaling pathway, MAP kinase and JNK signaling pathway, and ecdysone signaling are known to be involved in autophagy. Together with the identification of autophagy genes, the results of our screen suggest that autophagy counteracts Dcp-1-induced apoptosis. Consistent with this idea, we show that expression of eGFP-Atg5 rescued the eye phenotype caused by Dcp-1 GF. Paradoxically, we found that over-expression of full-length Dcp-1 induced autophagy, as Atg8b-GFP, an indicator of autophagy, was increased in the eye imaginal discs and in the S2 cell line. Taken together, these data suggest that autophagy suppresses Dcp-1-mediated apoptotic cell death, whereas Dcp-1 positively regulates autophagy, possibly through feedback regulation. Conclusions We identified a number of Dcp-1 modifiers that genetically interact with Dcp-1-induced cell death. Our results showing that Dcp-1 and autophagy-related genes influence each other will aid future

  4. Notes on an evolutionary medicine.

    Science.gov (United States)

    Weiner, H

    1998-01-01

    . This study will review aspects of evolutionary theory that would lead to a unified, integrated theory of health, illness, and disease, and to a clearer taxonomy in medicine.

  5. Evolutionary genetics: the Drosophila model

    Indian Academy of Sciences (India)

    Unknown

    In Evolutionary genetics: from molecules to morphology (ed. R. S. Singh and C. B. Krimbas), pp. 609–627. Cambridge Uni- versity Press, Cambridge. Houle D. 2001 Characters as the units of evolutionary change. In The character concept in evolutionary biology. (ed. G. P. Wagner), pp. 109–140. Academic Press, San Diego.

  6. Evolutionary impact assessment: accounting for evolutionary consequences of fishing in an ecosystem approach to fisheries management.

    Science.gov (United States)

    Laugen, Ane T; Engelhard, Georg H; Whitlock, Rebecca; Arlinghaus, Robert; Dankel, Dorothy J; Dunlop, Erin S; Eikeset, Anne M; Enberg, Katja; Jørgensen, Christian; Matsumura, Shuichi; Nusslé, Sébastien; Urbach, Davnah; Baulier, Loїc; Boukal, David S; Ernande, Bruno; Johnston, Fiona D; Mollet, Fabian; Pardoe, Heidi; Therkildsen, Nina O; Uusi-Heikkilä, Silva; Vainikka, Anssi; Heino, Mikko; Rijnsdorp, Adriaan D; Dieckmann, Ulf

    2014-03-01

    Managing fisheries resources to maintain healthy ecosystems is one of the main goals of the ecosystem approach to fisheries (EAF). While a number of international treaties call for the implementation of EAF, there are still gaps in the underlying methodology. One aspect that has received substantial scientific attention recently is fisheries-induced evolution (FIE). Increasing evidence indicates that intensive fishing has the potential to exert strong directional selection on life-history traits, behaviour, physiology, and morphology of exploited fish. Of particular concern is that reversing evolutionary responses to fishing can be much more difficult than reversing demographic or phenotypically plastic responses. Furthermore, like climate change, multiple agents cause FIE, with effects accumulating over time. Consequently, FIE may alter the utility derived from fish stocks, which in turn can modify the monetary value living aquatic resources provide to society. Quantifying and predicting the evolutionary effects of fishing is therefore important for both ecological and economic reasons. An important reason this is not happening is the lack of an appropriate assessment framework. We therefore describe the evolutionary impact assessment (EvoIA) as a structured approach for assessing the evolutionary consequences of fishing and evaluating the predicted evolutionary outcomes of alternative management options. EvoIA can contribute to EAF by clarifying how evolution may alter stock properties and ecological relations, support the precautionary approach to fisheries management by addressing a previously overlooked source of uncertainty and risk, and thus contribute to sustainable fisheries.

  7. Enzymatic RNA synthesis and RNase P. Evolutionary aspects.

    Science.gov (United States)

    Krupp, G

    TransferRNA recognition was used as leit-motiv in the illustration of possible links between a hypothetical primordial RNA world and the contemporary DNA world. In an RNA world, 'proto-tRNA' could have functioned as replication origin and as primitive telomere. Possibly, this primitive structure is preserved in a 'universal substrate' for modern tRNA-specific enzymes. The combination of acceptor stem and T arm (plus a linker) was finally revealed as sufficient for the recognition by prokaryotic and eukaryotic RNase P, as well as other tRNA enzymes. In modern life forms, a tRNA-like element in viral RNAs still serves as replication origin, and furthermore, the recognition of similar structures as cryptic promoters is universally conserved for template-dependent RNA polymerases. Another common property of modern polymerases is their high, but clearly limited and condition-dependent substrate specificity. Very likely, also substrate recognition by primitive polymerases was not more stringent, and this lead to the occurrence of mixed nucleic acids as intermediates in the transition of genomic RNA to contemporary genomic DNA.

  8. Plant Fructokinases: Evolutionary, Developmental, and Metabolic Aspects in Sink Tissues

    Directory of Open Access Journals (Sweden)

    Ofer Stein

    2018-03-01

    Full Text Available Sucrose, a glucose–fructose disaccharide, is the main sugar transported in the phloem of most plants and is the origin of most of the organic matter. Upon arrival in sink tissues, the sucrose must be cleaved by invertase or sucrose synthase. Both sucrose-cleaving enzymes yield free fructose, which must be phosphorylated by either fructokinase (FRK or hexokinase (HXK. The affinity of FRK to fructose is much higher than that of HXK, making FRKs central for fructose metabolism. An FRK gene family seems to exist in most, if not all plants and usually consists of several cytosolic FRKs and a single plastidic FRK. These genes are expressed mainly in sink tissues such as roots, stems, flowers, fruits, and seeds, with lower levels of expression often seen in leaves. Plant FRK enzymes vary in their biochemical properties such as affinity for fructose, inhibition by their substrate (i.e., fructose, and expression level in different tissues. This review describes recently revealed roles of plant FRKs in plant development, including the combined roles of the plastidic and cytosolic FRKs in vascular tissues and seed development.

  9. The ergot alkaloid gene cluster: Functional analyses and evolutionary aspects

    Czech Academy of Sciences Publication Activity Database

    Lorenz, N.; Haarmann, T.; Pažoutová, Sylvie; Jung, M.; Tudzynski, P.

    2009-01-01

    Roč. 70, 15-16 (2009), s. 1822-1832 ISSN 0031-9422 Institutional research plan: CEZ:AV0Z50200510 Keywords : Claviceps purpurea * Ergot fungus * Ergot alkaloid gene cluster Subject RIV: EE - Microbiology, Virology Impact factor: 3.104, year: 2009

  10. Evolutionary aspects of acoustic communication in Ribautodelphax planthoppers (Homoptera, Delphacidae)

    NARCIS (Netherlands)

    Winter, de A.J.

    1994-01-01

    Delphacidae (Homoptera), commonly referred to as planthoppers, are herbivores, which usually feed on grasses and sedges. During sexual behaviour males and females communicate by exchanging low-frequency vibrational signals, which are transmitted through the substrate, normally the host

  11. Bifurcation analysis can unify ecological and evolutionary aspects of ecosystems.

    NARCIS (Netherlands)

    Troost, T.A.; Kooi, B.W.; Kooijman, S.A.L.M.

    2007-01-01

    Bifurcation theory is commonly used to study the dynamical behaviour of ecosystems. It involves the analysis of points in the parameter space where the stability of the system changes qualitatively. Generally, such changes are related only to changes in environmental parameters, while the organism's

  12. Evolutionary aspects of ABO blood group in humans.

    Science.gov (United States)

    Franchini, Massimo; Bonfanti, Carlo

    2015-04-15

    The antigens of the ABO blood group system (A, B and H determinants) are complex carbohydrate molecules expressed on red blood cells and on a variety of other cell lines and tissues. Growing evidence is accumulating that ABO antigens, beyond their key role in transfusion medicine, may interplay with the pathogenesis of many human disorders, including infectious, cardiovascular and neoplastic diseases. In this narrative review, after succinct description of the current knowledge on the association between ABO blood groups and the most severe diseases, we aim to elucidate the particularly intriguing issue of the possible role of ABO system in successful aging. In particular, focus will be placed on studies evaluating the ABO phenotype in centenarians, the best human model of longevity. Copyright © 2015 Elsevier B.V. All rights reserved.

  13. From Biophysics to Evolutionary Genetics: Statistical Aspects of Gene Regulation

    Science.gov (United States)

    Lässig, Michael

    Genomic functions often cannot be understood at the level of single genes but require the study of gene networks. This systems biology credo is nearly commonplace by now. Evidence comes from the comparative analysis of entire genomes: current estimates put, for example, the number of human genes at around 22,000, hardly more than the 14,000 of the fruit fly, and not even an order of magnitude higher than the 6,000 of baker's yeast. The complexity and diversity of higher animals, therefore, cannot be explained in terms of their gene numbers. If, however, a biological function requires the concerted action of several genes, and conversely, a gene takes part in several functional contexts, an organism may be defined less by its individual genes but by their interactions. The emerging picture of the genome as a strongly interacting system with many degrees of freedom brings new challenges for experiment and theory, many of which are of a statistical nature. And indeed, this picture continues to make the subject attractive to a growing number of statistical physicists.

  14. Some cytological, ecological and evolutionary aspects of pollination

    Directory of Open Access Journals (Sweden)

    Ettore Pacini

    2014-01-01

    Full Text Available Different types of pollen dispersing units are described. The pollen of angiosperms may be dispersed in monads, tetrads, polyads, massulae or compact pollinia. The monads and tetrads may form larger clumps of pollen with the aid of the following substances: a pollenkitt, a product of in situ degeneration of the tapetum; b tryphine, a product of tapetal extra situm degeneration, found only in Cruciferae; c elastoviscin, a highly viscous product of the degeneration of a limited number of tapetal cells, found only in certain Orchidaceae; d viscin threads or sporopollenin filaments arising from the pollen exine. The number of pollen grains composing the clumps depends on pollen diameter and the cohesive forces holding the pollen grains together. The various types of pollen dispersing unit are discussed in relation to the type of pollination and number of ovules per ovary.

  15. GASP/WFIKKN proteins: evolutionary aspects of their functions.

    Directory of Open Access Journals (Sweden)

    Olivier Monestier

    Full Text Available Growth and differentiation factor Associated Serum Protein (GASP 1 and 2 are proteins known to be involved in the control of myostatin activity at least in vitro. Most deuterostome GASPs share a modular organization including WAP, follistatin/kazal, IGc2, two kunitz, and NTR domains. Based on an exon shuffling model, we performed independent phylogenetic analyses on these modules and assessed that papilin is probably a sister sequence to GASP with a divergence date estimated from the last common ancestor to bilateria. The final organization was acquired by the addition of the FS domain in early deuterostomes. Our study revealed that Gasp genes diverged during the first round of genome duplication in early vertebrates. By evaluating the substitution rate at different sites on the proteins, we showed a better conservation of the follistatin/kazal domain of GASP1 than GASP2 in mammals, suggesting a stronger interaction with myostatin. We also observed a progressive increase in the conservation of follistatin and kunitz domains from the ancestor of Ciona to early vertebrates. In situ hybridization performed on mouse embryos showed a weak Gasp1 expression in the formed somites at 10.5 dpc and in limb buds from embryonic E10.0 to E12.5. Similar results were obtained for zebrafish embryos. We propose a synthetic view showing possible interactions between GASP1 and myostatin and highlighting the role of the second kunitz domain in preventing myostatin proteolysis.

  16. Erythrocyte caspase-3 levels in children with chronic kidney disease.

    Science.gov (United States)

    Polak-Jonkisz, D; Purzyc, L; Szcepańska, M; Makulska, I

    2013-02-01

    In chronic kidney disease (CKD), a number of intra- and extracellular factors, e.g., uremic toxins, mechanic, oxidative or osmotic stress - induce changes (rearrangements) in the structure of cytoplasmatic membrane, while also simultaneously deregulating blood cell metabolism and, in consequence, contributing to preliminary ageing and suicidal death of red blood cells (RBCs).The aim of the reported study was an evaluation of caspase-3 and lactate dehydrogenase activities and of ATP concentrations in erythrocytes as cellular responses to CKD progress. Conservatively treated sixty (60) CKD children were enrolled into the study and divided, according to CKD progression (stage I-IV). The control group consisted of twenty-five (25) healthy children. The activity of caspase-3 (Casp-3) and lactate dehydrogenase (LDH) were spectrophotometrically assayed in haemolysed erythrocytes. Adenosine triphosphate (ATP(e)) concentrations were measured by means of a luciferin-luciferase kit. A gradual increase of LDH and ATP levels was observed in transition from CKD stage I to stage III. In Group IV, the levels of those parameters were statistically significantly lower than in the control group. The activity of Casp-3 in Group I was comparable to that in healthy children. The highest activity of Casp-3 was observed in Group III. 1. The activity of caspase-3 in RBCs of CKD children grows with progression of the disease. 2. The lower LDH activities and the ATP concentration drop below the values characteristic for the control group, as observed in stage IV of CKD, indicate a compromised energy balance. Copyright © 2012 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

  17. Expression and activation of Daphnia pulex Caspase-3 are involved in regulation of aging.

    Science.gov (United States)

    Tong, Qiaoqiong; Zhang, Mengmeng; Cao, Xiao; Xu, Shanliang; Wang, Danli; Zhao, Yunlong

    2017-11-15

    Death-mediating proteases such as Caspases have been implicated in aging. Remarkably, active Caspase-3 can trigger widespread damage and degeneration, playing a key role in causing cell death. In order to explore the relationship between Caspase-3 and aging in Daphnia pulex, we cloned and analyzed the full-length cDNA sequence of its Caspase-3 gene. Both mRNA expression and activity of D. pulex Caspase-3 increased with age. Moreover, different forms of Caspase-3 appeared with aging. The expression of casp3-L was higher and decreased with age, while that of casp3-S was weak and increased with age, consistent with the trend in Caspase-3 activity. Mhc mRNA expression declined over time and was negatively correlated with age and Caspase-3. In situ hybridization results showed that Caspase-3 mRNA was expressed in different growth and reproduction stages, and its expression levels in embryos and larva were lower than that in adult D. pulex. Western blot analysis revealed the presence of Caspase-3 in the form of zymogens with a molecular weight of ~36kDa. Overall, this study explored age-associated gene regulation to provide a basis for the molecular mechanism of D. pulex reproductive conversion. Copyright © 2017 Elsevier B.V. All rights reserved.

  18. AlCl3 induces lymphocyte apoptosis in rats through the mitochondria-caspase dependent pathway.

    Science.gov (United States)

    Li, Miao; Song, Miao; Ren, Li-Min; Xiu, Chun-Yu; Liu, Jian-Yu; Zhu, Yan-zhu; Li, Yan-Fei

    2016-04-01

    To investigate apoptosis mechanisms in lymphocytes induced by aluminum trichloride (AlCl3) through the mitochondria-caspase dependent pathway, the spleen lymphocytes of rats were cultured with RPMI-1640 medium and exposed to AlCl3·6H2O in the final concentrations of 0 (control group, CG), 0.3 (low-dose group, LG), 0.6 (mid-dose group, MG), and 1.2 (high-dose group, HG) mmol·L(-1) for 24 h, respectively. Mitochondrial transmembrane potential (ΔΨm), cytochrome C (Cyt C) protein expression in cytoplasm, Caspase-3 and Caspase-9 activity, Bcl-2, Bax, Caspase-3 and Caspase-9 mRNA expressions, DNA ladder and lymphocytes apoptosis index were detected. The results showed that Cyt C protein expression in cytoplasm, Caspase-3 and Caspase-9 activity, Bcl-2, Bax, Caspase-3 and Caspase-9 mRNA expressions, the ratio of Bcl-2 and Bax mRNA expression, lymphocytes apoptosis index increased, while ΔΨm decreased in the AlCl3-treated groups compared with those in CG. The results indicate that AlCl3 induces lymphocyte apoptosis in rats through the mitochondria-caspase dependent pathway. © 2014 Wiley Periodicals, Inc.

  19. Expression of Caspase Signaling Components in the Outer Membranes of Chronic Subdural Hematomas.

    Science.gov (United States)

    Osuka, Koji; Watanabe, Yasuo; Usuda, Nobuteru; Aoyama, Masahiro; Iwami, Kenichiro; Takeuchi, Mikinobu; Watabe, Takeya; Takayasu, Masakazu

    2017-11-15

    Chronic subdural hematoma (CSDH) is fundamentally treatable through surgery, although CSDH recurs in some cases. We have observed several cases of spontaneous resolution of CSDH outer membranes, including in trabecular CSDH, after trepanation surgery. In this study, we examined the expression of molecules involved in caspase signaling in CSDH outer membranes. Eight patients whose outer membranes were obtained successfully during trepanation surgery were included in this study. The expression of Fas; Fas-associated death domain (FADD); tumor necrosis factor receptor type 1-associated death domain (TRADD); receptor-interacting protein (RIP); caspases 3, 7, 8, and 9; poly-(ADP-ribose) polymerase (PARP); DNA fragmentation factor 45 (DFF45) and β-actin was examined by Western blot analysis. The expression levels of PARP, caspase-3, and cleaved caspase-3 were also examined by immunohistochemistry. Fas; FADD; TRADD; RIP; caspases 3, 7, 8, and 9; PARP, and DFF45 were detected in nearly all samples. Caspase-3 and PARP were localized in the endothelial cells of vessels and in fibroblasts in CSDH outer membranes. In addition, cleaved caspase-3 was detected in fibroblasts. We detected molecules of the caspase signaling pathway in CSDH outer membranes. In particular, cleaved caspase-3 was detected, which suggests that apoptosis may occur within these membranes. Thus, during the growth of CSDH outer membranes, the caspase signaling pathway may be restrained. Once the pathway is activated, gradual resolution of CSDH outer membranes may occur. Therefore, these molecules may be novel therapeutic targets for intractable CSDH.

  20. Caspase-12 is involved in stretch-induced apoptosis mediated endoplasmic reticulum stress.

    Science.gov (United States)

    Zhang, Qiang; Liu, Jianing; Chen, Shulan; Liu, Jing; Liu, Lijuan; Liu, Guirong; Wang, Fang; Jiang, Wenxin; Zhang, Caixia; Wang, Shuangyu; Yuan, Xiao

    2016-04-01

    It is well recognized that mandibular growth, which is caused by a variety of functional appliances, is considered to be the result of both neuromuscular and skeletal adaptations. Accumulating evidence has demonstrated that apoptosis plays an important role in the adaptation of skeletal muscle function. However, the underlying mechanism of apoptosis that is induced by stretch continues to be incompletely understood. Endoplasmic reticulum stress (ERS), a newly defined signaling pathway, initiates apoptosis. This study seeks to determine if caspase-12 is involved in stretch-induced apoptosis mediated endoplasmic reticulum stress in myoblast and its underlying mechanism. Apoptosis was assessed by Hochest staining, DAPI staining and annexin V binding and PI staining. ER chaperones, such as GRP78, CHOP and caspase-12, were determined by reverse transcription polymerase chain reaction (RT-PCR) and Western blot. Furthermore, caspase-12 inhibitor was used to value the mechanism of the caspase-12 pathway. Apoptosis of myoblast, which is subjected to cyclic stretch, was observed in a time-dependent manner. We found that GRP78 mRNA and protein were significantly increased and CHOP and caspase-12 were activated in myoblast that was exposed to cyclic stretch. Caspase-12 inhibition reduced stretch-induced apoptosis, and caspase-12 activated caspase-3 to induce apoptosis. We concluded that caspase-12 played an important role in stretch-induced apoptosis that is associated by endoplasmic reticulum stress by activating caspase-3.

  1. Apoptotic block in colon cancer cells may be rectified by lentivirus mediated overexpression of caspase-9.

    Science.gov (United States)

    Xu, D; Wang, C; Shen, X; Yu, Y; Rui, Y; Zhang, D; Zhou, Z

    2013-12-01

    At present, the inhibition of apoptosis during pathogenesis of colorectal cancer is widely recognized while the role of caspase-9 in this process remains controversial. We aimed to investigate the differential expression of caspase-9 and evaluate the therapeutic potential of expression intervention in this study. We first examined the different expression of caspase-9 in normal colon mucosa, adenoma and cancer, investigating the relationship between its expression and clinico-pathological characteristics. Secondly, overexpression of caspase-9 was established in colon cancer cell lines by lentivirus infection to study the changes in growth, proliferation and apoptosis. Compared with normal colon mucosa, the expression of caspase-9 was higher in adenoma while lower in cancer both at mRNA and protein level (P expression is more common in poorly differentiated cancers (P expression of caspase-9, poorer colony formation and slower cell proliferation. In terms of apoptosis related indicators, caspase-9 overexpression leads to higher apoptosis rate and GO/G1 arrest, while up-regulating the expression of caspase-3 (P expression from colon mucosa, adenoma to cancer suggested it may be involved in the carcinogenesis of colon cancer. The overexpression of caspase-9 exhibits an inhibitory role in cancer growth and proliferation while promoting apoptosis. However, a non-apoptotic role of caspase-9 facilitating differentiation was also implied.

  2. 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...

  3. Microparticulate Caspase-1 Regulates Gasdermin-D and Pulmonary Vascular Endothelial Cell Injury.

    Science.gov (United States)

    Mitra, Srabani; Exline, Matthew; Habyarimana, Fabien; Gavrilin, Mikhail; Baker, Paul; Masters, Seth L; Wewers, Mark D; Sarkar, Anasuya

    2018-01-24

    Lung endothelial cell apoptosis and injury occurs throughout all stages of acute lung injury (ALI/ARDS) and impacts disease progression. Caspases 1, 4 and 5 are essential for completion of the apoptotic program known as pyroptosis that also involves pro-inflammatory cytokines. Because GSDM-D mediates pyroptotic death and is essential for pore formation, we hypothesized that it may direct caspase-1 encapsulated microparticle (MP) release and mediate endothelial cell death. Our current work provides evidence that GSDM-D is released by LPS stimulated THP1 monocytic cells where it is packaged into microparticles along with active caspase-1. Furthermore, only MP released from stimulated monocytic cells that contain both cleaved GSDM-D and active caspase-1 induce endothelial cell apoptosis. MPs pretreated with caspase-1 inhibitor, YVAD, or pan-caspase inhibitor, ZVAD, do not contain cleaved GSDM-D. MPs from caspase-1KO cells are also deficient in p30 active GSDM-D, further confirming that caspase-1 regulates GSDM-D function. Although control MPs contained cleaved GSDM-D without caspase-1, these fractions were unable to induce cell death, suggesting that encapsulation of both caspase-1 and GSDM-D is essential for cell death induction. Release of microparticulate active caspase-1 was abrogated in GSDM-KO cells, although cytosolic caspase-1 activation was not impaired. Lastly, higher levels of microparticulate GSDM-D was detected in septic ARDS patient plasma when compared to healthy donors. Taken together, these findings suggest that GSDM-D regulates the release of microparticulate active caspase-1 from monocytes essential for induction of cell death and thereby may play a critical role in sepsis-induced endothelial cell injury.

  4. Anxiety: an evolutionary approach.

    OpenAIRE

    Bateson, M; Brilot, B; Nettle, D

    2011-01-01

    Anxiety disorders are among the most common mental illnesses, with huge attendant suffering. Current treatments are not universally effective, suggesting that a deeper understanding of the causes of anxiety is needed. To understand anxiety disorders better, it is first necessary to understand the normal anxiety response. This entails considering its evolutionary function as well as the mechanisms underlying it. We argue that the function of the human anxiety response, and homologues in other ...

  5. Evolutionary Dynamics of Globalization

    OpenAIRE

    Naci Canpolat; Hüseyin Ozel

    2008-01-01

    The expansion of markets –globalization– was reversed during early 20th century and unfettered markets gave in to the welfare state and central planning. But the markets have been striking back since the early 1980s. Governments are withdrawn from economic activities, and many structural market reforms are implemented. Now the question is: Can the forces that market expansion create again reverse this expansion? This paper seeks an answer to this question by constructing an evolutionary game ...

  6. Computational evolutionary perception.

    Science.gov (United States)

    Hoffman, Donald D; Singh, Manish

    2012-01-01

    Marr proposed that human vision constructs "a true description of what is there". He argued that to understand human vision one must discover the features of the world it recovers and the constraints it uses in the process. Bayesian decision theory (BDT) is used in modem vision research as a probabilistic framework for understanding human vision along the lines laid out by Marr. Marr's contribution to vision research is substantial and justly influential. We propose, however, that evolution by natural selection does not, in general, favor perceptions that are true descriptions of the objective world. Instead, research with evolutionary games shows that perceptual systems tuned solely to fitness routinely outcompete those tuned to truth. Fitness functions depend not just on the true state of the world, but also on the organism, its state, and the type of action. Thus, fitness and truth are distinct. Natural selection depends only on expected fitness. It shapes perceptual systems to guide fitter behavior, not to estimate truth. To study perception in an evolutionary context, we introduce the framework of Computational Evolutionary Perception (CEP). We show that CEP subsumes BDT, and reinterprets BDT as evaluating expected fitness rather than estimating truth.

  7. Asymmetric Evolutionary Games.

    Science.gov (United States)

    McAvoy, Alex; Hauert, Christoph

    2015-08-01

    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.

  8. Asymmetric Evolutionary Games.

    Directory of Open Access Journals (Sweden)

    Alex McAvoy

    2015-08-01

    Full Text Available 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.

  9. Caspase-2 mediates a Brucella abortus RB51-induced hybrid cell death having features of apoptosis and pyroptosis

    Directory of Open Access Journals (Sweden)

    Denise Nicole Bronner

    2013-11-01

    Full Text Available Programmed cell death (PCD can play a crucial role in tuning the immune response to microbial infection. Although PCD can occur in different forms, all are mediated by a family of proteases called caspases. Caspase-2 is the most conserved caspase; however its function in cell death is ill-defined. Previously we demonstrated that live attenuated cattle vaccine strain Brucella abortus RB51 induces caspase-2-mediated PCD of infected macrophages. However, the mechanism of caspase-2-mediated cell death pathway remained unclear. In this study, we found that caspase-2 mediated proinflammatory cell death of RB51-infected macrophages and regulated many genes in different PCD pathways. We show that the activation of proapoptotic caspases-3 and -8 was dependent upon caspase-2. Caspase-2 regulated mitochondrial cytochrome c release and TNFα production, both of which are known to activate caspase-3 and caspase-8, respectively. In addition to TNFα, RB51-induced caspase-1 and IL-1β production was also driven by caspase-2-mediated mitochondrial dysfunction. Interestingly, pore formation, a phenomenon commonly associated with caspase-1-mediated pyroptosis, occurred; however it did not contribute to RB51-induced proinflammatory cell death. Our data suggest that caspase-2 acts as an initiator caspase that mediates a novel RB51-induced hybrid cell death that simulates but differs from typical apoptosis and pyroptosis. The initiator role of the caspase-2-mediated cell death was also conserved in cellular stress-induced cell death of macrophages treated with etoposide, naphthalene, or anti-Fas. Caspase-2 also regulated caspase-3 and -8 activation, as well as cell death in macrophages treated with each of the three reagents. Taken together, our data has demonstrated that caspase-2 can play an important role in mediating a proinflammatory response and a hybrid cell death that demonstrates features of both apoptosis and pyroptosis.

  10. p53 increases caspase-6 expression and activation in muscle tissue expressing mutant huntingtin

    DEFF Research Database (Denmark)

    Ehrnhoefer, Dagmar E; Skotte, Niels H; Ladha, Safia

    2014-01-01

    as in muscle tissues from two different HD mouse models. p53, a transcriptional activator of caspase-6, is upregulated in neuronal cells and tissues expressing mutant huntingtin. Activation of p53 leads to a dramatic increase in levels of caspase-6 mRNA, caspase-6 activity and cleavage of lamin A. Using mouse...... embryonic fibroblasts (MEFs) from YAC128 mice, we show that this increase in caspase-6 activity can be mitigated by pifithrin-α (pifα), an inhibitor of p53 transcriptional activity, but not through the inhibition of p53's mitochondrial pro-apoptotic function. Remarkably, the p53-mediated increase in caspase......-6 expression and activation is exacerbated in cells and tissues of both neuronal and peripheral origin expressing mutant huntingtin (Htt). These findings suggest that the presence of the mutant Htt protein enhances p53 activity and lowers the apoptotic threshold, which activates caspase-6...

  11. Activation of two caspase cascades, caspase 8/3/6 and caspase 9/3/6, during photodynamic therapy using a novel photosensitizer, ATX-S10(Na), in normal human keratinocytes.

    Science.gov (United States)

    Takahashi, Hidetoshi; Itoh, Yasuhiro; Miyauchi, Yuki; Nakajima, Susumu; Sakata, Isao; Ishida-Yamamoto, Akemi; Iizuka, Hajime

    2003-11-01

    Photodynamic therapy (PDT) is a potent treatment for skin tumors. Although the therapeutic effect of PDT is supposed to be due to cellular cytotoxicity, the precise mechanism is still unknown. ATX-S10(Na) [13,17-bis(1-carboxypropionyl)carbamoylethyl-8-ethenyl-2-hydroxy-3-hydroxyiminoethylidene-2,7,12,18-tetramethylporphyrin sodium salt], a novel hydrophilic chlorin photosensitizer, shows good accumulation in tumors and is suitable for use in PDT. In this study, we investigated the mechanism of PDT-induced cell death using ATX-S10(Na). . Following ATX-S10(Na) treatment for 12 h, normal human keratinocytes (NHK) were irradiated using a diode laser. PDT-induced cell death and the activity of various caspases were measured. Activation of Fas antigen was also determined by immunoprecipitation analysis. The expression of Bax, cytochrome c, and apoptosis-inducing factor (AIF) was determined by Western blotting. ATX-S10(Na)-PDT had induced apoptosis of NHK by 2 h and the maximal effect was observed at 6 h following irradiation. The effect was suppressed by pretreatment of NHK with inhibitors of caspases 3, 6, 8 and 9. A caspase activity assay revealed the sequential activation of caspases 8, 3 and 6, and caspases 9, 3 and 6, respectively. Immunoprecipitation analysis indicated multimerization of Fas antigen without Fas ligand binding in ATX-S10(Na)-PDT-treated NHK. Western blotting revealed cytosolic release of cytochrome c and AIF accompanied by decreased Bax expression in the cytosol. ATX-S10(Na)-PDT induces apoptosis of NHK, and this was mediated by sequential activation of two caspase cascades, caspases 8, 3 and 6, and caspases 9, 3 and 6. This was accompanied by multimerization of Fas antigen and cytosolic release of cytochrome c and AIF.

  12. Engineering a light-activated caspase-3 for precise ablation of neurons in vivo.

    Science.gov (United States)

    Smart, Ashley D; Pache, Roland A; Thomsen, Nathan D; Kortemme, Tanja; Davis, Graeme W; Wells, James A

    2017-09-26

    The circuitry of the brain is characterized by cell heterogeneity, sprawling cellular anatomy, and astonishingly complex patterns of connectivity. Determining how complex neural circuits control behavior is a major challenge that is often approached using surgical, chemical, or transgenic approaches to ablate neurons. However, all these approaches suffer from a lack of precise spatial and temporal control. This drawback would be overcome if cellular ablation could be controlled with light. Cells are naturally and cleanly ablated through apoptosis due to the terminal activation of caspases. Here, we describe the engineering of a light-activated human caspase-3 (Caspase-LOV) by exploiting its natural spring-loaded activation mechanism through rational insertion of the light-sensitive LOV2 domain that expands upon illumination. We apply the light-activated caspase (Caspase-LOV) to study neurodegeneration in larval and adult Drosophila Using the tissue-specific expression system (UAS)-GAL4, we express Caspase-LOV specifically in three neuronal cell types: retinal, sensory, and motor neurons. Illumination of whole flies or specific tissues containing Caspase-LOV-induced cell death and allowed us to follow the time course and sequence of neurodegenerative events. For example, we find that global synchronous activation of caspase-3 drives degeneration with a different time-course and extent in sensory versus motor neurons. We believe the Caspase-LOV tool we engineered will have many other uses for neurobiologists and others for specific temporal and spatial ablation of cells in complex organisms.

  13. Mononuclear Phagocyte-Derived Microparticulate Caspase-1 Induces Pulmonary Vascular Endothelial Cell Injury

    Science.gov (United States)

    Mitra, Srabani

    2015-01-01

    Lung endothelial cell apoptosis and injury occurs throughout all stages of acute lung injury (ALI/ARDS) and impacts disease progression. Lung endothelial injury has traditionally been focused on the role of neutrophil trafficking to lung vascular integrin receptors induced by proinflammatory cytokine expression. Although much is known about the pathogenesis of cell injury and death in ALI/ARDS, gaps remain in our knowledge; as a result of which there is currently no effective pharmacologic therapy. Enzymes known as caspases are essential for completion of the apoptotic program and secretion of pro-inflammatory cytokines. We hypothesized that caspase-1 may serve as a key regulator of human pulmonary microvascular endothelial cell (HPMVEC) apoptosis in ALI/ARDS. Our recent experiments confirm that microparticles released from stimulated monocytic cells (THP1) induce lung endothelial cell apoptosis. Microparticles pretreated with the caspase-1 inhibitor, YVAD, or pan-caspase inhibitor, ZVAD, were unable to induce cell death of HPMVEC, suggesting the role of caspase-1 or its substrate in the induction of HPMVEC cell death. Neither un-induced microparticles (control) nor direct treatment with LPS induced apoptosis of HPMVEC. Further experiments showed that caspase-1 uptake into HPMVEC and the induction of HPMVEC apoptosis was facilitated by caspase-1 interactions with microparticulate vesicles. Altering vesicle integrity completely abrogated apoptosis of HPMVEC suggesting an encapsulation requirement for target cell uptake of active caspase-1. Taken together, we confirm that microparticle centered caspase-1 can play a regulator role in endothelial cell injury. PMID:26710067

  14. Mononuclear Phagocyte-Derived Microparticulate Caspase-1 Induces Pulmonary Vascular Endothelial Cell Injury.

    Science.gov (United States)

    Mitra, Srabani; Wewers, Mark D; Sarkar, Anasuya

    2015-01-01

    Lung endothelial cell apoptosis and injury occurs throughout all stages of acute lung injury (ALI/ARDS) and impacts disease progression. Lung endothelial injury has traditionally been focused on the role of neutrophil trafficking to lung vascular integrin receptors induced by proinflammatory cytokine expression. Although much is known about the pathogenesis of cell injury and death in ALI/ARDS, gaps remain in our knowledge; as a result of which there is currently no effective pharmacologic therapy. Enzymes known as caspases are essential for completion of the apoptotic program and secretion of pro-inflammatory cytokines. We hypothesized that caspase-1 may serve as a key regulator of human pulmonary microvascular endothelial cell (HPMVEC) apoptosis in ALI/ARDS. Our recent experiments confirm that microparticles released from stimulated monocytic cells (THP1) induce lung endothelial cell apoptosis. Microparticles pretreated with the caspase-1 inhibitor, YVAD, or pan-caspase inhibitor, ZVAD, were unable to induce cell death of HPMVEC, suggesting the role of caspase-1 or its substrate in the induction of HPMVEC cell death. Neither un-induced microparticles (control) nor direct treatment with LPS induced apoptosis of HPMVEC. Further experiments showed that caspase-1 uptake into HPMVEC and the induction of HPMVEC apoptosis was facilitated by caspase-1 interactions with microparticulate vesicles. Altering vesicle integrity completely abrogated apoptosis of HPMVEC suggesting an encapsulation requirement for target cell uptake of active caspase-1. Taken together, we confirm that microparticle centered caspase-1 can play a regulator role in endothelial cell injury.

  15. Dying glioma cells establish a proangiogenic microenvironment through a caspase 3 dependent mechanism

    Science.gov (United States)

    Feng, Xiao; Yu, Yang; He, Sijia; Cheng, Jin; Gong, Yanping; Zhang, Zhengxiang; Yang, Xuguang; Xu, Bing; Liu, Xinjian; Li, Chuan-Yuan; Tian, Ling; Huang, Qian

    2017-01-01

    Vascular recovery or re-angiogenesis after radiotherapy plays a significant role in tumor recurrence, whereas molecular mechanisms of this process remain elusive. In this work, we found that dying glioma cells promoted post-irradiation angiogenesis through a caspase 3 dependent mechanism. Evidence in vitro and in vivo indicated that caspase 3 inhibition undermined proangiogenic effects of dying glioma cells. Proteolytic inactivation of caspase 3 in glioma cells reduced tumorigenicity. Importantly, we identified that NF-κB/COX-2/PGE2 axis acted as downstream signaling of caspase 3, mediating proangiogenic response after irradiation. Additionally, VEGF-A, regulated by caspase 3 possibly through phosphorylated eIF4E, was recognized as another downstream factor participating in the proangiogenic response. In conclusion, these data demonstrated that caspase 3 in dying glioma cells supported the proangiogenic response after irradiation by governing NF-κB/COX-2/PGE2 axis and p-eIF4E/VEGF-A signaling. While inducing caspase 3 activation has been a generally-adopted notion in cancer therapeutics, our study counterintuitively illustrated that caspase 3 activation in dying glioma cells unfavorably supported post-irradiation angiogenesis, suggesting that radiotherapy combined with caspase 3 inhibitors may be more effective strategies due to restricted post-irradiation angiogenesis. PMID:27826040

  16. Mononuclear Phagocyte-Derived Microparticulate Caspase-1 Induces Pulmonary Vascular Endothelial Cell Injury.

    Directory of Open Access Journals (Sweden)

    Srabani Mitra

    Full Text Available Lung endothelial cell apoptosis and injury occurs throughout all stages of acute lung injury (ALI/ARDS and impacts disease progression. Lung endothelial injury has traditionally been focused on the role of neutrophil trafficking to lung vascular integrin receptors induced by proinflammatory cytokine expression. Although much is known about the pathogenesis of cell injury and death in ALI/ARDS, gaps remain in our knowledge; as a result of which there is currently no effective pharmacologic therapy. Enzymes known as caspases are essential for completion of the apoptotic program and secretion of pro-inflammatory cytokines. We hypothesized that caspase-1 may serve as a key regulator of human pulmonary microvascular endothelial cell (HPMVEC apoptosis in ALI/ARDS. Our recent experiments confirm that microparticles released from stimulated monocytic cells (THP1 induce lung endothelial cell apoptosis. Microparticles pretreated with the caspase-1 inhibitor, YVAD, or pan-caspase inhibitor, ZVAD, were unable to induce cell death of HPMVEC, suggesting the role of caspase-1 or its substrate in the induction of HPMVEC cell death. Neither un-induced microparticles (control nor direct treatment with LPS induced apoptosis of HPMVEC. Further experiments showed that caspase-1 uptake into HPMVEC and the induction of HPMVEC apoptosis was facilitated by caspase-1 interactions with microparticulate vesicles. Altering vesicle integrity completely abrogated apoptosis of HPMVEC suggesting an encapsulation requirement for target cell uptake of active caspase-1. Taken together, we confirm that microparticle centered caspase-1 can play a regulator role in endothelial cell injury.

  17. The limits for detection of activated caspases of spermatozoa by western blot in human semen.

    Science.gov (United States)

    Brugnon, F; Pons-Rejraji, H; Artonne, C; Janny, L; Grizard, G

    2012-08-01

    Detection of activated caspases of spermatozoa could be helpful to evaluate male infertility. Although western blot is validated as a highly specific method to detect the proteins extracted from cells, the ability of this technique to detect activated sperm caspases in human semen may be limited. Indeed, round cells, which potentially contain some activated caspases, may be present in semen and interfere with the detection of activated sperm caspases. Moreover, it is necessary to evaluate the minimum amount of spermatozoa necessary to optimise the detection of activated caspases in semen samples. Our results showed that interference due to round cells contained in semen with activated caspase-3 requires separation of spermatozoa by density migration. This sperm preparation selects a mature sperm population that does not reflect the whole sperm population, and in infertile men with oligoasthenoteratozoospermia, the amount of spermatozoa thus selected is usually low. Moreover, the western blot technique's low detection sensitivity and the low level of caspase enzyme activity in human spermatozoa for activated caspase-3, -8 and -9 mean that large quantities of spermatozoa are needed to detect the expression of the activated caspases. These limitations prevent this method being used for routine analysis in clinical practice. © 2012 Blackwell Verlag GmbH.

  18. Evolutionary patterns and processes

    DEFF Research Database (Denmark)

    Leonardi, Michela; Sanz, Pablo Librado; Der Sarkissian, Clio

    2017-01-01

    Ever since its emergence in 1984, the field of ancient DNA has struggled to overcome the challenges related to the decay of DNA molecules in the fossil record. With the recent development of high-throughput DNA sequencing technologies and molecular techniques tailored to ultra-damaged templates......, it has now come of age, merging together approaches in phylogenomics, population genomics, epigenomics, and metagenomics. Leveraging on complete temporal sample series, ancient DNA provides direct access to the most important dimension in evolution-time, allowing a wealth of fundamental evolutionary...

  19. 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...... anatomical diversity and include the bivalves (scallops, oysters, and clams), gastropods (limpets, snails, and slugs), and cephalopods (squid, cuttlefish, and octopus). This study treats each major taxon and supplies general information as well as overviews of evolution and phylogeny using data from...... different sources--morphological, ultrastructural, molecular, developmental, and from the fossil record....

  20. Evolutionary phenomena in galaxies

    International Nuclear Information System (INIS)

    Beckman, J.E.; Pagel, B.E.J.

    1989-01-01

    This book reviews the subject of evolutionary phenomena in galaxies, bringing together contributions by experts on all the relevant physics and astrophysics necessary to understand galaxies and how they work. The book is based on the proceedings of a conference held in July 1988 in Puerto de la Cruz, Tenerife which was timed to coincide with the first year of operation of the 4.2 m William Herschel Telescope. The broad topics covered include formation of galaxies and their ages, stellar dynamics, galactic scale gas and its role in star formation and the production and distribution of the chemical elements within galaxies. (author)

  1. Evolutionary genomics of Entamoeba

    Science.gov (United States)

    Weedall, Gareth D.; Hall, Neil

    2011-01-01

    Entamoeba histolytica is a human pathogen that causes amoebic dysentery and leads to significant morbidity and mortality worldwide. Understanding the genome and evolution of the parasite will help explain how, when and why it causes disease. Here we review current knowledge about the evolutionary genomics of Entamoeba: how differences between the genomes of different species may help explain different phenotypes, and how variation among E. histolytica parasites reveals patterns of population structure. The imminent expansion of the amount genome data will greatly improve our knowledge of the genus and of pathogenic species within it. PMID:21288488

  2. Evolution in health and medicine Sackler colloquium: Making evolutionary biology a basic science for medicine.

    Science.gov (United States)

    Nesse, Randolph M; Bergstrom, Carl T; Ellison, Peter T; Flier, Jeffrey S; Gluckman, Peter; Govindaraju, Diddahally R; Niethammer, Dietrich; Omenn, Gilbert S; Perlman, Robert L; Schwartz, Mark D; Thomas, Mark G; Stearns, Stephen C; Valle, David

    2010-01-26

    New applications of evolutionary biology in medicine are being discovered at an accelerating rate, but few physicians have sufficient educational background to use them fully. This article summarizes suggestions from several groups that have considered how evolutionary biology can be useful in medicine, what physicians should learn about it, and when and how they should learn it. Our general conclusion is that evolutionary biology is a crucial basic science for medicine. In addition to looking at established evolutionary methods and topics, such as population genetics and pathogen evolution, we highlight questions about why natural selection leaves bodies vulnerable to disease. Knowledge about evolution provides physicians with an integrative framework that links otherwise disparate bits of knowledge. It replaces the prevalent view of bodies as machines with a biological view of bodies shaped by evolutionary processes. Like other basic sciences, evolutionary biology needs to be taught both before and during medical school. Most introductory biology courses are insufficient to establish competency in evolutionary biology. Premedical students need evolution courses, possibly ones that emphasize medically relevant aspects. In medical school, evolutionary biology should be taught as one of the basic medical sciences. This will require a course that reviews basic principles and specific medical applications, followed by an integrated presentation of evolutionary aspects that apply to each disease and organ system. Evolutionary biology is not just another topic vying for inclusion in the curriculum; it is an essential foundation for a biological understanding of health and disease.

  3. Strategic analysis in evolutionary genetics and the theory of games

    Indian Academy of Sciences (India)

    Unknown

    This paper is written in memory of John Maynard Smith. In a brief survey it discusses essential aspects of how game theory in biology relates to its counterpart in eco- nomics, the major transition in game theory initiated by. Maynard Smith, the discrepancies between genetic and phenotypic models in evolutionary biology, ...

  4. Modeling evolutionary games in populations with demographic structure

    DEFF Research Database (Denmark)

    Li, Xiang-Yi; Giaimo, Stefano; Baudisch, Annette

    2015-01-01

    interactions, but usually omits life history and the demographic structure of the population. Here we show how an integration of both aspects can substantially alter the underlying evolutionary dynamics. We study the replicator dynamics of strategy interactions in life stage structured populations. Individuals...

  5. A Type III Effector NleF from EHEC Inhibits Epithelial Inflammatory Cell Death by Targeting Caspase-4

    Directory of Open Access Journals (Sweden)

    Ting Song

    2017-01-01

    Full Text Available Enterohemorrhagic E. coli (EHEC is a highly pathogenic bacterial strain capable of inducing severe gastrointestinal disease. Here, we show that EHEC uses the T3SS effector NleF to counteract the host inflammatory response by dampening caspase-4-mediated inflammatory epithelial cell death and by preventing the production of IL-1β. The other two inflammatory caspases, caspase-1 and caspase-5, are not involved in EHEC ΔnleF-induced inflammatory cell death. We found that NleF not only interrupted the heterodimerization of caspase-4-p19 and caspase-4-p10, but also inhibited the interaction of caspase-1 and caspase-4. The last four amino acids of the NleF carboxy terminus are essential in inhibiting caspase-4-dependent inflammatory cell death.

  6. Caspase-2 mediates a Brucella abortus RB51-induced hybrid cell death having features of apoptosis and pyroptosis.

    Science.gov (United States)

    Bronner, Denise N; O'Riordan, Mary X D; He, Yongqun

    2013-01-01

    Programmed cell death (PCD) can play a crucial role in tuning the immune response to microbial infection. Although PCD can occur in different forms, all are mediated by a family of proteases called caspases. Caspase-2 is the most conserved caspase, however, its function in cell death is ill-defined. Previously we demonstrated that live attenuated cattle vaccine strain Brucella abortus RB51 induces caspase-2-mediated and caspase-1-independent PCD of infected macrophages. We also discovered that rough attenuated B. suis strain VTRS1 induces a caspase-2-mediated and caspase-1-independent proinflammatory cell death in infected macrophages, which was tentatively coined "caspase-2-mediated pyroptosis". However, the mechanism of caspase-2-mediated cell death pathway remained unclear. In this study, we found that caspase-2 mediated proinflammatory cell death of RB51-infected macrophages and regulated many genes in different PCD pathways. We show that the activation of proapoptotic caspases-3 and -8 was dependent upon caspase-2. Caspase-2 regulated mitochondrial cytochrome c release and TNFα production, both of which are known to activate caspase-3 and caspase-8, respectively. In addition to TNFα, RB51-induced caspase-1 and IL-1β production was also driven by caspase-2-mediated mitochondrial dysfunction. Interestingly, pore formation, a phenomenon commonly associated with caspase-1-mediated pyroptosis, occurred; however, unlike its role in S. typhimurium-induced pyroptosis, pore formation did not contribute to RB51-induced proinflammatory cell death. Our data suggest that caspase-2 acts as an initiator caspase that mediates a novel RB51-induced hybrid cell death that simulates but differs from typical non-proinflammatory apoptosis and caspase-1-mediated proinflammatory pyroptosis. The initiator role of the caspase-2-mediated cell death was also conserved in cellular stress-induced cell death of macrophages treated with etoposide, naphthalene, or anti-Fas. Caspase-2 also

  7. 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

  8. 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.

  9. Parameterizing sequence alignment with an explicit evolutionary model.

    Science.gov (United States)

    Rivas, Elena; Eddy, Sean R

    2015-12-10

    Inference of sequence homology is inherently an evolutionary question, dependent upon evolutionary divergence. However, the insertion and deletion penalties in the most widely used methods for inferring homology by sequence alignment, including BLAST and profile hidden Markov models (profile HMMs), are not based on any explicitly time-dependent evolutionary model. Using one fixed score system (BLOSUM62 with some gap open/extend costs, for example) corresponds to making an unrealistic assumption that all sequence relationships have diverged by the same time. Adoption of explicit time-dependent evolutionary models for scoring insertions and deletions in sequence alignments has been hindered by algorithmic complexity and technical difficulty. We identify and implement several probabilistic evolutionary models compatible with the affine-cost insertion/deletion model used in standard pairwise sequence alignment. Assuming an affine gap cost imposes important restrictions on the realism of the evolutionary models compatible with it, as single insertion events with geometrically distributed lengths do not result in geometrically distributed insert lengths at finite times. Nevertheless, we identify one evolutionary model compatible with symmetric pair HMMs that are the basis for Smith-Waterman pairwise alignment, and two evolutionary models compatible with standard profile-based alignment. We test different aspects of the performance of these "optimized branch length" models, including alignment accuracy and homology coverage (discrimination of residues in a homologous region from nonhomologous flanking residues). We test on benchmarks of both global homologies (full length sequence homologs) and local homologies (homologous subsequences embedded in nonhomologous sequence). Contrary to our expectations, we find that for global homologies a single long branch parameterization suffices both for distant and close homologous relationships. In contrast, we do see an advantage in

  10. On the evolutionary origins of equity.

    Directory of Open Access Journals (Sweden)

    Stéphane Debove

    Full Text Available Equity, defined as reward according to contribution, is considered a central aspect of human fairness in both philosophical debates and scientific research. Despite large amounts of research on the evolutionary origins of fairness, the evolutionary rationale behind equity is still unknown. Here, we investigate how equity can be understood in the context of the cooperative environment in which humans evolved. We model a population of individuals who cooperate to produce and divide a resource, and choose their cooperative partners based on how they are willing to divide the resource. Agent-based simulations, an analytical model, and extended simulations using neural networks provide converging evidence that equity is the best evolutionary strategy in such an environment: individuals maximize their fitness by dividing benefits in proportion to their own and their partners' relative contribution. The need to be chosen as a cooperative partner thus creates a selection pressure strong enough to explain the evolution of preferences for equity. We discuss the limitations of our model, the discrepancies between its predictions and empirical data, and how interindividual and intercultural variability fit within this framework.

  11. Both the caspase CSP-1 and a caspase-independent pathway promote programmed cell death in parallel to the canonical pathway for apoptosis in Caenorhabditis elegans.

    Directory of Open Access Journals (Sweden)

    Daniel P Denning

    Full Text Available Caspases are cysteine proteases that can drive apoptosis in metazoans and have critical functions in the elimination of cells during development, the maintenance of tissue homeostasis, and responses to cellular damage. Although a growing body of research suggests that programmed cell death can occur in the absence of caspases, mammalian studies of caspase-independent apoptosis are confounded by the existence of at least seven caspase homologs that can function redundantly to promote cell death. Caspase-independent programmed cell death is also thought to occur in the invertebrate nematode Caenorhabditis elegans. The C. elegans genome contains four caspase genes (ced-3, csp-1, csp-2, and csp-3, of which only ced-3 has been demonstrated to promote apoptosis. Here, we show that CSP-1 is a pro-apoptotic caspase that promotes programmed cell death in a subset of cells fated to die during C. elegans embryogenesis. csp-1 is expressed robustly in late pachytene nuclei of the germline and is required maternally for its role in embryonic programmed cell deaths. Unlike CED-3, CSP-1 is not regulated by the APAF-1 homolog CED-4 or the BCL-2 homolog CED-9, revealing that csp-1 functions independently of the canonical genetic pathway for apoptosis. Previously we demonstrated that embryos lacking all four caspases can eliminate cells through an extrusion mechanism and that these cells are apoptotic. Extruded cells differ from cells that normally undergo programmed cell death not only by being extruded but also by not being engulfed by neighboring cells. In this study, we identify in csp-3; csp-1; csp-2 ced-3 quadruple mutants apoptotic cell corpses that fully resemble wild-type cell corpses: these caspase-deficient cell corpses are morphologically apoptotic, are not extruded, and are internalized by engulfing cells. We conclude that both caspase-dependent and caspase-independent pathways promote apoptotic programmed cell death and the phagocytosis of cell

  12. PQ1, a Quinoline Derivative, Induces Apoptosis in T47D Breast Cancer Cells through Activation of Caspase-8 and Caspase-9

    Science.gov (United States)

    Ding, Ying; Nguyen, Thu Annelise

    2013-01-01

    Apoptosis, a programmed cell death, is an important control mechanism of cell homeostasis. Deficiency in apoptosis is one of the key features of cancer cells, allowing cells to escape from death. Activation of apoptotic signaling pathway has been a target of anti-cancer drugs in an induction of cytotoxicity. PQ1, 6-methoxy-8-[(3-aminopropyl)amino]-4-methyl-5-(3-trifluoromethylphenyloxy)quinoline, has been reported to decrease the viability of cancer cells and attenuate xenograft tumor growth. However, the mechanism of the anti-cancer effect is still unclear. To evaluate whether the cytotoxicity of PQ1 is related to induction of apoptosis, the effect of PQ1 on apoptotic pathways was investigated in T47D breast cancer cells. PQ1-treated cells had an elevation of cleaved caspase-3 compared to controls. Studies of intrinsic apoptotic pathway showed that PQ1 can activate the intrinsic checkpoint protein caspase-9, enhance the level of pro-apoptotic protein Bax, and release cytochrome c from mitochondria to cytosol; however, PQ1 has no effect on the level of anti-apoptotic protein Bcl-2. Further studies also demonstrated that PQ1 can activate the key extrinsic player, caspase-8. Pre-treatment of T47D cells with caspase-8 or caspase-9 inhibitor suppressed the cell death induced by PQ1, while pre-treatment with caspase-3 inhibitor completely counteracted the effect of PQ1 on cell viability. This report provides evidence that PQ1 induces cytotoxicity via activation of both caspase-8 and caspase-9 in T47D breast cancer cells. PMID:23677255

  13. PQ1, a quinoline derivative, induces apoptosis in T47D breast cancer cells through activation of caspase-8 and caspase-9.

    Science.gov (United States)

    Ding, Ying; Nguyen, Thu Annelise

    2013-09-01

    Apoptosis, a programmed cell death, is an important control mechanism of cell homeostasis. Deficiency in apoptosis is one of the key features of cancer cells, allowing cells to escape from death. Activation of apoptotic signaling pathway has been a target of anti-cancer drugs in an induction of cytotoxicity. PQ1, 6-methoxy-8-[(3-aminopropyl)amino]-4-methyl-5-(3-trifluoromethylphenyloxy)quinoline, has been reported to decrease the viability of cancer cells and attenuate xenograft tumor growth. However, the mechanism of the anti-cancer effect is still unclear. To evaluate whether the cytotoxicity of PQ1 is related to induction of apoptosis, the effect of PQ1 on apoptotic pathways was investigated in T47D breast cancer cells. PQ1-treated cells had an elevation of cleaved caspase-3 compared to controls. Studies of intrinsic apoptotic pathway showed that PQ1 can activate the intrinsic checkpoint protein caspase-9, enhance the level of pro-apoptotic protein Bax, and release cytochrome c from mitochondria to cytosol; however, PQ1 has no effect on the level of anti-apoptotic protein Bcl-2. Further studies also demonstrated that PQ1 can activate the key extrinsic player, caspase-8. Pre-treatment of T47D cells with caspase-8 or caspase-9 inhibitor suppressed the cell death induced by PQ1, while pre-treatment with caspase-3 inhibitor completely counteracted the effect of PQ1 on cell viability. This report provides evidence that PQ1 induces cytotoxicity via activation of both caspase-8 and caspase-9 in T47D breast cancer cells.

  14. Evolutionary explanations for natural language: criteria from evolutionary biology

    NARCIS (Netherlands)

    Zuidema, W.; de Boer, B.

    2008-01-01

    Theories of the evolutionary origins of language must be informed by empirical and theoretical results from a variety of different fields. Complementing recent surveys of relevant work from linguistics, animal behaviour and genetics, this paper surveys the requirements on evolutionary scenarios that

  15. Overexpression of Smac promotes Cisplatin-induced apoptosis by activating caspase-3 and caspase-9 in lung cancer A549 cells.

    Science.gov (United States)

    Qin, Sida; Yang, Chengcheng; Wang, Xifang; Xu, Chongwen; Li, Shuo; Zhang, Boxiang; Ren, Hong

    2013-03-01

    Second mitochondrial-derived activator of caspase (Smac) plays crucial roles in mitochondrial apoptosis pathways and promotes chemotherapy-induced apoptosis. In this study, Smac levels were examined in various lung cancer cell lines, and the effects of overexpressed Smac in the nonsmall-cell lung cancer cell line A549 were assayed by stable transfection of Smac. Subsequently, MTT assays, cell counting, and flow cytometry were applied to show that overexpression of Smac inhibits cell viability and cell growth and enhances apoptosis after cisplatin treatment. Western blotting was performed before and after cisplatin treatment to demonstrate that drug treatment could release Smac from mitochondria into the cytosol and promote apoptosis by activating caspase-3 and caspase-9. Promotion of apoptosis by cytosolic Smac could be blocked by pretreating cells with the caspase-9 inhibitor z-LEHD-FMK. Our findings indicate that overexpressed Smac significantly inhibited A549 cell growth and promoted apoptosis following cisplatin treatment due to the release of Smac from mitochondria into the cytosol, which increased the activities of caspase-3 and caspase-9.

  16. Social traits, social networks and evolutionary biology.

    Science.gov (United States)

    Fisher, D N; McAdam, A G

    2017-12-01

    The social environment is both an important agent of selection for most organisms, and an emergent property of their interactions. As an aggregation of interactions among members of a population, the social environment is a product of many sets of relationships and so can be represented as a network or matrix. Social network analysis in animals has focused on why these networks possess the structure they do, and whether individuals' network traits, representing some aspect of their social phenotype, relate to their fitness. Meanwhile, quantitative geneticists have demonstrated that traits expressed in a social context can depend on the phenotypes and genotypes of interacting partners, leading to influences of the social environment on the traits and fitness of individuals and the evolutionary trajectories of populations. Therefore, both fields are investigating similar topics, yet have arrived at these points relatively independently. We review how these approaches are diverged, and yet how they retain clear parallelism and so strong potential for complementarity. This demonstrates that, despite separate bodies of theory, advances in one might inform the other. Techniques in network analysis for quantifying social phenotypes, and for identifying community structure, should be useful for those studying the relationship between individual behaviour and group-level phenotypes. Entering social association matrices into quantitative genetic models may also reduce bias in heritability estimates, and allow the estimation of the influence of social connectedness on trait expression. Current methods for measuring natural selection in a social context explicitly account for the fact that a trait is not necessarily the property of a single individual, something the network approaches have not yet considered when relating network metrics to individual fitness. Harnessing evolutionary models that consider traits affected by genes in other individuals (i.e. indirect genetic

  17. Cutting Edge in IFN Regulation: Inflammatory Caspases Cleave cGAS.

    Science.gov (United States)

    Heidegger, Simon; Haas, Tobias; Poeck, Hendrik

    2017-03-21

    Caspases have important functions beyond their established role in driving inflammation and apoptosis. In this issue of Immunity, Wang et al. (2017) demonstrate that inflammasome-triggered caspases cleave and inactivate the DNA sensor cGAS, thus restricting the type I interferon response to cytosolic DNA. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. A quantitative method for the specific assessment of caspase-6 activity in cell culture

    DEFF Research Database (Denmark)

    Ehrnhoefer, Dagmar E; Skotte, Niels H; Savill, Jane

    2011-01-01

    Aberrant activation of caspase-6 has recently emerged as a major contributor to the pathogeneses of neurodegenerative disorders such as Alzheimer's and Huntington disease. Commercially available assays to measure caspase-6 activity commonly use the VEID peptide as a substrate. However these methods...

  19. The Evolutionary Psychology of Envy and Jealousy

    Directory of Open Access Journals (Sweden)

    Vilayanur S. Ramachandran

    2017-09-01

    Full Text Available The old dogma has always been that the most complex aspects of human emotions are driven by culture; Germans and English are thought to be straight-laced whereas Italians and Indians are effusive. Yet in the last two decades there has been a growing realization that even though culture plays a major role in the final expression of human nature, there must be a basic scaffolding specified by genes. While this is recognized to be true for simple emotions like anger, fear, and joy, the relevance of evolutionary arguments for more complex nuances of emotion have been inadequately explored. In this paper, we consider envy or jealousy as an example; the feeling evoked when someone is better off than you. Our approach is broadly consistent with traditional evolutionary psychology (EP approaches, but takes it further by exploring the complexity and functional logic of the emotion – and the precise social triggers that elicit them – by using deliberately farfetched, and contrived “thought experiments” that the subject is asked to participate in. When common sense (e.g., we should be jealous of Bill Gates – not of our slightly richer neighbor appears to contradict observed behavior (i.e., we are more envious of our neighbor the paradox can often be resolved by evolutionary considerations which h predict the latter. Many – but not all – EP approaches fail because evolution and common sense do not make contradictory predictions. Finally, we briefly raise the possibility that gaining deeper insight into the evolutionary origins of certain undesirable emotions or behaviors can help shake them off, and may therefore have therapeutic utility. Such an approach would complement current therapies (such as cognitive behavior therapies, psychoanalysis, psychopharmacologies, and hypnotherapy, rather than negate them.

  20. 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.

  1. 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.

  2. Environmental evolutionary graph theory.

    Science.gov (United States)

    Maciejewski, Wes; Puleo, Gregory J

    2014-11-07

    Understanding the influence of an environment on the evolution of its resident population is a major challenge in evolutionary biology. Great progress has been made in homogeneous population structures while heterogeneous structures have received relatively less attention. Here we present a structured population model where different individuals are best suited to different regions of their environment. The underlying structure is a graph: individuals occupy vertices, which are connected by edges. If an individual is suited for their vertex, they receive an increase in fecundity. This framework allows attention to be restricted to the spatial arrangement of suitable habitat. We prove some basic properties of this model and find some counter-intuitive results. Notably, (1) the arrangement of suitable sites is as important as their proportion, and (2) decreasing the proportion of suitable sites may result in a decrease in the fixation time of an allele. Copyright © 2014 Elsevier Ltd. All rights reserved.

  3. Retinal Cell Death Caused by Sodium Iodate Involves Multiple Caspase-Dependent and Caspase-Independent Cell-Death Pathways

    Directory of Open Access Journals (Sweden)

    Jasmin Balmer

    2015-07-01

    Full Text Available Herein, we have investigated retinal cell-death pathways in response to the retina toxin sodium iodate (NaIO3 both in vivo and in vitro. C57/BL6 mice were treated with a single intravenous injection of NaIO3 (35 mg/kg. Morphological changes in the retina post NaIO3 injection in comparison to untreated controls were assessed using electron microscopy. Cell death was determined by TdT-mediated dUTP-biotin nick end labeling (TUNEL staining. The activation of caspases and calpain was measured using immunohistochemistry. Additionally, cytotoxicity and apoptosis in retinal pigment epithelial (RPE cells, primary retinal cells, and the cone photoreceptor (PRC cell line 661W were assessed in vitro after NaIO3 treatment using the ApoToxGlo™ assay. The 7-AAD/Annexin-V staining was performed and necrostatin (Nec-1 was administered to the NaIO3-treated cells to confirm the results. In vivo, degenerating RPE cells displayed a rounded shape and retracted microvilli, whereas PRCs featured apoptotic nuclei. Caspase and calpain activity was significantly upregulated in retinal sections and protein samples from NaIO3-treated animals. In vitro, NaIO3 induced necrosis in RPE cells and apoptosis in PRCs. Furthermore, Nec-1 significantly decreased NaIO3-induced RPE cell death, but had no rescue effect on treated PRCs. In summary, several different cell-death pathways are activated in retinal cells as a result of NaIO3.

  4. Caspase-11 Plays a Protective Role in Pulmonary Acinetobacter baumannii Infection.

    Science.gov (United States)

    Wang, Wei; Shao, Yue; Li, Shengjun; Xin, Na; Ma, Tingxian; Zhao, Chenghai; Song, Min

    2017-10-01

    Activation of caspase-11 by some Gram-negative bacteria triggers the caspase-1/interleukin 1β (IL-1β) pathway, independent of canonical inflammasomes. Acinetobacter baumannii is a Gram-negative, conditionally pathogenic bacterium that can cause severe pulmonary infection in hospitalized patients. A. baumannii was revealed to activate canonical and noncanonical inflammasome pathways in bone marrow-derived macrophages (BMDMs). Pulmonary infection of caspase-11 -/- mice with A. baumannii showed that caspase-11 deficiency impaired A. baumannii clearance, exacerbated pulmonary pathological changes, and enhanced susceptibility to A. baumannii These data indicate that the caspase-11-mediated innate immune response plays a crucial role in defending against A. baumannii . Copyright © 2017 American Society for Microbiology.

  5. Caspase-8 Binding to Cardiolipin in Giant Unilamellar Vesicles Provides a Functional Docking Platform for Bid

    DEFF Research Database (Denmark)

    Jalmar, Olivier; Franc¸ois-Moutal, Liberty; García-Sáez, Ana-Jesus

    2013-01-01

    Caspase-8 is involved in death receptor-mediated apoptosis in type II cells, the proapoptotic programme of which is triggered by truncated Bid. Indeed, caspase-8 and Bid are the known intermediates of this signalling pathway. Cardiolipin has been shown to provide an anchor and an essential...... system that mimics contact sites and/or cardiolipin-enriched microdomains at the outer mitochondrial surface in which the platform consisting of caspase-8, Bid and cardiolipin was reconstituted in giant unilamellar vesicles. We analysed these vesicles by flow cytometry and confirm previous results...... that demonstrate the requirement for intact mature cardiolipin for caspase-8 activation and Bid binding and cleavage. We also used confocal microscopy to visualise the rupture of the vesicles and their revesiculation at smaller sizes due to alteration of the curvature following caspase-8 and Bid binding...

  6. The Caspase Pathway as a Possible Therapeutic Target in Experimental Pemphigus

    Directory of Open Access Journals (Sweden)

    Deyanira Pacheco-Tovar

    2011-01-01

    Full Text Available Apoptosis plays a role in pemphigus IgG-dependent acantholysis; theoretically, the blockade of the caspase pathway could prevent the blistering that is caused by pemphigus autoantibodies. Using this strategy, we attempted to block the pathogenic effect of pemphigus IgG in Balb/c mice by using the caspase inhibitor Ac-DEVD-CMK. This inhibitor was administrated before the injection of pemphigus IgG into neonatal mice. The main results of the present investigation are as follows: (1 pemphigus IgG induces intraepidermal blisters in Balb/c neonatal mice; (2 keratinocytes around the blister and acantholytic cells undergo apoptosis; (3 the caspases inhibitor Ac-DEVD-CMK prevents apoptosis; (4 the inhibition of the caspase pathway prevents blister formation. In conclusion, inhibition of the caspase pathway may be a promising therapeutic tool that can help in the treatment of pemphigus flare ups.

  7. Topics of Evolutionary Computation 2001

    DEFF Research Database (Denmark)

    Ursem, Rasmus Kjær

    This booklet contains the student reports from the course: Topics of Evolutionary Computation, Fall 2001, given by Thiemo Krink, Rene Thomsen and Rasmus K. Ursem......This booklet contains the student reports from the course: Topics of Evolutionary Computation, Fall 2001, given by Thiemo Krink, Rene Thomsen and Rasmus K. Ursem...

  8. 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.

  9. Evolutionary dynamics in structured populations

    Science.gov (United States)

    Nowak, Martin A.; Tarnita, Corina E.; Antal, Tibor

    2010-01-01

    Evolutionary dynamics shape the living world around us. At the centre of every evolutionary process is a population of reproducing individuals. The structure of that population affects evolutionary dynamics. The individuals can be molecules, cells, viruses, multicellular organisms or humans. Whenever the fitness of individuals depends on the relative abundance of phenotypes in the population, we are in the realm of evolutionary game theory. Evolutionary game theory is a general approach that can describe the competition of species in an ecosystem, the interaction between hosts and parasites, between viruses and cells, and also the spread of ideas and behaviours in the human population. In this perspective, we review the recent advances in evolutionary game dynamics with a particular emphasis on stochastic approaches in finite sized and structured populations. We give simple, fundamental laws that determine how natural selection chooses between competing strategies. We study the well-mixed population, evolutionary graph theory, games in phenotype space and evolutionary set theory. We apply these results to the evolution of cooperation. The mechanism that leads to the evolution of cooperation in these settings could be called ‘spatial selection’: cooperators prevail against defectors by clustering in physical or other spaces. PMID:20008382

  10. 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.

  11. 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 ...

  12. PP128. Placental Caspase-3 gene polymorphisms is associated with preeclampsia.

    Science.gov (United States)

    Hsu, C-D; Polavarapu, S; Parton, L

    2012-07-01

    Increased placental trophoblastic apoptosis (programmed cell death) was previously reported in pregnancies complicated by preeclampsia. Caspase-3 is one of the key executioners of apoptosis. Caspase are expressed in many tissues including human placental trophoblast and other tissues. Variations in the promoter area of the Caspase genes may modulate apoptotic signaling, contributing to an increased risk of preeclampsia To determine if gene polymorphisms of Caspase 3 proteins differ between patient with and without preeclampsia. Forty-three singleton placentas were studied. Twenty-two placentas were with preeclampsia and 21 were normotensive controls. DNA was extracted from placentas using QIAAmp DNA Minikit. Genotyping of Caspase 3 +567 was determined by real-time PCR using the Applied Biosystems Prism 7900 HT SDS machine. Chi-square and Fisher's exact tests were used for statistical analysis. There were no significant differences in maternal age, parity or race between the two groups. Preeclamptic placentas had higher frequency of wild type TT of Caspase-3 SNP (+567) as compared with normotensive controls (59% versus 28.5%). Preeclamptic placentas expressed significantly more genotype of TT of Caspase-3 SNP (+567) than normotensive patients when compared to CC (p=0.02). The alle frequencies of the Caspase SNP (+567) in preeclampstic placentas were 0.77 and 0.23 for T and C, respectively, as compared to 0.52 and 0.48, respectively, in placentas from normotensive pregnancies. Immune intolerance of maternal and placental interaction plays an important role in the pathogenesis of preeclampsia. Increased of placental apoptosis was reported in pregnancy complicated with preeclamsia. Our findings indicate placental Caspase 3 (+567) gene polymorphisms is associated with preeclampsia. Altered placental alle frequencies and caspase-3 SNP (+567) in preeclampsia further suggests preeclampsia is a trophoblastic disorder. Copyright © 2012. Published by Elsevier B.V.

  13. Overexpression of FADD and Caspase-8 inhibits proliferation and promotes apoptosis of human glioblastoma cells.

    Science.gov (United States)

    Wang, Hong-Bin; Li, Tao; Ma, Dong-Zhou; Ji, Yan-Xin; Zhi, Hua

    2017-09-01

    The study aimed at exploring the effects involved in Fas-Associated protein with Death Domain (FADD) expression and cysteine-aspartic acid specific protease-8 (Caspase-8) in relation to the proliferation and apoptosis of human glioblastoma (GBM) cells. 93 GBM tissues and 64 normal brain tissues were the central mediums used for the investigation of the study. Cultured human GBM SC189 cells were divided into separate groups including the blank negative control (NC), FADD and Caspase-8 groups. The mRNA and protein expressions of FADD and Caspase-8 in tissues and human glioblastoma (GBM) cells were detected using qRT-PCR and Western blotting techniques. Cell proliferation was tested by CCK-8. Flow cytometry was used for the measure of cell cycle and apoptosis rates. The mRNA and protein expressions of FADD and Caspase-8 in GBM tissues were less than the levels of expression displayed in normal brain tissues. Correlations between the expressions of FADD and Caspase-8 in GBM tissues were analyzed as being linked with the clinical grades of GBM patients. Patients in stage III+IV displayed lower expressions of FADD and Caspase-8 than patients in stage I+II. In comparison with the blank group, the FADD and Caspase-8 groups showed decreased proliferation rates of SHG44 cells and lower ratios of cells in the S phase and Bcl-2 expression. Greater ratios of cells in the G0/G1 stage as well as increased cell apoptosis and expressions of Caspase-8 and Bax were exhibited. The expression of FADD in the FADD group was higher than the blank group, however no significant differences in FADD expression was observed between the blank and Caspase-8 groups. The data obtained during the study demonstrated that overexpression of FADD and Caspase-8 suppresses proliferation whilst promoting the apoptosis of human GBM cells. Copyright © 2017. Published by Elsevier Masson SAS.

  14. Caspase inhibitors of the P35 family are more active when purified from yeast than bacteria.

    Directory of Open Access Journals (Sweden)

    Ingo L Brand

    Full Text Available Many insect viruses express caspase inhibitors of the P35 superfamily, which prevent defensive host apoptosis to enable viral propagation. The prototypical P35 family member, AcP35 from Autographa californica M nucleopolyhedrovirus, has been extensively studied. Bacterially purified AcP35 has been previously shown to inhibit caspases from insect, mammalian and nematode species. This inhibition occurs via a pseudosubstrate mechanism involving caspase-mediated cleavage of a "reactive site loop" within the P35 protein, which ultimately leaves cleaved P35 covalently bound to the caspase's active site. We observed that AcP35 purifed from Saccharomyces cerevisae inhibited caspase activity more efficiently than AcP35 purified from Escherichia coli. This differential potency was more dramatic for another P35 family member, MaviP35, which inhibited human caspase 3 almost 300-fold more potently when purified from yeast than bacteria. Biophysical assays revealed that MaviP35 proteins produced in bacteria and yeast had similar primary and secondary structures. However, bacterially produced MaviP35 possessed greater thermal stability and propensity to form higher order oligomers than its counterpart purified from yeast. Caspase 3 could process yeast-purified MaviP35, but failed to detectably cleave bacterially purified MaviP35. These data suggest that bacterially produced P35 proteins adopt subtly different conformations from their yeast-expressed counterparts, which hinder caspase access to the reactive site loop to reduce the potency of caspase inhibition, and promote aggregation. These data highlight the differential caspase inhibition by recombinant P35 proteins purified from different sources, and caution that analyses of bacterially produced P35 family members (and perhaps other types of proteins may underestimate their activity.

  15. Evolutionary Explanations of Eating Disorders

    Directory of Open Access Journals (Sweden)

    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.

  16. How competition affects evolutionary rescue

    Science.gov (United States)

    Osmond, Matthew Miles; de Mazancourt, Claire

    2013-01-01

    Populations facing novel environments can persist by adapting. In nature, the ability to adapt and persist will depend on interactions between coexisting individuals. Here we use an adaptive dynamic model to assess how the potential for evolutionary rescue is affected by intra- and interspecific competition. Intraspecific competition (negative density-dependence) lowers abundance, which decreases the supply rate of beneficial mutations, hindering evolutionary rescue. On the other hand, interspecific competition can aid evolutionary rescue when it speeds adaptation by increasing the strength of selection. Our results clarify this point and give an additional requirement: competition must increase selection pressure enough to overcome the negative effect of reduced abundance. We therefore expect evolutionary rescue to be most likely in communities which facilitate rapid niche displacement. Our model, which aligns to previous quantitative and population genetic models in the absence of competition, provides a first analysis of when competitors should help or hinder evolutionary rescue. PMID:23209167

  17. Prostaglandin F2alpha- and FAS-activating antibody-induced regression of the corpus luteum involves caspase-8 and is defective in caspase-3 deficient mice

    Directory of Open Access Journals (Sweden)

    Flavell Richard A

    2003-02-01

    Full Text Available Abstract We recently demonstrated that caspase-3 is important for apoptosis during spontaneous involution of the corpus luteum (CL. These studies tested if prostaglandin F2α (PGF2α or FAS regulated luteal regression, utilize a caspase-3 dependent pathway to execute luteal cell apoptosis, and if the two receptors work via independent or potentially shared intracellular signaling components/pathways to activate caspase-3. Wild-type (WT or caspase-3 deficient female mice, 25–26 days old, were given 10 IU equine chorionic gonadotropin (eCG intraperitoneally (IP followed by 10 IU human chorionic gonadotropin (hCG IP 46 h later to synchronize ovulation. The animals were then injected with IgG (2 micrograms, i.v., the FAS-activating antibody Jo2 (2 micrograms, i.v., or PGF2α (10 micrograms, i.p. at 24 or 48 h post-ovulation. Ovaries from each group were collected 8 h later for assessment of active caspase-3 enzyme and apoptosis (measured by the TUNEL assay in the CL. Regardless of genotype or treatment, CL in ovaries collected from mice injected 24 h after ovulation showed no evidence of active caspase-3 or apoptosis. However, PGF2α or Jo2 at 48 h post-ovulation and collected 8 h later induced caspase-3 activation in 13.2 ± 1.8% and 13.7 ± 2.2 % of the cells, respectively and resulted in 16.35 ± 0.7% (PGF2α and 14.3 ± 2.5% TUNEL-positive cells when compared to 1.48 ± 0.8% of cells CL in IgG treated controls. In contrast, CL in ovaries collected from caspase-3 deficient mice whether treated with PGF2α , Jo2, or control IgG at 48 h post-ovulation showed little evidence of active caspase-3 or apoptosis. CL of WT mice treated with Jo2 at 48 h post-ovulation had an 8-fold increase in the activity of caspase-8, an activator of caspase-3 that is coupled to the FAS death receptor. Somewhat unexpectedly, however, treatment of WT mice with PGF2α at 48 h post-ovulation resulted in a 22-fold increase in caspase-8 activity in the CL, despite the fact

  18. Carbon ion beam triggers both caspase-dependent and caspase-independent pathway of apoptosis in HeLa and status of PARP-1 controls intensity of apoptosis.

    Science.gov (United States)

    Ghorai, Atanu; Sarma, Asitikantha; Bhattacharyya, Nitai P; Ghosh, Utpal

    2015-04-01

    High linear energy transfer (LET) carbon ion beam (CIB) is becoming very promising tool for various cancer treatments and is more efficient than conventional low LET gamma or X-rays to kill malignant or radio-resistant cells, although detailed mechanism of cell death is still unknown. Poly (ADP-ribose) polymerase-1 (PARP-1) is a key player in DNA repair and its inhibitors are well-known as radio-sensitizer for low LET radiation. The objective of our study was to find mechanism(s) of induction of apoptosis by CIB and role of PARP-1 in CIB-induced apoptosis. We observed overall higher apoptosis in PARP-1 knocked down HeLa cells (HsiI) compared with negative control H-vector cells after irradiation with CIB (0-4 Gy). CIB activated both intrinsic and extrinsic pathways of apoptosis via caspase-9 and caspase-8 activation respectively, followed by caspase-3 activation, apoptotic body, nucleosomal ladder formation and sub-G1 accumulation. Apoptosis inducing factor translocation into nucleus in H-vector but not in HsiI cells after CIB irradiation contributed caspase-independent apoptosis. Higher p53 expression was observed in HsiI cells compared with H-vector after exposure with CIB. Notably, we observed about 37 % fall of mitochondrial membrane potential, activation of caspase-9 and caspase-3 and mild activation of caspase-8 without any detectable apoptotic body formation in un-irradiated HsiI cells. We conclude that reduction of PARP-1 expression activates apoptotic signals via intrinsic and extrinsic pathways in un-irradiated cells. CIB irradiation further intensified both intrinsic and extrinsic pathways of apoptosis synergistically along with up-regulation of p53 in HsiI cells resulting overall higher apoptosis in HsiI than H-vector.

  19. Evolutionary Tracks for Betelgeuse

    Science.gov (United States)

    Dolan, Michelle M.; Mathews, Grant J.; Lam, Doan Duc; Quynh Lan, Nguyen; Herczeg, Gregory J.; Dearborn, David S. P.

    2016-03-01

    We have constructed a series of nonrotating quasi-hydrostatic evolutionary models for the M2 Iab supergiant Betelgeuse (α Orionis). Our models are constrained by multiple observed values for the temperature, luminosity, surface composition, and mass loss for this star, along with the parallax distance and high-resolution imagery that determines its radius. We have then applied our best-fit models to analyze the observed variations in surface luminosity and the size of detected surface bright spots as the result of up-flowing convective material from regions of high temperature in the surface convective zone. We also attempt to explain the intermittently observed periodic variability in a simple radial linear adiabatic pulsation model. Based on the best fit to all observed data, we suggest a best progenitor mass estimate of {20}-3+5 {M}⊙ and a current age from the start of the zero-age main sequence of 8.0-8.5 Myr based on the observed ejected mass while on the giant branch.

  20. The IAP-antagonist ARTS initiates caspase activation upstream of cytochrome C and SMAC/Diablo

    Science.gov (United States)

    Edison, N; Zuri, D; Maniv, I; Bornstein, B; Lev, T; Gottfried, Y; Kemeny, S; Garcia-Fernandez, M; Kagan, J; Larisch, S

    2012-01-01

    ARTS (Sept4_i2) is a pro-apoptotic tumor suppressor protein that functions as an antagonist of X-linked IAP (XIAP) to promote apoptosis. It is generally thought that mitochondrial outer membrane permeabilization (MOMP) occurs before activation of caspases and is required for it. Here, we show that ARTS initiates caspase activation upstream of MOMP. In living cells, ARTS is localized to the mitochondrial outer membrane. In response to apoptotic signals, ARTS translocates rapidly to the cytosol in a caspase-independent manner, where it binds XIAP and promotes caspase activation. This translocation precedes the release of cytochrome C and SMAC/Diablo, and ARTS function is required for the normal timing of MOMP. We also show that ARTS-induced caspase activation leads to cleavage of the pro-apoptotic Bcl-2 family protein Bid, known to promote MOMP. We propose that translocation of ARTS initiates a first wave of caspase activation that can promote MOMP. This leads to the subsequent release of additional mitochondrial factors, including cytochrome C and SMAC/Diablo, which then amplifies the caspase cascade and causes apoptosis. PMID:21869827

  1. Bicaudal is a conserved substrate for Drosophila and mammalian caspases and is essential for cell survival.

    LENUS (Irish Health Repository)

    Creagh, Emma M

    2009-01-01

    Members of the caspase family of cysteine proteases coordinate cell death through restricted proteolysis of diverse protein substrates and play a conserved role in apoptosis from nematodes to man. However, while numerous substrates for the mammalian cell death-associated caspases have now been described, few caspase substrates have been identified in other organisms. Here, we have utilized a proteomics-based approach to identify proteins that are cleaved by caspases during apoptosis in Drosophila D-Mel2 cells, a subline of the Schneider S2 cell line. This approach identified multiple novel substrates for the fly caspases and revealed that bicaudal\\/betaNAC is a conserved substrate for Drosophila and mammalian caspases. RNAi-mediated silencing of bicaudal expression in Drosophila D-Mel2 cells resulted in a block to proliferation, followed by spontaneous apoptosis. Similarly, silencing of expression of the mammalian bicaudal homologue, betaNAC, in HeLa, HEK293T, MCF-7 and MRC5 cells also resulted in spontaneous apoptosis. These data suggest that bicaudal\\/betaNAC is essential for cell survival and is a conserved target of caspases from flies to man.

  2. Axonal cleaved caspase-3 regulates axon targeting and morphogenesis in the developing auditory brainstem

    Directory of Open Access Journals (Sweden)

    Sarah E Rotschafer

    2016-10-01

    Full Text Available Caspase-3 is a cysteine protease that is most commonly associated with cell death. Recent studies have shown additional roles in mediating cell differentiation, cell proliferation, and development of cell morphology. We investigated the role of caspase-3 in the development of chick auditory brainstem nuclei during embryogenesis. Immunofluorescence from embryonic days E6-13 revealed that the temporal expression of cleaved caspase-3 follows the ascending anatomical pathway. Expression is first seen in the auditory portion of VIIIth nerve including central axonal regions projecting to nucleus magnocellularis (NM, then later in NM axons projecting to nucleus laminaris (NL, and subsequently in NL dendrites. To examine the function of cleaved caspase-3 in chick auditory brainstem development, we blocked caspase-3 cleavage in developing chick embryos with the caspase-3 inhibitor Z-DEVD-FMK from E6 to E9, then examined NM and NL morphology and NM axonal targeting on E10. NL lamination in treated embryos was disorganized and the neuropil around NL contained a significant number of glial cells normally excluded from this region. Additionally, NM axons projected into inappropriate portions of NL in Z-DEVD-FMK treated embyros. We found that the presence of misrouted axons was associated with more severe NL disorganization. The effects of axonal caspase-3 inhibition on both NL morphogenesis and NM axon targeting suggest that these developmental processes are coordinated, likely through communication between axons and their targets.

  3. Caspase-2 associates with FAN through direct interaction and overlapping functionality.

    Science.gov (United States)

    Forsberg, Jeremy; Li, Xinge; Zamaraev, Aleksey V; Panaretakis, Theocharis; Zhivotovsky, Boris; Olsson, Magnus

    2018-04-06

    Caspase-2 has been implicated in diverse cellular processes, and the identification of factors with which it interacts has steadily increased. In the present study, we report a direct interaction between caspase-2 and factor associated with neutral sphingomyelinase activation (FAN) using yeast two-hybrid screening and co-immunoprecipitation. Further, stable suppression of caspase-2 expression in HEK293T and HeLa cells enabled a systematic investigation of putative novel enzyme functionalities, especially with respect to ceramide production, cell migration, IL-6 production and vesicular homeostasis, all of which have been previously reported to be associated with FAN. Lipidomics excluded the involvement of caspase-2 in the generation of ceramide species, but caspase-2-dependent deregulation of IL-6 release, vesicular size and delayed cell relocation supported an association between caspase-2 and FAN. Collectively, these data identify a novel caspase-2-interacting factor, FAN, and expand the role for the enzyme in seemingly non-apoptotic cellular mechanisms. Copyright © 2018 Elsevier Inc. All rights reserved.

  4. Industrial Applications of Evolutionary Algorithms

    CERN Document Server

    Sanchez, Ernesto; Tonda, Alberto

    2012-01-01

    This book is intended as a reference both for experienced users of evolutionary algorithms and for researchers that are beginning to approach these fascinating optimization techniques. Experienced users will find interesting details of real-world problems, and advice on solving issues related to fitness computation, modeling and setting appropriate parameters to reach optimal solutions. Beginners will find a thorough introduction to evolutionary computation, and a complete presentation of all evolutionary algorithms exploited to solve different problems. The book could fill the gap between the

  5. Overexpression of caspase-1 in pancreatic disorders: implications for a function besides apoptosis.

    Science.gov (United States)

    Ramadani, M; Gansauge, F; Schlosser, S; Yang, Y; Beger, H G; Gansauge, S

    2001-01-01

    The caspases are known to play a crucial role in the triggering and execution of apoptosis in a variety of cell types. We assessed the expression of caspase-1 in 42 pancreatic cancer tissue samples, 38 chronic pancreatitis specimens, and nine normal pancreatic tissues by immunohistochemistry and Western blot analysis. We found a clear overexpression of caspase-1 in both disorders, but differences in the expression patterns in distinct morphologic compartments. Pancreatic cancer tissue showed a clear cytoplasmatic overexpression of caspase-1 in tumor cells in 71% of the tumors, whereas normal pancreatic tissue showed only occasional immunoreactivity. In chronic pancreatitis an overexpression of caspase-1 was found in atrophic acinar cells (89%), hyperplastic ducts (87%), and dedifferentiating acinar cells (84%). Although in atrophic cells a clear nuclear expression was found, hyperplastic ducts and dedifferentiating acinar cells showed clear cytoplasmic expression. Western blot analysis revealed a marked expression of the 45 kDa precursor of caspase-1 in pancreatic cancer and chronic pancreatitis (80% and 86%, respectively). Clear bands at 30 kDa, suggested to represent the p10-p20 heterodimer of active caspase-1, were found in 60% of the cancer tissue and 14% of the pancreatitis tissue specimens. Since we found a highly significant correlation between cytoplasm overexpression of caspase-1 in pancreatic cancer and overexpression of the known prognostic factors cyclin D1, epidermal growth factor, and epidermal growth factor receptor, it is plausible that caspase-1 has a yet unknown function in proliferative processes in addition to its well-known role in the apoptotic pathway.

  6. Cell-in-Cell Death Is Not Restricted by Caspase-3 Deficiency in MCF-7 Cells

    Science.gov (United States)

    Wang, Shan; He, Meifang; Li, Linmei; Liang, Zhihua; Zou, Zehong

    2016-01-01

    Purpose Cell-in-cell structures are created by one living cell entering another homotypic or heterotypic living cell, which usually leads to the death of the internalized cell, specifically through caspase-dependent cell death (emperitosis) or lysosome-dependent cell death (entosis). Although entosis has attracted great attention, its occurrence is controversial, because one cell line used in its study (MCF-7) is deficient in caspase-3. Methods We investigated this issue using MCF-7 and A431 cell lines, which often display cell-in-cell invasion, and have different levels of caspase-3 expression. Cell-in-cell death morphology, microstructures, and signaling pathways were compared in the two cell lines. Results Our results confirmed that MCF-7 cells are caspase-3 deficient with a partial deletion in the CASP-3 gene. These cells underwent cell death that lacked typical apoptotic properties after staurosporine treatment, whereas caspase-3-sufficient A431 cells displayed typical apoptosis. The presence of caspase-3 was related neither to the lysosome-dependent nor to the caspase-dependent cell-in-cell death pathway. However, the existence of caspase-3 was associated with a switch from lysosome-dependent cell-in-cell death to the apoptotic cell-in-cell death pathway during entosis. Moreover, cellular hypoxia, mitochondrial swelling, release of cytochrome C, and autophagy were observed in internalized cells during entosis. Conclusion The occurrence of caspase-independent entosis is not a cell-specific process. In addition, entosis actually represents a cellular self-repair system, functioning through autophagy, to degrade damaged mitochondria resulting from cellular hypoxia in cell-in-cell structures. However, sustained autophagy-associated signal activation, without reduction in cellular hypoxia, eventually leads to lysosome-dependent intracellular cell death. PMID:27721872

  7. Physiological regulatory networks: ecological roles and evolutionary constraints.

    Science.gov (United States)

    Cohen, Alan A; Martin, Lynn B; Wingfield, John C; McWilliams, Scott R; Dunne, Jennifer A

    2012-08-01

    Ecological and evolutionary physiology has traditionally focused on one aspect of physiology at a time. Here, we discuss the implications of considering physiological regulatory networks (PRNs) as integrated wholes, a perspective that reveals novel roles for physiology in organismal ecology and evolution. For example, evolutionary response to changes in resource abundance might be constrained by the role of dietary micronutrients in immune response regulation, given a particular pathogen environment. Because many physiological components impact more than one process, organismal homeostasis is maintained, individual fitness is determined and evolutionary change is constrained (or facilitated) by interactions within PRNs. We discuss how PRN structure and its system-level properties could determine both individual performance and patterns of physiological evolution. Copyright © 2012 Elsevier Ltd. All rights reserved.

  8. Acinetobacter calcoaceticus-baumannii complex strains induce caspase-dependent and caspase-independent death of human epithelial cells.

    Science.gov (United States)

    Krzymińska, Sylwia; Frąckowiak, Hanna; Kaznowski, Adam

    2012-09-01

    We investigated interactions of human isolates of Acinetobacter calcoaceticus-baumannii complex strains with epithelial cells. The results showed that bacterial contact with the cells as well as adhesion and invasion were required for induction of cytotoxicity. The infected cells revealed hallmarks of apoptosis characterized by cell shrinking, condensed chromatin, and internucleosomal fragmentation of nuclear DNA. The highest apoptotic index was observed for 4 of 10 A. calcoaceticus and 4 of 7 A. baumannii strains. Moreover, we observed oncotic changes: cellular swelling and blebbing, noncondensed chromatin, and the absence of DNA fragmentation. The highest oncotic index was observed in cells infected with 6 A. calcoaceticus isolates. Cell-contact cytotoxicity and cell death were not inhibited by the pan-caspase inhibitor z-VAD-fmk. Induction of oncosis was correlated with increased invasive ability of the strains. We demonstrated that the mitochondria of infected cells undergo structural and functional alterations which can lead to cell death. Infected apoptotic and oncotic cells exhibited loss of mitochondrial transmembrane potential (ΔΨ(m)). Bacterial infection caused generation of nitric oxide and reactive oxygen species. This study indicated that Acinetobacter spp. induced strain-dependent distinct types of epithelial cell death that may contribute to the pathogenesis of bacterial infection.

  9. Evolutionary Origin of Euglena.

    Science.gov (United States)

    Zakryś, Bożena; Milanowski, Rafał; Karnkowska, Anna

    2017-01-01

    Euglenids (Excavata, Discoba, Euglenozoa, Euglenida) is a group of free-living, single-celled flagellates living in the aquatic environments. The uniting and unique morphological feature of euglenids is the presence of a cell covering called the pellicle. The morphology and organization of the pellicle correlate well with the mode of nutrition and cell movement. Euglenids exhibit diverse modes of nutrition, including phagotrophy and photosynthesis. Photosynthetic species (Euglenophyceae) constitute a single subclade within euglenids. Their plastids embedded by three membranes arose as the result of a secondary endosymbiosis between phagotrophic eukaryovorous euglenid and the Pyramimonas-related green alga. Within photosynthetic euglenids three evolutionary lineages can be distinguished. The most basal lineage is formed by one mixotrophic species, Rapaza viridis. Other photosynthetic euglenids are split into two groups: predominantly marine Eutreptiales and freshwater Euglenales. Euglenales are divided into two families: Phacaceae, comprising three monophyletic genera (Discoplastis, Lepocinclis, Phacus) and Euglenaceae with seven monophyletic genera (Euglenaformis, Euglenaria, Colacium, Cryptoglena, Strombomonas, Trachelomonas, Monomorphina) and polyphyletic genus Euglena. For 150 years researchers have been studying Euglena based solely on morphological features what resulted in hundreds of descriptions of new taxa and many artificial intra-generic classification systems. In spite of the progress towards defining Euglena, it still remains polyphyletic and morphologically almost undistinguishable from members of the recently described genus Euglenaria; members of both genera have cells undergoing metaboly (dynamic changes in cell shape), large chloroplasts with pyrenoids and monomorphic paramylon grains. Model organisms Euglena gracilis Klebs, the species of choice for addressing fundamental questions in eukaryotic biochemistry, cell and molecular biology, is a

  10. Molluscan Evolutionary Genomics

    Energy Technology Data Exchange (ETDEWEB)

    Simison, W. Brian; Boore, Jeffrey L.

    2005-12-01

    In the last 20 years there have been dramatic advances in techniques of high-throughput DNA sequencing, most recently accelerated by the Human Genome Project, a program that has determined the three billion base pair code on which we are based. Now this tremendous capability is being directed at other genome targets that are being sampled across the broad range of life. This opens up opportunities as never before for evolutionary and organismal biologists to address questions of both processes and patterns of organismal change. We stand at the dawn of a new 'modern synthesis' period, paralleling that of the early 20th century when the fledgling field of genetics first identified the underlying basis for Darwin's theory. We must now unite the efforts of systematists, paleontologists, mathematicians, computer programmers, molecular biologists, developmental biologists, and others in the pursuit of discovering what genomics can teach us about the diversity of life. Genome-level sampling for mollusks to date has mostly been limited to mitochondrial genomes and it is likely that these will continue to provide the best targets for broad phylogenetic sampling in the near future. However, we are just beginning to see an inroad into complete nuclear genome sequencing, with several mollusks and other eutrochozoans having been selected for work about to begin. Here, we provide an overview of the state of molluscan mitochondrial genomics, highlight a few of the discoveries from this research, outline the promise of broadening this dataset, describe upcoming projects to sequence whole mollusk nuclear genomes, and challenge the community to prepare for making the best use of these data.

  11. Defining fitness in evolutionary models

    Indian Academy of Sciences (India)

    jgen/087/04/0339-0348. Keywords. fitness; invasion exponent; adaptive dynamics; game theory; Lyapunov exponent; invasibility; Malthusian parameter. Abstract. The analysis of evolutionary models requires an appropriate definition for fitness.

  12. Evolutionary Processes and Mental Deficiency

    Science.gov (United States)

    Spitz, Herman H.

    1973-01-01

    The author hypothesizes that central nervous system damage of deficiency associated with mental retardation affects primarily those cortical processes which developed at a late stage in man's evolutionary history. (Author)

  13. Evolutionary computation for reinforcement learning

    NARCIS (Netherlands)

    Whiteson, S.; Wiering, M.; van Otterlo, M.

    2012-01-01

    Algorithms for evolutionary computation, which simulate the process of natural selection to solve optimization problems, are an effective tool for discovering high-performing reinforcement-learning policies. Because they can automatically find good representations, handle continuous action spaces,

  14. 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.

  15. Camalexin induces apoptosis in T-leukemia Jurkat cells by increased concentration of reactive oxygen species and activation of caspase-8 and caspase-9.

    Science.gov (United States)

    Mezencev, Roman; Updegrove, Taylor; Kutschy, Peter; Repovská, Mária; McDonald, John F

    2011-07-01

    Camalexin, a major indole phytoalexin of Arabidopsis thaliana, accumulates in various cruciferous plants in response to environmental stress and reportedly displays antimicrobial activities against various plant pathogens. However, its cytotoxicity against eukaryotic cells and potential as a prospective drug for human diseases has been examined only in a limited context. Our data demonstrate the time- and concentration-dependent cytotoxicity of camalexin on human T-leukemia Jurkat cells in the micromolar range, and the lower potency of cytotoxic effects on human lymphoblasts and primary fibroblasts. Cytotoxicity of camalexin is enhanced by the glutathione-depleting agent buthionine sulfoximine and completely blocked by pan-caspase inhibitor Z-VAD-FMK. Treatment of Jurkat cells with camalexin resulted in activation of caspase-8, caspase-9, caspases-3/7, and apoptosis that was detected by the presence of a sub-G1 population of cells, externalization of phosphatidyl serine and decreased mitochondrial membrane potential. Staining with 2',7'-dichlorodihydrofluorescein diacetate and dihydroethidium bromide displayed increased concentration of reactive oxygen species (ROS) early in camalexin-treated Jurkat cells, prior to the onset of apoptosis, while staining with MitoSOX(™) dye identified mitochondria as a source of increased ROS. Our data suggest that this phytochemical, which has a wide range of predicted pharmacological activities, induces apoptosis in Jurkat leukemia cells through increased ROS followed by dissipation of mitochondrial membrane potential and execution of caspase-9- and caspase-8-initiated apoptosis. This is, to the best of our knowledge, the first report on antileukemic activity and mode of action of this unique indole phytoalexin.

  16. Neutronic and thermalhydraulic aspects

    Energy Technology Data Exchange (ETDEWEB)

    Thomas, J.B. [CEA Centre d`Etudes de Saclay, 91 - Gif-sur-Yvette (France). Dept. de Mecanique et de Technologie; Bergeonneau, P. [CEA Centre d`Etudes de Cadarache, 13 - Saint-Paul-lez-Durance (France). Dept. d`Etudes des Reacteurs

    1995-12-31

    Precise computation of neutron flux in the core of a nuclear reactor represents one of the basic aspects of reactor design and operation. Neutron flux is computed by solving Boltzmann`s linear equation. Anyway, the direct solution of the equation involves too great a number of operations for practical application, leading up to TeraFlops or even PetaFlops supercomputing capabilities. Physical and mathematical models are then required to handle the extensive variety of configurations encountered. Numerical methods must be adapted to the rapid evolution of computer power, as also computer architecture: sequential, vector or parallel. Physical and mathematical models must allow for very fast estimation for online control and monitoring, adequate quantification for industrial studies and high-precision, best estimate computations. Coupling of neutronics to mechanics and two-phase flow thermohydraulics must be implemented in order to improve the accuracy in best-estimate computation schemes and to take into account the transient behaviour of the plant during normal operation or incidents. In this field of continuous improvement, the new methods applied in Reactor Physics lead obviously to good results and provide the improvements required in the future for the needs of efficiency, safety and advanced fuel cycle. This trend and the ``evolutionary`` implementation in large and modular software systems will be illustrated by the example of the SAPHYR system. (authors). 3 tabs.

  17. The apoptotic function analysis of p53, Apaf1, Caspase3 and Caspase7 during the spermatogenesis of the Chinese fire-bellied newt Cynops orientalis.

    Directory of Open Access Journals (Sweden)

    Da-Hui Wang

    Full Text Available BACKGROUND: Spontaneous and stress-induced germ cell apoptosis during spermatogenesis of multicellular organisms have been investigated broadly in mammals. Spermatogenetic process in urodele amphibians was essentially like that in mammals in spite of morphological differences; however, the mechanism of germ cell apoptosis in urodele amphibians remains unknown. The Chinese fire-belly newt, Cynops orientalis, was an excellent organism for studying germ cell apoptosis due to its sensitiveness to temperature, strong endurance of starvation, and sensitive skin to heavy metal exposure. METHODOLOGY/PRINCIPAL FINDINGS: TUNEL result showed that spontaneous germ cell apoptosis took place in normal newt, and severe stress-induced apoptosis occurred to spermatids and sperm in response to heat shock (40°C 2 h, cold exposure (4°C 12 h, cadmium exposure (Cd 36 h, and starvation stress. Quantitative reverse transcription polymerase chain reactions (qRT-PCR showed that gene expression of Caspase3 or Caspase7 was obviously elevated after stress treatment. Apaf1 was not altered at its gene expression level, and p53 was significantly decreased after various stress treatment. Caspase assay demonstrated that Caspase-3, -8, -9 enzyme activities in newt testis were significantly elevated after heat shock (40°C 2 h, cold exposure (4°C 12 h, and cadmium exposure (Cd 36 h, while Caspase3 and Caspase8 activities were increased with Caspase9 significantly decreased after starvation treatment. CONCLUSIONS/SIGNIFICANCE: Severe germ cell apoptosis triggered by heat shock, cold exposure, and cadmium exposure was Caspase3 dependent, which probably involved both extrinsic and intrinsic pathways. Apaf1 may be involved in this process without elevating its gene expression. But starvation-induced germ cell apoptosis was likely mainly through extrinsic pathway. p53 was probably not responsible for stress-induced germ cell apoptosis in newt testis. The intriguing high occurrence

  18. Cleaved caspase-3 in lung epithelium of children who died with acute respiratory distress syndrome

    NARCIS (Netherlands)

    Bem, Reinout A.; van der Loos, Chris M.; van Woensel, Job B. M.; Bos, Albert P.

    2010-01-01

    OBJECTIVE: To investigate the extent of cleaved caspase-3 immunostaining in lung epithelial cells in children with acute respiratory distress syndrome. DESIGN: Observational study in sixteen children who died with acute respiratory distress syndrome and diffuse alveolar damage. SETTING: Pediatric

  19. Metabolic Regulation of CaMKII Protein and Caspases in Xenopus laevis Egg Extracts*

    Science.gov (United States)

    McCoy, Francis; Darbandi, Rashid; Chen, Si-Ing; Eckard, Laura; Dodd, Keela; Jones, Kelly; Baucum, Anthony J.; Gibbons, Jennifer A.; Lin, Sue-Hwa; Colbran, Roger J.; Nutt, Leta K.

    2013-01-01

    The metabolism of the Xenopus laevis egg provides a cell survival signal. We found previously that increased carbon flux from glucose-6-phosphate (G6P) through the pentose phosphate pathway in egg extracts maintains NADPH levels and calcium/calmodulin regulated protein kinase II (CaMKII) activity to phosphorylate caspase 2 and suppress cell death pathways. Here we show that the addition of G6P to oocyte extracts inhibits the dephosphorylation/inactivation of CaMKII bound to caspase 2 by protein phosphatase 1. Thus, G6P sustains the phosphorylation of caspase 2 by CaMKII at Ser-135, preventing the induction of caspase 2-mediated apoptotic pathways. These findings expand our understanding of oocyte biology and clarify mechanisms underlying the metabolic regulation of CaMKII and apoptosis. Furthermore, these findings suggest novel approaches to disrupt the suppressive effects of the abnormal metabolism on cell death pathways. PMID:23400775

  20. Caspase-1-dependent and -independent cell death pathways in Burkholderia pseudomallei infection of macrophages.

    Directory of Open Access Journals (Sweden)

    Antje Bast

    2014-03-01

    Full Text Available The cytosolic pathogen Burkholderia pseudomallei and causative agent of melioidosis has been shown to regulate IL-1β and IL-18 production through NOD-like receptor NLRP3 and pyroptosis via NLRC4. Downstream signalling pathways of those receptors and other cell death mechanisms induced during B. pseudomallei infection have not been addressed so far in detail. Furthermore, the role of B. pseudomallei factors in inflammasome activation is still ill defined. In the present study we show that caspase-1 processing and pyroptosis is exclusively dependent on NLRC4, but not on NLRP3 in the early phase of macrophage infection, whereas at later time points caspase-1 activation and cell death is NLRC4- independent. In the early phase we identified an activation pathway involving caspases-9, -7 and PARP downstream of NLRC4 and caspase-1. Analyses of caspase-1/11-deficient infected macrophages revealed a strong induction of apoptosis, which is dependent on activation of apoptotic initiator and effector caspases. The early activation pathway of caspase-1 in macrophages was markedly reduced or completely abolished after infection with a B. pseudomallei flagellin FliC or a T3SS3 BsaU mutant. Studies using cells transfected with the wild-type and mutated T3SS3 effector protein BopE indicated also a role of this protein in caspase-1 processing. A T3SS3 inner rod protein BsaK mutant failed to activate caspase-1, revealed higher intracellular counts, reduced cell death and IL-1β secretion during early but not during late macrophage infection compared to the wild-type. Intranasal infection of BALB/c mice with the BsaK mutant displayed a strongly decreased mortality, lower bacterial loads in organs, and reduced levels of IL-1β, myeloperoxidase and neutrophils in bronchoalveolar lavage fluid. In conclusion, our results indicate a major role for a functional T3SS3 in early NLRC4-mediated caspase-1 activation and pyroptosis and a contribution of late caspase-1

  1. Ordering of ceramide formation and caspase-9 activation in CD95L-induced Jurkat leukemia T cell apoptosis.

    Science.gov (United States)

    Lafont, Elodie; Dupont, Romain; Andrieu-Abadie, Nathalie; Okazaki, Toshiro; Schulze-Osthoff, Klaus; Levade, Thierry; Benoist, Hervé; Ségui, Bruno

    2012-04-01

    Ceramide, a biologically active sphingolipid in cell death signaling, accumulates upon CD95L treatment, concomitantly to apoptosis induction in Jurkat leukemia T cells. Herein, we show that ceramide did not increase in caspase-8 and -10-doubly deficient Jurkat cells in response to CD95L, indicating that apical caspases are essential for CD95L-triggered ceramide formation. Jurkat cells are typically defined as type 2 cells, which require the activation of the mitochondrial pathway for efficient apoptosis induction in response to CD95L. Caspase-9-deficient Jurkat cells significantly resisted CD95L-induced apoptosis, despite ceramide accumulation. Knock-down of sphingomyelin synthase 1, which metabolizes ceramide to sphingomyelin, enhanced (i) CD95L-triggered ceramide production, (ii) cytochrome c release from the mitochondria and (iii) caspase-9 activation. Exogenous ceramide-induced caspase-3 activation and apoptosis were impaired in caspase-9-deficient Jurkat cells. Conversely, caspase-9 re-expression in caspase-9-deficient Jurkat cells restored caspase-3 activation and apoptosis upon exogenous ceramide treatment. Collectively, our data provide genetic evidence that CD95L-triggered endogenous ceramide increase in Jurkat leukemia T cells (i) is not a mere consequence of cell death and occurs mainly in a caspase-9-independent manner, (ii) is likely involved in the pro-apoptotic mitochondrial pathway leading to caspase-9 activation. Copyright © 2012 Elsevier B.V. All rights reserved.

  2. Yin and yang surfaces: an evolutionary perspective.

    Science.gov (United States)

    Legge, David

    2014-12-01

    A search of the Chinese medicine literature reveals several conflicting explanations of the division of the body into yin and yang surfaces. This paper attempts to clarify this basic concept and reconcile the differing descriptions of it through an exploration of material from other disciplines. A remarkable similarity exists between the surfaces on the human body that are defined by the pathways of the yin and yang meridians and those that have evolved from the ventral and the dorsal aspects of early vertebrate structure. Many of the evolutionary changes described have parallels in our embryological development and are evident in the underlying anatomy of our limbs. The degree of convergence between the two descriptions strongly supports the definition of the yin and yang surfaces as those traversed by the yin and yang meridians. It also goes a long way towards reconciling the conflicting definitions found in the literature. Finding a solution to this question of yin and yang surfaces that is based on anatomy and evolutionary theories has several advantages. It can throw light on differences in the clinical effects of points on the yin and yang meridians and enable the identification of anomalies in the pathways of the main meridian network. Copyright © 2014. Published by Elsevier B.V.

  3. Predicting virus emergence amid evolutionary noise.

    Science.gov (United States)

    Geoghegan, Jemma L; Holmes, Edward C

    2017-10-01

    The study of virus disease emergence, whether it can be predicted and how it might be prevented, has become a major research topic in biomedicine. Here we show that efforts to predict disease emergence commonly conflate fundamentally different evolutionary and epidemiological time scales, and are likely to fail because of the enormous number of unsampled viruses that could conceivably emerge in humans. Although we know much about the patterns and processes of virus evolution on evolutionary time scales as depicted in family-scale phylogenetic trees, these data have little predictive power to reveal the short-term microevolutionary processes that underpin cross-species transmission and emergence. Truly understanding disease emergence therefore requires a new mechanistic and integrated view of the factors that allow or prevent viruses spreading in novel hosts. We present such a view, suggesting that both ecological and genetic aspects of virus emergence can be placed within a simple population genetic framework, which in turn highlights the importance of host population size and density in determining whether emergence will be successful. Despite this framework, we conclude that a more practical solution to preventing and containing the successful emergence of new diseases entails ongoing virological surveillance at the human-animal interface and regions of ecological disturbance. © 2017 The Authors.

  4. Overexpression of Caspase-1 in adenocarcinoma of pancreas and chronic pancreatitis.

    Science.gov (United States)

    Yang, Yin-Mo; Ramadani, Marco; Huang, Yan-Ting

    2003-12-01

    To identify the expression of Caspase-1(interleukin-1beta converting enzyme) and its role in adenoma of the pancreas and chronic pancreatitis. The expression of Caspase-1 was assessed in 42 pancreatic cancer tissue samples, 38 chronic pancreatitis specimens, and 9 normal pancreatic tissues by immunohistochemistry and Western blot analysis. Overexpression of Caspase-1 was observed in both disorders, but there were differences in the expression patterns in distinct morphologic compartments. Pancreatic cancer tissues showed a clear cytoplasmatic overexpression of Caspase-1 in tumor cells of 71% of the tumors, whereas normal pancreatic tissues showed only occasional immunoreactivity. In chronic pancreatitis, overexpression of Caspase-1 was found in atrophic acinar cells (89%), hyperplastic ducts (87%), and dedifferentiating acinar cells (84%). Although in atrophic cells a clear nuclear expression was found, hyperplastic ducts and dedifferentiating acinar cells showed clear cytoplasmic expression. Western blot analysis revealed a marked expression of the 45 kDa precursor of Caspase-1 in pancreatic cancer and chronic pancreatitis (80% and 86%, respectively). Clear bands at 30 kDa, which suggested the p10-p20 heterodimer of active Caspase-1, were found in 60% of the cancer tissue and 14% of the pancreatitis tissue specimens, but not in normal pancreatic tissues. Overexpression of Caspase-1 is a frequent event in pancreatic disorders and its differential expression patterns may reflect two functions of the protease. One is its participation in the apoptotic pathway in atrophic acinar cells and tumor-surrounding pancreatitis tissue, the other is its possible role in proliferative processes in pancreatic cancer cells and hyperplastic duct cells and dedifferentiating acinar cells in chronic pancreatitis.

  5. New insights into the apoptotic process in mollusks: characterization of caspase genes in Mytilus galloprovincialis.

    Directory of Open Access Journals (Sweden)

    Alejandro Romero

    2011-02-01

    Full Text Available Apoptosis is an essential biological process in the development and maintenance of immune system homeostasis. Caspase proteins constitute the core of the apoptotic machinery and can be categorized as either initiators or effectors of apoptosis. Although the genes encoding caspase proteins have been described in vertebrates and in almost all invertebrate phyla, there are few reports describing the initiator and executioner caspases or the modulation of their expression by different stimuli in different apoptotic pathways in bivalves. In the present work, we characterized two initiator and four executioner caspases in the mussel Mytilus galloprovincialis. Both initiators and executioners showed structural features that make them different from other caspase proteins already described. Evaluation of the genes' tissue expression patterns revealed extremely high expression levels within the gland and gills, where the apoptotic process is highly active due to the clearance of damaged cells. Hemocytes also showed high expression values, probably due to of the role of apoptosis in the defense against pathogens. To understand the mechanisms of caspase gene regulation, hemocytes were treated with UV-light, environmental pollutants and pathogen-associated molecular patterns (PAMPs and apoptosis was evaluated by microscopy, flow cytometry and qPCR techniques. Our results suggest that the apoptotic process could be tightly regulated in bivalve mollusks by overexpression/suppression of caspase genes; additionally, there is evidence of caspase-specific responses to pathogens and pollutants. The apoptotic process in mollusks has a similar complexity to that of vertebrates, but presents unique features that may be related to recurrent exposure to environmental changes, pollutants and pathogens imposed by their sedentary nature.

  6. Caspases and osteogenic markers-in vitro screening of inhibition impact

    Czech Academy of Sciences Publication Activity Database

    Adamová, Eva; Janečková, Eva; Klepárník, Karel; Matalová, Eva

    2016-01-01

    Roč. 52, č. 2 (2016), s. 144-148 ISSN 1071-2690 R&D Projects: GA ČR(CZ) GB14-37368G; GA ČR(CZ) GA14-28254S Institutional support: RVO:67985904 ; RVO:68081715 Keywords : osteogenesis * chondrogenesis * caspases * caspase-3 * gene expression Subject RIV: EA - Cell Biology; CB - Analytical Chemistry, Separation (UIACH-O) Impact factor: 0.897, year: 2016

  7. Dietary and behavioral interventions protect against age related activation of caspase cascades in the canine brain.

    Directory of Open Access Journals (Sweden)

    Shikha Snigdha

    Full Text Available Lifestyle interventions such as diet, exercise, and cognitive training represent a quietly emerging revolution in the modern approach to counteracting age-related declines in brain health. Previous studies in our laboratory have shown that long-term dietary supplementation with antioxidants and mitochondrial cofactors (AOX or behavioral enrichment with social, cognitive, and exercise components (ENR, can effectively improve cognitive performance and reduce brain pathology of aged canines, including oxidative damage and Aβ accumulation. In this study, we build on and extend our previous findings by investigating if the interventions reduce caspase activation and ceramide accumulation in the aged frontal cortex, since caspase activation and ceramide accumulation are common convergence points for oxidative damage and Aβ, among other factors associated with the aged and AD brain. Aged beagles were placed into one of four treatment groups: CON--control environment/control diet, AOX--control environment/antioxidant diet, ENR--enriched environment/control diet, AOX/ENR--enriched environment/antioxidant diet for 2.8 years. Following behavioral testing, brains were removed and frontal cortices were analyzed to monitor levels of active caspase 3, active caspase 9 and their respective cleavage products such as tau and semaphorin7a, and ceramides. Our results show that levels of activated caspase-3 were reduced by ENR and AOX interventions with the largest reduction occurring with combined AOX/ENR group. Further, reductions in caspase-3 correlated with reduced errors in a reversal learning task, which depends on frontal cortex function. In addition, animals treated with an AOX arm showed reduced numbers of cells expressing active caspase 9 or its cleavage product semaphorin 7A, while ENR (but not AOX reduced ceramide levels. Overall, these data demonstrate that lifestyle interventions curtail activation of pro-degenerative pathways to improve cellular

  8. Dietary and behavioral interventions protect against age related activation of caspase cascades in the canine brain.

    Science.gov (United States)

    Snigdha, Shikha; Berchtold, Nicole; Astarita, Giuseppe; Saing, Tommy; Piomelli, Daniele; Cotman, Carl W

    2011-01-01

    Lifestyle interventions such as diet, exercise, and cognitive training represent a quietly emerging revolution in the modern approach to counteracting age-related declines in brain health. Previous studies in our laboratory have shown that long-term dietary supplementation with antioxidants and mitochondrial cofactors (AOX) or behavioral enrichment with social, cognitive, and exercise components (ENR), can effectively improve cognitive performance and reduce brain pathology of aged canines, including oxidative damage and Aβ accumulation. In this study, we build on and extend our previous findings by investigating if the interventions reduce caspase activation and ceramide accumulation in the aged frontal cortex, since caspase activation and ceramide accumulation are common convergence points for oxidative damage and Aβ, among other factors associated with the aged and AD brain. Aged beagles were placed into one of four treatment groups: CON--control environment/control diet, AOX--control environment/antioxidant diet, ENR--enriched environment/control diet, AOX/ENR--enriched environment/antioxidant diet for 2.8 years. Following behavioral testing, brains were removed and frontal cortices were analyzed to monitor levels of active caspase 3, active caspase 9 and their respective cleavage products such as tau and semaphorin7a, and ceramides. Our results show that levels of activated caspase-3 were reduced by ENR and AOX interventions with the largest reduction occurring with combined AOX/ENR group. Further, reductions in caspase-3 correlated with reduced errors in a reversal learning task, which depends on frontal cortex function. In addition, animals treated with an AOX arm showed reduced numbers of cells expressing active caspase 9 or its cleavage product semaphorin 7A, while ENR (but not AOX) reduced ceramide levels. Overall, these data demonstrate that lifestyle interventions curtail activation of pro-degenerative pathways to improve cellular health and are the

  9. Caspase inhibition in select olfactory neurons restores innate attraction behavior in aged Drosophila.

    Directory of Open Access Journals (Sweden)

    Takahiro Chihara

    2014-06-01

    Full Text Available Sensory and cognitive performance decline with age. Neural dysfunction caused by nerve death in senile dementia and neurodegenerative disease has been intensively studied; however, functional changes in neural circuits during the normal aging process are not well understood. Caspases are key regulators of cell death, a hallmark of age-related neurodegeneration. Using a genetic probe for caspase-3-like activity (DEVDase activity, we have mapped age-dependent neuronal changes in the adult brain throughout the lifespan of Drosophila. Spatio-temporally restricted caspase activation was observed in the antennal lobe and ellipsoid body, brain structures required for olfaction and visual place memory, respectively. We also found that caspase was activated in an age-dependent manner in specific subsets of Drosophila olfactory receptor neurons (ORNs, Or42b and Or92a neurons. These neurons are essential for mediating innate attraction to food-related odors. Furthermore, age-induced impairments of neural transmission and attraction behavior could be reversed by specific inhibition of caspase in these ORNs, indicating that caspase activation in Or42b and Or92a neurons is responsible for altering animal behavior during normal aging.

  10. [The expression and significance of smac, XIAP, caspase-3 in nonnasal inverted papilloma].

    Science.gov (United States)

    Yang, Lihui; Shan, Chunguang; Huang, Hongmei; Xu, Qiurong; Zhao, Ying; Meng, Yajing; Zhang, Zhihong

    2012-07-01

    To explore the expression and significance of second mitochondria derived activator of caspase (Smac), X-linked inhibitor of apoptosis protein (XIAP)and cysteine containing aspartate specific protease 3 (caspase-3) in the growth, development and carcinogenesis of the nonnasal inverted papilloma (NIP). Immunohistochemical method was used to detect the expression of Smac, XIAP, caspase-3 in 10 cases of nasal cavity mucosae (NM) and 45 cases of NIP, the group of NIP including 25 cases of NIP without dysplasia, 11 cases of NIP with dysplasia, and 9 cases of NIP with malignant transformation to squamous cell carcinoma (SCC). The intensity of the positive expression of Smac, Caspase-3 in NIP were lower than NM, the intensity of the positive expression decreased with the decreasing degree of histological differentiation. There was a significant difference between NIP without dysplasia and SCC. It was presented with a progressive tendency for the expression of XIAP in the group of NM and NIP. The lower degree of histological differentiation, the higher intensity of the positive expression. The expression between NIP without dysplasia and SCC had a significant difference. Smac negatively correlated with XIAP (r(s) = -0.323, P Smac positively correlated with caspase 3 (r(s) = 0.424, P Smac, XIAP, caspase 3 might be associated with the growth and carcinogenesis of NIP.

  11. IMMUNOHISTOCHEMICAL ANALYSIS OF CASPASE-3 ACTIVITY IN LIVER BIOPSIES OF PATIENTS WITH MONO AND MIXED INFECTIONS

    Directory of Open Access Journals (Sweden)

    I. I. Tokin

    2015-01-01

    Full Text Available Objective: to study the activity of proapoptotic signal protein caspase-3 for determination of peculiarities of apoptosis regulation under liver chronic diseases.Subjects and methods. The immunohistochemical analysis of caspase-3 activity in 5 liver biopsies of the patients with mono infection of chronic hepatitis B and 5 liver biopsies of the patients with mixed infection of tuberculosis, chronic hepatitis C and human immunodeficiency virus was fulfilled. Morphological and morphometric analysis of serial microphotographs was performed using an image analysis system (microscope Leica DM 2500, digital camera Leica DFC320 R2 and a computer.Results. The activity of caspase-3 as dark brown granularity was revealed in all tis-sue components of liver (hepatocytes, epithelium of bile ducts, endotheliocytes, Kupffer cells of sinusoids, in compositions of lymphohistiocyte infiltrations. The maximal activity was discovered in hepatocytes nuclei. The expression of caspase-3 was significantly higher in liver biopsies of the patients with mixed infection. It is typical that the immunoreactive hepatocytes had not any morphological marks of apoptosis.Conclusion. The caspase-3 expression of proapoptotic signal protein caspase-3 may serve as an early marker of liver damage including the possibilities of apoptosis development.

  12. IMMUNOHISTOCHEMICAL ANALYSIS OF CASPASE-3 ACTIVITY IN LIVER BIOPSIES OF PATIENTS WITH MONO AND MIXED INFECTIONS

    Directory of Open Access Journals (Sweden)

    I. I. Tokin

    2014-01-01

    Full Text Available Objective: to study the activity of proapoptotic signal protein caspase-3 for determination of peculiarities of apoptosis regulation under liver chronic diseases.Subjects and methods. The immunohistochemical analysis of caspase-3 activity in 5 liver biopsies of the patients with mono infection of chronic hepatitis B and 5 liver biopsies of the patients with mixed infection of tuberculosis, chronic hepatitis C and human immunodeficiency virus was fulfilled. Morphological and morphometric analysis of serial microphotographs was performed using an image analysis system (microscope Leica DM 2500, digital camera Leica DFC320 R2 and a computer.Results. The activity of caspase-3 as dark brown granularity was revealed in all tis-sue components of liver (hepatocytes, epithelium of bile ducts, endotheliocytes, Kupffer cells of sinusoids, in compositions of lymphohistiocyte infiltrations. The maximal activity was discovered in hepatocytes nuclei. The expression of caspase-3 was significantly higher in liver biopsies of the patients with mixed infection. It is typical that the immunoreactive hepatocytes had not any morphological marks of apoptosis.Conclusion. The caspase-3 expression of proapoptotic signal protein caspase-3 may serve as an early marker of liver damage including the possibilities of apoptosis development.

  13. Caspase 3 in dying tumor cells mediates post-irradiation angiogenesis

    Science.gov (United States)

    Zhang, Zhengxiang; Yu, Yang; Cheng, Jin; Gong, Yanping; Li, Chuan-Yuan; Huang, Qian

    2015-01-01

    Cytotoxic radiotherapy unfavorably induces tumor cells to generate various proangiogenic substances, promoting post-irradiation angiogenesis (PIA), which is one of major causes of radiotherapy failure. Though several studies have reported some mechanisms behind PIA, they have not yet described the beginning proangiogenic motivator buried in the irradiated microenvironment. In this work, we revealed that dying tumor cells induced by irradiation prompted PIA via a caspase 3 dependent mechanism. Proteolytic inactivation of caspase 3 in dying tumor cells by transducing a dominant-negative version weakened proangiogenic effects in vitro and in vivo. In addition, inhibition of caspase 3 activity suppressed tumor angiogenesis and tumorigenesis in xenograft mouse model. Importantly, we identified vascular endothelial growth factor (VEGF)-A as a downstream proangiogenic factor regulated by caspase 3 possibly through Akt signaling. Collectively, these findings indicated that besides acting as a key executioner in apoptosis, caspase 3 in dying tumor cells may play a central role in driving proangiogenic response after irradiation. Thus, radiotherapy in combination with caspase 3 inhibitors may be a novel promising therapeutic strategy to reduce tumor recurrence due to restrained PIA. PMID:26431328

  14. Caffeic Acid Induced Apoptosis in MG63 Osteosarcoma Cells Through Activation of Caspases

    Directory of Open Access Journals (Sweden)

    Ferry Sandra

    2017-03-01

    Full Text Available Background: Caffeic acid has been reported that when it is combined with all-trans retinoic acid, it can inhibit proliferation activity of SaOS-2 or OSA-01 cells. In addition, caffeic acid merely could reduce cell viability of SaOS-2 cells. However, there is not any study in caffeic acid's possible effect to induce apoptosis in osteosarcoma cell. Materials and Methods: MG-63 cells were cultured in Dulbecco’s Modified Eagle Medium containing 10% fetal bovine serum. Cells were treated with various concentrations of caffeic acid. Apoptosis were analyzed with Sub-G1 assay and activation of caspase-8, -9, and -3 were analyzed with immunoblotting. Caffeic acid-induced percentage of apoptotic cells and cleaved-8, -9, -3 were then statistically analyzed. Results: Sub-G1 results showed that caffeic acid significantly induced apoptosis in MG-63 osteosarcoma cells in concentration dependent manner. Immunoblotting results showed that caffeic acid induced cleavage of caspase-8, -9 and -3. Cleaved-caspase-8 and -9 were increased at 1-hour treatment of caffeic acid, while cleaved-caspase 3 was increased markedly at 6-hours treatment of caffeic acid. Conclusions: Caffeic acid induces apoptosis significantly in concentration dependent manner through caspase-dependent intrinsic apoptotic pathway. Keywords: caffeic acid, osteosarcoma, MG-63, apoptosis, caspase

  15. Evolutionary impact assessment: Accounting for the evolutionary consequences of fishing in an ecosystem approach to fisheries management

    DEFF Research Database (Denmark)

    Laugen, Ane T.; Engelhard, Georg H.; Whitlock, Rebecca

    2014-01-01

    Managing fisheries resources to maintain healthy ecosystems is one of the main goals of the ecosystem approach to fisheries (EAF). While a number of international treaties call for the implementation of EAF, there are still gaps in the underlying methodology. One aspect that has received substant......Managing fisheries resources to maintain healthy ecosystems is one of the main goals of the ecosystem approach to fisheries (EAF). While a number of international treaties call for the implementation of EAF, there are still gaps in the underlying methodology. One aspect that has received...... modify the monetary value living aquatic resources provide to society. Quantifying and predicting the evolutionary effects of fishing is therefore important for both ecological and economic reasons. An important reason this is not happening is the lack of an appropriate assessment framework. We therefore...... describe the evolutionary impact assessment (EvoIA) as a structured approach for assessing the evolutionary consequences of fishing and evaluating the predicted evolutionary outcomes of alternative management options. EvoIA can contribute to EAF by clarifying how evolution may alter stock properties...

  16. Cas Ilgly Induces Apoptosis in Glioma C6 Cells In Vitro and In Vivo through Caspase-Dependent and Caspase-Independent Mechanisms

    Directory of Open Access Journals (Sweden)

    Cristina Trejo-Solís

    2005-06-01

    Full Text Available In this work, we investigated the effects of Casiopeina Il-gly (Cas ILgly—a new copper compound exhibiting antineoplastic activity—on glioma C6 cells under both in vitro and in vivo conditions, as an approach to identify potential therapeutic agents against malignant glioma. The exposure of C6 cells to Cas Ilgly significantly inhibited cell proliferation, increased reactive oxygen species (ROS formation, and induced apoptosis in a dose-dependent manner. In cultured C6 cells, Cas Ilgly caused mitochondrio-nuclear translocation of apoptosis induction factor (AIF and endonuclease G at all concentrations tested; in contrast, fragmentation of nucleosomal DNA, cytochrome c release, and caspase-3 activation were observed at high concentrations. Administration of N-acetyl-l-cystein, an antioxidant, resulted in significant inhibition of AIF translocation, nucleosomal DNA fragmentation, and caspase-3 activation induced by Cas Ilgly. These results suggest that caspase-dependent and caspase-independent pathways both participate in apoptotic events elicited by Cas Ilgly. ROS formation induced by Cas Ilgly might also be involved in the mitochondrio-nuclear translocation of AIF and apoptosis. In addition, treatment of glioma C6-positive rats with Cas Ilgly reduced tumor volume and mitotic and cell proliferation indexes, and increased apoptotic index. Our findings support the use of Cas Ilgly for the treatment of malignant gliomas.

  17. 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.

  18. Evolutionary genomics of environmental pollution.

    Science.gov (United States)

    Whitehead, Andrew

    2014-01-01

    Chemical toxins have been a persistent source of evolutionary challenges throughout the history of life, and deep within the genomic storehouse of evolutionary history lay ancient adaptations to diverse chemical poisons. However, the rate of change of contemporary environments mediated by human-introduced pollutants is rapidly screening this storehouse and severely testing the adaptive potential of many species. In this chapter, we briefly review the deep history of evolutionary adaptation to environmental toxins, and then proceed to describe the attributes of stressors and populations that may facilitate contemporary adaptation to pollutants introduced by humans. We highlight that phenotypes derived to enable persistence in polluted habitats may be multi-dimensional, requiring global genome-scale tools and approaches to uncover their mechanistic basis, and include examples of recent progress in the field. The modern tools of genomics offer promise for discovering how pollutants interact with genomes on physiological timescales, and also for discovering what genomic attributes of populations may enable resistance to pollutants over evolutionary timescales. Through integration of these sophisticated genomics tools and approaches with an understanding of the deep historical forces that shaped current populations, a more mature understanding of the mechanistic basis of contemporary ecological-evolutionary dynamics should emerge.

  19. Evolutionary inevitability of sexual antagonism.

    Science.gov (United States)

    Connallon, Tim; Clark, Andrew G

    2014-02-07

    Sexual antagonism, whereby mutations are favourable in one sex and disfavourable in the other, is common in natural populations, yet the root causes of sexual antagonism are rarely considered in evolutionary theories of adaptation. Here, we explore the evolutionary consequences of sex-differential selection and genotype-by-sex interactions for adaptation in species with separate sexes. We show that sexual antagonism emerges naturally from sex differences in the direction of selection on phenotypes expressed by both sexes or from sex-by-genotype interactions affecting the expression of such phenotypes. Moreover, modest sex differences in selection or genotype-by-sex effects profoundly influence the long-term evolutionary trajectories of populations with separate sexes, as these conditions trigger the evolution of strong sexual antagonism as a by-product of adaptively driven evolutionary change. The theory demonstrates that sexual antagonism is an inescapable by-product of adaptation in species with separate sexes, whether or not selection favours evolutionary divergence between males and females.

  20. Molecular dynamics-assisted pharmacophore modeling of caspase-3-isatin sulfonamide complex: Recognizing essential intermolecular contacts and features of sulfonamide inhibitor class for caspase-3 binding.

    Science.gov (United States)

    Kumar, Sivakumar Prasanth; Patel, Chirag N; Jha, Prakash C; Pandya, Himanshu A

    2017-12-01

    The identification of isatin sulfonamide as a potent small molecule inhibitor of caspase-3 had fuelled the synthesis and characterization of the numerous sulfonamide class of inhibitors to optimize for potency. Recent works that relied on the ligand-based approaches have successfully shown the regions of optimizations for sulfonamide scaffold. We present here molecular dynamics-based pharmacophore modeling of caspase-3-isatin sulfonamide crystal structure, to elucidate the essential non-covalent contacts and its associated pharmacophore features necessary to ensure caspase-3 optimal binding. We performed 20ns long dynamics of this crystal structure to extract global conformation states and converted into structure-based pharmacophore hypotheses which were rigorously validated using an exclusive focussed library of experimental actives and inactives of sulfonamide class by Receiver Operating Characteristic (ROC) statistic. Eighteen structure-based pharmacophore hypotheses with better sensitivity and specificity measures (>0.6) were chosen which collectively showed the role of pocket residues viz. Cys163 (S 1 sub-site; required for covalent and H bonding with Michael acceptor of inhibitors), His121 (S 1 ; π stack with bicyclic isatin moiety), Gly122 (S 1 ; H bond with carbonyl oxygen) and Tyr204 (S 2 ; π stack with phenyl group of the isatin sulfonamide molecule) as stringent binding entities for enabling caspase-3 optimal binding. The introduction of spatial pharmacophore site points obtained from dynamics-based pharmacophore models in a virtual screening strategy will be helpful to screen and optimize molecules belonging to sulfonamide class of caspase-3 inhibitors. Copyright © 2017 Elsevier Ltd. All rights reserved.

  1. Amplification activation loop between caspase-8 and -9 dominates artemisinin-induced apoptosis of ASTC-a-1 cells.

    Science.gov (United States)

    Xiao, Fenglian; Gao, Weijie; Wang, Xiaoping; Chen, Tongsheng

    2012-06-01

    Although caspases have been demonstrated to be involved in artemisinin (ARTE)-induced apoptosis, their exact functions are not well understood. The aim of this report is to explore the roles of caspase-8, -9 and -3 during ARTE-induced apoptosis in human lung adenocarcinoma (ASTC-a-1) cells. ARTE treatment induces a rapid generation of reactive oxygen species (ROS), and ROS-dependent apoptosis as well as the activation of caspase-8, -9 and -3 via time- and dose-dependent fashion. Of upmost importance, inhibition of caspase-8 or -9, but not caspase-3, almost completely blocks the ARTE-induced not only activation of the caspase-8, -9 and -3 but also apoptosis. In addition, the apoptotic process triggered by ARTE does not involve the Bid cleavage, tBid translocation, significant loss of mitochondrial membrane potential and cytochrome c release from mitochondria. Moreover, silencing Bax/Bak does not prevent the ATRE-induced cell death as well as the activation of caspase-8, -9 and -3. Collectively, our data firstly demonstrate that ARTE triggers a ROS-mediated positive feedback amplification activation loop between caspase-8 and -9 independent of mitochondria, which dominantly mediated the ARTE-induced apoptosis via a caspase-3-independent apoptotic pathway in ASTC-a-1 cells. Our findings imply a potential to develop new derivatives from artemisinin to effectively initiate the amplification activation loop of caspases.

  2. Apoptosis of CTLL-2 cells induced by an immunosuppressant, ISP-I, is caspase-3-like protease-independent.

    Science.gov (United States)

    Yamaji, T; Nakamura, S; Takematsu, H; Kawasaki, T; Kozutsumi, Y

    2001-04-01

    In our previous study, the sphingosine-like immunosuppressant ISP-1 was shown to induce apoptosis in the mouse cytotoxic T cell line CTLL-2. In this study, we characterized the ISP-1-induced apoptotic pathway. Although caspase-3-like protease activity increases concomitantly with ISP-1-induced apoptosis in CTLL-2 cells, the apoptosis is not inhibited by caspase-3-like protease inhibitors, i.e. DEVD-cho and z-DEVD-fmk. In contrast, sphingosine-induced apoptosis in CTLL-2 cells is caspase-3-like protease-dependent. A caspase inhibitor with broad specificity, z-VAD-fmk, protects cells from apoptosis induced by ISP-1, indicating that ISP-1-induced apoptosis is dependent on caspase(s) other than caspase-3. Overexpression of Bcl-2 or Bcl-xL suppresses the apoptosis induced by ISP-1, although sphingosine-induced apoptosis is not efficiently inhibited by Bcl-2. Finally, ISP-1-induced mitochondrial depolarization, which is thought to be a checkpoint dividing the apoptotic pathway into upstream and downstream stages, is not inhibited by DEVD-cho, but is inhibited by z-VAD-fmk. These data suggest that a pathway dependent on caspase(s) other than caspase-3 is involved upstream of mitochondrial depolarization in ISP-1-induced apoptosis.

  3. Overexpression of caspase-1 (interleukin-1beta converting enzyme) in chronic pancreatitis and its participation in apoptosis and proliferation.

    Science.gov (United States)

    Ramadani, M; Yang, Y; Gansauge, F; Gansauge, S; Beger, H G

    2001-05-01

    Caspase-1, formerly designated interleukin-1beta converting enzyme, was the first described member of a group of cysteine proteases called caspases. It is suggested that caspases play an important role in apoptosis, but recent observations could show that caspase-1 might also be involved in cellular proliferation. We investigated the expression of caspase-1 in 38 chronic pancreatitis tissues, six pancreatitis tissues from patients with pancreatic carcinoma and nine normal pancreatic tissues by immunohistochemistry. Western blot analysis was used to confirm the immunohistochemical findings. We found a clear expression of caspase-1 in chronic pancreatitis, but not in normal pancreatic tissues. Interestingly, we found expression of caspase-1 in three distinct morphologic compartments: (i) in atrophic acinar cells (31 of 35; 89%), (ii) proliferating cells of ductal origin (33 of 38; 87%), and (iii) in acinar cells redifferentiating to form tubular structures (26 of 31; 83%). These immunohistochemical findings were confirmed by Western blot analysis, which showed an expression of caspase-1 in 85% of the tissues. No correlation was found between any of the examined clinicopathologic features and the caspase-1 expression in chronic pancreatitis. In conclusion, the expression of caspase-1 is a frequent event in chronic pancreatitis and its distribution pattern may reflect two functions of this protease: on one hand its participation in the apoptotic pathway in atrophic acinar cells and, on the other hand, its role in proliferation and differentiation in proliferating duct cells.

  4. Lentiviral-mediated RNAi targeting caspase-3 inhibits apoptosis induced by serum deprivation in rat endplate chondrocytes in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Ding, L.; Wu, J.P. [Fudan University, Jinshan Hospital, Department of Orthopaedics, Shanghai, China, Department of Orthopaedics, Jinshan Hospital, Fudan University, Shanghai (China); Xu, G. [Fudan University, Jinshan Hospital, Center Laboratory, Shanghai, China, Center Laboratory, Jinshan Hospital, Fudan University, Shanghai (China); Zhu, B.; Zeng, Q.M.; Li, D.F.; Lu, W. [Fudan University, Jinshan Hospital, Department of Orthopaedics, Shanghai, China, Department of Orthopaedics, Jinshan Hospital, Fudan University, Shanghai (China)

    2014-05-09

    Current studies find that degenerated cartilage endplates (CEP) of vertebrae, with fewer diffusion areas, decrease nutrient supply and accelerate intervertebral disc degeneration. Many more apoptotic cells have been identified in degenerated than in normal endplates, and may be responsible for the degenerated grade. Previous findings suggest that inhibition of apoptosis is one possible approach to improve disc regeneration. It is postulated that inhibition of CEP cell apoptosis may be responsible for the regeneration of endplates. Caspase-3, involved in the execution phase of apoptosis, is a candidate for regulating the apoptotic process. In the present study, CEP cells were incubated in 1% fetal bovine serum. Activated caspases were detected to identify the apoptotic pathway, and apoptosis was quantified by flow cytometry. Lentiviral caspase-3 short hairpin RNA (shRNA) was employed to study its protective effects against serum deprivation. Silencing of caspase-3 expression was quantified by reverse transcription-polymerase chain reaction and Western blots, and inhibition of apoptosis was quantified by flow cytometry. Serum deprivation increased apoptosis of rat CEP cells through activation of a caspase cascade. Lentiviral caspase-3 shRNA was successfully transduced into CEP cells, and specifically silenced endogenous caspase-3 expression. Surviving cells were protected by the downregulation of caspase-3 expression and activation. Thus, lentiviral caspase-3 shRNA-mediated RNAi successfully silenced endogenous caspase-3 expression, preventing inappropriate or premature apoptosis.

  5. Lentiviral-mediated RNAi targeting caspase-3 inhibits apoptosis induced by serum deprivation in rat endplate chondrocytes in vitro

    Directory of Open Access Journals (Sweden)

    L. Ding

    2014-06-01

    Full Text Available Current studies find that degenerated cartilage endplates (CEP of vertebrae, with fewer diffusion areas, decrease nutrient supply and accelerate intervertebral disc degeneration. Many more apoptotic cells have been identified in degenerated than in normal endplates, and may be responsible for the degenerated grade. Previous findings suggest that inhibition of apoptosis is one possible approach to improve disc regeneration. It is postulated that inhibition of CEP cell apoptosis may be responsible for the regeneration of endplates. Caspase-3, involved in the execution phase of apoptosis, is a candidate for regulating the apoptotic process. In the present study, CEP cells were incubated in 1% fetal bovine serum. Activated caspases were detected to identify the apoptotic pathway, and apoptosis was quantified by flow cytometry. Lentiviral caspase-3 short hairpin RNA (shRNA was employed to study its protective effects against serum deprivation. Silencing of caspase-3 expression was quantified by reverse transcription-polymerase chain reaction and Western blots, and inhibition of apoptosis was quantified by flow cytometry. Serum deprivation increased apoptosis of rat CEP cells through activation of a caspase cascade. Lentiviral caspase-3 shRNA was successfully transduced into CEP cells, and specifically silenced endogenous caspase-3 expression. Surviving cells were protected by the downregulation of caspase-3 expression and activation. Thus, lentiviral caspase-3 shRNA-mediated RNAi successfully silenced endogenous caspase-3 expression, preventing inappropriate or premature apoptosis.

  6. Lentiviral-mediated RNAi targeting caspase-3 inhibits apoptosis induced by serum deprivation in rat endplate chondrocytes in vitro

    International Nuclear Information System (INIS)

    Ding, L.; Wu, J.P.; Xu, G.; Zhu, B.; Zeng, Q.M.; Li, D.F.; Lu, W.

    2014-01-01

    Current studies find that degenerated cartilage endplates (CEP) of vertebrae, with fewer diffusion areas, decrease nutrient supply and accelerate intervertebral disc degeneration. Many more apoptotic cells have been identified in degenerated than in normal endplates, and may be responsible for the degenerated grade. Previous findings suggest that inhibition of apoptosis is one possible approach to improve disc regeneration. It is postulated that inhibition of CEP cell apoptosis may be responsible for the regeneration of endplates. Caspase-3, involved in the execution phase of apoptosis, is a candidate for regulating the apoptotic process. In the present study, CEP cells were incubated in 1% fetal bovine serum. Activated caspases were detected to identify the apoptotic pathway, and apoptosis was quantified by flow cytometry. Lentiviral caspase-3 short hairpin RNA (shRNA) was employed to study its protective effects against serum deprivation. Silencing of caspase-3 expression was quantified by reverse transcription-polymerase chain reaction and Western blots, and inhibition of apoptosis was quantified by flow cytometry. Serum deprivation increased apoptosis of rat CEP cells through activation of a caspase cascade. Lentiviral caspase-3 shRNA was successfully transduced into CEP cells, and specifically silenced endogenous caspase-3 expression. Surviving cells were protected by the downregulation of caspase-3 expression and activation. Thus, lentiviral caspase-3 shRNA-mediated RNAi successfully silenced endogenous caspase-3 expression, preventing inappropriate or premature apoptosis

  7. 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.

  8. Evolutionary Aesthetics and Print Advertising

    Directory of Open Access Journals (Sweden)

    Kamil Luczaj

    2015-06-01

    Full Text Available The article analyzes the extent to which predictions based on the theory of evolutionary aesthetics are utilized by the advertising industry. The purpose of a comprehensive content analysis of print advertising is to determine whether the items indicated by evolutionists such as animals, flowers, certain types of landscapes, beautiful humans, and some colors are part of real advertising strategies. This article has shown that many evolutionary hypotheses (although not all of them are supported by empirical data. Along with these hypotheses, some inferences from Bourdieu’s cultural capital theory were tested. It turned out that advertising uses both biological schemata and cultural patterns to make an image more likable.

  9. Diversity-Guided Evolutionary Algorithms

    DEFF Research Database (Denmark)

    Ursem, Rasmus Kjær

    2002-01-01

    Population diversity is undoubtably a key issue in the performance of evolutionary algorithms. A common hypothesis is that high diversity is important to avoid premature convergence and to escape local optima. Various diversity measures have been used to analyze algorithms, but so far few...... algorithms have used a measure to guide the search. The diversity-guided evolutionary algorithm (DGEA) uses the wellknown distance-to-average-point measure to alternate between phases of exploration (mutation) and phases of exploitation (recombination and selection). The DGEA showed remarkable results...

  10. Regulation of caspase-3 expression to maintain fetal growth in Porphyromonas gingivalis-infected pregnant rats

    Directory of Open Access Journals (Sweden)

    Banun Kusumawardani

    2016-04-01

    Full Text Available Periodontal disease has been involved in a variety of systemic disorders and suspected as a potential risk factor for fetal growth restriction. Periodontal pathogenic bacteria may actively regulate embryonic development, implantation and placental trophoblast cell invasion. This study aimed to analyze the role of TNF-α, IL-10 and caspase-3 to maintain fetal growth in Porphyromonasgingivalis-infected pregnant rats. Female rats were infected with live-Porphyromonas gingivalis at concentration of 2x109 cells/ml into subgingival sulcus area of the maxillary first molar before and during pregnancy. They were sacrificed on gestational day (GD-14 and GD20. The weight and length of placentas and fetuses were evaluated. The expression of TNF-α, IL-10 and caspase-3 in macrophages and trophoblast cells were detected by immunohistochemistry. On GD14, TNF-α (R2=0.416;P=0.000 and IL-10 (R2=0.187;P=0.012 had an important role to increase expression of caspase-3 in the placenta, but only TNF-α (R2=0.393;P=0.000 was able to increase the expression of caspase-3 on GD20. TNF-α and caspase-3 also had an important role (P0.000. The increasing expressions of TNF-α and IL-10 did not only enhance immune protection, but also maintained the trophoblast cells survival by regulating expression of caspase-3. Porphyromonas gingivalis infection in maternal periodontal tissue can lead to decrease in placental weight, fetal weight and fetal length which mediated by increasing expression of TNF-α, IL-10 and caspase-3 in the placenta.

  11. Cytoprotective effect of selective small-molecule caspase inhibitors against staurosporine-induced apoptosis

    Directory of Open Access Journals (Sweden)

    Wu J

    2014-05-01

    Full Text Available Jianghong Wu, Yuren Wang, Shuguang Liang, Haiching Ma Reaction Biology Corp, Malvern, PA, USA Abstract: Caspases are currently known as the central executioners of the apoptotic pathways. Inhibition of apoptosis and promotion of normal cell survival by caspase inhibitors would be a tremendous benefit for reducing the side effects of cancer therapy and for control of neurodegenerative disorders such as Parkinson's, Alzheimer's, and Huntington's diseases. The objective of this study was to discover small-molecule caspase inhibitors with which to achieve cytoprotective effect. We completed the high-throughput screening of Bionet's 37,500-compound library (Key Organics Limited, Camelford, Cornwall, UK against caspase-1, -3, and -9 and successfully identified 43 initial hit compounds. The 43 hit compounds were further tested for cytoprotective activity against staurosporine-induced cell death in NIH3T3 cells. Nineteen compounds were found to have significant cytoprotective effects in cell viability assays. One of the compounds, RBC1023, was demonstrated to protect NIH3T3 cells from staurosporine-induced caspase-3 cleavage and activation. RBC1023 was also shown to protect against staurosporine-induced impairment of mitochondrial membrane potential. DNA microarray analysis demonstrated that staurosporine treatment induced broad global gene expression alterations, and RBC1023 co-treatment significantly restored these changes, especially of the genes that are related to cell growth and survival signaling such as Egr1, Cdc25c, cdkn3, Rhob, Nek2, and Taok1. Collectively, RBC1023 protects NIH3T3 cells against staurosporine-induced apoptosis via inhibiting caspase activity, restoring mitochondrial membrane potential, and possibly upregulating some cell survival-related gene expressions and pathways. Keywords: cell death, caspase inhibition, mitochondria, RBC1023

  12. High LET radiation enhances apoptosis in mutated p53 cancer cells through Caspase-9 activation

    International Nuclear Information System (INIS)

    Yamakawa, Nobuhiro; Takahashi, Akihisa; Mori, Eiichiro; Imai, Yuichiro; Ohnishi, Ken; Kirita, Tadaaki; Ohnishi, Takeo; Furusawa, Yoshiya

    2008-01-01

    Although mutations in the p53 gene can lead to resistance to radiotherapy, chemotherapy and thermotherapy, high linear energy transfer (LET) radiation induces apoptosis regardless of p53 gene status in cancer cells. The aim of this study was to clarify the mechanisms involved in high LET radiation-induced apoptosis. Human gingival cancer cells (Ca9-22 cells) containing a mutated p53 (mp53) gene were irradiated with X-rays, C-ion (13-100 KeV/μm), or Fe-ion beams (200 KeV/μm). Cellular sensitivities were determined using colony forming assays. Apoptosis was detected and quantified with Hoechst 33342 staining. The activity of Caspase-3 was analyzed with Western blotting and flow cytometry. Cells irradiated with high LET radiation showed a high sensitivity with a high frequency of apoptosis induction. The relative biological effectiveness (RBE) values for the surviving fraction and apoptosis induction increased in a LET-dependent manner. Both RBE curves reached a peak at 100 KeV/μm, and then decreased at values over 100 KeV/μm. When cells were irradiated with high LET radiation, Caspase-3 was cleaved and activated, leading to poly (ADP-ribose) polymerase (PARP) cleavage. In addition, Caspase-9 inhibitor suppressed Caspase-3 activation and apoptosis induction resulting from high LET radiation to a greater extent than Caspase-8 inhibitor. These results suggest that high LET radiation enhances apoptosis by activation of Caspase-3 through Caspase-9, even in the presence of mp53. (author)

  13. Ofloxacin induces apoptosis in microencapsulated juvenile rabbit chondrocytes by caspase-8-dependent mitochondrial pathway

    International Nuclear Information System (INIS)

    Sheng Zhiguo; Cao Xiaojuan; Peng Shuangqing; Wang Changyong; Li Qianqian; Wang Yimei; Liu Mifeng

    2008-01-01

    Quinolones (QNs)-induced arthropathy is an important toxic effect in immature animals leading to restriction of their therapeutic use in pediatrics. However, the exact mechanism still remains unclear. Recently, we have demonstrated that ofloxacin, a typical QN, induces apoptosis of alginate microencapsulated juvenile rabbit joint chondrocytes by disturbing the β 1 integrin functions and inactivating the ERK/MAPK signaling pathway. In this study, we extend our initial observations to further elucidate the mechanism(s) of ofloxacin-induced apoptosis by utilizing specific caspase inhibitors. Pretreatment with both caspase-9-specific inhibitor zLEHD-fmk and caspase-8 inhibitor zIETD-fmk attenuated ofloxacin-induced apoptosis and activation of caspase-3 of chondrocyte in a concentration-dependent manner, as determined by fluorescent dye staining, enzyme activity assay and immunoblotting. Furthermore, the activation of caspase-9, -8 and -3 stimulated by ofloxacin was significantly inhibited in the presence of zIETD-fmk while pretreatment with zLEHD-fmk only blocked the activation of caspase-9 and -3. Ofloxacin also stimulated a concentration-dependent translocation of cytochrome c from mitochondria into the cytosol and a decrease of mitochondrial transmembrane potential, which was completely inhibited by zIETD-fmk. In addition, ofloxacin was found to increase the level of Bax, tBid, p53 in a concentration- and time-dependent manner. Taken together, The current results indicate that the caspase-8-dependent mitochondrial pathway is primarily involved in the ofloxacin-induced apoptosis of microencapsulated juvenile rabbit joint chondrocytes

  14. Evolutionary biology today and the call for an extended synthesis.

    Science.gov (United States)

    Futuyma, Douglas J

    2017-10-06

    Evolutionary theory has been extended almost continually since the evolutionary synthesis (ES), but except for the much greater importance afforded genetic drift, the principal tenets of the ES have been strongly supported. Adaptations are attributable to the sorting of genetic variation by natural selection, which remains the only known cause of increase in fitness. Mutations are not adaptively directed, but as principal authors of the ES recognized, the material (structural) bases of biochemistry and development affect the variety of phenotypic variations that arise by mutation and recombination. Against this historical background, I analyse major propositions in the movement for an 'extended evolutionary synthesis'. 'Niche construction' is a new label for a wide variety of well-known phenomena, many of which have been extensively studied, but (as with every topic in evolutionary biology) some aspects may have been understudied. There is no reason to consider it a neglected 'process' of evolution. The proposition that phenotypic plasticity may engender new adaptive phenotypes that are later genetically assimilated or accommodated is theoretically plausible; it may be most likely when the new phenotype is not truly novel, but is instead a slight extension of a reaction norm already shaped by natural selection in similar environments. However, evolution in new environments often compensates for maladaptive plastic phenotypic responses. The union of population genetic theory with mechanistic understanding of developmental processes enables more complete understanding by joining ultimate and proximate causation; but the latter does not replace or invalidate the former. Newly discovered molecular phenomena have been easily accommodated in the past by elaborating orthodox evolutionary theory, and it appears that the same holds today for phenomena such as epigenetic inheritance. In several of these areas, empirical evidence is needed to evaluate enthusiastic speculation

  15. Impacts of Bone Marrow Stem Cells on Caspase-3 Levels after Spinal Cord Injury in Mice.

    Science.gov (United States)

    Gashmardi, Noushin; Hosseini, Seyed Ebrahim; Mehrabani, Davood; Edalatmanesh, Mohammad Amin; Khodabandeh, Zahra

    2017-11-01

    Spinal cord injury (SCI) is a drastic disability that leads to spinal cord impairment. This study sought to determine the effects of bone marrow stem cells (BMSCs) on caspase-3 levels after acute SCI in mice. Forty-two mice were randomly divided into 3 groups: control (2 subcategories), subjected to no intervention; sham (3 subcategories), subjected to acute SCI; and experimental (2 subcategories), subjected to SCI and cell transplantation. In the experimental group, 2×10 5 BMSCs were injected intravenously 1 day after SCI. The mesenchymal property of the cells was assessed. The animals in the 3 groups were sacrificed 1, 21, and 35 days after the induction of injury and caspase-3 levels were evaluated using a caspase-3 assay kit. The obtained values were analyzed with ANOVA and Tukey tests using GraphPad and SPSS. Based on the assessments, the transplanted cells were spindle-shaped and were negative for the hematopoietic markers of CD34 and CD45 and positive for the expression of the mesenchymal marker of CD90 and osteogenic induction. The caspase-3 levels showed a significant increase in the sham and experimental groups in comparison to the control group. One day after SCI, the caspase-3 level was significantly higher in the sham group (1.157±0.117) than in the other groups (P<0.000). Twenty-one days after SCI, the caspase-3 level was significantly lower in the experimental group than in the sham group (0.4±0.095 vs. 0.793±0.076; P˂0.000). Thirty-five days following SCI, the caspase-3 level was lower in the experimental group than in the sham group (0.223±0.027 vs. 0.643±0.058; P˂0.000). We conclude that BMSC transplantation was able to downregulate the caspase-3 level after acute SCI, underscoring the role of caspase-3 as a marker for the assessment of treatment efficacy in acute SCI.

  16. Impacts of Bone Marrow Stem Cells on Caspase-3 Levels after Spinal Cord Injury in Mice

    Directory of Open Access Journals (Sweden)

    Noushin Gashmardi

    2017-11-01

    Full Text Available Spinal cord injury (SCI is a drastic disability that leads to spinal cord impairment. This study sought to determine the effects of bone marrow stem cells (BMSCs on caspase-3 levels after acute SCI in mice. Forty-two mice were randomly divided into 3 groups: control (2 subcategories, subjected to no intervention; sham (3 subcategories, subjected to acute SCI; and experimental (2 subcategories, subjected to SCI and cell transplantation. In the experimental group, 2×105 BMSCs were injected intravenously 1 day after SCI. The mesenchymal property of the cells was assessed. The animals in the 3 groups were sacrificed 1, 21, and 35 days after the induction of injury and caspase-3 levels were evaluated using a caspase-3 assay kit. The obtained values were analyzed with ANOVA and Tukey tests using GraphPad and SPSS. Based on the assessments, the transplanted cells were spindle-shaped and were negative for the hematopoietic markers of CD34 and CD45 and positive for the expression of the mesenchymal marker of CD90 and osteogenic induction. The caspase-3 levels showed a significant increase in the sham and experimental groups in comparison to the control group. One day after SCI, the caspase-3 level was significantly higher in the sham group (1.157±0.117 than in the other groups (P<0.000. Twenty-one days after SCI, the caspase-3 level was significantly lower in the experimental group than in the sham group (0.4±0.095 vs. 0.793±0.076; P˂0.000. Thirty-five days following SCI, the caspase-3 level was lower in the experimental group than in the sham group (0.223±0.027 vs. 0.643±0.058; P˂0.000. We conclude that BMSC transplantation was able to downregulate the caspase-3 level after acute SCI, underscoring the role of caspase-3 as a marker for the assessment of treatment efficacy in acute SCI.

  17. Caspase-1 as a central regulator of high fat diet-induced non-alcoholic steatohepatitis.

    Directory of Open Access Journals (Sweden)

    Laura J Dixon

    Full Text Available Nonalcoholic steatohepatitis (NASH is associated with caspase activation. However, a role for pro-inflammatory caspases or inflammasomes has not been explored in diet-induced liver injury. Our aims were to examine the role of caspase-1 in high fat-induced NASH. C57BL/6 wild-type and caspase 1-knockout (Casp1(-/- mice were placed on a 12-week high fat diet. Wild-type mice on the high fat diet increased hepatic expression of pro-caspase-1 and IL-1β. Both wild-type and Casp1(-/- mice on the high fat diet gained more weight than mice on a control diet. Hepatic steatosis and TG levels were increased in wild-type mice on high fat diet, but were attenuated in the absence of caspase-1. Plasma cholesterol and free fatty acids were elevated in wild-type, but not Casp1(-/- mice, on high fat diet. ALT levels were elevated in both wild-type and Casp1(-/- mice on high fat diet compared to control. Hepatic mRNA expression for genes associated with lipogenesis was lower in Casp1(-/- mice on high fat diet compared to wild-type mice on high fat diet, while genes associated with fatty acid oxidation were not affected by diet or genotype. Hepatic Tnfα and Mcp-1 mRNA expression was increased in wild-type mice on high fat diet, but not in Casp1(-/- mice on high fat diet. αSMA positive cells, Sirius red staining, and Col1α1 mRNA were increased in wild-type mice on high fat diet compared to control. Deficiency of caspase-1 prevented those increases. In summary, the absence of caspase-1 ameliorates the injurious effects of high fat diet-induced obesity on the liver. Specifically, mice deficient in caspase-1 are protected from high fat-induced hepatic steatosis, inflammation and early fibrogenesis. These data point to the inflammasome as an important therapeutic target for NASH.

  18. Triglyceride-induced macrophage cell death is triggered by caspase-1.

    Science.gov (United States)

    Son, Sin Jee; Rhee, Ki-Jong; Lim, Jaewon; Kim, Tae Ue; Kim, Tack-Joong; Kim, Yoon Suk

    2013-01-01

    Triglyceride (TG) induces macrophage cell death which contributes to the development of atherosclerosis. We confirmed that exogenous TG accumulates in human THP-1 macrophages and causes cell death. TG treated THP-1 macrophages exhibited no change in tumor necrosis factor (TNF)-α, interleukin (IL)-18, macrophage inflammatory protein (MIP)-1α, and IL-1R1 receptor mRNA expression. However, there was a marked decrease in IL-1β mRNA expression but an increase in IL-1β protein secretion. Decreased expression of IL-1β mRNA and increased secretion of IL-1β protein was not the direct cause of cell death. Until now, TG was assumed to induce necrotic cell death in macrophages. Since caspase-1 is known to be involved in activation and secretion of IL-1β protein and pyroptotic cell death, next we determined whether caspase-1 is associated with TG-induced macrophage cell death. We found an increase in caspase-1 activity in TG-treated THP-1 macrophages and inhibition of caspase-1 activity using a specific inhibitor partially rescued cell death. These results suggest activation of the pyroptotic pathway by TG. This is the first report implicating the activation of caspase-1 and the triggering of the pyroptosis pathway in TG-induced macrophage cell death.

  19. Early apoptotic reorganization of spliceosomal proteins involves caspases, CAD and rearrangement of NuMA.

    Science.gov (United States)

    Dieker, Jürgen; Iglesias-Guimarais, Victoria; Décossas, Marion; Stevenin, James; van der Vlag, Johan; Yuste, Victor J; Muller, Sylviane

    2012-02-01

    The reorganization of nuclear structures is an important early feature of apoptosis and involves the activity of specific proteases and nucleases. Well-known is the condensation and fragmentation of chromatin; however, much less is understood about the mechanisms involved in the reorganization of structures from the interchromatin space, such as interchromatin granule clusters (IGCs). In this study, we show that the initial enlargement and rounding-up of IGCs correlate with a decrease in mRNA transcription and are caspase-independent, but involve protein phosphatases PP1/PP2A. Subsequently, multiple enlarged IGCs dissociate from chromatin and fuse into a single structure. The dissociation requires caspase activity and involves caspase-activated DNase (CAD). Apoptotic IMR-5 cells, lacking a proper processing of CAD, show multiple enlarged IGCs that remain linked with chromatin. Overexpression of CAD in IMR-5 cells results in the dissociation of IGCs from chromatin, but the fusion into a single structure remains disturbed. Nuclear matrix protein NuMA is reorganized in a caspase-dependent way around fused IGCs. In conclusion, we show here that the apoptotic rearrangement of IGCs, the nuclear matrix and chromatin are closely associated, occur in defined stages and depend on the activity of protein phosphatases, caspases and CAD. © 2011 John Wiley & Sons A/S.

  20. A Krebs Cycle Component Limits Caspase Activation Rate through Mitochondrial Surface Restriction of CRL Activation.

    Science.gov (United States)

    Aram, Lior; Braun, Tslil; Braverman, Carmel; Kaplan, Yosef; Ravid, Liat; Levin-Zaidman, Smadar; Arama, Eli

    2016-04-04

    How cells avoid excessive caspase activity and unwanted cell death during apoptotic caspase-mediated removal of large cellular structures is poorly understood. We investigate caspase-mediated extrusion of spermatid cytoplasmic contents in Drosophila during spermatid individualization. We show that a Krebs cycle component, the ATP-specific form of the succinyl-CoA synthetase β subunit (A-Sβ), binds to and activates the Cullin-3-based ubiquitin ligase (CRL3) complex required for caspase activation in spermatids. In vitro and in vivo evidence suggests that this interaction occurs on the mitochondrial surface, thereby limiting the source of CRL3 complex activation to the vicinity of this organelle and reducing the potential rate of caspase activation by at least 60%. Domain swapping between A-Sβ and the GTP-specific SCSβ (G-Sβ), which functions redundantly in the Krebs cycle, show that the metabolic and structural roles of A-Sβ in spermatids can be uncoupled, highlighting a moonlighting function of this Krebs cycle component in CRL activation. Copyright © 2016 Elsevier Inc. All rights reserved.

  1. Detergent sclerosants at sub-lytic concentrations induce endothelial cell apoptosis through a caspase dependent pathway.

    Science.gov (United States)

    Cooley-Andrade, Osvaldo; Cheung, Kelvin; Chew, An-Ning; Connor, David Ewan; Parsi, Kurosh

    2016-07-01

    To investigate the apoptotic effects of detergent sclerosants sodium tetradecylsulphate (STS) and polidocanol (POL) on endothelial cells at sub-lytic concentrations. Human umbilical vein endothelial cells (HUVECs) were isolated and labelled with antibodies to assess for apoptosis and examined with confocal microscopy and flow cytometry. Isolated HUVECs viability was assessed using propidium iodide staining. Early apoptosis was determined by increased phosphatidylserine exposure by lactadherin binding. Caspase 3, 8, 9 and Bax activation as well as inhibitory assays with Pan Caspase (Z-VAD-FMK) and Bax (BI-6C9) were assessed to identify apoptotic pathways. Porimin activation was used to assess cell membrane permeability. Cell lysis reached almost 100 % with STS at 0.3 % and with POL at 0.6 %. Apoptosis was seen with both STS and POL at concentrations ranging from 0.075 to 0.15 %. PS exposure increased with both STS and POL and exhibited a dose-dependent trend. Active Caspase 3, 8 and 9 but not Bax were increased in HUVECs stimulated with low concentrations of both STS and POL. Inhibitory assays demonstrated Caspase 3, 8, 9 inhibition at low concentrations (0.075 to 0.6 %) with both STS and POL. Both agents increased the activation of porimin at all concentrations. Both sclerosants induced endothelial cell (EC) apoptosis at sub-lytic concentrations through a caspase-dependant pathway. Both agents induced EC oncosis.

  2. Caspase-like proteins: Acanthamoeba castellanii metacaspase and Dictyostelium discoideum paracaspase, what are their functions?

    Science.gov (United States)

    Saheb, Entsar; Trzyna, Wendy; Bush, John

    2014-12-01

    Caspases are cysteine proteases that are important regulators of programmed cell death in animals. Two novel relatives to members of the caspase families metacaspases and paracaspase have been discovered. Metacaspase type-1 was identified in Acanthamoeba castellanii, an opportunistic protozoan parasite that causes severe diseases in humans. Paracaspase was found in the non-pathogenic protozoan Dictyostelium discoideum. Since their discovery in Acanthamoeba and Dictyostelium, metacaspases and paracaspases have remained poorly characterized. At present we do not have sufficient data about the molecular function of these caspase-like proteins or their role, if any, in programmed cell death. How these caspase proteins function at the molecular level is an important area of study that will provide insight into their potential for treatment therapies against Acanthamoeba infection and other similar parasitic protozoan. Additionally, finding the molecular functions of these caspase-like proteins will provide information concerning their role in more complex organisms.The aim of this article was to review recent discoveries about metacaspases and paracaspases as regulators of apoptotic and non-apoptotic processes.

  3. Caspase-8 inactivation in T cells increases necroptosis and suppresses autoimmunity in Bim−/− mice

    Science.gov (United States)

    Bohgaki, Toshiyuki; Mozo, Julien; Salmena, Leonardo; Matysiak-Zablocki, Elzbieta; Bohgaki, Miyuki; Sanchez, Otto; Strasser, Andreas

    2011-01-01

    Dysregulation of either the extrinsic or intrinsic apoptotic pathway can lead to various diseases including immune disorders and cancer. In addition to its role in the extrinsic apoptotic pathway, caspase-8 plays nonapoptotic functions and is essential for T cell homeostasis. The pro-apoptotic BH3-only Bcl-2 family member Bim is important for the intrinsic apoptotic pathway and its inactivation leads to autoimmunity that is further exacerbated by loss of function of the death receptor Fas. We report that inactivation of caspase-8 in T cells of Bim−/− mice restrained their autoimmunity and extended their life span. We show that, similar to caspase-8−/− T cells, Bim−/− T cells that also lack caspase-8 displayed elevated levels of necroptosis and that inhibition of this cell death process fully rescued the survival and proliferation of these cells. Collectively, our data demonstrate that inactivation of caspase-8 suppresses the survival and proliferative capacity of Bim−/− T cells and restrains autoimmunity in Bim−/− mice. PMID:22006951

  4. Intracellular antibody-caspase-mediated cell killing: An approach for application in cancer therapy

    Science.gov (United States)

    Tse, Eric; Rabbitts, Terence H.

    2000-10-01

    Antibodies have been expressed inside cells in an attempt to ablate the function of oncogene products. To make intracellular antibodies more generally applicable and effective in cancer therapy, we have devised a method in which programmed cell death or apoptosis can be triggered by specific antibody-antigen interaction. When intracellular antibodies are linked to caspase 3, the "executioner" in the apoptosis pathway, and bind to the target antigen, the caspase 3 moieties are self-activated and thereby induce cell killing. We have used this strategy in a model system with two pairs of intracellular antibodies and antigens. In vivo coexpression of an antibody-caspase 3 fusion with its antigenic target induced apoptosis that was specific for antibody, antigen, and active caspase 3. Moreover, the antibody-caspase 3 fusion protein was not toxic to cells in the absence of antigen. Therefore, intracellular antibody-mediated apoptosis should be useful as a specific therapeutic approach for the treatment of cancers, a situation where target cell killing is required.

  5. Evolutionary genetics: the Drosophila model

    Indian Academy of Sciences (India)

    Unknown

    ral selection is provided by studies—sometimes characterized as evolutionary ecology—that attempt to understand how and why particular fitness functions are defined on the distribution of phenotypes in a population by its ecology. Studying how the interaction between phenotype and environment results in a fitness ...

  6. Conceptual foundations of evolutionary thought

    Indian Academy of Sciences (India)

    2017-07-04

    Jul 4, 2017 ... Home; Journals; Journal of Genetics; Volume 96; Issue 3. Conceptual foundations of evolutionary thought. K. P. MOHANAN. Perspectives Volume 96 Issue 3 July 2017 pp 401-412. Fulltext. Click here to view fulltext PDF. Permanent link: http://www.ias.ac.in/article/fulltext/jgen/096/03/0401-0412. Abstract ...

  7. Evolutionary robotics–A review

    Indian Academy of Sciences (India)

    2016-08-26

    Aug 26, 2016 ... 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 ...

  8. Haldane and modern evolutionary genetics

    Indian Academy of Sciences (India)

    Home; Journals; Journal of Genetics; Volume 96; Issue 5. Haldane and modern evolutionary genetics. BRIAN CHARLESWORTH. HALDANE AT 125 Volume 96 Issue 5 November 2017 pp 773-782. Fulltext. Click here to view fulltext PDF. Permanent link: http://www.ias.ac.in/article/fulltext/jgen/096/05/0773-0782. Keywords.

  9. Scalable Computing for Evolutionary Genomics

    NARCIS (Netherlands)

    Prins, J.C.P.; Belhachemi, D.; Möller, S.; Smant, G.

    2012-01-01

    Genomic data analysis in evolutionary biology is becoming so computationally intensive that analysis of multiple hypotheses and scenarios takes too long on a single desktop computer. In this chapter, we discuss techniques for scaling computations through parallelization of calculations, after giving

  10. Evolutionary Biology Research in India

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education; Volume 5; Issue 10. Evolutionary Biology Research in India. Information and Announcements Volume 5 Issue 10 October 2000 pp 102-104. Fulltext. Click here to view fulltext PDF. Permanent link: http://www.ias.ac.in/article/fulltext/reso/005/10/0102-0104 ...

  11. Realism, Relativism, and Evolutionary Psychology

    NARCIS (Netherlands)

    Derksen, M.

    Against recent attempts to forge a reconciliation between constructionism and realism, I contend that, in psychology at least, stirring up conflict is a more fruitful strategy. To illustrate this thesis, I confront a school of psychology with strong realist leanings, evolutionary psychology, with

  12. Cryptic eco-evolutionary dynamics.

    Science.gov (United States)

    Kinnison, Michael T; Hairston, Nelson G; Hendry, Andrew P

    2015-12-01

    Natural systems harbor complex interactions that are fundamental parts of ecology and evolution. These interactions challenge our inclinations and training to seek the simplest explanations of patterns in nature. Not least is the likelihood that some complex processes might be missed when their patterns look similar to predictions for simpler mechanisms. Along these lines, theory and empirical evidence increasingly suggest that environmental, ecological, phenotypic, and genetic processes can be tightly intertwined, resulting in complex and sometimes surprising eco-evolutionary dynamics. The goal of this review is to temper inclinations to unquestioningly seek the simplest explanations in ecology and evolution, by recognizing that some eco-evolutionary outcomes may appear very similar to purely ecological, purely evolutionary, or even null expectations, and thus be cryptic. We provide theoretical and empirical evidence for observational biases and mechanisms that might operate among the various links in eco-evolutionary feedbacks to produce cryptic patterns. Recognition that cryptic dynamics can be associated with outcomes like stability, resilience, recovery, or coexistence in a dynamically changing world provides added impetus for finding ways to study them. © 2015 New York Academy of Sciences.

  13. Darwinian foundations for evolutionary economics

    NARCIS (Netherlands)

    Stoelhorst, J.W.

    2008-01-01

    This paper engages with the methodological debate on the contribution of Darwinism to Veblen's (1898) evolutionary research program for economics. I argue that ontological continuity, generalized Darwinism, and multi-level selection are necessary building blocks for an explanatory framework that can

  14. Evolutionary Psychology and Intelligence Research

    Science.gov (United States)

    Kanazawa, Satoshi

    2010-01-01

    This article seeks to unify two subfields of psychology that have hitherto stood separately: evolutionary psychology and intelligence research/differential psychology. I suggest that general intelligence may simultaneously be an evolved adaptation and an individual-difference variable. Tooby and Cosmides's (1990a) notion of random quantitative…

  15. Diversity-Guided Evolutionary Algorithms

    DEFF Research Database (Denmark)

    Ursem, Rasmus Kjær

    2002-01-01

    Population diversity is undoubtably a key issue in the performance of evolutionary algorithms. A common hypothesis is that high diversity is important to avoid premature convergence and to escape local optima. Various diversity measures have been used to analyze algorithms, but so far few algorit...

  16. Testing evolutionary theories of menopause.

    Science.gov (United States)

    Shanley, Daryl P; Sear, Rebecca; Mace, Ruth; Kirkwood, Thomas B L

    2007-12-07

    Why do women cease fertility rather abruptly through menopause at an age well before generalized senescence renders child rearing biologically impossible? The two main evolutionary hypotheses are that menopause serves either (i) to protect mothers from rising age-specific maternal mortality risks, thereby protecting their highly dependent younger children from death if the mother dies or (ii) to provide post-reproductive grandmothers who enhance their inclusive fitness by helping to care and provide for their daughters' children. Recent theoretical work indicates that both factors together are necessary if menopause is to provide an evolutionary advantage. However, these ideas need to be tested using detailed data from actual human life histories lived under reasonably 'natural' conditions; for obvious reasons, such data are extremely scarce. We here describe a study based on a remarkably complete dataset from The Gambia. The data provided quantitative estimates for key parameters for the theoretical model, which were then used to assess the actual effects on fitness. Empirically based numerical analysis of this nature is essential if the enigma of menopause is to be explained satisfactorily in evolutionary terms. Our results point to the distinctive (and perhaps unique) role of menopause in human evolution and provide important support for the hypothesized evolutionary significance of grandmothers.

  17. Defining fitness in evolutionary models

    Indian Academy of Sciences (India)

    2008-12-23

    Dec 23, 2008 ... The analysis of evolutionary models requires an appropriate definition for fitness. ..... of dimorphism for dormancy in plants (Cohen 1966). .... yses have assumed nonoverlapping generations (i.e. no age- structure). The solution to defining fitness when the environ- ment is spatially variable and there is a ...

  18. Evolutionary dynamics of mammalian karyotypes

    Directory of Open Access Journals (Sweden)

    Carlo Alberto Redi

    2012-12-01

    Full Text Available This special volume of Cytogenetic and Genome Research (edited by Roscoe Stanyon, University of Florence and Alexander Graphodatsky, Siberian division of the Russian Academy of Sciences is dedicated to the fascinating long search of the forces behind the evolutionary dynamics of mammalian karyotypes, revealed after the hypotonic miracle of the 1950s....

  19. Euryhalinity in an evolutionary context

    Science.gov (United States)

    Schultz, Eric T.; McCormick, Stephen D.; McCormick, Stephen D.; Farrell, Anthony Peter; Brauner, Colin J.

    2013-01-01

    This chapter focuses on the evolutionary importance and taxonomic distribution of euryhalinity. Euryhalinity refers to broad halotolerance and broad halohabitat distribution. Salinity exposure experiments have demonstrated that species vary tenfold in their range of tolerable salinity levels, primarily because of differences in upper limits. Halotolerance breadth varies with the species’ evolutionary history, as represented by its ordinal classification, and with the species’ halohabitat. Freshwater and seawater species tolerate brackish water; their empirically-determined fundamental haloniche is broader than their realized haloniche, as revealed by the halohabitats they occupy. With respect to halohabitat distribution, a minority of species (basal actinopterygian fishes, is largely absent from orders arising from intermediate nodes, and reappears in the most derived taxa. There is pronounced family-level variability in the tendency to be halohabitat-euryhaline, which may have arisen during a burst of diversification following the Cretaceous-Palaeogene extinction. Low prevalence notwithstanding, euryhaline species are potent sources of evolutionary diversity. Euryhalinity is regarded as a key innovation trait whose evolution enables exploitation of new adaptive zone, triggering cladogenesis. We review phylogenetically-informed studies that demonstrate freshwater species diversifying from euryhaline ancestors through processes such as landlocking. These studies indicate that some euryhaline taxa are particularly susceptible to changes in halohabitat and subsequent diversification, and some geographic regions have been hotspots for transitions to freshwater. Comparative studies on mechanisms among multiple taxa and at multiple levels of biological integration are needed to clarify evolutionary pathways to, and from, euryhalinity.

  20. Ernst Mayr and Evolutionary Biology

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education; Volume 10; Issue 7. Polemics and Synthesis: Ernst Mayr and Evolutionary Biology. Renee M Borges. General Article Volume 10 Issue 7 July 2005 pp 21-33. Fulltext. Click here to view fulltext PDF. Permanent link:

  1. Evolutionary Biology Research in India

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education; Volume 5; Issue 10. Evolutionary Biology Research in India. Information and Announcements Volume 5 Issue 10 October 2000 pp 102-104. Fulltext. Click here to view fulltext PDF. Permanent link: https://www.ias.ac.in/article/fulltext/reso/005/10/0102-0104 ...

  2. Evolutionary robotics – A review

    Indian Academy of Sciences (India)

    R. Narasimhan (Krishtel eMaging) 1461 1996 Oct 15 13:05:22

    to solve this problem. This paper provides a survey on some of these important studies carried out in the recent past. Keywords. Evolutionary robotics; genetic ... neural network (NN) (Kosko 1994), to study the interaction between evolution and learning. .... After GA-based learning of the neural controller, the navigation.

  3. Hydrogen peroxide-mediated necrosis induction in HUVECs is associated with an atypical pattern of caspase-3 cleavage.

    Science.gov (United States)

    Csordas, Adam; Wick, Georg; Bernhard, David

    2006-06-10

    Oxidative stress, continuously exerted during chronic inflammation, has been implicated as a major causative agent of cellular dysfunction and cell death. In the present study, we investigated the impact of oxidative stress on the mode of cell death in HUVECs using H2O2 as a model reagent. We found that the predominant form of cell death was necrosis. Necrosis induction was accompanied by a distinct mode of caspase-3 cleavage, yielding a 29-kDa fragment. While inhibition of caspases could not prevent the generation of the 29-kDa fragment, general protease inhibitors, such as leupeptin and LLNL, proved to be effective in inhibiting the distinct processing pattern of caspase-3. These results suggest that caspases can act as substrates for non-caspase proteases in cells primed for necrosis induction. Thus, the pattern of caspase-3 cleavage might reflect the proteolytic system engaged in the cell death machinery in HUVECs.

  4. Towards a mechanistic foundation of evolutionary theory.

    Science.gov (United States)

    Doebeli, Michael; Ispolatov, Yaroslav; Simon, Burt

    2017-02-15

    Most evolutionary thinking is based on the notion of fitness and related ideas such as fitness landscapes and evolutionary optima. Nevertheless, it is often unclear what fitness actually is, and its meaning often depends on the context. Here we argue that fitness should not be a basal ingredient in verbal or mathematical descriptions of evolution. Instead, we propose that evolutionary birth-death processes, in which individuals give birth and die at ever-changing rates, should be the basis of evolutionary theory, because such processes capture the fundamental events that generate evolutionary dynamics. In evolutionary birth-death processes, fitness is at best a derived quantity, and owing to the potential complexity of such processes, there is no guarantee that there is a simple scalar, such as fitness, that would describe long-term evolutionary outcomes. We discuss how evolutionary birth-death processes can provide useful perspectives on a number of central issues in evolution.

  5. Evolutionary biology of bacterial and fungal pathogens

    National Research Council Canada - National Science Library

    Cassell, Gail H; Gutierrez-Fuentes, Jose A; Barquero, Fernando; Nombela, Cesar

    2008-01-01

    ... and Evolutionary Dynamics of Pathogens * 21 Keith A. Crandall and Marcos Pérez-Losada II. Evolutionary Genetics of Microbial Pathogens 4. Environmental and Social Influences on Infectious Disea...

  6. Ecological and evolutionary effects of stickleback on community structure.

    Directory of Open Access Journals (Sweden)

    Simone Des Roches

    Full Text Available Species' ecology and evolution can have strong effects on communities. Both may change concurrently when species colonize a new ecosystem. We know little, however, about the combined effects of ecological and evolutionary change on community structure. We simultaneously examined the effects of top-predator ecology and evolution on freshwater community parameters using recently evolved generalist and specialist ecotypes of three-spine stickleback (Gasterosteus aculeatus. We used a mesocosm experiment to directly examine the effects of ecological (fish presence and density and evolutionary (phenotypic diversity and specialization factors on community structure at lower trophic levels. We evaluated zooplankton biomass and composition, periphyton and phytoplankton chlorophyll-a concentration, and net primary production among treatments containing different densities and diversities of stickleback. Our results showed that both ecological and evolutionary differences in the top-predator affect different aspects of community structure and composition. Community structure, specifically the abundance of organisms at each trophic level, was affected by stickleback presence and density, whereas composition of zooplankton was influenced by stickleback diversity and specialization. Primary productivity, in terms of chlorophyll-a concentration and net primary production was affected by ecological but not evolutionary factors. Our results stress the importance of concurrently evaluating both changes in density and phenotypic diversity on the structure and composition of communities.

  7. Ecological and evolutionary effects of stickleback on community structure.

    Science.gov (United States)

    Des Roches, Simone; Shurin, Jonathan B; Schluter, Dolph; Harmon, Luke J

    2013-01-01

    Species' ecology and evolution can have strong effects on communities. Both may change concurrently when species colonize a new ecosystem. We know little, however, about the combined effects of ecological and evolutionary change on community structure. We simultaneously examined the effects of top-predator ecology and evolution on freshwater community parameters using recently evolved generalist and specialist ecotypes of three-spine stickleback (Gasterosteus aculeatus). We used a mesocosm experiment to directly examine the effects of ecological (fish presence and density) and evolutionary (phenotypic diversity and specialization) factors on community structure at lower trophic levels. We evaluated zooplankton biomass and composition, periphyton and phytoplankton chlorophyll-a concentration, and net primary production among treatments containing different densities and diversities of stickleback. Our results showed that both ecological and evolutionary differences in the top-predator affect different aspects of community structure and composition. Community structure, specifically the abundance of organisms at each trophic level, was affected by stickleback presence and density, whereas composition of zooplankton was influenced by stickleback diversity and specialization. Primary productivity, in terms of chlorophyll-a concentration and net primary production was affected by ecological but not evolutionary factors. Our results stress the importance of concurrently evaluating both changes in density and phenotypic diversity on the structure and composition of communities.

  8. Caspase-1 contributes to Chlamydia trachomatis-induced upper urogenital tract inflammatory pathologies without affecting the course of infection.

    Science.gov (United States)

    Cheng, Wen; Shivshankar, Pooja; Li, Zhongyu; Chen, Lili; Yeh, I-Tien; Zhong, Guangming

    2008-02-01

    Chlamydia trachomatis infection induces inflammatory pathologies in the upper genital tract, potentially leading to ectopic pregnancy and infertility in the affected women. Caspase-1 is required for processing and release of the inflammatory cytokines interleukin-1beta (IL-1beta), IL-18, and possibly IL-33. In the present study, we evaluated the role of caspase-1 in chlamydial infection and pathogenesis. Although chlamydial infection induced caspase-1 activation and processing of IL-1beta, mice competent and mice deficient in caspase-1 experienced similar courses of chlamydial infection in their urogenital tracts, suggesting that Chlamydia-activated caspase-1 did not play a significant role in resolution of chlamydial infection. However, when genital tract tissue pathologies were examined, the caspase-1-deficient mice displayed much reduced inflammatory damage. The reduction in inflammation was most obvious in the fallopian tube tissue. These observations demonstrated that although caspase-1 is not required for controlling chlamydial infection, caspase-1-mediated responses can exacerbate the Chlamydia-induced inflammatory pathologies in the upper genital tract, suggesting that the host caspase-1 may be targeted for selectively attenuating chlamydial pathogenicity without affecting the host defense against chlamydial infection.

  9. The co-chaperone p23 is degraded by caspases and the proteasome during apoptosis

    DEFF Research Database (Denmark)

    Mollerup, Jens; Berchtold, Martin Werner

    2005-01-01

    The heat shock protein 90 co-chaperone p23 has recently been shown to be up-regulated in cancer cells and down-regulated in atheroschlerotic plaques. We found that p23 is degraded during apoptosis induced by several stimuli, including Fas and TNFa-receptor activation as well as staurosporine...... treatment. Caspase inhibition protected p23 from degradation in several cell lines. In addition, recombinant caspase-3 and 8 cleaved p23 at Asp 142 generating a degradation product of 18 kDa as seen in apoptotic cells. Truncated p23 is further degraded in a proteasome dependent process during apoptosis....... Furthermore, we found that the anti-aggregating activity of truncated p23 was reduced compared to full length p23 indicating that caspase mediated p23 degradation contributes to protein destabilisation in apoptosis....

  10. Essential roles of Caspase-3 in facilitating Myc-induced genetic instability and carcinogenesis.

    Science.gov (United States)

    Cartwright, Ian M; Liu, Xinjian; Zhou, Min; Li, Fang; Li, Chuan-Yuan

    2017-07-10

    The mechanism for Myc-induced genetic instability is not well understood. Here we show that sublethal activation of Caspase-3 plays an essential, facilitative role in Myc-induced genomic instability and oncogenic transformation. Overexpression of Myc resulted in increased numbers of chromosome aberrations and γH2AX foci in non-transformed MCF10A human mammary epithelial cells. However, such increases were almost completely eliminated in isogenic cells with CASP3 gene ablation. Furthermore, we show that endonuclease G, an apoptotic nuclease downstream of Caspase-3, is directly responsible for Myc-induced genetic instability. Genetic ablation of either CASP3 or ENDOG prevented Myc-induced oncogenic transformation of MCF10A cells. Taken together, we believe that Caspase-3 plays a critical, unexpected role in mediating Myc-induced genetic instability and transformation in mammalian cells.

  11. Regulatory effect of caspase-11 on interleukin-1β in the fungal keratitis.

    Science.gov (United States)

    Zhu, Keke; Mu, Hongmei; Pi, Baimu

    2016-11-01

    Caused by fungus, fungal keratitis is a kind of infections corneal disease with high rate of blindness, which patients are mainly farmers in developing countries. Interleukin, as important proinflammatory cytokines, involve in immune defense process against fungal infection of cornea. The expression of interleukin in the pathogenesis of fungal keratitis, especially the main source of its cells, is not clear and the cell signaling pathways which regulate the synthesis and modification of interleukin is still unknown. Caspase-11 was obtained and cultured. And the ELISA and Western-blot methods were used to explore the regulatory effect of Caspse-11 on Interleukin-1β in the fungal keratitis. neutrophils were the main cell lineage of IL-1β to take part in the innate anti-fungi immunity in the cornea; IL-1β generation induced by fungal infection might not be through the pre-excitation in the classical signal pathway; TLR4/TRIF pathway was not involved in pro-IL-1β generation; while Dectin-1/syk pathway was involved in IL-1β generation in the fungal keratitis; Caspase-l participated in the modification of IL-1β to change from the precursor into the mature body; but NLRP3 inflammasome and ASC inflammasome were not involved in IL-1β generation; Caspase-11 was involved in IL-1β generation through regulating the modified process of Caspase-l to turning from precursor into mature body. TLR4/TRIF pathway and NLRP3 inflammasome and ASC inflammasome are not involved in the pro-IL-1β generation, while Caspase-l, Caspase-11 and Dectin-1/syk pathway are involved in the IL-1β generation.

  12. Caspase-2 mediated apoptotic and necrotic murine macrophage cell death induced by rough Brucella abortus.

    Directory of Open Access Journals (Sweden)

    Fang Chen

    Full Text Available Brucella species are Gram-negative, facultative intracellular bacteria that cause zoonotic brucellosis. Survival and replication inside macrophages is critical for establishment of chronic Brucella infection. Virulent smooth B. abortus strain 2308 inhibits programmed macrophage cell death and replicates inside macrophages. Cattle B. abortus vaccine strain RB51 is an attenuated rough, lipopolysaccharide O antigen-deficient mutant derived from smooth strain 2308. B. abortus rough mutant RA1 contains a single wboA gene mutation in strain 2308. Our studies demonstrated that live RB51 and RA1, but not strain 2308 or heat-killed Brucella, induced both apoptotic and necrotic cell death in murine RAW264.7 macrophages and bone marrow derived macrophages. The same phenomenon was also observed in primary mouse peritoneal macrophages from mice immunized intraperitoneally with vaccine strain RB51 using the same dose as regularly performed in protection studies. Programmed macrophage cell death induced by RB51 and RA1 was inhibited by a caspase-2 inhibitor (Z-VDVAD-FMK. Caspase-2 enzyme activation and cleavage were observed at the early infection stage in macrophages infected with RB51 and RA1 but not strain 2308. The inhibition of macrophage cell death promoted the survival of rough Brucella cells inside macrophages. The critical role of caspase-2 in mediating rough B. abortus induced macrophage cell death was confirmed using caspase-2 specific shRNA. The mitochondrial apoptosis pathway was activated in macrophages infected with rough B. abortus as demonstrated by increase in mitochondrial membrane permeability and the release of cytochrome c to cytoplasm in macrophages infected with rough Brucella. These results demonstrate that rough B. abortus strains RB51 and RA1 induce apoptotic and necrotic murine macrophage cell death that is mediated by caspase-2. The biological relevance of Brucella O antigen and caspase-2-mediated macrophage cell death in Brucella

  13. Caspase-2 mediated apoptotic and necrotic murine macrophage cell death induced by rough Brucella abortus.

    Science.gov (United States)

    Chen, Fang; He, Yongqun

    2009-08-28

    Brucella species are Gram-negative, facultative intracellular bacteria that cause zoonotic brucellosis. Survival and replication inside macrophages is critical for establishment of chronic Brucella infection. Virulent smooth B. abortus strain 2308 inhibits programmed macrophage cell death and replicates inside macrophages. Cattle B. abortus vaccine strain RB51 is an attenuated rough, lipopolysaccharide O antigen-deficient mutant derived from smooth strain 2308. B. abortus rough mutant RA1 contains a single wboA gene mutation in strain 2308. Our studies demonstrated that live RB51 and RA1, but not strain 2308 or heat-killed Brucella, induced both apoptotic and necrotic cell death in murine RAW264.7 macrophages and bone marrow derived macrophages. The same phenomenon was also observed in primary mouse peritoneal macrophages from mice immunized intraperitoneally with vaccine strain RB51 using the same dose as regularly performed in protection studies. Programmed macrophage cell death induced by RB51 and RA1 was inhibited by a caspase-2 inhibitor (Z-VDVAD-FMK). Caspase-2 enzyme activation and cleavage were observed at the early infection stage in macrophages infected with RB51 and RA1 but not strain 2308. The inhibition of macrophage cell death promoted the survival of rough Brucella cells inside macrophages. The critical role of caspase-2 in mediating rough B. abortus induced macrophage cell death was confirmed using caspase-2 specific shRNA. The mitochondrial apoptosis pathway was activated in macrophages infected with rough B. abortus as demonstrated by increase in mitochondrial membrane permeability and the release of cytochrome c to cytoplasm in macrophages infected with rough Brucella. These results demonstrate that rough B. abortus strains RB51 and RA1 induce apoptotic and necrotic murine macrophage cell death that is mediated by caspase-2. The biological relevance of Brucella O antigen and caspase-2-mediated macrophage cell death in Brucella pathogenesis and

  14. Q-VE-OPh, a Negative Control for O-Phenoxy-Conjugated Caspase Inhibitors

    Directory of Open Access Journals (Sweden)

    Benjamin Southerland

    2010-06-01

    Full Text Available The broad-spectrum apoptosis (caspase inhibitor, Q-VD-OPh, has been shown to have no side effects and is effective at a much lower concentration than other FMK-type caspase inhibitors. However, an appropriate negative control to use with this inhibi- tor has not been available. In this study, we developed and analyzed a new compound, based on the Q-VD-OPh backbone, which acts as a cognate negative control. To create the negative control, we substituted a glutamate residue for the aspartate residue to create Q-VE-OPh, thereby retaining the identical charge and molecular properties with only the addition of an extra –CH2 group. The purity and quality were assessed by ion trap mass spectrometry and verified by nuclear magnetic resonance. We determined the effectiveness of Q-VE-OPh, in comparison to Q-VD-OPh, to prevent DNA fragmentation in human Jurkat T leukemia cells that were induced to undergo apoptosis. DNA fragmentation was analyzed by agarose gel electrophoresis for the presence of DNA laddering, the hallmark indicator of apoptosis. Our results indicate that apoptosis was potently inhibited by Q-VD-OPh. In stark contrast, Q-VE-OPh did not inhibit apoptosis at a similar dose but required at least 20 times greater concentration than Q-VD-OPh to have any inhibitory effect. Western blot analysis showed that Q-VE-OPh was similarly less effective at inhibiting the activation of the extrinsic (caspase 8 and intrinsic (caspase 9 initiator caspases. Cell proliferation and viability studies further demonstrate that Q-VE-OPh is non-toxic, even at high concentration. Our data indicate that the specificity, effectiveness, and absence of toxicity of Q-VE-OPh provides the appropriate and superior negative control for in vitro and in vivo studies when analyzing the effects of o-phenoxy caspase inhibitors.

  15. Q-VE-OPh, a Negative Control for O-Phenoxy-Conjugated Caspase Inhibitors

    Directory of Open Access Journals (Sweden)

    Benjamin Southerland

    2010-01-01

    Full Text Available The broad-spectrum apoptosis (caspase inhibitor, Q-VD-OPh, has been shown to have no side effects and is effective at a much lower concentration than other FMK-type caspase inhibitors. However, an appropriate negative control to use with this inhibitor has not been available. In this study, we developed and analyzed a new compound, based on the Q-VD-OPh backbone, which acts as a cognate negative control. To create the negative control, we substituted a glutamate residue for the aspartate residue to create Q-VE-OPh , thereby retaining the identical charge and molecular properties with only the addition of an extra -CH2 group. The purity and quality were assessed by ion trap mass spectrometry and verified by nuclear magnetic resonance. We determined the effectiveness of Q-VE-OPh, in comparison to Q-VD-OPh, to prevent DNA fragmentation in human Jurkat T leukemia cells that were induced to undergo apoptosis. DNA fragmentation was analyzed by agarose gel electrophoresis for the presence of DNA laddering, the hallmark indicator of apoptosis. Our results indicate that apoptosis was potently inhibited by Q-VD-OPh. In stark contrast, Q-VE-OPh did not inhibit apoptosis at a similar dose but required at least 20 times greater concentration than Q-VD-OPh to have any inhibitory effect. Western blot analysis showed that Q-VE-OPh was similarly less effective at inhibiting the activation of the extrinsic (caspase 8 and intrinsic (caspase 9 initiator caspases. Cell proliferation and viability studies further demonstrate that Q-VE-OPh is non-toxic, even at high concentration. Our data indicate that the specificity, effectiveness, and absence of toxicity of Q-VE-OPh provides the appropriate and superior negative control for in vitro and in vivo studies when analyzing the effects of o-phenoxy caspase inhibitors.

  16. The citation field of evolutionary economics

    NARCIS (Netherlands)

    Dolfsma, Wilfred; Leydesdorff, Loet

    2010-01-01

    Evolutionary economics has developed into an academic field of its own, institutionalized around, amongst others, the Journal of Evolutionary Economics (JEE). This paper analyzes the way and extent to which evolutionary economics has become an interdisciplinary journal, as its aim was: a journal

  17. Optimization aspects of carcinogenesis.

    Science.gov (United States)

    Brutovsky, B; Horvath, D

    2010-05-01

    Any process in which competing solutions replicate with errors and numbers of their copies depend on their respective fitnesses is the evolutionary optimization process. As during carcinogenesis mutated genomes replicate according to their respective qualities, carcinogenesis obviously qualifies as the evolutionary optimization process and conforms to common mathematical basis. The optimization view accents statistical nature of carcinogenesis proposing that during it the crucial role is actually played by the allocation of trials. Optimal allocation of trials requires reliable schemas' fitnesses estimations which necessitate appropriate, fitness landscape dependent, statistics of population. In the spirit of the applied conceptual framework, features which are known to decrease efficiency of any evolutionary optimization procedure (or inhibit it completely) are anticipated as "therapies" and reviewed. Strict adherence to the evolutionary optimization framework leads us to some counterintuitive implications which are, however, in agreement with recent experimental findings, such as sometimes observed more aggressive and malignant growth of therapy surviving cancer cells.

  18. Optimization Aspects of Carcinogenesis

    OpenAIRE

    Brutovsky, B.; Horvath, D.

    2009-01-01

    Any process in which competing solutions replicate with errors and numbers of their copies depend on their respective fitnesses is the evolutionary optimization process. As during carcinogenesis mutated genomes replicate according to their respective qualities, carcinogenesis obviously qualifies as the evolutionary optimization process and conforms to common mathematical basis. The optimization view accents statistical nature of carcinogenesis proposing that during it the crucial role is actu...

  19. Schroedinger operators and evolutionary strategies

    International Nuclear Information System (INIS)

    Asselmeyer, T.

    1997-01-01

    First we introduce a simple model for the description of evolutionary algorithms, which is based on 2nd order partial differential equations for the distribution function of the individuals. Then we turn to the properties of Boltzmann's and Darwin's strategy. the next chapter is dedicated to the mathematical properties of Schroedinger operators. Both statements on the spectral density and their reproducibility during the simulation are summarized. The remaining of this chapter are dedicated to the analysis of the kernel as well as the dependence of the Schroedinger operator on the potential. As conclusion from the results of this chapter we obtain the classification of the strategies in dependence of the fitness. We obtain the classification of the evolutionary strategies, which are described by a 2nd order partial differential equation, in relation to their solution behaviour. Thereafter we are employed with the variation of the mutation distribution

  20. Incorporating Development Into Evolutionary Psychology

    OpenAIRE

    David F. Bjorklund

    2016-01-01

    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 ch...

  1. Evolutionary dynamics of diploid populations

    Science.gov (United States)

    Desimone, Ralph; Newman, Timothy

    2003-10-01

    There has been much recent interest in constructing computer models of evolutionary dynamics. Typically these models focus on asexual population dynamics, which are appropriate for haploid organsims such as bacteria. Using a recently developed ``genome template'' model, we extend the algorithm to a sexual population of diploid organisms. We will present some early results showing the temporal evolution of mean fitness and genetic variation, and compare this to typical results from haploid populations.

  2. Natural pedagogy as evolutionary adaptation

    OpenAIRE

    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...

  3. Evolutionary Theories in Environmental and Resource Economics: Approaches and Applications

    NARCIS (Netherlands)

    van den Bergh, J.C.J.M.; Gowdy, J.M.

    2000-01-01

    Recent advances in evolutionary theory have important implications for environmental economics. A short overview is offered of evolutionary thinking in economics. Subsequently, major concepts and approaches in evolutionary biology and evolutionary economics are presented and compared. Attention is

  4. 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.

  5. Evolutionary computation and QSAR research.

    Science.gov (United States)

    Aguiar-Pulido, Vanessa; Gestal, Marcos; Cruz-Monteagudo, Maykel; Rabuñal, Juan R; Dorado, Julian; Munteanu, Cristian R

    2013-06-01

    The successful high throughput screening of molecule libraries for a specific biological property is one of the main improvements in drug discovery. The virtual molecular filtering and screening relies greatly on quantitative structure-activity relationship (QSAR) analysis, a mathematical model that correlates the activity of a molecule with molecular descriptors. QSAR models have the potential to reduce the costly failure of drug candidates in advanced (clinical) stages by filtering combinatorial libraries, eliminating candidates with a predicted toxic effect and poor pharmacokinetic profiles, and reducing the number of experiments. To obtain a predictive and reliable QSAR model, scientists use methods from various fields such as molecular modeling, pattern recognition, machine learning or artificial intelligence. QSAR modeling relies on three main steps: molecular structure codification into molecular descriptors, selection of relevant variables in the context of the analyzed activity, and search of the optimal mathematical model that correlates the molecular descriptors with a specific activity. Since a variety of techniques from statistics and artificial intelligence can aid variable selection and model building steps, this review focuses on the evolutionary computation methods supporting these tasks. Thus, this review explains the basic of the genetic algorithms and genetic programming as evolutionary computation approaches, the selection methods for high-dimensional data in QSAR, the methods to build QSAR models, the current evolutionary feature selection methods and applications in QSAR and the future trend on the joint or multi-task feature selection methods.

  6. What's wrong with evolutionary biology?

    Science.gov (United States)

    Welch, John J

    2017-01-01

    There have been periodic claims that evolutionary biology needs urgent reform, and this article tries to account for the volume and persistence of this discontent. It is argued that a few inescapable properties of the field make it prone to criticisms of predictable kinds, whether or not the criticisms have any merit. For example, the variety of living things and the complexity of evolution make it easy to generate data that seem revolutionary (e.g. exceptions to well-established generalizations, or neglected factors in evolution), and lead to disappointment with existing explanatory frameworks (with their high levels of abstraction, and limited predictive power). It is then argued that special discontent stems from misunderstandings and dislike of one well-known but atypical research programme: the study of adaptive function, in the tradition of behavioural ecology. To achieve its goals, this research needs distinct tools, often including imaginary agency, and a partial description of the evolutionary process. This invites mistaken charges of narrowness and oversimplification (which come, not least, from researchers in other subfields), and these chime with anxieties about human agency and overall purpose. The article ends by discussing several ways in which calls to reform evolutionary biology actively hinder progress in the field.

  7. 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.

  8. Evolutionary dynamics of group formation.

    Science.gov (United States)

    Javarone, Marco Alberto; Marinazzo, Daniele

    2017-01-01

    Group formation is a quite ubiquitous phenomenon across different animal species, whose individuals cluster together forming communities of diverse size. Previous investigations suggest that, in general, this phenomenon might have similar underlying reasons across the interested species, despite genetic and behavioral differences. For instance improving the individual safety (e.g. from predators), and increasing the probability to get food resources. Remarkably, the group size might strongly vary from species to species, e.g. shoals of fishes and herds of lions, and sometimes even within the same species, e.g. tribes and families in human societies. Here we build on previous theories stating that the dynamics of group formation may have evolutionary roots, and we explore this fascinating hypothesis from a purely theoretical perspective, with a model using the framework of Evolutionary Game Theory. In our model we hypothesize that homogeneity constitutes a fundamental ingredient in these dynamics. Accordingly, we study a population that tries to form homogeneous groups, i.e. composed of similar agents. The formation of a group can be interpreted as a strategy. Notably, agents can form a group (receiving a 'group payoff'), or can act individually (receiving an 'individual payoff'). The phase diagram of the modeled population shows a sharp transition between the 'group phase' and the 'individual phase', characterized by a critical 'individual payoff'. Our results then support the hypothesis that the phenomenon of group formation has evolutionary roots.

  9. Asteroseismology of pulsating DA white dwarfs with fully evolutionary models

    Directory of Open Access Journals (Sweden)

    Althaus L.G.

    2013-03-01

    Full Text Available We present a new approach for asteroseismology of DA white dwarfs that consists in the employment of a large set of non-static, physically sound, fully evolutionary models representative of these stars. We already have applied this approach with success to pulsating PG1159 stars (GW Vir variables. Our white dwarf models, which cover a wide range of stellar masses, effective temperatures, and envelope thicknesses, are the result of fully evolutionary computations that take into account the complete history of the progenitor stars from the ZAMS. In particular, the models are characterized by self-consistent chemical structures from the centre to the surface, a crucial aspect of white dwarf asteroseismology. We apply this approach to an ensemble of 44 bright DAV (ZZ Ceti stars.

  10. Recent advances in evolutionary multi-objective optimization

    CERN Document Server

    Datta, Rituparna; Gupta, Abhishek

    2017-01-01

    This book covers the most recent advances in the field of evolutionary multiobjective optimization. With the aim of drawing the attention of up-andcoming scientists towards exciting prospects at the forefront of computational intelligence, the authors have made an effort to ensure that the ideas conveyed herein are accessible to the widest audience. The book begins with a summary of the basic concepts in multi-objective optimization. This is followed by brief discussions on various algorithms that have been proposed over the years for solving such problems, ranging from classical (mathematical) approaches to sophisticated evolutionary ones that are capable of seamlessly tackling practical challenges such as non-convexity, multi-modality, the presence of multiple constraints, etc. Thereafter, some of the key emerging aspects that are likely to shape future research directions in the field are presented. These include:< optimization in dynamic environments, multi-objective bilevel programming, handling high ...

  11. Pharmacological inhibition of caspase and calpain proteases: a novel strategy to enhance the homing responses of cord blood HSPCs during expansion.

    Directory of Open Access Journals (Sweden)

    V M Sangeetha

    Full Text Available BACKGROUND: Expansion of hematopoietic stem/progenitor cells (HSPCs is a well-known strategy employed to facilitate the transplantation outcome. We have previously shown that the prevention of apoptosis by the inhibition of cysteine proteases, caspase and calpain played an important role in the expansion and engraftment of cord blood (CB derived HSPCs. We hypothesize that these protease inhibitors might have maneuvered the adhesive and migratory properties of the cells rendering them to be retained in the bone marrow for sustained engraftment. The current study was aimed to investigate the mechanism of the homing responses of CB cells during expansion. METHODOLOGY/PRINCIPAL FINDINGS: CB derived CD34(+ cells were expanded using a combination of growth factors with and without Caspase inhibitor -zVADfmk or Calpain 1 inhibitor- zLLYfmk. The cells were analyzed for the expression of homing-related molecules. In vitro adhesive/migratory interactions and actin polymerization dynamics of HSPCs were assessed. In vivo homing assays were carried out in NOD/SCID mice to corroborate these observations. We observed that the presence of zVADfmk or zLLYfmk (inhibitors caused the functional up regulation of CXCR4, integrins, and adhesion molecules, reflecting in a higher migration and adhesive interactions in vitro. The enhanced actin polymerization and the RhoGTPase protein expression complemented these observations. Furthermore, in vivo experiments showed a significantly enhanced homing to the bone marrow of NOD/SCID mice. CONCLUSION/SIGNIFICANCE: Our present study reveals another novel aspect of the regulation of caspase and calpain proteases in the biology of HSPCs. The priming of the homing responses of the inhibitor-cultured HSPCs compared to the cytokine-graft suggests that the modulation of these proteases may help in overcoming the major homing defects prevalent in the expansion cultures thereby facilitating the manipulation of cells for transplant

  12. Evolutionary process of deep-sea bathymodiolus mussels.

    Directory of Open Access Journals (Sweden)

    Jun-Ichi Miyazaki

    Full Text Available BACKGROUND: Since the discovery of deep-sea chemosynthesis-based communities, much work has been done to clarify their organismal and environmental aspects. However, major topics remain to be resolved, including when and how organisms invade and adapt to deep-sea environments; whether strategies for invasion and adaptation are shared by different taxa or unique to each taxon; how organisms extend their distribution and diversity; and how they become isolated to speciate in continuous waters. Deep-sea mussels are one of the dominant organisms in chemosynthesis-based communities, thus investigations of their origin and evolution contribute to resolving questions about life in those communities. METHODOLOGY/PRINCIPAL FINDING: We investigated worldwide phylogenetic relationships of deep-sea Bathymodiolus mussels and their mytilid relatives by analyzing nucleotide sequences of the mitochondrial cytochrome c oxidase subunit I (COI and NADH dehydrogenase subunit 4 (ND4 genes. Phylogenetic analysis of the concatenated sequence data showed that mussels of the subfamily Bathymodiolinae from vents and seeps were divided into four groups, and that mussels of the subfamily Modiolinae from sunken wood and whale carcasses assumed the outgroup position and shallow-water modioline mussels were positioned more distantly to the bathymodioline mussels. We provisionally hypothesized the evolutionary history of Bathymodilolus mussels by estimating evolutionary time under a relaxed molecular clock model. Diversification of bathymodioline mussels was initiated in the early Miocene, and subsequently diversification of the groups occurred in the early to middle Miocene. CONCLUSIONS/SIGNIFICANCE: The phylogenetic relationships support the "Evolutionary stepping stone hypothesis," in which mytilid ancestors exploited sunken wood and whale carcasses in their progressive adaptation to deep-sea environments. This hypothesis is also supported by the evolutionary transition of

  13. The uncertain foundation of neo-Darwinism: metaphysical and epistemological pluralism in the evolutionary synthesis.

    Science.gov (United States)

    Delisle, Richard G

    2009-06-01

    The Evolutionary Synthesis is often seen as a unification process in evolutionary biology, one which provided this research area with a solid common theoretical foundation. As such, neo-Darwinism is believed to constitute from this time onward a single, coherent, and unified movement offering research guidelines for investigations. While this may be true if evolutionary biology is solely understood as centred around evolutionary mechanisms, an entirely different picture emerges once other aspects of the founding neo-Darwinists' views are taken into consideration, aspects potentially relevant to the elaboration of an evolutionary worldview: the tree of life, the ontological distinctions of the main cosmic entities (inert matter, biological organisms, mind), the inherent properties of self-organizing matter, evolutionary ethics, and so on. Profound tensions and inconsistencies are immediately revealed in the neo-Darwinian movement once this broader perspective is adopted. This pluralism is such that it is possible to identify at least three distinct and quasi-incommensurable epistemological/metaphysical frameworks as providing a proper foundation for neo-Darwinism. The analysis of the views of Theodosius Dobzhansky, Bernhard Rensch, and Ernst Mayr will illustrate this untenable pluralism, one which requires us to conceive of the neo-Darwinian research agenda as being conducted in more than one research programme or research tradition at the same time.

  14. Morphometric alterations, steatosis, fibrosis and active caspase-3 detection in carbamate bendiocarb treated rabbit liver

    Czech Academy of Sciences Publication Activity Database

    Petrovová, E.; Purzyc, H.; Mazenský, D.; Luptáková, L.; Torma, N.; Sopoliga, I.; Sedmera, David

    2015-01-01

    Roč. 30, č. 2 (2015), s. 212-222 ISSN 1520-4081 Institutional research plan: CEZ:AV0Z50110509 Institutional support: RVO:67985823 Keywords : bendiocarb * caspase-3 activity * fibrosis * toxicity * rabbit * liver Subject RIV: EA - Cell Biology Impact factor: 2.868, year: 2015

  15. Caspase-3 cleavage of GGA3 stabilizes BACE: implications for Alzheimer's disease.

    Science.gov (United States)

    Vassar, Robert

    2007-06-07

    BACE initiates the production of beta-amyloid (Abeta), the likely cause of Alzheimer's disease (AD). In this issue of Neuron, Tesco et al. show that during apoptosis caspase-3 cleaves the adaptor protein GGA3, which is required for BACE lysosomal degradation, consequently stabilizing BACE and elevating Abeta generation.

  16. TNFα inhibits skeletal myogenesis through a PW1-dependent pathway by recruitment of caspase pathways

    Science.gov (United States)

    Coletti, Dario; Yang, Ellen; Marazzi, Giovanna; Sassoon, David

    2002-01-01

    Cachexia is associated with poor prognosis in patients with chronic disease. Tumor necrosis factor-alpha (TNFα) plays a pivotal role in mediating cachexia and has been demonstrated to inhibit skeletal muscle differentiation in vitro. It has been proposed that TNFα-mediated activation of NFκB leads to down regulation of MyoD, however the mechanisms underlying TNFα effects on skeletal muscle remain poorly understood. We report here a novel pathway by which TNFα inhibits muscle differentiation through activation of caspases in the absence of apoptosis. TNFα-mediated caspase activation and block of differentiation are dependent upon the expression of PW1, but occur independently of NFκB activation. PW1 has been implicated previously in p53-mediated cell death and can induce bax translocation to the mitochondria. We show that bax-deficient myoblasts do not activate caspases and differentiate in the presence of TNFα, highlighting a role for bax-dependent caspase activation in mediating TNFα effects. Taken together, our data reveal that TNFα inhibits myogenesis by recruiting components of apoptotic pathways through PW1. PMID:11847111

  17. Mitochondrial permeabilisation engages NF-κB dependent anti-tumour activity under caspase deficiency

    Science.gov (United States)

    Giampazolias, Evangelos; Bock, Florian; Cloix, Catherine; Cao, Kai; Roca, Alba; Lopez, Jonathan; Ichim, Gabriel; Proïcs, Emma; Rubio-Patiño, Camila; Fort, Loic; Yatim, Nader; Woodham, Emma; Orozco, Susana; Taraborrelli, Lucia; Peltzer, Nieves; Lecis, Daniele; Machesky, Laura; Walczak, Henning; Albert, Matthew L.; Milling, Simon; Oberst, Andrew; Ricci, Jean-Ehrland; Ryan, Kevin M.; Blyth, Karen; Tait, Stephen W.G.

    2017-01-01

    Apoptosis represents a key anti-cancer therapeutic effector mechanism. During apoptosis, mitochondrial outer membrane permeabilisation (MOMP) typically kills cells even in the absence of caspase activity. Caspase activity can also have a variety of unwanted consequences that include DNA-damage. We therefore investigated whether MOMP-induced caspase-independent cell death (CICD) might be a better way to kill cancer cells. We find that cells undergoing CICD display potent pro-inflammatory effects relative to apoptosis. Underlying this, MOMP was found to stimulate NF-κB activity through the down-regulation of inhibitor of apoptosis (IAP) proteins. Strikingly, engagement of CICD displays potent anti-tumorigenic effects, often promoting complete tumour regression in a manner dependent on intact immunity. Our data demonstrate that by activating NF-κB, MOMP can exert additional signalling functions besides triggering cell death. Moreover, they support a rationale for engaging caspase-independent cell death in cell-killing anti-cancer therapies. PMID:28846096

  18. Involvement of JNK and Caspase Activation in Hoiamide A-Induced Neurotoxicity in Neocortical Neurons

    Directory of Open Access Journals (Sweden)

    Zhengyu Cao

    2015-02-01

    Full Text Available The frequent occurrence of Moorea producens (formerly Lyngbya majuscula blooms has been associated with adverse effects on human health. Hoiamide A is a structurally unique cyclic depsipeptide isolated from an assemblage of the marine cyanobacteria M. producens and Phormidium gracile. We examined the influence of hoiamide A on neurite outgrowth in neocortical neurons and found that it suppressed neurite outgrowth with an IC50 value of 4.89 nM. Further study demonstrated that hoiamide A stimulated lactic acid dehydrogenase (LDH efflux, nuclear condensation and caspase-3 activity with EC50 values of 3.66, 2.55 and 4.33 nM, respectively. These data indicated that hoiamide A triggered a unique neuronal death profile that involves both necrotic and apoptotic mechanisms. The similar potencies and similar time-response relationships between LDH efflux and caspase-3 activation/nuclear condensation suggested that both necrosis and apoptosis may derive from interaction with a common molecular target. The broad-spectrum caspase inhibitor, Z-VAD-FMK completely inhibited hoiamide A-induced neurotoxicity. Additionally, hoiamide A stimulated JNK phosphorylation, and a JNK inhibitor attenuated hoiamide A-induced neurotoxicity. Collectively, these data demonstrate that hoiamide A-induced neuronal death requires both JNK and caspase signaling pathways. The potent neurotoxicity and unique neuronal cell death profile of hoiamide A represents a novel neurotoxic chemotype from marine cyanobacteria.

  19. Chalcone-Induced Apoptosis through Caspase-Dependent Intrinsic Pathways in Human Hepatocellular Carcinoma Cells

    Science.gov (United States)

    Ramirez-Tagle, Rodrigo; Escobar, Carlos A.; Romero, Valentina; Montorfano, Ignacio; Armisén, Ricardo; Borgna, Vincenzo; Jeldes, Emanuel; Pizarro, Luis; Simon, Felipe; Echeverria, Cesar

    2016-01-01

    Hepatocellular carcinoma (HCC) is one of the most commonly diagnosed cancers worldwide. Chemoprevention of HCC can be achieved through the use of natural or synthetic compounds that reverse, suppress or prevent the development of cancer progression. In this study, we investigated the antiproliferative effects and the mechanism of action of two compounds, 2,3,4′-trimethoxy-2′-hydroxy-chalcone (CH1) and 3′-bromo-3,4-dimethoxy-chalcone (CH2), over human hepatoma cells (HepG2 and Huh-7) and cultured mouse hepatocytes (HepM). Cytotoxic effects were observed over the HepG2 and Huh-7, and no effects were observed over the HepM. For HepG2 cells, treated separately with each chalcone, typical apoptotic laddering and nuclear condensation were observed. Additionally, the caspases and Bcl-2 family proteins activation by using Western blotting and immunocytochemistry were studied. Caspase-8 was not activated, but caspase-3 and -9 were both activated by chalcones in HepG2 cells. Chalcones also induced reactive oxygen species (ROS) accumulation after 4, 8 and 24 h of treatment in HepG2 cells. These results suggest that apoptosis in HepG2 was induced through: (i) a caspase-dependent intrinsic pathway; and (ii) by alterations in the cellular levels of Bcl-2 family proteins, and also, that the chalcone moiety could be a potent candidate as novel anticancer agents acting on human hepatomas. PMID:26907262

  20. Chalcone-Induced Apoptosis through Caspase-Dependent Intrinsic Pathways in Human Hepatocellular Carcinoma Cells

    Directory of Open Access Journals (Sweden)

    Rodrigo Ramirez-Tagle

    2016-02-01

    Full Text Available Hepatocellular carcinoma (HCC is one of the most commonly diagnosed cancers worldwide. Chemoprevention of HCC can be achieved through the use of natural or synthetic compounds that reverse, suppress or prevent the development of cancer progression. In this study, we investigated the antiproliferative effects and the mechanism of action of two compounds, 2,3,4′-trimethoxy-2′-hydroxy-chalcone (CH1 and 3′-bromo-3,4-dimethoxy-chalcone (CH2, over human hepatoma cells (HepG2 and Huh-7 and cultured mouse hepatocytes (HepM. Cytotoxic effects were observed over the HepG2 and Huh-7, and no effects were observed over the HepM. For HepG2 cells, treated separately with each chalcone, typical apoptotic laddering and nuclear condensation were observed. Additionally, the caspases and Bcl-2 family proteins activation by using Western blotting and immunocytochemistry were studied. Caspase-8 was not activated, but caspase-3 and -9 were both activated by chalcones in HepG2 cells. Chalcones also induced reactive oxygen species (ROS accumulation after 4, 8 and 24 h of treatment in HepG2 cells. These results suggest that apoptosis in HepG2 was induced through: (i a caspase-dependent intrinsic pathway; and (ii by alterations in the cellular levels of Bcl-2 family proteins, and also, that the chalcone moiety could be a potent candidate as novel anticancer agents acting on human hepatomas.

  1. Non-apoptotic role for caspase-7 in hair follicles and the surrounding tissue

    Czech Academy of Sciences Publication Activity Database

    Veselá, Barbora; Švandová, Eva; Vanden Berghe, T.; Tucker, A. S.; Vandenabeele, P.; Matalová, Eva

    2015-01-01

    Roč. 46, 4-5 (2015), s. 443-455 ISSN 1567-2379 R&D Projects: GA ČR GB14-37368G Institutional support: RVO:67985904 Keywords : caspase-7 * development * hair follicles Subject RIV: EA - Cell Biology Impact factor: 2.221, year: 2015

  2. Neural Cell Apoptosis Induced by Microwave Exposure Through Mitochondria-dependent Caspase-3 Pathway

    Science.gov (United States)

    Zuo, Hongyan; Lin, Tao; Wang, Dewen; Peng, Ruiyun; Wang, Shuiming; Gao, Yabing; Xu, Xinping; Li, Yang; Wang, Shaoxia; Zhao, Li; Wang, Lifeng; Zhou, Hongmei

    2014-01-01

    To determine whether microwave (MW) radiation induces neural cell apoptosis, differentiated PC12 cells and Wistar rats were exposed to 2.856GHz for 5min and 15min, respectively, at an average power density of 30 mW/cm2. JC-1 and TUNEL staining detected significant apoptotic events, such as the loss of mitochondria membrane potential and DNA fragmentation, respectively. Transmission electron microscopy and Hoechst staining were used to observe chromatin ultrastructure and apoptotic body formation. Annexin V-FITC/PI double staining was used to quantify the level of apoptosis. The expressions of Bax, Bcl-2, cytochrome c, cleaved caspase-3 and PARP were examined by immunoblotting or immunocytochemistry. Caspase-3 activity was measured using an enzyme-linked immunosorbent assay. The results showed chromatin condensation and apoptotic body formation in neural cells 6h after microwave exposure. Moreover, the mitochondria membrane potential decreased, DNA fragmentation increased, leading to an increase in the apoptotic cell percentage. Furthermore, the ratio of Bax/Bcl-2, expression of cytochrome c, cleaved caspase-3 and PARP all increased. In conclusion, microwave radiation induced neural cell apoptosis via the classical mitochondria-dependent caspase-3 pathway. This study may provide the experimental basis for further investigation of the mechanism of the neurological effects induced by microwave radiation. PMID:24688304

  3. Multiple Pseudomonas species secrete exolysin-like toxins and provoke Caspase-1-dependent macrophage death.

    Science.gov (United States)

    Basso, Pauline; Wallet, Pierre; Elsen, Sylvie; Soleilhac, Emmanuelle; Henry, Thomas; Faudry, Eric; Attrée, Ina

    2017-10-01

    Pathogenic bacteria secrete protein toxins that provoke apoptosis or necrosis of eukaryotic cells. Here, we developed a live-imaging method, based on incorporation of a DNA-intercalating dye into membrane-damaged host cells, to study the kinetics of primary bone marrow-derived macrophages (BMDMs) mortality induced by opportunistic pathogen Pseudomonas aeruginosa expressing either Type III Secretion System (T3SS) toxins or the pore-forming toxin, Exolysin (ExlA). We found that ExlA promotes the activation of Caspase-1 and maturation of interleukin-1β. BMDMs deficient for Caspase-1 and Caspase-11 were resistant to ExlA-induced death. Furthermore, by using KO BMDMs, we determined that the upstream NLRP3/ASC complex leads to the Caspase-1 activation. We also demonstrated that Pseudomonas putida and Pseudomonas protegens and the Drosophila pathogen Pseudomonas entomophila, which naturally express ExlA-like toxins, are cytotoxic toward macrophages and provoke the same type of pro-inflammatory death as does ExlA + P. aeruginosa. These results demonstrate that ExlA-like toxins of two-partner secretion systems from diverse Pseudomonas species activate the NLRP3 inflammasome and provoke inflammatory pyroptotic death of macrophages. © 2017 Society for Applied Microbiology and John Wiley & Sons Ltd.

  4. IAPs: from caspase inhibitors to modulators of NF-kappaB, inflammation and cancer

    DEFF Research Database (Denmark)

    Gyrd-Hansen, Mads; Meier, Pascal

    2010-01-01

    . The development of such inhibitors has radically changed our knowledge of the signalling processes that are regulated by IAPs. Recent studies indicate that IAPs not only regulate caspases and apoptosis, but also modulate inflammatory signalling and immunity, mitogenic kinase signalling, proliferation and mitosis...

  5. Hepatocyte caspase-8 is an essential modulator of steatohepatitis in rodents

    NARCIS (Netherlands)

    Hatting, M.; Zhao, G.; Schumacher, F.; Sellge, G.; Masaoudi, Al M.; Gaßler, N.; Boekschoten, M.V.; Müller, M.R.; Liedtke, C.; Cubero, F.J.; Trautwein, C.

    2013-01-01

    In human and murine models of nonalcoholic steatohepatitis (NASH), increased hepatocyte apoptosis is a critical mechanism contributing to inflammation and fibrogenesis. Caspase 8 (Casp8) is essential for death-receptor-mediated apoptosis activity and therefore its modulation might be critical for

  6. Simvastatin induces caspase-independent apoptosis in LPS-activated RAW264.7 macrophage cells

    International Nuclear Information System (INIS)

    Kim, Yong Chan; Song, Seok Bean; Lee, Mi Hee; Kang, Kwang Il; Lee, Hayyoung; Paik, Sang-Gi; Kim, Kyoon Eon; Kim, Young Sang

    2006-01-01

    Macrophages participate in several inflammatory pathologies such as sepsis and arthritis. We examined the effect of simvastatin on the LPS-induced proinflammatory macrophage RAW264.7 cells. Co-treatment of LPS and a non-toxic dose of simvastatin induced cell death in RAW264.7 cells. The cell death was accompanied by disruption of mitochondrial membrane potential (MMP), genomic DNA fragmentation, and caspase-3 activation. Surprisingly, despite caspase-dependent apoptotic cascade being completely blocked by Z-VAD-fmk, a pan-caspase inhibitor, the cell death was only partially repressed. In the presence of Z-VAD-fmk, DNA fragmentation was blocked, but DNA condensation, disruption of MMP, and nuclear translocation of apoptosis inducing factor were obvious. The cell death by simvastatin and LPS was effectively decreased by both the FPP and GGPP treatments as well as mevalonate. Our findings indicate that simvastatin triggers the cell death of LPS-treated RAW264.7 cells through both caspase-dependent and -independent apoptotic pathways, suggesting a novel mechanism of statins for the severe inflammatory disease therapy

  7. Chalcone-Induced Apoptosis through Caspase-Dependent Intrinsic Pathways in Human Hepatocellular Carcinoma Cells.

    Science.gov (United States)

    Ramirez-Tagle, Rodrigo; Escobar, Carlos A; Romero, Valentina; Montorfano, Ignacio; Armisén, Ricardo; Borgna, Vincenzo; Jeldes, Emanuel; Pizarro, Luis; Simon, Felipe; Echeverria, Cesar

    2016-02-22

    Hepatocellular carcinoma (HCC) is one of the most commonly diagnosed cancers worldwide. Chemoprevention of HCC can be achieved through the use of natural or synthetic compounds that reverse, suppress or prevent the development of cancer progression. In this study, we investigated the antiproliferative effects and the mechanism of action of two compounds, 2,3,4'-trimethoxy-2'-hydroxy-chalcone (CH1) and 3'-bromo-3,4-dimethoxy-chalcone (CH2), over human hepatoma cells (HepG2 and Huh-7) and cultured mouse hepatocytes (HepM). Cytotoxic effects were observed over the HepG2 and Huh-7, and no effects were observed over the HepM. For HepG2 cells, treated separately with each chalcone, typical apoptotic laddering and nuclear condensation were observed. Additionally, the caspases and Bcl-2 family proteins activation by using Western blotting and immunocytochemistry were studied. Caspase-8 was not activated, but caspase-3 and -9 were both activated by chalcones in HepG2 cells. Chalcones also induced reactive oxygen species (ROS) accumulation after 4, 8 and 24 h of treatment in HepG2 cells. These results suggest that apoptosis in HepG2 was induced through: (i) a caspase-dependent intrinsic pathway; and (ii) by alterations in the cellular levels of Bcl-2 family proteins, and also, that the chalcone moiety could be a potent candidate as novel anticancer agents acting on human hepatomas.

  8. Effect of Turkish pollen and propolis extracts on caspase-3 activity in ...

    African Journals Online (AJOL)

    Management, High School of Health, University of Gumushane, Gumushane, 4Karadeniz Advanced Technology Research and. Application Centre ... Conclusion: Turkish pollen and propolis individually increase apoptosis and the activity of caspase-3 in. HL-60 cells. ... essential and aromatic oils, 5 % pollen and 5 %.

  9. Cordycepin, a Natural Antineoplastic Agent, Induces Apoptosis of Breast Cancer Cells via Caspase-dependent Pathways.

    Science.gov (United States)

    Wang, Di; Zhang, Yongfeng; Lu, Jiahui; Wang, Yang; Wang, Junyue; Meng, Qingfan; Lee, Robert J; Wang, Di; Teng, Lesheng

    2016-01-01

    Cordycepin, a major compound separated from Cordyceps sinensis, is known as a potential novel candidate for cancer therapy. Breast cancer, the most typical cancer diagnosed among women, remains a global health problem. In this study, the anti-breast cancer property of cordycepin and its underlying mechanisms was investigated. The direct effects of cordycepin on breast cancer cells both in in vitro and in vivo experiments were evaluated. Cordycepin exerted cytotoxicity in MCF-7 and MDA-MB-231 cells confirmed by reduced cell viability, inhibition of cell proliferation, enhanced lactate dehydrogenase release and reactive oxygen species accumulation, induced mitochondrial dysfunction and nuclear apoptosis in human breast cancer cells. Cordycepin increased the activation of pro-apoptotic proteins, including caspase-8, caspase-9, caspase-3 and Bax, and suppressed the expression of the anti-apoptotic protein, B-cell lymphoma 2 (Bcl-2). The inhibition on MCF-7-xenografted tumor growth in nude mice further confirmed cordycepin's anti-breast cancer effect. These aforementioned results reveal that cordycepin induces apoptosis in human breast cancer cells via caspase-dependent pathways. The data shed light on the possibility of cordycepin being a safe agent for breast cancer treatment.

  10. Real-time monitoring of caspase cascade activation in living cells.

    Science.gov (United States)

    Zhu, Lei; Huang, Xinglu; Choi, Ki Young; Ma, Ying; Zhang, Fan; Liu, Gang; Lee, Seulki; Chen, Xiaoyuan

    2012-10-10

    We introduce a simple, versatile and robust one-step technique that enables real-time imaging of multiple intracellular caspase activities in living cells without the need for complicated synthetic protocols. Conventional fluorogenic probes or recently reported activatable probes have been designed to target various proteases but are limited to extracellular molecules. Only a few have been applied to image intracellular proteases in living cells because most of these probes have limited cell-permeability. Our platform does not need complicated synthetic processes; instead it involves a straightforward peptide synthesis and a simple mixing step with a commercial transfection agent. The transfection agent efficiently delivered the highly quenched fluorogenic probes, comprised of distinctive pairs of dyes and quenchers, to the initiator caspase-8 and the effector caspase-3 in MDA-MB-435 cells, allowing dual-imaging of the activities of both caspases during the apoptotic process induced by TNF-related apoptosis induced ligand (TRAIL). With the combination of multiple fluorogenic probes, this simple platform can be applied to multiplexed imaging of selected intracellular proteases to study apoptotic processes in pathologies or for cell-based high throughput screening systems for drug discovery. Published by Elsevier B.V.

  11. Association of caspase-1 polymorphisms with Chagas cardiomyopathy among individuals in Santa Cruz, Bolivia.

    Science.gov (United States)

    Fu, Katherine Yih-Jia; Zamudio, Roxana; Henderson-Frost, Jo; Almuedo, Alex; Steinberg, Hannah; Clipman, Steven Joseph; Duran, Gustavo; Marcus, Rachel; Crawford, Thomas; Alyesh, Daniel; Colanzi, Rony; Flores, Jorge; Gilman, Robert Hugh; Bern, Caryn

    2017-01-01

    Trypanosoma cruzi (Tc) infection is usually acquired in childhood in endemic areas, leading to Chagas disease, which progresses to Chagas cardiomyopathy in 20-30% of infected individuals over decades. The pathogenesis of Chagas cardiomyopathy involves the host inflammatory response to T. cruzi, in which upstream caspase-1 activation prompts the cascade of inflammatory chemokines/cytokines, cardiac remodeling, and myocardial dysfunction. The aim of the present study was to examine the association of two caspase-1 single nucleotide polymorphisms (SNPs) with cardiomyopathy. We recruited infected (Tc+, n = 149) and uninfected (Tc-, n = 87) participants in a hospital in Santa Cruz, Bolivia. Cardiac status was classified (I, II, III, IV) based on Chagas cardiomyopathy-associated electrocardiogram findings and ejection fractions on echocardiogram. Genotypes were determined using Taqman probes via reverse transcription-polymerase chain reaction of peripheral blood DNA. Genotype frequencies were analyzed according to three inheritance patterns (dominant, recessive, additive) using logistic regression adjusted for age and sex. The AA allele for the caspase-1 SNP rs501192 was more frequent in Tc+ cardiomyopathy (classes II, III, IV) patients compared to those with a normal cardiac status (class I) [odds ratio (OR) = -2.18, p = 0.117]. This trend approached statistical significant considering only Tc+ patients in class I and II (OR = -2.64, p = 0.064). Caspase-1 polymorphisms may play a role in Chagas cardiomyopathy development and could serve as markers to identify individuals at higher risk for priority treatment.

  12. Caspase-6 Induces 7A6 Antigen Localization to Mitochondria During FAS-induced Apoptosis of Jurkat Cells.

    Science.gov (United States)

    Suita, Hiroaki; Shinomiya, Takahisa; Nagahara, Yukitoshi

    2017-04-01

    Mitochondria are central to apoptosis. However, apoptosis progression involving mitochondria is not fully understood. A factor involved in mitochondria-mediated apoptosis is 7A6 antigen. 7A6 localizes to mitochondria from the cytosol during apoptosis, which seems to involve 'effector' caspases. In this study, we investigated the precise role of effector caspases in 7A6 localization to mitochondria during apoptosis. Human T-cell lymphoma Jurkat cells were treated with an antibody against FAS. 7A6 localization was analyzed by confocal laser scanning microscopy and flow cytometry. Caspases activation was determined by western blot analysis. 7A6 localization to mitochondria during anti-FAS-induced apoptosis was significantly reduced by the caspase-6 inhibitor, N-acetyl-Val-Glu-Ile-Asp-aldehyde, but not by the caspase-3 inhibitor, N-acetyl-Asp-Asn-Leu-Asp-aldehyde, nor caspase-7/3 inhibitor, N-acetyl-Asp-Gln-Thr-Asp-aldehyde. Moreover, caspase-6 down-regulation suppressed 7A6 localization to mitochondria. Caspase-6 regulates 7A6 localization to mitochondria during anti-FAS-induced apoptosis of Jurkat cells. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  13. Independent Induction of Caspase-8 and cFLIP Expression during Colorectal Carcinogenesis in Sporadic and HNPCC Adenomas and Carcinomas

    Directory of Open Access Journals (Sweden)

    D. M. Heijink

    2007-01-01

    Full Text Available Background: TNF-Related Apoptosis Inducing Ligand (TRAIL is a promising agent for the induction of apoptosis in neoplastic tissues. Important determinants of TRAIL sensitivity are two intracellular proteins of the TRAIL pathway, caspase-8 and its anti-apoptotic competitor cellular Flice-Like Inhibitory Protein (cFLIP. Methods: The aim of this study was to investigate basic expression of caspase-8 and cFLIP in normal colorectal epithelium (n = 20, colorectal adenomas (n = 66 and colorectal carcinomas (n = 44 using immunohistochemistry performed on both sporadic and Hereditary Non-Polyposis Colorectal Cancer (HNPCC or Lynch syndrome-associated adenomas and carcinomas. Results: Expression of both caspase-8 and cFLIP was similar in cases with sporadic and hereditary origin. Expression of caspase-8 in colorectal adenomas and carcinomas was increased when compared to normal colon tissue (P = 0.02. Nuclear, paranuclear as well as cytoplasmic localizations of caspase-8 were detected. Immunohistochemistry revealed an upregulation of cFLIP in colorectal carcinomas in comparison to normal epithelium and colorectal adenomas (P < 0.001. A large variation in the caspase-8/cFLIP ratio was observed between the individual adenomas and carcinomas. Conclusion: Caspase-8 and cFLIP are upregulated during colorectal carcinogenesis. Upregulation of caspase-8 and/or downregulation of cFLIP may be interesting approaches to maximize TRAIL sensitivity in colorectal neoplasms.

  14. Toxoplasma gondii inhibits cytochrome c-induced caspase activation in its host cell by interference with holo-apoptosome assembly

    Directory of Open Access Journals (Sweden)

    Kristin Graumann

    2015-05-01

    Full Text Available Inhibition of programmed cell death pathways of mammalian cells often facilitates the sustained survival of intracellular microorganisms. The apicomplexan parasite Toxoplasma gondii is a master regulator of host cell apoptotic pathways. Here, we have characterized a novel anti-apoptotic activity of T. gondii. Using a cell-free cytosolic extract model, we show that T. gondii interferes with the activities of caspase 9 and caspase 3/7 which have been induced by exogenous cytochrome c and dATP. Proteolytic cleavage of caspases 9 and 3 is also diminished suggesting inhibition of holo-apoptosome function. Parasite infection of Jurkat T cells and subsequent triggering of apoptosome formation by exogenous cytochrome c in vitro and in vivo indicated that T. gondii also interferes with caspase activation in infected cells. Importantly, parasite inhibition of cytochrome c-induced caspase activation considerably contributes to the overall anti-apoptotic activity of T. gondii as observed in staurosporine-treated cells. Co-immunoprecipitation showed that T. gondii abolishes binding of caspase 9 to Apaf-1 whereas the interaction of cytochrome c with Apaf-1 remains unchanged. Finally, T. gondii lysate mimics the effect of viable parasites and prevents holo-apoptosome functionality in a reconstituted in vitro system comprising recombinant Apaf-1 and caspase 9. Beside inhibition of cytochrome c release from host cell mitochondria, T. gondii thus also targets the holo-apoptosome assembly as a second mean to efficiently inhibit the caspase-dependent intrinsic cell death pathway.

  15. The broad-spectrum caspase inhibitor Boc-Asp-CMK induces cell death in human leukaemia cells.

    Science.gov (United States)

    Frydrych, Ivo; Mlejnek, Petr; Dolezel, Petr; Zoumpourlis, Vassilis; Krumpochova, Petra

    2008-08-01

    Synthetic caspase inhibitors and particularly broad-spectrum caspase inhibitors can prevent cells from death or at least slow down cell death process and abrogate some apoptotic hallmarks [Kitanaka, C., Kuchino, Y., 1999. Caspase-independent programmed cell death with necrotic morphology. Cell Death and Differentiation 6, 508-515]. However, not all synthetic caspase inhibitors diminish cell death. We have found that the broad-spectrum caspase inhibitor Boc-Asp-CMK induced cell death at micromolar concentrations in human leukaemia cells. Interestingly, low concentrations of Boc-Asp-CMK induced cell death with apoptotic hallmarks. Increasing concentrations of Boc-Asp-CMK led to necrotic cell death. The switch between apoptosis and necrosis seemed to depend upon the degree of inhibition of executioner caspases, including caspase-3/7 with Boc-Asp-CMK. Interestingly, caspase-3 processing was not inhibited even for the highest concentration of Boc-Asp-CMK used. We assume, that toxic properties of Boc-Asp-CMK can be attributed to the chloromethylketone residuum in its molecule, as its analogue Boc-Asp-FMK with fluoromethylketone residuum was more than 13 times less toxic. Our results further indicated that toxicity of Boc-Asp-CMK might arise from its interference with mitochondrial metabolism.

  16. Practical aspects of protein co-evolution.

    Science.gov (United States)

    Ochoa, David; Pazos, Florencio

    2014-01-01

    Co-evolution is a fundamental aspect of Evolutionary Theory. At the molecular level, co-evolutionary linkages between protein families have been used as indicators of protein interactions and functional relationships from long ago. Due to the complexity of the problem and the amount of genomic data required for these approaches to achieve good performances, it took a relatively long time from the appearance of the first ideas and concepts to the quotidian application of these approaches and their incorporation to the standard toolboxes of bioinformaticians and molecular biologists. Today, these methodologies are mature (both in terms of performance and usability/implementation), and the genomic information that feeds them large enough to allow their general application. This review tries to summarize the current landscape of co-evolution-based methodologies, with a strong emphasis on describing interesting cases where their application to important biological systems, alone or in combination with other computational and experimental approaches, allowed getting new insight into these.

  17. Aspects and Polymorphism in AspectJ

    DEFF Research Database (Denmark)

    Lorenz, David Harel; Ernst, Erik

    2003-01-01

    There are two important points of view on inclusion or subtype polymorphism in object-oriented programs, namely polymorphic access and dynamic dispatch. These features are essential for object-oriented programming, and it is worthwhile to consider whether they are supported in aspect......-oriented programming (AOP). In AOP, pieces of crosscutting behavior are extracted from the base code and localized in aspects, losing as a result their polymorphic capabilities while introducing new and unexplored issues. In this paper, we explore what kinds of polymorphism AOP languages should support, using Aspect......J as the basis for the presentation. The results are not exclusive to AspectJ---aspectual polymorphism may make aspects in any comparable AOSD language more expressive and reusable across programs, while preserving safety....

  18. Natural activation of caspase-3 is required for the development of operant behavior in postnatal ontogenesis.

    Science.gov (United States)

    Kudryashova, I V; Stepanichev, M Yu; Gulyaeva, N V

    2009-01-01

    We have previously demonstrated transient increases in caspase-3 activity in the hippocampus of rat pups from age 17 days. We report here our studies on the effects of inhibition of caspase-3 during this period on the acquisition of a two-way avoidance reaction. Rat pups received intracerebroventricular doses of the caspase-3 inhibitor Z-DEVD-FMK On postnatal day 18. Control animals of the same age received the inactive peptide Z-FA-FMK or isotonic saline solution. Inhibition of caspase-3 during the period of its natural activation in the hippocampus during early ontogenesis was found to impair the development of operant behavior in rats. This was apparent as a reduction in the efficiency of learning during acquisition of active avoidance reactions and decreases in the numbers of intersignal reactions. Administration of the inhibitor had no specific action on the types of conditioned reflex activity less associated with operant learning. Thus, there were no differences between the experimental and control groups in the numbers of emotional reactions to the conditioned stimulus. The number of orientational-investigative conditioned reactions also showed no change after administration of Z-DEVD-FMK. On the background of the reduction in the efficiency of the acquisition of the conditioned active avoidance reflex, the number of incomplete acts, in contrast to other types of conditioned reactions, increased significantly after administration of Z-DEVD-FMK, which is evidence for the persistence of the ability to form associative connections between activation of the conditioned signal and the need to move to the other sector. The difficulty in these animals arose at the decision-taking stage on choosing the appropriate form of behavior. Changes in orientational-investigative behavior were not associated with inhibition of caspase-3 during the critical period of development, as the effects of Z-DEVD-FMK and Z-FA-FMK were similar.

  19. Hypoxia/reoxygenation impairs memory formation via adenosine-dependent activation of caspase 1.

    Science.gov (United States)

    Chiu, Gabriel S; Chatterjee, Diptaman; Darmody, Patrick T; Walsh, John P; Meling, Daryl D; Johnson, Rodney W; Freund, Gregory G

    2012-10-03

    After hypoxia, a critical adverse outcome is the inability to create new memories. How anterograde amnesia develops or resolves remains elusive, but a link to brain-based IL-1 is suggested due to the vital role of IL-1 in both learning and brain injury. We examined memory formation in mice exposed to acute hypoxia. After reoxygenation, memory recall recovered faster than memory formation, impacting novel object recognition and cued fear conditioning but not spatially cued Y-maze performance. The ability of mice to form new memories after hypoxia/reoxygenation was accelerated in IL-1 receptor 1 knockout (IL-1R1 KO) mice, in mice receiving IL-1 receptor antagonist (IL-1RA), and in mice given the caspase 1 inhibitor Ac-YVAD-CMK. Mechanistically, hypoxia/reoxygenation more than doubled caspase 1 activity in the brain, which was localized to the amygdala compared to the hippocampus. This reoxygenation-dependent activation of caspase 1 was prevented by broad-spectrum adenosine receptor (AR) antagonism with caffeine and by targeted A1/A2A AR antagonism with 8-cyclopentyl-1,3-dipropylxanthine plus 3,7-dimethyl-1-propargylxanthine. Additionally, perfusion of adenosine activated caspase 1 in the brain, while caffeine blocked this action by adenosine. Finally, resolution of anterograde amnesia was improved by both caffeine and by targeted A1/A2A AR antagonism. These findings indicate that amygdala-based anterograde amnesia after hypoxia/reoxygenation is sustained by IL-1β generated through adenosine-dependent activation of caspase 1 after reoxygenation.

  20. Cordycepin Induced MA-10 Mouse Leydig Tumor Cell Apoptosis through Caspase-9 Pathway

    Directory of Open Access Journals (Sweden)

    Chun-Yi Jen

    2011-01-01

    Full Text Available In the present study, the apoptotic effect of cordycepin on MA-10 cells, a mouse Leydig tumor cell line, was investigated. Results demonstrated that the number of rounding-up cell increased by cordycepin (10 μM to 5 mM for 24 h, and cells with plasma membrane blebbing could be observed by 100 μM cordycepin. In viability test, MA-10 cell surviving rate significantly decreased as the dosage (10 μM to 5 mM and duration (3–24 h of cordycepin treatment increased (P < 0.05. Cordycepin at 100 μM and 1 mM for 24 h treatment induced significant DNA fragmentation (P < 0.05. In addition, the percentage of G1 and G2/M phase cell significantly declined by cordycepin (100 μM and 1 mM for 24 h treatment, while the percentages of subG1 phase cell increased by 100 μM and/or 1 mM cordycepin in 6, 12 and 24 h treatments (P < 0.05, respectively, which highly suggested that cordycepin induced MA-10 cell apoptosis. In mechanism study with the treatments of caspases, c-Jun NH2 terminal kinase (JNK or reactive oxygen species (ROS inhibitors plus cordycepin for 24 h, only caspases inhibitor suppressed subG1 phase in MA-10 cells. Moreover, western blotting results showed that cordycepin induced caspase-9, -3 and -7 protein expressions, but not caspase-8, in time- and dose-dependent manners. In conclusion, cordycepin induced apoptosis in MA-10 mouse Leydig tumor cells through a caspase-9 and -3 and -7 dependent pathway.

  1. Regulation of axon arborization pattern in the developing chick ciliary ganglion: Possible involvement of caspase 3.

    Science.gov (United States)

    Katow, Hidetaka; Kanaya, Teppei; Ogawa, Tomohisa; Egawa, Ryo; Yawo, Hiromu

    2017-04-01

    During a certain critical period in the development of the central and peripheral nervous systems, axonal branches and synapses are massively reorganized to form mature connections. In this process, neurons search their appropriate targets, expanding and/or retracting their axons. Recent work suggested that the caspase superfamily regulates the axon morphology. Here, we tested the hypothesis that caspase 3, which is one of the major executioners in apoptotic cell death, is involved in regulating the axon arborization. The embryonic chicken ciliary ganglion was used as a model system of synapse reorganization. A dominant negative mutant of caspase-3 precursor (C3DN) was made and overexpressed in presynaptic neurons in the midbrain to interfere with the intrinsic caspase-3 activity using an in ovo electroporation method. The axon arborization pattern was 3-dimensionally and quantitatively analyzed in the ciliary ganglion. The overexpression of C3DN significantly reduced the number of branching points, the branch order and the complexity index, whereas it significantly elongated the terminal branches at E6. It also increased the internodal distance significantly at E8. But, these effects were negligible at E10 or later. During E6-8, there appeared to be a dynamic balance in the axon arborization pattern between the "targeting" mode, which is accompanied by elongation of terminal branches and the pruning of collateral branches, and the "pathfinding" mode, which is accompanied by the retraction of terminal branches and the sprouting of new collateral branches. The local and transient activation of caspase 3 could direct the balance towards the pathfinding mode. © 2017 Japanese Society of Developmental Biologists.

  2. Tissue inhibitor of metalloproteinase-3 (TIMP3) promotes endothelial apoptosis via a caspase-independent mechanism.

    Science.gov (United States)

    Qi, Jian Hua; Anand-Apte, Bela

    2015-04-01

    Tissue inhibitor of metalloproteinases-3 (TIMP3) is a tumor suppressor and a potent inhibitor of angiogenesis. TIMP3 exerts its anti-angiogenic effect via a direct interaction with vascular endothelial growth factor (VEGF) receptor-2 (KDR) and inhibition of proliferation, migration and tube formation of endothelial cells (ECs). TIMP3 has also been shown to induce apoptosis in some cancer cells and vascular smooth muscle cells via MMP inhibition and caspase-dependent mechanisms. In this study, we examined the molecular mechanisms of TIMP3-mediated apoptosis in endothelial cells. We have previously demonstrated that mice developed smaller tumors with decreased vascularity when injected with breast carcinoma cells overexpressing TIMP3, than with control breast carcinoma cells. TIMP3 overexpression resulted in increased apoptosis in human breast carcinoma (MDA-MB435) in vivo but not in vitro. However, TIMP3 could induce apoptosis in ECs in vitro. The apoptotic activity of TIMP3 in ECs appears to be independent of MMP inhibitory activity. Furthermore, the equivalent expression of functional TIMP3 promoted apoptosis and caspase activation in ECs expressing KDR (PAE/KDR), but not in ECs expressing PDGF beta-receptor (PAE/β-R). Surprisingly, the apoptotic activity of TIMP3 appears to be independent of caspases. TIMP3 inhibited matrix-induced focal adhesion kinase (FAK) tyrosine phosphorylation and association with paxillin and disrupted the incorporation of β3 integrin, FAK and paxillin into focal adhesion contacts on the matrix, which were not affected by caspase inhibitors. Thus, TIMP3 may induce apoptosis in ECs by triggering a caspase-independent cell death pathway and targeting a FAK-dependent survival pathway.

  3. Paradoxical sleep deprivation changes testicular malondialdehyde and caspase-3 expression in male rats

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    Fitranto Arjadi

    2015-08-01

    Full Text Available BACKGROUND Sleep deprivation is a significant problem among adult men and is considered as a risk factor for several diseases. Paradoxical sleep deprivation (PSD induces Leydig cell apoptosis through elevation of corticosterone, with testicular malondialdehyde (MDA and Leydig cell caspase-3 expression as parameters. The aim of this study was to observe testicular MDA level and caspase-3 expression treated with paradoxical sleep deprivation (PSD, immobilization, and footshock stress and to determine the stress model with a significant effect in white male rats (Rattus norvegicus . METHODS This experimental randomized study of posttest only with control group design was conducted on 24 white male Wistar strain rats, randomly allocated into four treatment groups, i.e. control (K1 without any stress treatment, PSD (KII, immobilization (KIII, and footshock stress (KIV. Treatments were given for 25 days to produce chronic stress. Testicular MDA concentration was examined by the ELISA method while caspase-3 was examined by the TUNEL method. RESULTS Mean testicular MDA concentration with one-way ANOVA test showed differences in means between the groups (p=0.000 and post hoc Tukey-HSD test showed significant results between PSD stress group versus control, immobilization and footshock stress groups. One-way ANOVA test showed a significant difference in caspase-3 expression in at least two treatment groups (p=0.008 and post-hoc Tuckey-LSD test showed significant differences between controls and all stress groups. CONCLUSION Sleep deprivation is a type of stress inducing changes in testicular MDA concentration and caspase-3 expression in male rat testes.

  4. A Crohn's disease variant in Atg16l1 enhances its degradation by caspase 3

    Science.gov (United States)

    Murthy, Aditya; Li, Yun; Peng, Ivan; Reichelt, Mike; Katakam, Anand Kumar; Noubade, Rajkumar; Roose-Girma, Merone; Devoss, Jason; Diehl, Lauri; Graham, Robert R.; van Lookeren Campagne, Menno

    2014-02-01

    Crohn's disease is a debilitating inflammatory bowel disease (IBD) that can involve the entire digestive tract. A single-nucleotide polymorphism (SNP) encoding a missense variant in the autophagy gene ATG16L1 (rs2241880, Thr300Ala) is strongly associated with the incidence of Crohn's disease. Numerous studies have demonstrated the effect of ATG16L1 deletion or deficiency; however, the molecular consequences of the Thr300Ala (T300A) variant remains unknown. Here we show that amino acids 296-299 constitute a caspase cleavage motif in ATG16L1 and that the T300A variant (T316A in mice) significantly increases ATG16L1 sensitization to caspase-3-mediated processing. We observed that death-receptor activation or starvation-induced metabolic stress in human and murine macrophages increased degradation of the T300A or T316A variants of ATG16L1, respectively, resulting in diminished autophagy. Knock-in mice harbouring the T316A variant showed defective clearance of the ileal pathogen Yersinia enterocolitica and an elevated inflammatory cytokine response. In turn, deletion of the caspase-3-encoding gene, Casp3, or elimination of the caspase cleavage site by site-directed mutagenesis rescued starvation-induced autophagy and pathogen clearance, respectively. These findings demonstrate that caspase 3 activation in the presence of a common risk allele leads to accelerated degradation of ATG16L1, placing cellular stress, apoptotic stimuli and impaired autophagy in a unified pathway that predisposes to Crohn's disease.

  5. Plasma concentration of Caspase-8 is associated with short sleep duration and the risk of incident diabetes mellitus.

    Science.gov (United States)

    Svensson, Thomas; Svensson, Akiko Kishi; Kitlinski, Mariusz; Almgren, Peter; Engström, Gunnar; Nilsson, Jan; Orho-Melander, Marju; Nilsson, Peter M; Melander, Olle

    2018-02-01

    The biological mechanism for the association between sleep duration and incident diabetes mellitus (DM) is unclear. Sleep duration and Caspase-8, a marker of apoptotic activity, have both been implicated in beta cell function. To investigate the associations between sleep duration and plasma Caspase-8, and incident DM, respectively. Prospective cohort study. The Malmö Diet and Cancer (MDC) Study is a population-based, prospective study run in the city of Malmö, Sweden. 4023 individuals from the MDC Study aged 45-68 years at baseline without a history of prevalent DM, and with information on habitual sleep duration. Incident DM. Mean follow-up time was 17.8 years. Sleep duration was the only behavioural variable significantly associated with plasma Caspase-8. Plasma Caspase-8 was significantly associated with incident DM per standard deviation of its transformed continuous form (hazard ratio [HR]= 1.24, 95% confidence interval [CI] 1.13-1.36), and when dichotomized into high (quartile 4) (HR=1.44, 95%CI: 1.19-1.74) compared to low (quartiles 1-3) concentrations. Caspase-8 interacted with sleep duration; compared to 7-8 hours of sleep and low plasma Caspase-8, individuals with high plasma Caspase-8 and sleep duration <6 hours (HR=3.54, 95%CI: 2.12-5.90), 6-7 hours (HR=1.81, 95%CI: 1.24-2.65), and 8-9 hours (HR=1.54, 95%CI: 1.09-2.18) were at significantly increased risks of incident DM. Sleep duration is associated with plasma Caspase-8. Caspase-8 independently predicts DM years before disease onset and modifies the effect of sleep duration on incident DM. Future studies should investigate if change of sleep duration modifies plasma concentrations of Caspase-8. Copyright © 2018 Endocrine Society

  6. Macrophage specific caspase-1/11 deficiency protects against cholesterol crystallization and hepatic inflammation in hyperlipidemic mice.

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    Tim Hendrikx

    Full Text Available While non-alcoholic steatohepatitis (NASH is characterized by hepatic steatosis combined with inflammation, the mechanisms triggering hepatic inflammation are unknown. In Ldlr(-/- mice, we have previously shown that lysosomal cholesterol accumulation in Kupffer cells (KCs correlates with hepatic inflammation and cholesterol crystallization. Previously, cholesterol crystals have been shown to induce the activation of inflammasomes. Inflammasomes are protein complexes that induce the processing and release of pro-inflammatory cytokines IL-1b and IL-18 via caspase-1 activation. Whereas caspase-1 activation is independent of caspase-11 in the canonical pathway of inflammasome activation, caspase-11 was found to trigger caspase-1-dependent IL-1b and IL-18 in response to non-canonical inflammasome activators. So far, it has not been investigated whether inflammasome activation stimulates the formation of cholesterol crystals. We hypothesized that inflammasome activation in KCs stimulates cholesterol crystallization, thereby leading to hepatic inflammation.Ldlr (-/- mice were transplanted (tp with wild-type (Wt or caspase-1/11(-/- (dKO bone marrow and fed either regular chow or a high-fat, high-cholesterol (HFC diet for 12 weeks. In vitro, bone marrow derived macrophages (BMDM from wt or caspase-1/11(-/- mice were incubated with oxLDL for 24h and autophagy was assessed.In line with our hypothesis, caspase-1/11(-/--tp mice had less severe hepatic inflammation than Wt-tp animals, as evident from liver histology and gene expression analysis in isolated KCs. Mechanistically, KCs from caspase-1/11(-/--tp mice showed less cholesterol crystals, enhanced cholesterol efflux and increased autophagy. In wt BMDM, oxLDL incubation led to disturbed autophagy activity whereas BMDM from caspase-1/11(-/- mice had normal autophagy activity.Altogether, these data suggest a vicious cycle whereby disturbed autophagy and decreased cholesterol efflux leads to newly formed

  7. Effects of Clonal Reproduction on Evolutionary Lag and Evolutionary Rescue.

    Science.gov (United States)

    Orive, Maria E; Barfield, Michael; Fernandez, Carlos; Holt, Robert D

    2017-10-01

    Evolutionary lag-the difference between mean and optimal phenotype in the current environment-is of keen interest in light of rapid environmental change. Many ecologically important organisms have life histories that include stage structure and both sexual and clonal reproduction, yet how stage structure and clonality interplay to govern a population's rate of evolution and evolutionary lag is unknown. Effects of clonal reproduction on mean phenotype partition into two portions: one that is phenotype dependent, and another that is genotype dependent. This partitioning is governed by the association between the nonadditive genetic plus random environmental component of phenotype of clonal offspring and their parents. While clonality slows phenotypic evolution toward an optimum, it can dramatically increase population survival after a sudden step change in optimal phenotype. Increased adult survival slows phenotypic evolution but facilitates population survival after a step change; this positive effect can, however, be lost given survival-fecundity trade-offs. Simulations indicate that the benefits of increased clonality under environmental change greatly depend on the nature of that change: increasing population persistence under a step change while decreasing population persistence under a continuous linear change requiring de novo variation. The impact of clonality on the probability of persistence for species in a changing world is thus inexorably linked to the temporal texture of the change they experience.

  8. Multiple explanations in Darwinian evolutionary theory.

    Science.gov (United States)

    Bock, Walter J

    2010-03-01

    Variational evolutionary theory as advocated by Darwin is not a single theory, but a bundle of related but independent theories, namely: (a) variational evolution; (b) gradualism rather than large leaps; (c) processes of phyletic evolution and of speciation; (d) causes for the formation of varying individuals in populations and for the action of selective agents; and (e) all organisms evolved from a common ancestor. The first four are nomological-deductive explanations and the fifth is historical-narrative. Therefore evolutionary theory must be divided into nomological and historical theories which are both testable against objective empirical observations. To be scientific, historical evolutionary theories must be based on well corroborated nomological theories, both evolutionary and functional. Nomological and general historical evolutionary theories are well tested and must be considered as strongly corroborated scientific theories. Opponents of evolutionary theory are concerned only with historical evolutionary theories, having little interest in nomological theory. Yet given a well corroborated nomological evolutionary theory, historical evolutionary theories follow automatically. If understood correctly, both forms of evolutionary theories stand on their own as corroborated scientific theories and should not be labeled as facts.

  9. Phytochemical composition, antibacterial and anticancer activities of Trifolium cherleri extract on lung cancer cell line (A549 and analysis of caspase 3 and caspase 9 apoptosis genes expression

    Directory of Open Access Journals (Sweden)

    Amir Mirzaie

    2017-08-01

    Methods: This experimental study was performed in Islamic Azad University, from December 2016 to February 2017. At first, the phytochemical constituents of T. cherleri extract were determined using gas chromatography-mass spectrometry (GC-MS method. Subsequently, the antibacterial activity of the extract was evaluated against some gram positive and negative pathogenic bacteria included Staphylococcus aureus ATCC 25923, Streptococcus pyogenes ATCC 19615, Salmonella enteritidis ATCC 13076 and Listeria monocytogenes ATCC 35152 via minimum inhibitory concentration (MIC method. Moreover, anticancer potential of extract was examined by colorimetric MTT assay toward lung cancer (A549 cell line. Then, the evaluation of caspase 3 and 9 apoptosis gene expression was determined using Real-Time Polymerase Chain Reaction (Real-Time PCR technique. Moreover, the Real-Time PCR was performed using relative quantitative method. Results: The phytochemical analyses of T. cherleri extract showed the 20 major components and the most frequent component was belonged to hexadecanoic acid, ethyl ester (20.7% and 2-Pentadecanone, 6,10,14-trimethyl (19.9%. The extract had maximum antibacterial effects against Staphylococcus aureus and Streptococcus pyogenes. There was a dose dependent increase in the cytotoxicity effect of extract against A549 cancer cell. Moreover, the Real-Time PCR results indicated that the caspase 3 and caspase 9 gene expression was significantly up-regulated 2.57±0.27 (P<0.05, and 3.3±0.46 (P<0.05, respectively. Conclusion: The results of this study showed that the T. cherleri extract had significant anti-bacterial and anti-cancer effects and it appear that the extract has potential uses for pharmaceutical industries. Moreover, it could be considered as a promising source for novel drug compounds, but more studies are needed.

  10. Evolutionary Accessibility of Mutational Pathways

    Science.gov (United States)

    Franke, Jasper; Klözer, Alexander; de Visser, J. Arjan G. M.; Krug, Joachim

    2011-01-01

    Functional effects of different mutations are known to combine to the total effect in highly nontrivial ways. For the trait under evolutionary selection (‘fitness’), measured values over all possible combinations of a set of mutations yield a fitness landscape that determines which mutational states can be reached from a given initial genotype. Understanding the accessibility properties of fitness landscapes is conceptually important in answering questions about the predictability and repeatability of evolutionary adaptation. Here we theoretically investigate accessibility of the globally optimal state on a wide variety of model landscapes, including landscapes with tunable ruggedness as well as neutral ‘holey’ landscapes. We define a mutational pathway to be accessible if it contains the minimal number of mutations required to reach the target genotype, and if fitness increases in each mutational step. Under this definition accessibility is high, in the sense that at least one accessible pathway exists with a substantial probability that approaches unity as the dimensionality of the fitness landscape (set by the number of mutational loci) becomes large. At the same time the number of alternative accessible pathways grows without bounds. We test the model predictions against an empirical 8-locus fitness landscape obtained for the filamentous fungus Aspergillus niger. By analyzing subgraphs of the full landscape containing different subsets of mutations, we are able to probe the mutational distance scale in the empirical data. The predicted effect of high accessibility is supported by the empirical data and is very robust, which we argue reflects the generic topology of sequence spaces. Together with the restrictive assumptions that lie in our definition of accessibility, this implies that the globally optimal configuration should be accessible to genome wide evolution, but the repeatability of evolutionary trajectories is limited owing to the presence of a

  11. Evolutionary Origin of the Proepicardium

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    Elena Cano

    2013-05-01

    Full Text Available The embryonic epicardium and the cardiac mesenchyme derived from it are critical to heart development. The embryonic epicardium arises from an extracardiac progenitor tissue called the proepicardium, a proliferation of coelomic cells located at the limit between the liver and the sinus venosus. A proepicardium has not been described in invertebrates, and the evolutionary origin of this structure in vertebrates is unknown. We herein suggest that the proepicardium might be regarded as an evolutionary derivative from an ancient pronephric external glomerulus that has lost its excretory role. In fact, we previously described that the epicardium arises by cell migration from the primordia of the right pronephric external glomerulus in a representative of the most primitive vertebrate lineage, the lamprey Petromyzon marinus. In this review, we emphasize the striking similarities between the gene expression profiles of the proepicardium and the developing kidneys, as well as the parallelisms in the signaling mechanisms involved in both cases. We show some preliminary evidence about the existence of an inhibitory mechanism blocking glomerular differentiation in the proepicardium. We speculate as to the possibility that this developmental link between heart and kidney can be revealing a phylogenetically deeper association, supported by the existence of a heart-kidney complex in Hemichordates. Finally, we suggest that primitive hematopoiesis could be related with this heart-kidney complex, thus accounting for the current anatomical association of the hematopoietic stem cells with an aorta-gonad-mesonephros area. In summary, we think that our hypothesis can provide new perspectives on the evolutionary origin of the vertebrate heart.

  12. The evolutionary origins of patriarchy.

    Science.gov (United States)

    Smuts, B

    1995-03-01

    This article argues that feminist analyses of patriarchy should be expanded to address the evolutionary basis of male motivation to control female sexuality. Evidence from other primates of male sexual coercion and female resistance to it indicates that the sexual conflicts of interest that underlie patriarchy predate the emergence of the human species. Humans, however, exhibit more extensive male dominance and male control of female sexuality than is shown by most other primates. Six hypotheses are proposed to explain how, over the course of human evolution, this unusual degree of gender inequality came about. This approach emphasizes behavioral flexibility, cross-cultural variability in the degree of partriarchy, and possibilities for future change.

  13. Policy folklists and evolutionary theory.

    Science.gov (United States)

    O'Neill, Barry

    2014-07-22

    Policy folklists present a set of alleged historical facts seen as relevant to some social issue. Although the validity of these folklists is dubious, leaders and writers circulate them in the media, variants arise, and the lists continue on, sometimes for decades. Folklists are repeated because their messages are appealing and their users are credible. Because folklists are on the record, we can examine their origins and changes. This report draws an analogy with evolutionary theory and suggests that biological mechanisms of self-repair, boundary maintenance, plasticity, speciation, and predation have significant interpretations for folklists, and clarify how the lists win the credence of otherwise skeptical people.

  14. Evolutionary Games and Social Conventions

    DEFF Research Database (Denmark)

    Hansen, Pelle Guldborg

    2007-01-01

    Some thirty years ago Lewis published his Convention: A Philosophical Study (Lewis, 2002). This laid the foundation for a game-theoretic approach to social conventions, but became more famously known for its seminal analysis of common knowledge; the concept receiving its canonical analysis...... which any theory of convention must revolve. In response, the so-called evolutionary turn has developed. While retaining the broad framework, in which games are described in terms of strategies and payoffs, this marks a transition from the classical assumptions of perfect rationality and common...

  15. EFEK PERLAKUAN LOGAM BERAT KADMIUM TERHADAP APOPTOSIS MELALUI AKTIVASI CASPASE-3 BULU BABI Deadema setosum: APLIKASI BIOMONITORING PENCEMARAN DI PERAIRAN LAUT (Effect of Cadmium Heavy Metal Treatment Toward Apoptosis Through Caspase-3 Activation of Sea

    Directory of Open Access Journals (Sweden)

    Dominggus Rumahlatu

    2014-05-01

    Full Text Available ABSTRAK Kadmium yang terakumulasi pada hewan dapat menyebabkan karsinogenik, mutagenik, dan teratogenik. Pada penelitian ini, dilakukan secara eksperimen nonfaktorial dalam RAL 6 level dengan 7 ulangan selama 4 minggu, untuk mengkaji efek perlakuan logam berat Cd terhadap apoptosis melalui aktivasi protein caspase-3 bulu babi Deadema setosum. Penelitian dilakukan di laboratorium Balai LIPI Ambon dalam 6 bak aquarium berukuran 100 x 60 x 70 cm3.Tiap bak perlakuan diisi 200 L air laut yang diganti satu kali setiap minggu. Konsentrasi perlakuan adalah 0, 1, 3, 6, 9, dan 12 µg/L Cd terlarut. Pada tiap bak diterapkan satu level perlakuan konsentrasi Cd, dan tiap bak itu dihuni oleh 7 individu D. setosum sebagai ulangan. Usia hewan uji sekitar 8 bulan berbobot 90 g dengan lingkar tubuh 15 cm. Hewan uji diberi pakan lamun. Pengukuran konsentrasi protein caspase-3 dilakukan pada organ hepar dengan metode Caspase Colorimetric Assay Kit, sedangkan pemeriksaan apoptosis dilakukan dengan teknik pengecatan Hematoxilen-Eosin (HE. Data penelitian terkait konsentrasi protein caspase-3 dianalisis dengan One Way Anova dan uji lanjut dihitung dengan Duncan 0,05. Hasil penelitian memperlihatkan bahwa perlakuan Cd sangat signifikan meningkatkan kadar protein caspase-3; semakin tinggi kadar Cd, kadar protein caspase-3 juga makin tinggi. Konsentrasi protein caspase-3 pada konsentrasi perlakuan 12 µg/L Cd adalah yang paling tinggi dibanding kontrol. Gambaran histologi hepar D. setosum yang mengalami apoptosis atas dasar pengecatan HE sangat sesuai dengan tiap konsentrasi protein caspase-3 yang terekam. Hasil ini menunjukkan bahwa protein caspase-3 memiliki potensi sebagai satu alternatif biomonitoring pencemaran Cd pada tingkat seluler D. setosum di perairan laut.    ABSTRACT Cadmium which accumulated in animals could cause carcinogenic, mutagenic and teratogenic. In this research, non factorial experiments conducted in Complete Random Design (CRD 6 level with 7

  16. Symbioses: a key driver of insect physiological processes, ecological interactions, evolutionary diversification, and impacts on humans

    Science.gov (United States)

    K.D. Klepzig; A.S. Adams; J. Handelsman; K.F. Raffa

    2009-01-01

    Symbiosis is receiving increased attention among all aspects of biology because of the unifying themes it helps construct across ecological,evolutionary, developmental, semiochemical, and pest management theory. Insects show a vast array of symbiotic relationships with a wide diversity of microorganisms. These relationships may confer a variety of benefits to the host...

  17. Pheromone-mediated aggregation in nonsocial arthropods: an evolutionary ecological perspective

    NARCIS (Netherlands)

    Wertheim, B.; van Baalen, E-J.A.; Dicke, M.; Vet, L.E.M.

    2005-01-01

    Although the use of aggregation pheromones has been reported for hundreds of nonsocial arthropod species, the evolutionary ecological aspects of this behavior have received little attention. Despite the elaborate literature on mechanisms, robust data on costs and benefits of aggregation pheromones

  18. Inherit the Policy: A Sociocultural Approach to Understanding Evolutionary Biology Policy in South Carolina

    Science.gov (United States)

    Moore, Gregory D.

    2012-01-01

    South Carolina biology Indicator 5.6 calls for students to "Summarize ways that scientists use data from a variety of sources to investigate and critically analyze aspects of evolutionary theory" (South Carolina Department of Education, 2006). Levinson and Sutton (2001) offered a sociocultural approach to policy that considers cultural…

  19. Naturalizing Perception Developing the Gibsonian Approach to Perception along Evolutionary Lines

    NARCIS (Netherlands)

    Withagen, Rob; Chemero, Anthony

    We believe that one of the most important aspects of Gibson's ecological psychology is his attempted naturalization of perception, that is, his attempt to place perception in the context of evolutionary theory. However, the dominant neo-Gibsonian approach to perception has been criticized for being

  20. Space, time and thrips: biogeographic issues in the evolutionary ecology of Thysanoptera

    Science.gov (United States)

    John R. Grehan

    1991-01-01

    Most participants of this symposium will be concerned with understanding thrips ecology primarily in order to develop practical and effective control strategies. Questions dealing with historical aspects (evolution) may seem of only isolated "theoretical" interest with little significance for everyday pragmatic concerns. Evolutionary theory is widely...

  1. Pheromone-mediated aggregation in nonsocial arthropods : An evolutionary ecological perspective

    NARCIS (Netherlands)

    Wertheim, B; van Baalen, EJA; Dicke, M; Vet, LEM

    2005-01-01

    Although the use of aggregation pheromones has been reported for hundreds of nonsocial arthropod species, the evolutionary ecological aspects of this behavior have received little attention. Despite the elaborate literature on mechanisms. robust data on costs and benefits of aggregation pheromones

  2. Evolutionary developmental biology its roots and characteristics.

    Science.gov (United States)

    Morange, Michel

    2011-09-01

    The rise of evolutionary developmental biology was not the progressive isolation and characterization of developmental genes and gene networks. Many obstacles had to be overcome: the idea that all genes were more or less involved in development; the evidence that developmental processes in insects had nothing in common with those of vertebrates. Different lines of research converged toward the creation of evolutionary developmental biology, giving this field of research its present heterogeneity. This does not prevent all those working in the field from sharing the conviction that a precise characterization of evolutionary variations is required to fully understand the evolutionary process. Some evolutionary developmental biologists directly challenge the Modern Synthesis. I propose some ways to reconcile these apparently opposed visions of evolution. The turbulence seen in evolutionary developmental biology reflects the present entry of history into biology. Copyright © 2011 Elsevier Inc. All rights reserved.

  3. Conceptual Barriers to Progress Within Evolutionary Biology.

    Science.gov (United States)

    Laland, Kevin N; Odling-Smee, John; Feldman, Marcus W; Kendal, Jeremy

    2009-08-01

    In spite of its success, Neo-Darwinism is faced with major conceptual barriers to further progress, deriving directly from its metaphysical foundations. Most importantly, neo-Darwinism fails to recognize a fundamental cause of evolutionary change, "niche construction". This failure restricts the generality of evolutionary theory, and introduces inaccuracies. It also hinders the integration of evolutionary biology with neighbouring disciplines, including ecosystem ecology, developmental biology, and the human sciences. Ecology is forced to become a divided discipline, developmental biology is stubbornly difficult to reconcile with evolutionary theory, and the majority of biologists and social scientists are still unhappy with evolutionary accounts of human behaviour. The incorporation of niche construction as both a cause and a product of evolution removes these disciplinary boundaries while greatly generalizing the explanatory power of evolutionary theory.

  4. The structure of microbial evolutionary theory.

    Science.gov (United States)

    Sapp, J

    2007-12-01

    The study of microbial phylogeny and evolution has emerged as an interdisciplinary synthesis, divergent in both methods and concepts from the classical evolutionary biology. The deployment of macromolecular sequencing in microbial classification has provided a deep evolutionary taxonomy hitherto deemed impossible. Microbial phylogenetics has greatly transformed the landscape of evolutionary biology, not only in revitalizing the field in the pursuit of life's history over billions of years, but also in transcending the structure of thought that has shaped evolutionary theory since the time of Darwin. A trio of primary phylogenetic lineages, along with the recognition of symbiosis and lateral gene transfer as fundamental processes of evolutionary innovation, are core principles of microbial evolutionary biology today. Their scope and significance remain contentious among evolutionists.

  5. The Evolving Theory of Evolutionary Radiations.

    Science.gov (United States)

    Simões, M; Breitkreuz, L; Alvarado, M; Baca, S; Cooper, J C; Heins, L; Herzog, K; Lieberman, B S

    2016-01-01

    Evolutionary radiations have intrigued biologists for more than 100 years, and our understanding of the patterns and processes associated with these radiations continues to grow and evolve. Recently it has been recognized that there are many different types of evolutionary radiation beyond the well-studied adaptive radiations. We focus here on multifarious types of evolutionary radiations, paying special attention to the abiotic factors that might trigger diversification in clades. We integrate concepts such as exaptation, species selection, coevolution, and the turnover-pulse hypothesis (TPH) into the theoretical framework of evolutionary radiations. We also discuss other phenomena that are related to, but distinct from, evolutionary radiations that have relevance for evolutionary biology. Copyright © 2015 Elsevier Ltd. All rights reserved.

  6. The Evolutionary Puzzle of Suicide

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    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.

  7. Evolutionary potential games on lattices

    Energy Technology Data Exchange (ETDEWEB)

    Szabó, György, E-mail: szabo@mfa.kfki.hu; Borsos, István, E-mail: borsos@mfa.kfki.hu

    2016-04-05

    Game theory provides a general mathematical background to study the effect of pair interactions and evolutionary rules on the macroscopic behavior of multi-player games where players with a finite number of strategies may represent a wide scale of biological objects, human individuals, or even their associations. In these systems the interactions are characterized by matrices that can be decomposed into elementary matrices (games) and classified into four types. The concept of decomposition helps the identification of potential games and also the evaluation of the potential that plays a crucial role in the determination of the preferred Nash equilibrium, and defines the Boltzmann distribution towards which these systems evolve for suitable types of dynamical rules. This survey draws parallel between the potential games and the kinetic Ising type models which are investigated for a wide scale of connectivity structures. We discuss briefly the applicability of the tools and concepts of statistical physics and thermodynamics. Additionally the general features of ordering phenomena, phase transitions and slow relaxations are outlined and applied to evolutionary games. The discussion extends to games with three or more strategies. Finally we discuss what happens when the system is weakly driven out of the “equilibrium state” by adding non-potential components representing games of cyclic dominance.

  8. Evolutionary potential games on lattices

    International Nuclear Information System (INIS)

    Szabó, György; Borsos, István

    2016-01-01

    Game theory provides a general mathematical background to study the effect of pair interactions and evolutionary rules on the macroscopic behavior of multi-player games where players with a finite number of strategies may represent a wide scale of biological objects, human individuals, or even their associations. In these systems the interactions are characterized by matrices that can be decomposed into elementary matrices (games) and classified into four types. The concept of decomposition helps the identification of potential games and also the evaluation of the potential that plays a crucial role in the determination of the preferred Nash equilibrium, and defines the Boltzmann distribution towards which these systems evolve for suitable types of dynamical rules. This survey draws parallel between the potential games and the kinetic Ising type models which are investigated for a wide scale of connectivity structures. We discuss briefly the applicability of the tools and concepts of statistical physics and thermodynamics. Additionally the general features of ordering phenomena, phase transitions and slow relaxations are outlined and applied to evolutionary games. The discussion extends to games with three or more strategies. Finally we discuss what happens when the system is weakly driven out of the “equilibrium state” by adding non-potential components representing games of cyclic dominance.

  9. Evolutionary Biology Needs Wild Microbiomes.

    Science.gov (United States)

    Hird, Sarah M

    2017-01-01

    The microbiome is a vital component to the evolution of a host and much of what we know about the microbiome derives from studies on humans and captive animals. But captivity alters the microbiome and mammals have unique biological adaptations that affect their microbiomes (e.g., milk). Birds represent over 30% of known tetrapod diversity and possess their own suite of adaptations relevant to the microbiome. In a previous study, we showed that 59 species of birds displayed immense variation in their microbiomes and host (bird) taxonomy and ecology were most correlated with the gut microbiome. In this Frontiers Focused Review, I put those results in a broader context by discussing how collecting and analyzing wild microbiomes contributes to the main goals of evolutionary biology and the specific ways that birds are unique microbial hosts. Finally, I outline some of the methodological considerations for adding microbiome sampling to the research of wild animals and urge researchers to do so. To truly understand the evolution of a host, we need to understand the millions of microorganisms that inhabit it as well: evolutionary biology needs wild microbiomes.

  10. Evolutionary epistemology a multiparadigm program

    CERN Document Server

    Pinxten, Rik

    1987-01-01

    This volume has its already distant origin in an inter­national conference on Evolutionary Epistemology the editors organized at the University of Ghent in November 1984. This conference aimed to follow up the endeavor started at the ERISS (Epistemologically Relevant Internalist Sociology of Science) conference organized by Don Campbell and Alex Rosen­ berg at Cazenovia Lake, New York, in June 1981, whilst in­ jecting the gist of certain current continental intellectual developments into a debate whose focus, we thought, was in danger of being narrowed too much, considering the still underdeveloped state of affairs in the field. Broadly speaking, evolutionary epistemology today con­ sists of two interrelated, yet qualitatively distinct inves­ tigative efforts. Both are drawing on Darwinian concepts, which may explain why many people have failed to discriminate them. One is the study of the evolution of the cognitive apparatus of living organisms, which is first and foremost the province of biologists and...

  11. Evolutionary expansion of the Monogenea.

    Science.gov (United States)

    Kearn, G C

    1994-12-01

    The evolutionary expansion of the monogeneans has taken place in parallel with the diversification of the fish-like vertebrates. In this article the main trends in monogenean evolution are traced from a hypothetical skin-parasitic ancestor on early vertebrates. Special consideration is given to the following topics: early divergence between skin feeders and blood feeders; diversification and specialization of the haptor for attachment to skin; transfer from host to host, viviparity and the success of the gyrodactylids; predation on skin parasites and camouflage; colonization of the buccal and branchial cavities; diversification and specialization of the haptor for attachment to the gills; phoresy in gill parasites; the development of endoparasitism and the origin of the cestodes; the success of dactylogyroidean gill parasites; the uniqueness of the polyopisthocotyleans; ovoviviparity and the colonization of the tetrapods. Host specificity has been the guiding force of coevolution between monogeneans and their vertebrate hosts, but the establishment of monogeneans on unrelated hosts sharing the same environment (host-switching) may have been underestimated. Host-switching has provided significant opportunities for evolutionary change of direction and is probably responsible for the establishment of monogeneans on cephalopod molluscs, on the hippopotamus and possibly on chelonians. There are indications that host-switching may be more common in monogeneans that spread by direct transfer of adults/juveniles from host to host. A limitation on the further expansion of monogeneans is the need for water for the dispersal of the infective larva (oncomiracidium).

  12. The emerging empirics of evolutionary economic geography

    OpenAIRE

    Ron Boschma; KOen Frenken

    2010-01-01

    Following last decadeÕs programmatic papers on Evolutionary Economic Geography, we report on recent empirical advances and how this empirical work can be positioned vis-ˆ-vis other strands of research in economic geography. First, we review studies on the path dependent nature of clustering, and how the evolutionary perspective relates to that of New Economic Geography. Second, we discuss research on agglomeration externalities in Regional Science, and how Evolutionary Economic Geography cont...

  13. Apoptosis induced by chlormethine and ionizing radiations in normal and tumoral lymphocytes: role of caspase-3

    International Nuclear Information System (INIS)

    Holl, V.P.

    2000-01-01

    Apoptosis can be induced by various stimuli like ionizing radiations or alkylating agents. Recent works have shown that apoptosis due to ionizing radiations can be initiated by DNA and cell membrane alterations, via radical species generation, implying the in fine activation of effector caspases, and in particular caspase-3. The main goal of this work is to clarify the role of caspase-3 in the radio-induced apoptosis mechanisms and to study the effects of apoptosis inhibition on the behaviour of the damaged cells. The effects of activation and caspase-3 activity inhibition on the progress of spontaneous, radio-induced or chlormethine-induced apoptosis have been evaluated for normal and tumoral lymphocytes. A chemical molecule, the ebselen, which can mime the action of the endogenous glutathione peroxidase, and a tetra-peptide inhibitor, AC-DEVD-CHO, selective of effector caspases, have been selected. The results indicate an inhibition by ebselen of all morphological and biochemical characteristics of chlormethine-induced apoptosis and a restoring of the cells viability. This seleno-organic compound also reduces the drop of the intra-cellular glutathione level and the loss of the trans-membrane potential (M) of the mitochondrion in the MOLT-4 tumoral cells treated with chlormethine. In parallel, the AC-DEVD-CHO effect on apoptosis induction has been tested. This inhibitor stops some chlormethine-induced criteria of apoptosis without affecting the final loss of the mitochondrial M and the cells proliferation. AC-DEVD-CHO has been also incubated just before the irradiation of the culture cells. The inhibition of the specific DEVD caspases prevents the inter-nucleosomal fragmentation of DNA and partially delays the externalization of phosphatidylserine without changing the viability of the irradiated cells. Moreover, the analysis of the AC-DEVD-CHO pre-treated irradiated cells floating on the surface shows a strong mitochondrial lactate dehydrogenase activity, which

  14. Evolutionary computation for dynamic optimization problems

    CERN Document Server

    Yao, Xin

    2013-01-01

    This book provides a compilation on the state-of-the-art and recent advances of evolutionary computation for dynamic optimization problems. The motivation for this book arises from the fact that many real-world optimization problems and engineering systems are subject to dynamic environments, where changes occur over time. Key issues for addressing dynamic optimization problems in evolutionary computation, including fundamentals, algorithm design, theoretical analysis, and real-world applications, are presented. "Evolutionary Computation for Dynamic Optimization Problems" is a valuable reference to scientists, researchers, professionals and students in the field of engineering and science, particularly in the areas of computational intelligence, nature- and bio-inspired computing, and evolutionary computation.

  15. Evolutionary Autonomous Health Monitoring System (EAHMS) Project

    Data.gov (United States)

    National Aeronautics and Space Administration — For supporting NASA's Robotics, Tele-Robotics and Autonomous Systems Roadmap, we are proposing the "Evolutionary Autonomous Health Monitoring System" (EAHMS) for...

  16. Zebrafish Xenograft: An Evolutionary Experiment in Tumour Biology.

    Science.gov (United States)

    Wyatt, Rachael A; Trieu, Nhu P V; Crawford, Bryan D

    2017-09-05

    Though the cancer research community has used mouse xenografts for decades more than zebrafish xenografts, zebrafish have much to offer: they are cheap, easy to work with, and the embryonic model is relatively easy to use in high-throughput assays. Zebrafish can be imaged live, allowing us to observe cellular and molecular processes in vivo in real time. Opponents dismiss the zebrafish model due to the evolutionary distance between zebrafish and humans, as compared to mice, but proponents argue for the zebrafish xenograft's superiority to cell culture systems and its advantages in imaging. This review places the zebrafish xenograft in the context of current views on cancer and gives an overview of how several aspects of this evolutionary disease can be addressed in the zebrafish model. Zebrafish are missing homologs of some human proteins and (of particular interest) several members of the matrix metalloproteinase (MMP) family of proteases, which are known for their importance in tumour biology. This review draws attention to the implicit evolutionary experiment taking place when the molecular ecology of the xenograft host is significantly different than that of the donor.

  17. Extended evolutionary psychology: the importance of transgenerational developmental plasticity.

    Science.gov (United States)

    Stotz, Karola

    2014-01-01

    What kind mechanisms one deems central for the evolutionary process deeply influences one's understanding of the nature of organisms, including cognition. Reversely, adopting a certain approach to the nature of life and cognition and the relationship between them or between the organism and its environment should affect one's view of evolutionary theory. This paper explores this reciprocal relationship in more detail. In particular it argues that the view of living and cognitive systems, especially humans, as deeply integrated beings embedded in and transformed by their genetic, epigenetic (molecular and cellular), behavioral, ecological, socio-cultural and cognitive-symbolic legacies calls for an extended evolutionary synthesis that goes beyond either a theory of genes juxtaposed against a theory of cultural evolution and or even more sophisticated theories of gene-culture coevolution and niche construction. Environments, particularly in the form of developmental environments, do not just select for variation, they also create new variation by influencing development through the reliable transmission of non-genetic but heritable information. This paper stresses particularly views of embodied, embedded, enacted and extended cognition, and their relationship to those aspects of extended inheritance that lie between genetic and cultural inheritance, the still gray area of epigenetic and behavioral inheritance systems that play a role in parental effect. These are the processes that can be regarded as transgenerational developmental plasticity and that I think can most fruitfully contribute to, and be investigated by, developmental psychology.

  18. [Schizophrenia in the light of the evolutionary theories].

    Science.gov (United States)

    Wiener, Dawid; Rybakowski, Janusz

    2003-01-01

    The aim of the article was to review the hypotheses of schizophrenia in the light of the evolutionary theory. The authors distinguished adaptationist and non-adaptationist hypotheses concerning the evolutionary underpinnings of schizophrenia. The adaptationist hypotheses are firmly based on notions of adaptation, natural selection and proximate and ultimate causes. The standard hypotheses of this sort proposed by Steven and Price as well as by Pollimeni and Reiss were discussed. Also, the other similar conceptions originated from McGuire and Troisi and proposed by David Horrobin were presented of which the latter is especially promising and worth further investigating. The non-adaptationistic authors criticised many assumptions of the adapationist program i.e. too broad use of term "adaptation" in the area of human behaviour or the very idea of proximate and ultimate causes. Unlike the adaptionists, they focus their attention on other aspects of the evolutionary processes i.e. the role of the mutation and also they are searching in a much intensive way than their opponents for verification of the hypotheses based on the empirical evidence. The theories developed by Crow and by Yeo were listed among the non-adaptationistic ones and presented.

  19. Testing evolutionary models of senescence: traditional approaches and future directions.

    Science.gov (United States)

    Robins, Chloe; Conneely, Karen N

    2014-12-01

    From an evolutionary perspective, the existence of senescence is a paradox. Why has senescence not been more effectively selected against given its associated decreases in Darwinian fitness? Why does senescence exist and how has it evolved? Three major theories offer explanations: (1) the theory of mutation accumulation suggested by PB Medawar; (2) the theory of antagonistic pleiotropy suggested by GC Williams; and (3) the disposable soma theory suggested by TBL Kirkwood. These three theories differ in the underlying causes of aging that they propose but are not mutually exclusive. This paper compares the specific biological predictions of each theory and discusses the methods and results of previous empirical tests. Lifespan is found to be the most frequently used estimate of senescence in evolutionary investigations. This measurement acts as a proxy for an individual's rate of senescence, but provides no information on an individual's senescent state or "biological age" throughout life. In the future, use of alternative longitudinal measures of senescence may facilitate investigation of previously neglected aspects of evolutionary models, such as intra- and inter-individual heterogeneity in the process of aging. DNA methylation data are newly proposed to measure biological aging and are suggested to be particularly useful for such investigations.

  20. The Inflammasome Drives GSDMD-Independent Secondary Pyroptosis and IL-1 Release in the Absence of Caspase-1 Protease Activity.

    Science.gov (United States)

    Schneider, Katharina S; Groß, Christina J; Dreier, Roland F; Saller, Benedikt S; Mishra, Ritu; Gorka, Oliver; Heilig, Rosalie; Meunier, Etienne; Dick, Mathias S; Ćiković, Tamara; Sodenkamp, Jan; Médard, Guillaume; Naumann, Ronald; Ruland, Jürgen; Kuster, Bernhard; Broz, Petr; Groß, Olaf

    2017-12-26

    Inflammasomes activate the protease caspase-1, which cleaves interleukin-1β and interleukin-18 to generate the mature cytokines and controls their secretion and a form of inflammatory cell death called pyroptosis. By generating mice expressing enzymatically inactive caspase-1 C284A , we provide genetic evidence that caspase-1 protease activity is required for canonical IL-1 secretion, pyroptosis, and inflammasome-mediated immunity. In caspase-1-deficient cells, caspase-8 can be activated at the inflammasome. Using mice either lacking the pyroptosis effector gasdermin D (GSDMD) or expressing caspase-1 C284A , we found that GSDMD-dependent pyroptosis prevented caspase-8 activation at the inflammasome. In the absence of GSDMD-dependent pyroptosis, the inflammasome engaged a delayed, alternative form of lytic cell death that was accompanied by the release of large amounts of mature IL-1 and contributed to host protection. Features of this cell death modality distinguished it from apoptosis, suggesting it may represent a distinct form of pro-inflammatory regulated necrosis. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

  1. RNA silencing of Mcl-1 enhances ABT-737-mediated apoptosis in melanoma: role for a caspase-8-dependent pathway.

    Science.gov (United States)

    Keuling, Angela M; Felton, Kathleen E A; Parker, Arabesque A M; Akbari, Majid; Andrew, Susan E; Tron, Victor A

    2009-08-17

    Malignant melanoma is resistant to almost all conventional forms of chemotherapy. Recent evidence suggests that anti-apoptotic proteins of the Bcl-2 family are overexpressed in melanoma and may contribute to melanoma's striking resistance to apoptosis. ABT-737, a small-molecule inhibitor of Bcl-2, Bcl-xl and Bcl-w, has demonstrated efficacy in several forms of leukemia, lymphoma as well as solid tumors. However, overexpression of Mcl-1, a frequent observance in melanoma, is known to confer ABT-737 resistance. Here we report that knockdown of Mcl-1 greatly reduces cell viability in combination with ABT-737 in six different melanoma cell lines. We demonstrate that the cytotoxic effect of this combination treatment is due to apoptotic cell death involving not only caspase-9 activation but also activation of caspase-8, caspase-10 and Bid, which are normally associated with the extrinsic pathway of apoptosis. Caspase-8 (and caspase-10) activation is abrogated by inhibition of caspase-9 but not by inhibitors of the death receptor pathways. Furthermore, while caspase-8/-10 activity is required for the full induction of cell death with treatment, the death receptor pathways are not. Finally, we demonstrate that basal levels of caspase-8 and Bid correlate with treatment sensitivity. Our findings suggest that the combination of ABT-737 and Mcl-1 knockdown represents a promising, new treatment strategy for malignant melanoma. We also report a death receptor-independent role for extrinsic pathway proteins in treatment response and suggest that caspase-8 and Bid may represent potential markers of treatment sensitivity.

  2. RNA silencing of Mcl-1 enhances ABT-737-mediated apoptosis in melanoma: role for a caspase-8-dependent pathway.

    Directory of Open Access Journals (Sweden)

    Angela M Keuling

    Full Text Available BACKGROUND: Malignant melanoma is resistant to almost all conventional forms of chemotherapy. Recent evidence suggests that anti-apoptotic proteins of the Bcl-2 family are overexpressed in melanoma and may contribute to melanoma's striking resistance to apoptosis. ABT-737, a small-molecule inhibitor of Bcl-2, Bcl-xl and Bcl-w, has demonstrated efficacy in several forms of leukemia, lymphoma as well as solid tumors. However, overexpression of Mcl-1, a frequent observance in melanoma, is known to confer ABT-737 resistance. METHODOLOGY/PRINCIPAL FINDINGS: Here we report that knockdown of Mcl-1 greatly reduces cell viability in combination with ABT-737 in six different melanoma cell lines. We demonstrate that the cytotoxic effect of this combination treatment is due to apoptotic cell death involving not only caspase-9 activation but also activation of caspase-8, caspase-10 and Bid, which are normally associated with the extrinsic pathway of apoptosis. Caspase-8 (and caspase-10 activation is abrogated by inhibition of caspase-9 but not by inhibitors of the death receptor pathways. Furthermore, while caspase-8/-10 activity is required for the full induction of cell death with treatment, the death receptor pathways are not. Finally, we demonstrate that basal levels of caspase-8 and Bid correlate with treatment sensitivity. CONCLUSIONS/SIGNIFICANCE: Our findings suggest that the combination of ABT-737 and Mcl-1 knockdown represents a promising, new treatment strategy for malignant melanoma. We also report a death receptor-independent role for extrinsic pathway proteins in treatment response and suggest that caspase-8 and Bid may represent potential markers of treatment sensitivity.

  3. Acute fasting inhibits central caspase-1 activity reducing anxiety-like behavior and increasing novel object and object location recognition.

    Science.gov (United States)

    Towers, Albert E; Oelschlager, Maci L; Patel, Jay; Gainey, Stephen J; McCusker, Robert H; Freund, Gregory G

    2017-06-01

    Inflammation within the central nervous system (CNS) is frequently comorbid with anxiety. Importantly, the pro-inflammatory cytokine most commonly associated with anxiety is IL-1β. The bioavailability and activity of IL-1β are regulated by caspase-1-dependent proteolysis vis-a-vis the inflammasome. Thus, interventions regulating the activation or activity of caspase-1 should reduce anxiety especially in states that foster IL-1β maturation. Male C57BL/6j, C57BL/6j mice treated with the capase-1 inhibitor biotin-YVAD-cmk, caspase-1 knockout (KO) mice and IL-1R1 KO mice were fasted for 24h or allowed ad libitum access to food. Immediately after fasting, caspase-1 activity was measured in brain region homogenates while activated caspase-1 was localized in the brain by immunohistochemistry. Mouse anxiety-like behavior and cognition were tested using the elevated zero maze and novel object/object location tasks, respectively. A 24h fast in mice reduced the activity of caspase-1 in whole brain and in the prefrontal cortex, amygdala, hippocampus, and hypothalamus by 35%, 25%, 40%, 40%, and 40% respectively. A 24h fast also reduced anxiety-like behavior by 40% and increased novel object and object location recognition by 21% and 31%, respectively. IL-1β protein, however, was not reduced in the brain by fasting. ICV administration of YVAD decreased caspase-1 activity in the prefrontal cortex and amygdala by 55%, respectively leading to a 64% reduction in anxiety like behavior. Importantly, when caspase-1 KO or IL1-R1 KO mice are fasted, no fasting-dependent reduction in anxiety-like behavior was observed. Results indicate that fasting decrease anxiety-like behavior and improves memory by a mechanism tied to reducing caspase-1 activity throughout the brain. Copyright © 2017 Elsevier Inc. All rights reserved.

  4. Combination of Vorinostat and caspase-8 inhibition exhibits high anti-tumoral activity on endometrial cancer cells.

    Science.gov (United States)

    Bergadà, Laura; Sorolla, Annabel; Yeramian, Andree; Eritja, Nuria; Mirantes, Cristina; Matias-Guiu, Xavier; Dolcet, Xavier

    2013-08-01

    Histone deacetylase inhibitors such as Vorinostat display anti-neoplastic activity against a variety of solid tumors. Here, we have investigated the anti-tumoral activity of Vorinostat on endometrial cancer cells. We have found that Vorinostat caused cell growth arrest, loss of clonogenic growth and apoptosis of endometrial cancer cells. Vorinostat-induced the activation of caspase-8 and -9, the initiators caspases of the extrinsic and the intrinsic apoptotic pathways, respectively. Next, we investigated the role of the extrinsic pathway in apoptosis triggered by Vorinostat. We found that Vorinostat caused a dramatic decrease of FLIP mRNA and protein levels. However, overexpression of the long from of FLIP did not block Vorinostat-induced apoptosis. To further investigate the role of extrinsic apoptotic pathway in Vorinostat-induced apoptosis, we performed an shRNA-mediated knock-down of caspase-8. Surprisingly, downregulation of caspase-8 alone caused a marked decrease in clonogenic ability and reduced the growth of endometrial cancer xenografts in vivo, revealing that targeting caspase-8 may be an attractive target for anticancer therapy on endometrial tumors. Furthermore, combination of caspase-8 inhibition and Vorinostat treatment caused an enhancement of apoptotic cell death and a further decrease of clonogenic growth of endometrial cancer cells. More importantly, combination of Vorinostat and caspase-8 inhibition caused a nearly complete inhibition of tumor xenograft growth. Finally, we demonstrate that cell death triggered by Vorinostat alone or in combination with caspase-8 shRNAs was inhibited by the anti-apoptotic protein Bcl-XL. Our results suggest that combinatory therapies using Vorinostat treatment and caspase-8 inhibition can be an effective treatment for endometrial carcinomas. Copyright © 2013 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

  5. Discovering Early Aspects

    NARCIS (Netherlands)

    Baniassad, E.; Clements, P.; Araujo, J.; Moreira, A; Rashid, A.; Tekinerdogan, B.

    2006-01-01

    Traditionally, aspect-oriented software development (AOSD) has focused on the software life cycle's implementation phase: aspects are identified and captured mainly in code. But aspects are evident earlier in the life cycle, such as during requirements gathering and architecture development.

  6. Mouse strain-dependent caspase activation during acetaminophen hepatotoxicity does not result in apoptosis or modulation of inflammation

    Energy Technology Data Exchange (ETDEWEB)

    Williams, C. David [Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, Kansas City, KS 66160 (United States); Koerner, Michael R., E-mail: mkoern2@illinois.edu [Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, Kansas City, KS 66160 (United States); Lampe, Jed N. [Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, Kansas City, KS 66160 (United States); Farhood, Anwar [Department of Pathology, Brackenridge Hospital, Austin, TX 78701 (United States); Jaeschke, Hartmut, E-mail: hjaeschke@kumc.edu [Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, Kansas City, KS 66160 (United States)

    2011-12-15

    The mechanisms of acetaminophen (APAP)-mediated hepatic oncotic necrosis have been extensively characterized. However, it was recently demonstrated that fed CD-1 mice have a transient caspase activation which initiates apoptosis. To evaluate these findings in more detail, outbred (Swiss Webster, SW) and inbred (C57BL/6) mice were treated with APAP with or without pan-caspase inhibitor and compared to the apoptosis model of galactosamine (GalN)/endotoxin (ET). Fasted or fed APAP-treated C57BL/6 mice showed no evidence of caspase-3 processing or activity. Interestingly, a minor, temporary increase in caspase-3 processing and activity (150% above baseline) was observed after APAP treatment only in fed SW mice. The degree of caspase-3 activation in SW mice after APAP was minor compared to that observed in GalN/ET-treated mice (1600% above baseline). The pancaspase inhibitor attenuated caspase activation and resulted in increased APAP-induced injury (plasma ALT, necrosis scoring). The caspase inhibitor did not affect apoptosis because regardless of treatment only < 0.5% of hepatocytes showed consistent apoptotic morphology after APAP. In contrast, > 20% apoptotic cells were observed in GalN/ET-treated mice. Presence of the caspase inhibitor altered hepatic glutathione levels in SW mice, which could explain the exacerbation of injury. Additionally, the infiltration of hepatic neutrophils was not altered by the fed state of either mouse strain. Conclusion: Minor caspase-3 activation without apoptotic cell death can be observed only in fed mice of some outbred strains. These findings suggest that although the severity of APAP-induced liver injury varies between fed and fasted animals, the mechanism of cell death does not fundamentally change. -- Highlights: Black-Right-Pointing-Pointer During acetaminophen overdose caspase-3 can be activated in fed mice of certain outbred strains. Black-Right-Pointing-Pointer Hepatic ATP levels are not the determining factor for caspase

  7. Caspase activity and apoptotic signaling in proliferating C2C12 cells following cisplatin or A23187 exposure

    Directory of Open Access Journals (Sweden)

    Darin Bloemberg

    2016-06-01

    Full Text Available Investigating cell death signaling using cell culture is commonly performed to examine the effects of novel pharmaceuticals or to further characterize discrete cellular signaling pathways. Here, we provide data regarding the cell death response to either cisplatin or A23187 in sub-confluent C2C12 cells, by utilizing several concentrations and incubation times for each chemical. These data include an assessment of the activation of the proteolytic enzymes caspase-3, caspase-8, caspase-9, calpain, and cathepsin B/L. Additionally, the expression of the apoptosis-regulating proteins Bax, Bcl2, and p53 are presented.

  8. Cytosolic caspases mediate mislocalised SOD2 depletion in an in vitro model of chronic prion infection

    Directory of Open Access Journals (Sweden)

    Layla Sinclair

    2013-07-01

    Oxidative stress as a contributor to neuronal death during prion infection is supported by the fact that various oxidative damage markers accumulate in the brain during the course of this disease. The normal cellular substrate of the causative agent, the prion protein, is also linked with protective functions against oxidative stress. Our previous work has found that, in chronic prion infection, an apoptotic subpopulation of cells exhibit oxidative stress and the accumulation of oxidised lipid and protein aggregates with caspase recruitment. Given the likely failure of antioxidant defence mechanisms within apoptotic prion-infected cells, we aimed to investigate the role of the crucial antioxidant pathway components, superoxide dismutases (SOD 1 and 2, in an in vitro model of chronic prion infection. Increased total SOD activity, attributable to SOD1, was found in the overall population coincident with a decrease in SOD2 protein levels. When apoptotic cells were separated from the total population, the induction of SOD activity in the infected apoptotic cells was lost, with activity reduced back to levels seen in mock-infected control cells. In addition, mitochondrial superoxide production was increased and mitochondrial numbers decreased in the infected apoptotic subpopulation. Furthermore, a pan-caspase probe colocalised with SOD2 outside of mitochondria within cytosolic aggregates in infected cells and inhibition of caspase activity was able to restore cellular levels of SOD2 in the whole unseparated infected population to those of mock-infected control cells. Our results suggest that prion propagation exacerbates an apoptotic pathway whereby mitochondrial dysfunction follows mislocalisation of SOD2 to cytosolic caspases, permitting its degradation. Eventually, cellular capacity to maintain oxidative homeostasis is overwhelmed, thus resulting in cell death.

  9. Novel mechanisms for caspase inhibition protecting cardiac function with chronic pressure overload

    OpenAIRE

    Park, Misun; Vatner, Stephen F.; Yan, Lin; Gao, Shumin; Yoon, Seunghun; Lee, Grace Jung Ah; Xie, Lai-Hua; Kitsis, Richard N.; Vatner, Dorothy E.

    2013-01-01

    Myocyte apoptosis is considered a major mechanism in the pathogenesis of heart failure. Accordingly, manipulations that inhibit apoptosis are assumed to preserve cardiac function by maintaining myocyte numbers. We tested this assumption by examining the effects of caspase inhibition (CI) on cardiac structure and function in C57BL/6 mouse with pressure overload model induced by transverse aortic constriction (TAC). CI preserved left ventricular (LV) function following TAC compared with the veh...

  10. Caspase-7 participates in differentiation of cells forming dental hard tissues

    Czech Academy of Sciences Publication Activity Database

    Matalová, Eva; Lesot, H.; Švandová, Eva; Vanden Berghe, T.; Sharpe, P. T.; Healy, C.; Vandenabeele, P.; Tucker, A. S.

    2013-01-01

    Roč. 55, č. 5 (2013), s. 615-621 ISSN 0012-1592 R&D Projects: GA ČR GAP304/11/1418 Grant - others:GA ČR(CZ) GAP502/12/1285 Program:GA Institutional support: RVO:67985904 Keywords : ameloblast * apoptosis * caspase Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.178, year: 2013

  11. Sulfur Mustard Induces Apoptosis in Lung Epithelial Cells via a Caspase Amplification Loop

    Science.gov (United States)

    2010-01-01

    SM inhalation by normal breathing. Twenty-four hours after SM exposure, bronchoalveolar lavage (BAL) samples were collected to analyze cellular com...grafted onto nude mice . ol et al. (2009) recently showed that peptide inhibitors specific or caspase-8 or -9 could prevent SM-induced microvesication...ntibodies and reprobed with other antibodies to compare different proteins from he same blot as described in Rosenthal et al. (2003). .5. Bronchoalveolar

  12. The loss of functional caspase-12 in Europe is a pre-neolithic event.

    Directory of Open Access Journals (Sweden)

    Montserrat Hervella

    Full Text Available Caspase-12 (CASP12 modulates the susceptibility to sepsis. In humans, the "C" allele at CASP12 rs497116 has been associated with an increased risk of sepsis. Instead, the derived "T" allele encodes for an inactive caspase-12. Interestingly, Eurasians are practically fixed for the inactive variant, whereas in Sub-Saharan Africa the active variant is still common (~24%. This marked structure has been explained as a function of the selective advantage that the inactive caspase-12 confers by increasing resistance to infection. As regards to both when positive selection started acting and as to the speed with which fixation was achieved in Eurasia, estimates depend on the method and assumptions used, and can vary substantially. Using experimental evidence, we propose that, least in Eurasia, the increase in the frequency of the T allele might be related to the selective pressure exerted by the increase in zoonotic diseases transmission caused by the interplay between increased human population densities and a closer contact with animals during the Neolithic. METHODOLOG/PRINCIPAL FINDINGS: We genotyped CASP12 rs497116 in prehistoric individuals from 6 archaeological sites from the North of the Iberian Peninsula that date from Late Upper Paleolithic to Late Neolithic. DNA extraction was done from teeth lacking cavities or breakages using standard anti-contamination procedures, including processing of the samples in a positive pressure, ancient DNA-only chamber, quantitation of DNAs by qPCR, duplication, replication, genotyping of associated animals, or cloning of PCR products. Out of 50, 24 prehistoric individuals could finally be genotyped for rs497116. Only the inactive form of CASP12 was found.We demonstrate that the loss of caspase-12 in Europe predates animal domestication and that consequently CASP12 loss is unlikely to be related to the impact of zoonotic infections transmitted by livestock.

  13. Crocetin prevents retinal degeneration induced by oxidative and endoplasmic reticulum stresses via inhibition of caspase activity.

    Science.gov (United States)

    Yamauchi, Mika; Tsuruma, Kazuhiro; Imai, Shunsuke; Nakanishi, Tomohiro; Umigai, Naofumi; Shimazawa, Masamitsu; Hara, Hideaki

    2011-01-10

    Crocetin is a carotenoid that is the aglicone of crocin, which are found in saffron stigmas (Crocus sativus L.) and gardenia fruit (Gardenia jasminoides Ellis). In this study, we investigated the effects of crocetin on retinal damage. To examine whether crocetin affects stress pathways, we investigated intracellular oxidation induced by reactive oxygen species, expression of endoplasmic reticulum (ER) stress-related proteins, disruption of the mitochondrial membrane potential (ΔΨ(m)), and caspases activation. In vitro, we employed cultured retinal ganglion cells (RGC-5, a mouse ganglion cell-line transformed using E1A virus). Cell damage was induced by tunicamycin or hydrogen peroxide (H(2)O(2)) exposure. Crocetin at a concentration of 3μM showed the inhibitory effect of 50-60% against tunicamycin- and H(2)O(2)-induced cell death and inhibited increase in caspase-3 and -9 activity. Moreover, crocetin inhibited the enzymatic activity of caspase-9 in a cell-free system. In vivo, retinal damage in mice was induced by exposure to white light at 8000lx for 3h after dark adaptation. Photoreceptor damage was evaluated by measuring the outer nuclear layer thickness at 5days after light exposure and recording the electroretinogram (ERG). Retinal cell damage was also detected with Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining at 48h after light exposure. Crocetin at 100mg/kg, p.o. significantly inhibited photoreceptor degeneration and retinal dysfunction and halved the expression of TUNEL-positive cells. These results indicate that crocetin has protective effects against retinal damage in vitro and in vivo, suggesting that the mechanism may inhibit increase in caspase-3 and -9 activities after retinal damage. Copyright © 2010 Elsevier B.V. All rights reserved.

  14. Caspase 3 activation in the primary enamel knot of developing molar tooth

    Czech Academy of Sciences Publication Activity Database

    Matalová, Eva; Kovářů, František; Míšek, Ivan

    2006-01-01

    Roč. 55, 2 (2006), s. 183-188 ISSN 0862-8408 R&D Projects: GA ČR GA304/04/0101; GA AV ČR KJB500450503; GA MŠk OC B23.001 Institutional research plan: CEZ:AV0Z50450515 Keywords : apoptosis * caspase 3 * primary enamel knot Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.093, year: 2006

  15. Association of caspase-1 polymorphisms with Chagas cardiomyopathy among individuals in Santa Cruz, Bolivia

    Directory of Open Access Journals (Sweden)

    Katherine Yih-Jia Fu

    Full Text Available Abstract INTRODUCTION: Trypanosoma cruzi (Tc infection is usually acquired in childhood in endemic areas, leading to Chagas disease, which progresses to Chagas cardiomyopathy in 20-30% of infected individuals over decades. The pathogenesis of Chagas cardiomyopathy involves the host inflammatory response to T. cruzi, in which upstream caspase-1 activation prompts the cascade of inflammatory chemokines/cytokines, cardiac remodeling, and myocardial dysfunction. The aim of the present study was to examine the association of two caspase-1 single nucleotide polymorphisms (SNPs with cardiomyopathy. METHODS: We recruited infected (Tc+, n = 149 and uninfected (Tc−, n = 87 participants in a hospital in Santa Cruz, Bolivia. Cardiac status was classified (I, II, III, IV based on Chagas cardiomyopathy-associated electrocardiogram findings and ejection fractions on echocardiogram. Genotypes were determined using Taqman probes via reverse transcription-polymerase chain reaction of peripheral blood DNA. Genotype frequencies were analyzed according to three inheritance patterns (dominant, recessive, additive using logistic regression adjusted for age and sex. RESULTS: The AA allele for the caspase-1 SNP rs501192 was more frequent in Tc+ cardiomyopathy (classes II, III, IV patients compared to those with a normal cardiac status (class I [odds ratio (OR = −2.18, p = 0.117]. This trend approached statistical significant considering only Tc+ patients in class I and II (OR = −2.64, p = 0.064. CONCLUSIONS: Caspase-1 polymorphisms may play a role in Chagas cardiomyopathy development and could serve as markers to identify individuals at higher risk for priority treatment.

  16. Caspase 2 activation and ER stress drive rapid Jurkat cell apoptosis by clofibrate.

    Directory of Open Access Journals (Sweden)

    Fabio Penna

    Full Text Available Differently from the antiapoptotic action most commonly assigned to peroxisome proliferators (PPs, we demonstrated that some of them, clofibrate (CF in particular, display clearcut apoptogenic properties on rat hepatoma cell lines. We and others could confirm that CF as well as various other PPs can induce apoptosis in a variety of cells, including human liver, breast and lung cancer cell lines. The present study was aimed at investigating the cytotoxic action of CF on a neoplastic line of different origin, the human T leukemia Jurkat cells. We observed that CF rapidly triggers an extensive and morphologically typical apoptotic process on Jurkat cells, though not in primary T cells, which is completely prevented by the polycaspase inhibitor zVADfmk. Gene silencing studies demonstrated that CF-induced apoptosis in Jurkat cells is partially dependent on activation of caspase 2. Looking for a possible trigger of caspase 2 activation, we observed increased levels of phosphorylated eIF2α and JNK in CF-treated cells. Moreover, intracellular Ca(2+ homeostasis was perturbed. Together, these findings are suggestive for the occurrence of ER stress, an event that is known to have the potential to activate caspase 2. The present observations demonstrate that CF induces in Jurkat cells a very fast and extensive apoptosis, that involves induction of ER stress and activation of caspases 2 and 3. Since apoptosis in Jurkat cells occurs at pharmacologically relevant concentrations of CF, the present findings encourage further in depth analysis in order to work out the potential implications of CF cytotoxcity on leukemic cells.

  17. Antiproliferative activity and caspase enhancement properties of Annona muricata leaves extract against colorectal cancer cells

    Directory of Open Access Journals (Sweden)

    Lili Indrawati

    2016-10-01

    Full Text Available Background: The prevalence of colorectal cancer is rising in Asia including Indonesia. Annona muricata tea leaves, that is traditionally used for maintaining health, and lately being used by cancer patients. The objectives of this study is to investigate its effects in human colorectal cancer cell in vitro and ex vivo.Methods: Thirty patients with colorectal cancer (CRC were enrolled in a randomized double-blind placebo-controlled trial. They were equally divided into two groups: those treated with 300 mg A. muricata leaf extract and placebo daily for 8 weeks. Serum from supplemented CRC patients of both groups was compared for caspase 9 and caspase 8 enhancement activity. Antiproliferative effect of water extract of A. muricata leaves and its fractions were evaluated against colorectal cancer cell line (DLD-1 and COLO 205 compared with 5-fluorouracil and placebo, the dose range was 62.5-2,000 µg/mL. Method used was 3-(4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide (MTT assay. Data were analyzed by Mann-Whitney U test. The p value was set at 0.05.Results: Ethanol-soluble fraction of A. muricata leaves extract water extract (ESFAM leaves extract had cytotoxicity effects on DLD-1 as well as COLO 205 cell line, as shown by the lower IC50 compared to 5-fluorouracil and placebo, 20.59 μg/mL and 654.9μg/mL, respectively. Serum of subjects supplemented with extract significantly induced caspase 9 (p=0.001 activity of DLD-1 colorectal cancer cell line, but not for caspase 8 activity (p=0.372.Conclusion: The study's results suggest the cytotoxicity potential of  A. muricata  leaves extract  in in vitro and ex vivo studies.

  18. Primary enamel knot cell death in Apaf-1 and caspase-9 deficient mice

    Czech Academy of Sciences Publication Activity Database

    Šetková, Jana; Matalová, Eva; Sharpe, P. T.; Míšek, Ivan; Tucker, A. S.

    2007-01-01

    Roč. 52, 1 (2007), s. 15-19 ISSN 0003-9969 R&D Projects: GA AV ČR KJB500450503; GA ČR GA304/04/0101; GA MŠk OC B23.001 Institutional research plan: CEZ:AV0Z50450515 Keywords : dental apoptosis * apoptosome * apaf-1 knockout * caspase-9 knockout Subject RIV: FF - HEENT, Dentistry Impact factor: 1.554, year: 2007

  19. HSV and glycoprotein J inhibit caspase activation and apoptosis induced by granzyme B or Fas.

    Science.gov (United States)

    Jerome, K R; Chen, Z; Lang, R; Torres, M R; Hofmeister, J; Smith, S; Fox, R; Froelich, C J; Corey, L

    2001-10-01

    HSV-1 inhibits apoptosis of infected cells, presumably to ensure that the infected cell survives long enough to allow completion of viral replication. Because cytotoxic lymphocytes kill their targets via the induction of apoptosis, protection from apoptosis could constitute a mechanism of immune evasion for HSV. Several HSV genes are involved in the inhibition of apoptosis, including Us5, which encodes glycoprotein J (gJ). Viruses deleted for Us5 showed defects in inhibition of caspase activation after Fas ligation or UV irradiation. Transfected cells expressing the Us5 gene product gJ were protected from Fas- or UV-induced apoptosis, as measured by morphology, caspase activation, membrane permeability changes, or mitochondrial transmembrane potential. In contrast, caspase 3 activation in mitochondria-free cell lysates by granzyme (gr)B was inhibited equivalently by Us5 deletion and rescue viruses, suggesting that gJ is not required for HSV to inhibition this process. However, mitochondria-free lysates from transfected cells expressing Us5/gJ were protected from grB-induced caspase activation, suggesting that Us5/gJ is sufficient to inhibit this process. Transfected cells expressing Us5/gJ were also protected from death induced by incubation with purified grB and perforin. These findings suggest that HSV has a comprehensive set of immune evasion functions that antagonize both Fas ligand- and grB-mediated pathways of CTL-induced apoptosis. The understanding of HSV effects on killing by CTL effector mechanisms may shed light on the incomplete control of HSV infections by the immune system and may allow more rational approaches to the development of immune modulatory treatments for HSV infection.

  20. Numerical and Evolutionary Optimization Workshop

    CERN Document Server

    Trujillo, Leonardo; Legrand, Pierrick; Maldonado, Yazmin

    2017-01-01

    This volume comprises a selection of works presented at the Numerical and Evolutionary Optimization (NEO) workshop held in September 2015 in Tijuana, Mexico. The development of powerful search and optimization techniques is of great importance in today’s world that requires researchers and practitioners to tackle a growing number of challenging real-world problems. In particular, there are two well-established and widely known fields that are commonly applied in this area: (i) traditional numerical optimization techniques and (ii) comparatively recent bio-inspired heuristics. Both paradigms have their unique strengths and weaknesses, allowing them to solve some challenging problems while still failing in others. The goal of the NEO workshop series is to bring together people from these and related fields to discuss, compare and merge their complimentary perspectives in order to develop fast and reliable hybrid methods that maximize the strengths and minimize the weaknesses of the underlying paradigms. Throu...

  1. Quantum Mechanics predicts evolutionary biology.

    Science.gov (United States)

    Torday, J S

    2018-01-11

    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. Published by Elsevier Ltd.

  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. Language and imagination: Evolutionary explorations.

    Science.gov (United States)

    Reuland, Eric

    2017-10-01

    This article provides a functional analysis of the conditions for language to emerge, and analyzes its role in imagination. It starts with some initial reflections on imagination and its evolutionary beginnings in relation to the role of working memory and tool use by chimpanzees and humans up to modernity. It then presents an analysis of what it takes to develop language, and how language gives rise to higher orders of imagination. An important theme in the discussion is which of the changes in the development leading to language may have been gradual and which changes must reflect a discontinuity. It concludes with a paradoxical property of imagination: One part of our mind is able to imagine and create systems that another part of our mind is unable to deal with. It shows how this tension manifests itself in the notion of an impossible language, but crucially also in conceptions of human society at large. Copyright © 2016 Elsevier Ltd. All rights reserved.

  4. Steps towards an evolutionary physics

    CERN Document Server

    Tiezzi, E

    2006-01-01

    If thermodynamics is to physics as logic is to philosophy, recent theoretical advancements lend new coherence to the marvel and dynamism of life on Earth. Enzo Tiezzi's "Steps Towards an Evolutionary Physics" is a primer and guide, to those who would to stand on the shoulders of giants to attain this view: Heisenberg, Planck, Bateson, Varela, and Prigogine as well as notable contemporary scientists. The adventure of such a free and enquiring spirit thrives not so much on answers as on new questions. The book offers a new gestalt on the uncertainty principle and concept of probability. A wide range of examples, enigmas, and paradoxes lead one's imagination on an exquisite dance. Among the applications are: songs and shapes of nature, oscillatory reactions, orientors, goal functions and configurations of processes, and "dissipative structures and the city". Ecodynamics is a new science, which proposes a cross-fertilization between Charles Darwin and Ilya Prigogine. As an enigma in thermodynamics, Entropy forms ...

  5. TNFα-induced macrophage death via caspase-dependent and independent pathways

    Science.gov (United States)

    Tran, Tri M.; Temkin, Vladislav; Shi, Bo; Pagliari, Lisa; Daniel, Soizic; Ferran, Christiane; Pope, Richard M.

    2009-01-01

    Macrophages are the principal source of TNFα, yet they are highly resistant to TNFα-mediated cell death. Previously, employing in vitro differentiated human macrophages, we showed that following the inhibition of NF-κB, TNFα-induced caspase-8 activation contributes to DNA fragmentation but is not necessary for the loss of the inner mitochondrial transmembrane potential (ΔΨm) or cell death. We here extend these observations to demonstrate that, when NF-κB is inhibited in macrophages, TNFα alters lysosomal membrane permeability (LMP). This results in the release of cathepsin B with subsequent loss of ΔΨm and caspase-8 independent cell death. Interestingly, the cytoprotective, NF-κB-dependent protein A20 was rapidly induced in macrophages treated with TNFα. Ectopic expression of A20 in macrophages preserves LMP following treatment with TNFα, and as a result, mitochondrial integrity is safeguarded and macrophages are protected from cell death. These observations demonstrate that TNFα triggers both caspase 8-dependent and -independent cell death pathways in macrophages and identify a novel mechanism by which A20 protects these cells against both pathways. PMID:19152111

  6. Sequential Cdk1 and Plk1 phosphorylation of caspase-8 triggers apoptotic cell death during mitosis.

    Science.gov (United States)

    Matthess, Yves; Raab, Monika; Knecht, Rainald; Becker, Sven; Strebhardt, Klaus

    2014-05-01

    Caspase-8 is crucial for cell death induction, especially via the death receptor pathway. The dysregulated expression or function of caspase-8 can promote tumor formation, progression and treatment resistance in different human cancers. Here, we show procaspase-8 is regulated during the cell cycle through the concerted inhibitory action of Cdk1/cyclin B1 and polo-like kinase 1 (Plk1). By phosphorylating S387 in procaspase-8 Cdk1/cyclin B1 generates a phospho-epitope for the binding of the PBD of Plk1. Subsequently, S305 in procaspase-8 is phosphorylated by Plk1 during mitosis. Using an RNAi-based strategy we could demonstrate that the extrinsic cell death is increased upon Fas-stimulation when endogenous caspase-8 is replaced by a mutant (S305A) mimicking the non-phosphorylated form. Together, our data show that sequential phosphorylation by Cdk1/cyclin B1 and Plk1 decreases the sensitivity of cells toward stimuli of the extrinsic pathway during mitosis. Thus, the clinical Plk1 inhibitor BI 2536 decreases the threshold of different cancer cell types toward Fas-induced cell death. Copyright © 2013 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

  7. Expression of caspase-3, p53 and Bcl-2 in generalized aggressive periodontitis

    Directory of Open Access Journals (Sweden)

    Özdemir B Handan

    2006-06-01

    Full Text Available Abstract Background Apoptosis, or programmed cell death is a form of physiological cell death. It is increased or decreased in the presence of infection, inflammation or tissue remodelling. Previous studies suggest that apoptosis is involved in the pathogenesis of inflammatory periodontal disease. The aim of the present study was to investigate the clinical features and known indicators of apoptosis (p53, Bcl-2, Caspase-3 in patients with generalized aggressive periodontitis (GAP Methods Eight patients with GAP, who had sites with probing depths (PD > 5 mm, and 10 periodontally-healthy persons were included in the study. Clinical examinations and PD were performed, and the plaque index and gingival index were recorded. Gingival tissues biopsies were obtained from active site of each patient and from healthy individuals. The expression of caspase-3, Bcl-2, and p53 was evaluated by immunohistochemistry Results There were no significant differences between GAP and control group with respect to levels of caspase-3 and p53 expression (P > 0.05. Contrary, the frequency of grade 3 expression of Bcl-2 was higher in GAP group than the control group. Conclusion The higher frequency of Bcl-2 expression in GAP group indicates and delayed apoptosis can lead to increasing resident inflammatory cells in periodontal tissues and resulting in progressive periodontal destruction.

  8. Primary enamel knot cell death in Apaf-1 and caspase-9 deficient mice.

    Science.gov (United States)

    Setkova, J; Matalova, E; Sharpe, P T; Misek, I; Tucker, A S

    2007-01-01

    During molar development, apoptosis occurs in a well-characterised pattern suggesting several roles for cell death in odontogenesis. However, molecular mechanisms of dental apoptosis are only poorly understood. In this study, Apaf-1 and caspase-9 knockouts were used to uncover the engagement of these members of the apoptotic machinery during early tooth development, concentrating primarily on their function in the apoptotic elimination of primary enamel knot cells. Molar tooth germ morphology, proliferation and apoptosis were investigated on frontal histological sections of murine heads at embryonic days (ED) 15.5, the stage when the primary enamel knot is eliminated apoptotically. In molar tooth germs of both knockouts, no apoptosis was observed according to morphological (haematoxylin-eosin) as well as biochemical criteria (TUNEL). Morphology of the mutant tooth germs, however, was not changed. Additionally, knockout mice showed no changes in proliferation compared to wild type mice. According to our findings on knockout embryos, Apaf-1 and caspase-9 are involved in apoptosis during tooth development; however, they seem dispensable and not necessary for proper tooth shaping. Compensatory or other mechanisms of cell death may act to eliminate the primary enamel knot cells in the absence of Apaf-1 and caspase-9.

  9. Endogenous α-crystallin inhibits expression of caspase-3 induced by hypoxia in retinal neurons.

    Science.gov (United States)

    Ying, Xi; Peng, Yanli; Zhang, Jiaping; Wang, Xingli; Wu, Nan; Zeng, Yuxiao; Wang, Yi

    2014-08-28

    To investigate the expression of endogenous, hypoxic stress-induced α-crystallin and caspase-3 in rat retinal neurons in vitro. Retinal neurons were cultured from Long-Evans rats. The expression of endogenous α-crystallin was analyzed by immunohistochemistry and reverse transcriptase-polymerase chain reaction (RT-PCR). Furthermore, hypoxic exposure was performed in cultured cells, and the expression of endogenous α-crystallin and caspase-3 was assayed by Western blotting. Positive α-crystallin staining was observed in cultured retinal neurons, and expression of endogenous α-crystallin mRNA peaked 3-5d after inoculation (Pendogenous, hypoxic stress-induced α-crystallin expression increased gradually, peaking 6h after hypoxia. The expression was more abundant compared to the control (Pendogenous α-crystallin in retinal neurons, especially over-expression induced by hypoxic stress, results in the down regulation of caspase-3. The data suggest that endogenous α-crystallin may act as an endogenous neuroprotective factor in retinal neurons. Copyright © 2014 Elsevier Inc. All rights reserved.

  10. Relationship between triterpenoid anticancer drug resistance, autophagy, and caspase-1 in adult T-cell leukemia

    Directory of Open Access Journals (Sweden)

    Tsukasa Nakanishi

    2016-05-01

    Full Text Available We previously reported that the inflammasome inhibitor cucurbitacin D (CuD induces apoptosis in human leukemia cell lines. Here, we investigated the effects of CuD and a B-cell lymphoma extra-large (Bcl-xL inhibitor on autophagy in peripheral blood lymphocytes (PBL isolated from adult T-cell leukemia (ATL patients. CuD induced PBL cell death in patients but not in healthy donors. This effect was not significantly inhibited by treatment with rapamycin or 3-methyladenine (3-MA. The Bcl-xL inhibitor Z36 induced death in primary cells from ATL patients including that induced by CuD treatment, effects that were partly inhibited by 3-MA. Similarly, cell death induced by the steroid prednisolone was enhanced in the presence of Z36. A western blot analysis revealed that Z36 also promoted CuD-induced poly(ADP ribose polymerase cleavage. Interestingly, the effects of CuD and Z36 were attenuated in primary ATL patient cells obtained upon recurrence after umbilical cord blood transplantation, as compared to those obtained before chemotherapy. Furthermore, cells from this patient expressed a high level of caspase-1, and treatment with caspase-1 inhibitor-enhanced CuD-induced cell death. Taken together, these results suggest that rescue from resistance to steroid drugs can enhance chemotherapy, and that caspase-1 is a good marker for drug resistance in ATL patients.

  11. Nickel induces interleukin-1β secretion via the NLRP3-ASC-caspase-1 pathway.

    Science.gov (United States)

    Li, Xiujin; Zhong, Fei

    2014-04-01

    Exposure to nickel (Ni(2+)) can trigger allergic reactions in susceptible individuals, which is widely accepted as the major cause of allergic contact hypersensitivity (CHS) worldwide. Although Ni(2+)-induced proinflammatory responses clearly play a pivotal role in CHS, the underlying molecular mechanism has not been fully defined. Here we report that Ni(2+) activates the NLRP3-ASC-caspase-1 immune signaling pathway in antigen-presenting cells, leading to the proteolytic processing and secretion of a proinflammatory cytokine, interleukin-1β (IL-1β). The activation of this signaling axis is independent of phagolysosome-cathepsin B pathway. Instead, Ni(2+) induces mitochondrial reactive oxygen species accumulation and cation fluxes, both of which are required for activating the NLRP3-ASC-caspase-1 pathway. Together, these results identified a novel innate immune signaling pathway (NLRP3-ASC-caspase-1-IL-1β) activated by Ni(2+) and provided a mechanistic basis for optimizing the therapeutic intervention against Ni(2+)-induced allergy in patients.

  12. Artemisinin induces ROS-mediated caspase3 activation in ASTC-a-1 cells

    Science.gov (United States)

    Xiao, Feng-Lian; Chen, Tong-Sheng; Qu, Jun-Le; Liu, Cheng-Yi

    2010-02-01

    Artemisinin (ART), an antimalarial phytochemical from the sweet wormwood plant or a naturally occurring component of Artemisia annua, has been shown a potential anticancer activity by apoptotic pathways. In our report, cell counting kit (CCK-8) assay showed that treatment of human lung adenocarcinoma (ASTC-a-1) cells with ART effectively increase cell death by inducing apoptosis in a time- and dose-dependent fashion. Hoechst 33258 staining was used to detect apoptosis as well. Reactive oxygen species (ROS) generation was observed in cells exposed to ART at concentrations of 400 μM for 48 h. N-acetyl-L-cysteine (NAC), an oxygen radical scavenger, suppressed the rate of ROS generation and inhibited the ART-induced apoptosis. Moreover, AFC assay (Fluorometric assay for Caspase3 activity) showed that ROS was involved in ART-induced caspase3 acitvation. Taken together, our data indicate that ART induces ROS-mediated caspase3 activation in a time-and dose-dependent way in ASCT-a-1 cells.

  13. Hypothesis for thermal activation of the caspase cascade in apoptotic cell death at elevated temperatures

    Science.gov (United States)

    Pearce, John A.

    2013-02-01

    Apoptosis is an especially important process affecting disease states from HIV-AIDS to auto-immune disease to cancer. A cascade of initiator and executioner capsase functional proteins is the hallmark of apoptosis. When activated the various caspases activate other caspases or cleave structural proteins of the cytoskeleton, resulting in "blebbing" of the plasma membrane forming apoptotic bodies that completely enclose the disassembled cellular components. Containment of the cytosolic components within the apoptotic bodies differentiates apoptosis from necroptosis and necrosis, both of which release fragmented cytosol and other cellular constituents into the intracellular space. Biochemical models of caspase activation reveal the extensive feedback loops characteristic of apoptosis. They clearly explain the failure of Arrhenius models to give accurate predictions of cell survival curves in hyperthermic heating protocols. Nevertheless, each of the individual reaction velocities can reasonably be assumed to follow Arrhenius kinetics. If so, the thermal sensitivity of the reaction velocity to temperature elevation is: ∂k/∂T = Ea [k/RT2]. Particular reaction steps described by higher activation energies, Ea, are likely more thermally-sensitive than lower energy reactions and may initiate apoptosis in the absence of other stress signals. Additionally, while the classical irreversible Arrhenius formulation fails to accurately represent many cell survival and/or dye uptake curves - those that display an early stage shoulder region - an expanded reversible model of the law of mass action equation seems to prove effective and is directly based on a firm theoretical thermodynamic foundation.

  14. STEREOLOGIC ESTIMATION OF KI-67, CASPASE 3 AND GSTP1 POSITIVE CELLS IN PROSTATE LESIONS

    Directory of Open Access Journals (Sweden)

    Luis Santamaría

    2011-05-01

    Full Text Available Cell proliferation, caspase 3 and pi-form of glutathione S transferase (GSTP1 were evaluated in prostate carcinoma (PCA, proliferative inflammatory atrophy (PIA and prostate intraepithelial neoplasia (PIN. Forty biopsies were classified as: without morphological lesions (controls: CTR, PIA, PIN and PCA. Ki67, caspase3 and GSTP1 were immunostained. The following estimates were performed: Numerical densities of Ki67+ cells (NVEPKi67, of all epithelial cells (NVEPtotal and of GSTP1+ cells (NVEPGSTP1; labelling index for Ki67 (LIKi67; volume fraction to caspase 3 positive tissue (VVcaspase 3 and of GSTP1 positive tissue (VVGSTP1. ANOVA was performed to compare the groups. NVEPtotal and NVEPKi67 were increased in PIA. LIKi67 was only increased in PCA. VVcaspase 3 was decreased in PIN and PCA. VVEGSTP1 was decreased in PCA. In our results PIA lacks the characteristics of a premalignant lesion. The result may be explained by the use of unbiased quantitative methods, the inadequate definition of PIA and the scarce inflammation observed in the samples with PIA included in this study.

  15. Impact of caspase-1/11, -3, -7, or IL-1β/IL-18 deficiency on rabies virus-induced macrophage cell death and onset of disease

    Science.gov (United States)

    Kip, E; Nazé, F; Suin, V; Vanden Berghe, T; Francart, A; Lamoral, S; Vandenabeele, P; Beyaert, R; Van Gucht, S; Kalai, M

    2017-01-01

    Rabies virus is a highly neurovirulent RNA virus, which causes about 59000 deaths in humans each year. Previously, we described macrophage cytotoxicity upon infection with rabies virus. Here we examined the type of cell death and the role of specific caspases in cell death and disease development upon infection with two laboratory strains of rabies virus: Challenge Virus Standard strain-11 (CVS-11) is highly neurotropic and lethal for mice, while the attenuated Evelyn–Rotnycki–Abelseth (ERA) strain has a broader cell tropism, is non-lethal and has been used as an oral vaccine for animals. Infection of Mf4/4 macrophages with both strains led to caspase-1 activation and IL-1β and IL-18 production, as well as activation of caspases-3, -7, -8, and -9. Moreover, absence of caspase-3, but not of caspase-1 and -11 or -7, partially inhibited virus-induced cell death of bone marrow-derived macrophages. Intranasal inoculation with CVS-11 of mice deficient for either caspase-1 and -11 or -7 or both IL-1β and IL-18 led to general brain infection and lethal disease similar to wild-type mice. Deficiency of caspase-3, on the other hand, significantly delayed the onset of disease, but did not prevent final lethal outcome. Interestingly, deficiency of caspase-1/11, the key executioner of pyroptosis, aggravated disease severity caused by ERA virus, whereas wild-type mice or mice deficient for either caspase-3, -7, or both IL-1β and IL-18 presented the typical mild symptoms associated with ERA virus. In conclusion, rabies virus infection of macrophages induces caspase-1- and caspase-3-dependent cell death. In vivo caspase-1/11 and caspase-3 differently affect disease development in response to infection with the attenuated ERA strain or the virulent CVS-11 strain, respectively. Inflammatory caspases seem to control attenuated rabies virus infection, while caspase-3 aggravates virulent rabies virus infection. PMID:28280602

  16. Evolutionary design assistants for architecture

    Directory of Open Access Journals (Sweden)

    N. Onur Sönmez

    2015-04-01

    Full Text Available In its parallel pursuit of an increased competitivity for design offices and more pleasurable and easier workflows for designers, artificial design intelligence is a technical, intellectual, and political challenge. While human-machine cooperation has become commonplace through Computer Aided Design (CAD tools, a more improved collaboration and better support appear possible only through an endeavor into a kind of artificial design intelligence, which is more sensitive to the human perception of affairs. Considered as part of the broader Computational Design studies, the research program of this quest can be called Artificial / Autonomous / Automated Design (AD. The current available level of Artificial Intelligence (AI for design is limited and a viable aim for current AD would be to develop design assistants that are capable of producing drafts for various design tasks. Thus, the overall aim of this thesis is the development of approaches, techniques, and tools towards artificial design assistants that offer a capability for generating drafts for sub-tasks within design processes. The main technology explored for this aim is Evolutionary Computation (EC, and the target design domain is architecture. The two connected research questions of the study concern, first, the investigation of the ways to develop an architectural design assistant, and secondly, the utilization of EC for the development of such assistants. While developing approaches, techniques, and computational tools for such an assistant, the study also carries out a broad theoretical investigation into the main problems, challenges, and requirements towards such assistants on a rather overall level. Therefore, the research is shaped as a parallel investigation of three main threads interwoven along several levels, moving from a more general level to specific applications. The three research threads comprise, first, theoretical discussions and speculations with regard to both

  17. 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...... the integrated design automation idea using these evolutionary approaches....

  18. 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

    2011-01-01

    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 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. PMID:25567966

  19. Handbook of differential equations evolutionary equations

    CERN Document Server

    Dafermos, CM

    2008-01-01

    The material collected in this volume discusses the present as well as expected future directions of development of the field with particular emphasis on applications. The seven survey articles present different topics in Evolutionary PDE's, written by leading experts.- Review of new results in the area- Continuation of previous volumes in the handbook series covering Evolutionary PDEs- Written by leading experts

  20. On the Evolutionary Stability of Bargaining Inefficiency

    DEFF Research Database (Denmark)

    Poulsen, Anders

    This paper investigates whether 'tough' bargaining behavior, which gives rise to inefficiency, can be evolutionary stable. We show that in a two-stage Nash Demand Game tough behavior survives. Indeed, almost all the surplus may be wasted. We also study the Ultimatum Game. Here evolutionary...

  1. Toward a unifying framework for evolutionary processes.

    Science.gov (United States)

    Paixão, Tiago; Badkobeh, Golnaz; Barton, Nick; Çörüş, Doğan; Dang, Duc-Cuong; Friedrich, Tobias; Lehre, Per Kristian; Sudholt, Dirk; Sutton, Andrew M; Trubenová, Barbora

    2015-10-21

    The theory of population genetics and evolutionary computation have been evolving separately for nearly 30 years. Many results have been independently obtained in both fields and many others are unique to its respective field. We aim to bridge this gap by developing a unifying framework for evolutionary processes that allows both evolutionary algorithms and population genetics models to be cast in the same formal framework. The framework we present here decomposes the evolutionary process into its several components in order to facilitate the identification of similarities between different models. In particular, we propose a classification of evolutionary operators based on the defining properties of the different components. We cast several commonly used operators from both fields into this common framework. Using this, we map different evolutionary and genetic algorithms to different evolutionary regimes and identify candidates with the most potential for the translation of results between the fields. This provides a unified description of evolutionary processes and represents a stepping stone towards new tools and results to both fields. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  2. Democratizing evolutionary biology, lessons from insects

    DEFF Research Database (Denmark)

    Dunn, Robert Roberdeau; Beasley, DeAnna E.

    2016-01-01

    The engagement of the public in the scientific process is an old practice. Yet with recent advances in technology, the role of the citizen scientist in studying evolutionary processes has increased. Insects provide ideal models for understanding these evolutionary processes at large scales...

  3. Oversimplifying Evolutionary Psychology Leads to Explanatory Gaps

    Science.gov (United States)

    Tate, Chuck; Ledbetter, Jay N.

    2010-01-01

    Comments on Evolutionary psychology: Controversies, questions, prospects, and limitations by Confer et al. They argued that SST cannot explain the existence of either homosexuality or suicide within the human species. We contend that a sufficiently nuanced evolutionary position has no difficulties explaining either phenomenon. Also in this…

  4. Inherit the policy: A sociocultural approach to understanding evolutionary biology policy in South Carolina

    Science.gov (United States)

    Moore, Gregory D.

    South Carolina biology Indicator 5.6 calls for students to "Summarize ways that scientists use data from a variety of sources to investigate and critically analyze aspects of evolutionary theory" (South Carolina Department of Education, 2006). Levinson and Sutton (2001) offered a sociocultural approach to policy that considers cultural and historical influences at all levels of the policy process. Lipsky (1980/2010) and others have identified teachers as de facto policy makers, exercising broad discretion in the execution of their work. This study looks to Ajzen's Theory of Planned Behavior as an initial framework to inform how evolutionary biology policy in South Carolina is conceptualized and understood at different levels of the policy process. The results of this study indicate that actors in the state's evolutionary biology policy process draw upon a myriad of Discourses (Gee, 1999/2005). These Discourses shape cultural dynamics and the agency of the policy actors as they navigate conflicting messages between testing mandates and evolutionary biology policy. There indeed exist gaps between how evolutionary biology policy in South Carolina is conceptualized and understood at the different levels of the policy process. Evidence from this study suggests that appropriation-level policy actors must be brought into the Discourse related to the critical analysis of evolutionary biology and academic freedom legislation must be enacted if South Carolina biology Indicator 5.6 is to realize practical significance in educational policy.

  5. Conceptual foundations of evolutionary thought

    Indian Academy of Sciences (India)

    K. P. MOHANAN

    2017-07-04

    Jul 4, 2017 ... emergence of structures, systems, and functions, as well as to the evolution of constraints on these aspects of .... solar system, and the atomic theory of matter, are two of the most important features of the 'modern' ..... systems, with the following subfunctions: (a) Sensory: to receive information from outside.

  6. Ulinastatin Alone Does Not Reduce Caspase 3-mediated Apoptosis in Protease-positive Aeromonas hydrophilia-induced Sepsis

    Directory of Open Access Journals (Sweden)

    Bai-Horng Su

    2007-01-01

    Conclusion: PPAH-induced sepsis has a high mortality that is related to lymphocyte apoptosis. Ulinastatin alone does not significantly reduce caspase 3-mediated lymphocyte apoptosis. [J Formos Med Assoc 2007; 106(2:97-104

  7. Evaluation of Bcl-2, Bcl-x and Cleaved Caspase-3 in Malignant Peripheral Nerve Sheath Tumors and Neurofibromas

    Directory of Open Access Journals (Sweden)

    KARIN S. CUNHA

    2013-11-01

    Full Text Available AIMS: To study the expression of Bcl-2, Bcl-x, as well the presence of cleaved caspase-3 in neurofibromas and malignant peripheral nerve sheath tumors. The expression of Bcl-2 and Bcl-x and the presence of cleaved caspase 3 were compared to clinicopathological features of malignant peripheral nerve sheath tumors and their impact on survival rates were also investigated. MATERIALS AND METHODS: The evaluation of Bcl-2, Bcl-x and cleaved caspase-3 was performed by immunohistochemistry using tissue microarrays in 28 malignant peripheral nerve sheath tumors and 38 neurofibromas. Immunoquantification was performed by computerized digital image analysis. CONCLUSIONS: Apoptosis is altered in neurofibromas and mainly in malignant peripheral nerve sheath tumors. High levels of cleaved caspase-3 are more common in tumors with more aggressive histological features and it is associated with lower disease free survival of patients with malignant peripheral nerve sheath tumors.

  8. Evolutionary biosemiotics and multilevel construction networks.

    Science.gov (United States)

    Sharov, Alexei A

    2016-12-01

    In contrast to the traditional relational semiotics, biosemiotics decisively deviates towards dynamical aspects of signs at the evolutionary and developmental time scales. The analysis of sign dynamics requires constructivism (in a broad sense) to explain how new components such as subagents, sensors, effectors, and interpretation networks are produced by developing and evolving organisms. Semiotic networks that include signs, tools, and subagents are multilevel, and this feature supports the plasticity, robustness, and evolvability of organisms. The origin of life is described here as the emergence of simple self-constructing semiotic networks that progressively increased the diversity of their components and relations. Primitive organisms have no capacity to classify and track objects; thus, we need to admit the existence of proto-signs that directly regulate activities of agents without being associated with objects. However, object recognition and handling became possible in eukaryotic species with the development of extensive rewritable epigenetic memory as well as sensorial and effector capacities. Semiotic networks are based on sequential and recursive construction, where each step produces components (i.e., agents, scaffolds, signs, and resources) that are needed for the following steps of construction. Construction is not limited to repair and reproduction of what already exists or is unambiguously encoded, it also includes production of new components and behaviors via learning and evolution. A special case is the emergence of new levels of organization known as metasystem transition . Multilevel semiotic networks reshape the phenotype of organisms by combining a mosaic of features developed via learning and evolution of cooperating and/or conflicting subagents.

  9. [Changes in Ca(2+)concentration and caspase-3 expression and their relationship in Raji cells exposed to electromagnetic radiation].

    Science.gov (United States)

    Wang, Wei; Liu, Huan-xin; Wang, De-wen; Zuo, Hong-yan; Peng, Rui-yun

    2013-02-01

    To study the effects of electromagnetic pulse (EMP), S-band high power microwave (S-HPM), and X-band high power microwave (X-HPM) on the Ca(2+) concentration and caspase-3 expression in Raji cells and the relationship between Ca(2+) concentration and caspase-3 expression, and to investigate the regulatory mechanism of electromagnetic radiation damage. Raji cells were cultured conventionally. Some cells were irradiated by EMP, S-HPM, and X-HPM in the logarithmic growth phase for 6 hours and then collected; others received sham irradiation as a control. The Ca(2+) concentration in the cells was measured by laser scanning confocal microscope; the caspase-3 expression in the cells was evaluated by Western blot. Compared with the control group (Ca(2+) fluorescence intensity = 43.08 ± 2.08; caspase-3 expression level = 0.444 ± 0.13), the EMP,S-HPM, and X-HPM groups had significantly increased Ca(2+) concentrations, with Ca(2+) fluorescence intensities of 69.56 ± 1.71, 50.06 ± 1.89, and 70.68 ± 1.59, respectively (P < 0.01), and had upregulated caspase-3 expression, with expression levels of 0.964 ± 0.12, 0.586 ± 0.16, and 0.970 ± 0.07, respectively (P < 0.01). Each of the EMP and X-HPM groups had significantly higher Ca(2+) fluorescence intensity and caspase-3 expression level than the S-HPM group (P < 0.01), but there were no significant differences between the EMP and X-HPM groups. The linear regression analysis showed that the caspase-3 expression was upregulated as the Ca(2+) concentration increased, with a positive correlation between them (P < 0.01). EMP, S-HPM, and X-HPM cause damage probably by increasing the Ca(2+) concentration in cells and in turn inducing caspase-3 overexpression.

  10. Differential regulation of caspase-1 activation, pyroptosis, and autophagy via Ipaf and ASC in Shigella-infected macrophages.

    Directory of Open Access Journals (Sweden)

    Toshihiko Suzuki

    2007-08-01

    Full Text Available Shigella infection, the cause of bacillary dysentery, induces caspase-1 activation and cell death in macrophages, but the precise mechanisms of this activation remain poorly understood. We demonstrate here that caspase-1 activation and IL-1beta processing induced by Shigella are mediated through Ipaf, a cytosolic pattern-recognition receptor of the nucleotide-binding oligomerization domain (NOD-like receptor (NLR family, and the adaptor protein apoptosis-associated speck-like protein containing a C-terminal caspase recruitment domain (ASC. We also show that Ipaf was critical for pyroptosis, a specialized form of caspase-1-dependent cell death induced in macrophages by bacterial infection, whereas ASC was dispensable. Unlike that observed in Salmonella and Legionella, caspase-1 activation induced by Shigella infection was independent of flagellin. Notably, infection of macrophages with Shigella induced autophagy, which was dramatically increased by the absence of caspase-1 or Ipaf, but not ASC. Autophagy induced by Shigella required an intact bacterial type III secretion system but not VirG protein, a bacterial factor required for autophagy in epithelial-infected cells. Treatment of macrophages with 3-methyladenine, an inhibitor of autophagy, enhanced pyroptosis induced by Shigella infection, suggesting that autophagy protects infected macrophages from pyroptosis. Thus, Ipaf plays a critical role in caspase-1 activation induced by Shigella independently of flagellin. Furthermore, the absence of Ipaf or caspase-1, but not ASC, regulates pyroptosis and the induction of autophagy in Shigella-infected macrophages, providing a novel function for NLR proteins in bacterial-host interactions.

  11. AspectKE*

    DEFF Research Database (Denmark)

    Yang, Fan; Masuhara, Hidehiko; Aotani, Tomoyuki

    2010-01-01

    mechanism for pointcuts, so that pointcuts can uniformly specify join points based on both static and dynamic information about the program. Our implementation strategy performs fundamental static analysis at load-time, so as to retain runtime overheads minimal. We implemented a compiler for Aspect......Enforcing security policies to distributed systems is difficult, in particular, when a system contains untrusted components. We designed AspectKE*, a distributed AOP language based on a tuple space, to tackle this issue. In AspectKE*, aspects can enforce access control policies that depend...... on future behavior of running processes. One of the key language features is the predicates and functions that extract results of static program analysis, which are useful for defining security aspects that have to know about future behavior of a program. AspectKE* also provides a novel variable binding...

  12. Inflated impact factors? The true impact of evolutionary papers in non-evolutionary journals.

    Directory of Open Access Journals (Sweden)

    Erik Postma

    Full Text Available Amongst the numerous problems associated with the use of impact factors as a measure of quality are the systematic differences in impact factors that exist among scientific fields. While in theory this can be circumvented by limiting comparisons to journals within the same field, for a diverse and multidisciplinary field like evolutionary biology, in which the majority of papers are published in journals that publish both evolutionary and non-evolutionary papers, this is impossible. However, a journal's overall impact factor may well be a poor predictor for the impact of its evolutionary papers. The extremely high impact factors of some multidisciplinary journals, for example, are by many believed to be driven mostly by publications from other fields. Despite plenty of speculation, however, we know as yet very little about the true impact of evolutionary papers in journals not specifically classified as evolutionary. Here I present, for a wide range of journals, an analysis of the number of evolutionary papers they publish and their average impact. I show that there are large differences in impact among evolutionary and non-evolutionary papers within journals; while the impact of evolutionary papers published in multidisciplinary journals is substantially overestimated by their overall impact factor, the impact of evolutionary papers in many of the more specialized, non-evolutionary journals is significantly underestimated. This suggests that, for evolutionary biologists, publishing in high-impact multidisciplinary journals should not receive as much weight as it does now, while evolutionary papers in more narrowly defined journals are currently undervalued. Importantly, however, their ranking remains largely unaffected. While journal impact factors may thus indeed provide a meaningful qualitative measure of impact, a fair quantitative comparison requires a more sophisticated journal classification system, together with multiple field

  13. Perceived consequences of evolution: College students perceive negative personal and social impact in evolutionary theory

    Science.gov (United States)

    Brem, Sarah K.; Ranney, Michael; Schindel, Jennifer

    2003-03-01

    Evolutionary science has consequences for individuals and society, ranging from the way we interpret human behavior to our notions of spirituality and the purpose of our existence. Popular portrayals of evolution depict a paradoxical theory, a source of knowledge and human connections, but also a threat to our humanity and freedom. Using quantitative and qualitative methodology, we examined how college-educated adults (n = 135) from diverse ethnic and religious backgrounds perceive the impact of evolutionary theory on individuals and society. We identified a continuum of perspectives, ranging from strong creationist to strong evolutionist. Using the model of knowledge as an ecology (Demastes, Good, & Peebles, Science Education, 79, 637-666, 1995; Nardi & O'Day, Information ecologies: Using technology with heart, MIT Press, Cambridge, MA, 1999), we examined the relationships among participants' beliefs, their perceptions regarding the social and personal impact of evolutionary theory, their prior exposure to and knowledge of evolutionary theory, and their opinions regarding the teaching of evolution. Evolutionists and creationists differed in their prior exposure to evolutionary theory, and their opinions about some aspects of teaching, but showed striking similarities regarding perceived impact. All groups viewed the consequences of accepting evolutionary principles in a way that might be considered undesirable: increased selfishness and racism, decreased spirituality, and a decreased sense of purpose and self-determination. From a science education perspective, this one-sided interpretation is troublesome because it runs counter to the available evidence and theories in evolutionary science, and we consider ways of fostering more balanced presentation and appraisal of evolutionary theory.

  14. Abrogation of the presenilin 1/beta-catenin interaction and preservation of the heterodimeric presenilin 1 complex following caspase activation.

    Science.gov (United States)

    Tesco, G; Kim, T W; Diehlmann, A; Beyreuther, K; Tanzi, R E

    1998-12-18

    beta-Catenin has previously been shown to interact with presenilin 1 (PS1) in transfected cells. Here we report that beta-catenin co-immunoprecipitates with the endogenous C-terminal fragment of presenilin 1 (PS1-CTF) but not with the endogenous CTF of presenilin 2 (PS2-CTF) in H4 human neuroglioma cells. During staurosporine (STS)-induced cell death, beta-catenin and PS1-CTF undergo a caspase-mediated cleavage. After 12 h of STS treatment, the beta-catenin.PS1-CTF interaction is abrogated. While PS1-CTF immunoprecipitated with all caspase-cleaved species of beta-catenin, beta-catenin holoprotein did not co-immunoprecipitate with the "alternative" caspase-derived PS1-CTF (PS1-aCTF). Thus, the abrogation of the beta-catenin.PS1-CTF complex was due to caspase cleavage of PS1-CTF. beta-Catenin co-immunoprecipitated with PS1-NTF, but only when PS1-NTF was associated with PS1-CTF. Even though PS1-NTF.CTF complex stability was not altered by caspase cleavage, its ability to bind beta-catenin was abolished. Thus, while the PS1-NTF.CTF complex is preserved after caspase cleavage, it may no longer be fully functional.

  15. The Value of Caspase-3 after the Application of Annona muricata Leaf Extract in COLO-205 Colorectal Cancer Cell Line

    Science.gov (United States)

    Syam, Ari Fahrial; Meilany, Sofy; Laksono, Bayu; Prabu, Oryza Gryagus; Bekti, Heri Setiyo; Indrawati, Lili; Makmun, Dadang

    2017-01-01

    Annona muricata, commonly known as soursop, contains annonacin, acetogenin, and polyphenol which are known to have chemopreventive effects on cancer. In this study, we tend to evaluate the apoptosis-inducing effect of soursop (Annona muricata) leaf extract on the colorectal cancer cell line COLO-205 through the activities of caspase-3 which is a marker of cell apoptosis. Cell cultures were incubated with soursop leaf with a concentration of 10 μg/ml and then compared with those of the incubated positive control leucovorin 10 μg/ml and placebo as a negative control. The apoptotic activity of caspase-3 was measured with ELISA. After the administration of each treatment in the colorectal cancer cell line COLO-205, the expression of caspase-3 activity was 1422 ng/ml after incubation with the extract of Annona muricata leaves, 1373 ng/ml after the administration of leucovorin, and 1297 ng/ml in the one with placebo. Annona muricata leaf extract elevated caspase-3 by 1.09 times compared to that of the pure cell line. Annona muricata leaf extract had a higher value of caspase-3 activity than leucovorin and placebo in the COLO-205 colorectal cancer cell line. These results may suggest that Annona muricata leaf extract had anticancer properties by enhancing caspase-3 activity which is a proapoptotic marker. PMID:28487731

  16. Activation of the NLRP3/caspase-1 inflammasome in human dental pulp tissue and human dental pulp fibroblasts.

    Science.gov (United States)

    Jiang, Wenkai; Lv, Haipeng; Wang, Haijing; Wang, Diya; Sun, Shukai; Jia, Qian; Wang, Peina; Song, Bing; Ni, Longxing

    2015-08-01

    The NLRP3/caspase-1 inflammasome pathway plays an important role in cellular immune defence against bacterial infection; however, its function in human dental pulp tissue and human dental pulp fibroblasts remains poorly understood. We demonstrate that NLRP3 protein expression occurs to a greater extent in pulp tissue with irreversible pulpitis than in normal pulp tissue and in tissue with reversible pulpitis. Caspase-1 is present in its active (cleaved) form only in pulp tissue with irreversible pulpitis. NLRP3 and caspase-1 are expressed in the odontoblast layers in normal human dental pulp tissue, whereas in inflamed pulp tissue, the odontoblast layers are disrupted and dental pulp cells are positive for NLRP3 and caspase-1. Additionally, we investigate the role of the NLRP3/caspase-1 inflammasome pathway in human dental pulp fibroblasts and show that ATP activates the P2X7 receptor on the cell membrane triggering K(+) efflux and inducing the gradual recruitment of the membrane pore pannexin-1. Extracellular lipopolysaccharide is able to penetrate the cytosol and activate NLRP3. Furthermore, the low intracellular K(+) concentration in the cytosol triggers reactive oxygen species generation, which also induces the NLRP3 inflammasome. Thus, the NLRP3/caspase-1 pathway has a biological role in the innate immune response mounted by human dental pulp fibroblasts.

  17. Caspase pathway of elaidic acid (9t-C18:1)-induced apoptosis in human umbilical vein endothelial cells.

    Science.gov (United States)

    Qiu, Bin; Hu, Jiang-Ning; Liu, Rong; Fan, Ya-Wei; Li, Jing; Li, Yu; Deng, Ze-Yuan

    2012-03-01

    Although TFAs (trans fatty acids) do have effects on many endothelial functions, systemic inflammation and immune disorders, only limited experimental evidence is available that TFAs participate in the pathogenesis of endothelial cell apoptosis. HUVEC (human umbilical vein endothelial cells) were grown in medium with elaidic acid (9t-C18:1) at 50, 100, 200 and 400 μmol/l for 24 h. Apoptosis was measured by flow cytometry, and caspase 3, 8 and 9 activities by colorimetric assay and their mRNA expression by qRT-PCR (quantitative real-time PCR). Results showed that 9t-C18:1 induced apoptosis of HUVEC in a dose-dependent manner. The activities and mRNA expression of caspases 8, 9 and 3 were significantly increased compared with that of the control. Z-IETD-FMK and Z-LEHD-FMK inhibited the activation of caspase 3 and apoptosis induced by 9t-C18:1. Also Z-IETD-FMK inhibited the activation of caspase 9. mRNA expressions of Bid and Smac (second mitochondria-derived activator of caspase)/DIABLO [direct IAP (inhibitor of apoptosis)-binding protein with low pI] were also significantly elevated. We conclude that 9t-C18:1 induces apoptosis of HUVEC through activating caspases 8, 9 and 3. The death receptor pathway and the mitochondrial pathway both participated in the apoptosis course induced by 9t-C18:1.

  18. Imaging of activated caspase-3 in living cell by fluorescence resonance energy transfer during photosensitization-induced apoptosis

    Science.gov (United States)

    Wu, Yunxia; Xing, Da; Chen, Qun; Tang, Yonghong

    2005-01-01

    Photodynamic therapy (PDT) is a novel and promising cancer treatment that employs a combination of a photosensitizing chemical and visible light, induces apoptosis in cell, and activation of caspase-3 is considered to be the final step in many apoptosis pathways. The changes of caspase-3 activation in cell during TNFα- and photodynamic therapy-induced apoptosis was measured by fluorescence resonance energy transfer (FRET) analysis. FRET probe consisting of fusions of an enhanced cyan fluorescent protein (ECFP), Venus and a linker peptide containing the caspase-3 cleavage sequence DEVD was utilized. Therefore, activated caspase-3 cleaved the linker peptide of FRET probe and disrupted the FRET signal. Human lung adenocarcinoma cell line (ASTC-a-1) were stably transfected with the plasmid (ECFP-DEVD-Venus) and then were treated by TNF-α and PDT, respectively. Experimental results indicated that caspase-3 activation resulted in cleavage of linker peptide and subsequent disruption of the FRET signal during TNFα- and photodynamic therapy-induced apoptosis, and that the activation of caspase-3 induced by photodynamic therapy was faster than that induce by TNF-α. The study supports that using FRET technique and different recombinant substrates as FRET probes could be used to detect the process of PDT-induced apoptosis and provide a new means to investigate apoptotic mechanism of PDT.

  19. Caspase 3 activity in isolated fetal rat lung fibroblasts and rat periodontal ligament fibroblasts: cigarette smoke-induced alterations

    Directory of Open Access Journals (Sweden)

    James Elliot Scott

    2016-03-01

    Full Text Available Background Cigarette smoking is the leading cause of preventable death in the world. It has been implicated in the pathogenesis of pulmonary, oral and systemic diseases. Smoking during pregnancy is clearly a risk factor for the developing fetus and may be a major cause of infant mortality. Moreover, the oral cavity is the first site of exposure to cigarette smoke and may be a possible source for the spread of toxins to other organs of the body. Fibroblasts in general are morphologically heterogeneous connective tissue cells with diverse functions. Apoptosis or programmed cell death is a crucial process during embryogenesis and for the maintenance of homeostasis throughout life. Deregulation of apoptosis has been implicated in abnormal lung development in the fetus and disease progression in adults. Caspases, are proteases which belong to the family of cysteine aspartic acid proteases and are the key components for the downstream amplification of intra-cellular apoptotic signals. Of the 14 caspases known, caspase-3 is the key executioner of apoptosis. Fetal rat lung fibroblasts but not PDL viability is reduced by exposure to CSE. In addition Caspase 3 activity is elevated after CSE exposure in fetal lung fibroblasts but not in PDLs. Expression of caspase 3 is induced in CSE exposed lung fibroblasts but not in PDLs. Caspase 3 was localized to the cytoplasm in both cell types.

  20. Implications of caspase-dependent proteolytic cleavage of cyclin A1 in DNA damage-induced cell death

    Energy Technology Data Exchange (ETDEWEB)

    Woo, Sang Hyeok; Seo, Sung-Keum [Division of Radiation Cancer Research, Korea Institute of Radiological and Medical Sciences, 215-4 Gongneung-dong, Nowon-gu, Seoul (Korea, Republic of); An, Sungkwan; Choe, Tae-Boo [Department of Microbiological Engineering, Kon-Kuk University, Gwangjin-gu, Seoul (Korea, Republic of); Hong, Seok-Il [Department of Laboratory Medicine, Korea Cancer Center Hospital, Korea Institute of Radiological and Medical Sciences, 215-4 Gongneung-dong, Nowon-gu, Seoul (Korea, Republic of); Lee, Yun-Han, E-mail: yhlee87@yuhs.ac [Department of Radiation Oncology, College of Medicine, Yonsei University, 250 Seongsan-no, Seodaemun-gu, Seoul (Korea, Republic of); Park, In-Chul, E-mail: parkic@kcch.re.kr [Division of Radiation Cancer Research, Korea Institute of Radiological and Medical Sciences, 215-4 Gongneung-dong, Nowon-gu, Seoul (Korea, Republic of)

    2014-10-24

    Highlights: • Caspase-1 mediates doxorubicin-induced downregulation of cyclin A1. • Active caspase-1 effectively cleaved cyclin A1 at D165. • Cyclin A1 expression is involved in DNA damage-induced cell death. - Abstract: Cyclin A1 is an A-type cyclin that directly binds to CDK2 to regulate cell-cycle progression. In the present study, we found that doxorubicin decreased the expression of cyclin A1 at the protein level in A549 lung cancer cells, while markedly downregulating its mRNA levels. Interestingly, doxorubicin upregulated caspase-1 in a concentration-dependent manner, and z-YAVD-fmk, a specific inhibitor of caspase-1, reversed the doxorubicin-induced decrease in cyclin A1 in A549 lung cancer and MCF7 breast cancer cells. Active caspase-1 effectively cleaved cyclin A1 at D165 into two fragments, which in vitro cleavage assays showed were further cleaved by caspase-3. Finally, we found that overexpression of cyclin A1 significantly reduced the cytotoxicity of doxorubicin, and knockdown of cyclin A1 by RNA interference enhanced the sensitivity of cells to ionizing radiation. Our data suggest a new mechanism for the downregulation of cyclin A1 by DNA-damaging stimuli that could be intimately involved in the cell death induced by DNA damage-inducing stimuli, including doxorubicin and ionizing radiation.

  1. The Value of Caspase-3 after the Application of Annona muricata Leaf Extract in COLO-205 Colorectal Cancer Cell Line.

    Science.gov (United States)

    Abdullah, Murdani; Syam, Ari Fahrial; Meilany, Sofy; Laksono, Bayu; Prabu, Oryza Gryagus; Bekti, Heri Setiyo; Indrawati, Lili; Makmun, Dadang

    2017-01-01

    Annona muricata , commonly known as soursop, contains annonacin, acetogenin, and polyphenol which are known to have chemopreventive effects on cancer. In this study, we tend to evaluate the apoptosis-inducing effect of soursop ( Annona muricata ) leaf extract on the colorectal cancer cell line COLO-205 through the activities of caspase-3 which is a marker of cell apoptosis. Cell cultures were incubated with soursop leaf with a concentration of 10  μ g/ml and then compared with those of the incubated positive control leucovorin 10  μ g/ml and placebo as a negative control. The apoptotic activity of caspase-3 was measured with ELISA. After the administration of each treatment in the colorectal cancer cell line COLO-205, the expression of caspase-3 activity was 1422 ng/ml after incubation with the extract of Annona muricata leaves, 1373 ng/ml after the administration of leucovorin, and 1297 ng/ml in the one with placebo. Annona muricata leaf extract elevated caspase-3 by 1.09 times compared to that of the pure cell line. Annona muricata leaf extract had a higher value of caspase-3 activity than leucovorin and placebo in the COLO-205 colorectal cancer cell line. These results may suggest that Annona muricata leaf extract had anticancer properties by enhancing caspase-3 activity which is a proapoptotic marker.

  2. The Value of Caspase-3 after the Application of Annona muricata Leaf Extract in COLO-205 Colorectal Cancer Cell Line

    Directory of Open Access Journals (Sweden)

    Murdani Abdullah

    2017-01-01

    Full Text Available Annona muricata, commonly known as soursop, contains annonacin, acetogenin, and polyphenol which are known to have chemopreventive effects on cancer. In this study, we tend to evaluate the apoptosis-inducing effect of soursop (Annona muricata leaf extract on the colorectal cancer cell line COLO-205 through the activities of caspase-3 which is a marker of cell apoptosis. Cell cultures were incubated with soursop leaf with a concentration of 10 μg/ml and then compared with those of the incubated positive control leucovorin 10 μg/ml and placebo as a negative control. The apoptotic activity of caspase-3 was measured with ELISA. After the administration of each treatment in the colorectal cancer cell line COLO-205, the expression of caspase-3 activity was 1422 ng/ml after incubation with the extract of Annona muricata leaves, 1373 ng/ml after the administration of leucovorin, and 1297 ng/ml in the one with placebo. Annona muricata leaf extract elevated caspase-3 by 1.09 times compared to that of the pure cell line. Annona muricata leaf extract had a higher value of caspase-3 activity than leucovorin and placebo in the COLO-205 colorectal cancer cell line. These results may suggest that Annona muricata leaf extract had anticancer properties by enhancing caspase-3 activity which is a proapoptotic marker.

  3. High-order epistasis shapes evolutionary trajectories.

    Science.gov (United States)

    Sailer, Zachary R; Harms, Michael J

    2017-05-01

    High-order epistasis-where the effect of a mutation is determined by interactions with two or more other mutations-makes small, but detectable, contributions to genotype-fitness maps. While epistasis between pairs of mutations is known to be an important determinant of evolutionary trajectories, the evolutionary consequences of high-order epistasis remain poorly understood. To determine the effect of high-order epistasis on evolutionary trajectories, we computationally removed high-order epistasis from experimental genotype-fitness maps containing all binary combinations of five mutations. We then compared trajectories through maps both with and without high-order epistasis. We found that high-order epistasis strongly shapes the accessibility and probability of evolutionary trajectories. A closer analysis revealed that the magnitude of epistasis, not its order, predicts is effects on evolutionary trajectories. We further find that high-order epistasis makes it impossible to predict evolutionary trajectories from the individual and paired effects of mutations. We therefore conclude that high-order epistasis profoundly shapes evolutionary trajectories through genotype-fitness maps.

  4. Evolutionary dynamics from a variational principle

    Science.gov (United States)

    Klimek, Peter; Thurner, Stefan; Hanel, Rudolf

    2010-07-01

    We demonstrate with a thought experiment that fitness-based population dynamical approaches to evolution are not able to make quantitative, falsifiable predictions about the long-term behavior of some evolutionary systems. A key characteristic of evolutionary systems is the ongoing endogenous production of new species. These novel entities change the conditions for already existing species. Even Darwin’s Demon, a hypothetical entity with exact knowledge of the abundance of all species and their fitness functions at a given time, could not prestate the impact of these novelties on established populations. We argue that fitness is always a posteriori knowledge—it measures but does not explain why a species has reproductive success or not. To overcome these conceptual limitations, a variational principle is proposed in a spin-model-like setup of evolutionary systems. We derive a functional which is minimized under the most general evolutionary formulation of a dynamical system, i.e., evolutionary trajectories causally emerge as a minimization of a functional. This functional allows the derivation of analytic solutions of the asymptotic diversity for stochastic evolutionary systems within a mean-field approximation. We test these approximations by numerical simulations of the corresponding model and find good agreement in the position of phase transitions in diversity curves. The model is further able to reproduce stylized facts of timeseries from several man-made and natural evolutionary systems. Light will be thrown on how species and their fitness landscapes dynamically coevolve.

  5. Evolutionary psychology. Controversies, questions, prospects, and limitations.

    Science.gov (United States)

    Confer, Jaime C; Easton, Judith A; Fleischman, Diana S; Goetz, Cari D; Lewis, David M G; Perilloux, Carin; Buss, David M

    2010-01-01

    Evolutionary psychology has emerged over the past 15 years as a major theoretical perspective, generating an increasing volume of empirical studies and assuming a larger presence within psychological science. At the same time, it has generated critiques and remains controversial among some psychologists. Some of the controversy stems from hypotheses that go against traditional psychological theories; some from empirical findings that may have disturbing implications; some from misunderstandings about the logic of evolutionary psychology; and some from reasonable scientific concerns about its underlying framework. This article identifies some of the most common concerns and attempts to elucidate evolutionary psychology's stance pertaining to them. These include issues of testability and falsifiability; the domain specificity versus domain generality of psychological mechanisms; the role of novel environments as they interact with evolved psychological circuits; the role of genes in the conceptual structure of evolutionary psychology; the roles of learning, socialization, and culture in evolutionary psychology; and the practical value of applied evolutionary psychology. The article concludes with a discussion of the limitations of current evolutionary psychology. 2009 APA, all rights reserved.

  6. Phylogenetic inference with weighted codon evolutionary distances.

    Science.gov (United States)

    Criscuolo, Alexis; Michel, Christian J

    2009-04-01

    We develop a new approach to estimate a matrix of pairwise evolutionary distances from a codon-based alignment based on a codon evolutionary model. The method first computes a standard distance matrix for each of the three codon positions. Then these three distance matrices are weighted according to an estimate of the global evolutionary rate of each codon position and averaged into a unique distance matrix. Using a large set of both real and simulated codon-based alignments of nucleotide sequences, we show that this approach leads to distance matrices that have a significantly better treelikeness compared to those obtained by standard nucleotide evolutionary distances. We also propose an alternative weighting to eliminate the part of the noise often associated with some codon positions, particularly the third position, which is known to induce a fast evolutionary rate. Simulation results show that fast distance-based tree reconstruction algorithms on distance matrices based on this codon position weighting can lead to phylogenetic trees that are at least as accurate as, if not better, than those inferred by maximum likelihood. Finally, a well-known multigene dataset composed of eight yeast species and 106 codon-based alignments is reanalyzed and shows that our codon evolutionary distances allow building a phylogenetic tree which is similar to those obtained by non-distance-based methods (e.g., maximum parsimony and maximum likelihood) and also significantly improved compared to standard nucleotide evolutionary distance estimates.

  7. Evolutionary approaches to understanding sleep.

    Science.gov (United States)

    Lee Kavanau, J

    2005-04-01

    A major controversy over REM sleep's role in memory processing may owe to inadequate allowances for the highly conservative nature of evolutionary adaptations. The controversy hinges on whether NREM sleep, alone, retains primitive memory processing capabilities. The selective pressure for primitive sleep, is thought to have been the need to obviate conflicts between enormous neural processing requirements of complex visual analysis and split-second control of movements, on the one hand, and memory processing, on the other. The most efficient memory processing during mammalian and avian sleep appears to be a two-step process: synapses in individual component circuits of events are reinforced primarily by slow brain waves during NREM sleep, with the reinforced components temporally bound by fast waves, and manifested as dreams, during REM sleep. This dual action could account for partitioning of sleep periods into multiple NREM-REM cycles. It is proposed that in the absence of REM sleep, all needed memory processing can be accomplished by NREM sleep, alone, though less efficiently. Many symptoms of fatal familial insomnia are attributed to subnormal nightly reinforcement of brain circuitry because of almost total loss of sleep, and compensatory responses thereto during waking. During this disorder, sensory circuitry seemingly is spared by virtue of its supernormal reinforcement during almost continuous waking. Contrariwise, sparing of an adult's 'higher faculties' in encephalitis lethargica appears to owe to supernormal circuit reinforcement during almost continuous sleep.

  8. Evolutionary Dynamics of Biological Auctions

    Science.gov (United States)

    Chatterjee, Krishnendu; Reiter, Johannes G.; Nowak, Martin A.

    2011-01-01

    Many scenarios in the living world, where individual organisms compete for winning positions (or resources), have properties of auctions. Here we study the evolution of bids in biological auctions. For each auction n individuals are drawn at random from a population of size N. Each individual makes a bid which entails a cost. The winner obtains a benefit of a certain value. Costs and benefits are translated into reproductive success (fitness). Therefore, successful bidding strategies spread in the population. We compare two types of auctions. In “biological all-pay auctions” the costs are the bid for every participating individual. In “biological second price all-pay auctions” the cost for everyone other than the winner is the bid, but the cost for the winner is the second highest bid. Second price all-pay auctions are generalizations of the “war of attrition” introduced by Maynard Smith. We study evolutionary dynamics in both types of auctions. We calculate pairwise invasion plots and evolutionarily stable distributions over the continuous strategy space. We find that the average bid in second price all-pay auctions is higher than in all-pay auctions, but the average cost for the winner is similar in both auctions. In both cases the average bid is a declining function of the number of participants, n. The more individuals participate in an auction the smaller is the chance of winning, and thus expensive bids must be avoided. PMID:22120126

  9. Evolutionary dynamics under interactive diversity

    Science.gov (United States)

    Su, Qi; Li, Aming; Wang, Long

    2017-10-01

    As evidenced by many cases in human societies, individuals often make different behavior decisions in different interactions, and adaptively adjust their behavior in changeable interactive scenarios. However, up to now, how such diverse interactive behavior affects cooperation dynamics has still remained unknown. Here we develop a general framework of interactive diversity, which models individuals’ separated behavior against distinct opponents and their adaptive adjustment in response to opponents’ strategies, to explore the evolution of cooperation. We find that interactive diversity enables individuals to reciprocate every single opponent, and thus sustains large-scale reciprocal interactions. Our work witnesses an impressive boost of cooperation for a notably extensive range of parameters and for all pairwise games. These results are robust against well-mixed and various networked populations, and against degree-normalized and cumulative payoff patterns. From the perspective of network dynamics, distinguished from individuals competing for nodes in most previous work, in this paper, the system evolves in the form of behavior disseminating along edges. We propose a theoretical method based on evolution of edges, which predicts well both the frequency of cooperation and the compact cooperation clusters. Our thorough investigation clarifies the positive role of interactive diversity in resolving social dilemmas and highlights the significance of understanding evolutionary dynamics from the viewpoint of edge dynamics.

  10. The Evolutionary Origins of Hierarchy.

    Directory of Open Access Journals (Sweden)

    Henok Mengistu

    2016-06-01

    Full Text Available Hierarchical organization-the recursive composition of sub-modules-is ubiquitous in biological networks, including neural, metabolic, ecological, and genetic regulatory networks, and in human-made systems, such as large organizations and the Internet. To date, most research on hierarchy in networks has been limited to quantifying this property. However, an open, important question in evolutionary biology is why hierarchical organization evolves in the first place. It has recently been shown that modularity evolves because of the presence of a cost for network connections. Here we investigate whether such connection costs also tend to cause a hierarchical organization of such modules. In computational simulations, we find that networks without a connection cost do not evolve to be hierarchical, even when the task has a hierarchical structure. However, with a connection cost, networks evolve to be both modular and hierarchical, and these networks exhibit higher overall performance and evolvability (i.e. faster adaptation to new environments. Additional analyses confirm that hierarchy independently improves adaptability after controlling for modularity. Overall, our results suggest that the same force-the cost of connections-promotes the evolution of both hierarchy and modularity, and that these properties are important drivers of network performance and adaptability. In addition to shedding light on the emergence of hierarchy across the many domains in which it appears, these findings will also accelerate future research into evolving more complex, intelligent computational brains in the fields of artificial intelligence and robotics.

  11. 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.

  12. Flourishing: An Evolutionary Concept Analysis.

    Science.gov (United States)

    Agenor, Christine; Conner, Norma; Aroian, Karen

    2017-11-01

    Mental health is an important measure of public health (WHO, 2004); however, nursing practice and research continues to prioritize mental illness, rather than well-being (Wand, 2011). Flourishing is a recent concept in the field of well-being. The term has been used sparingly in nursing practice and research, and conceptual clarification is needed to promote comprehensive understanding of the phenomenon. The purpose of this study is to critically analyze flourishing, assess the maturity of the concept, and provide recommendations for future research, education, and practice. The concept of flourishing was analyzed using the evolutionary approach to concept analysis (Rodgers, 2000). A search for articles on flourishing within the context of well-being was conducted through CINAHL, MEDLINE, and PsycINFO. A sample of 32 articles and 1 book was reviewed. Data were reviewed for concept attributes, antecedents, consequences, surrogate terms and related concepts. Four models of flourishing were identified with six overlapping attributes: meaning, positive relationships, engagement, competence, positive emotion, and self-esteem. Limited longitudinal and predictive studies have been conducted, but there is evidence for several antecedents and outcomes of flourishing. Research is ongoing primarily in psychology and sociology and is lacking in other disciplines. The concept of flourishing is immature; however, evidence is building for related concepts. A lack of consistent terminology regarding flourishing prevents knowledge development of flourishing as a distinct concept. Further multidisciplinary research is needed to establish standard operational and conceptual definitions and develop effective interventions.

  13. Evolutionary optimization of protein folding.

    Directory of Open Access Journals (Sweden)

    Cédric Debès

    Full Text Available Nature has shaped the make up of proteins since their appearance, [Formula: see text]3.8 billion years ago. However, the fundamental drivers of structural change responsible for the extraordinary diversity of proteins have yet to be elucidated. Here we explore if protein evolution affects folding speed. We estimated folding times for the present-day catalog of protein domains directly from their size-modified contact order. These values were mapped onto an evolutionary timeline of domain appearance derived from a phylogenomic analysis of protein domains in 989 fully-sequenced genomes. Our results show a clear overall increase of folding speed during evolution, with known ultra-fast downhill folders appearing rather late in the timeline. Remarkably, folding optimization depends on secondary structure. While alpha-folds showed a tendency to fold faster throughout evolution, beta-folds exhibited a trend of folding time increase during the last [Formula: see text]1.5 billion years that began during the "big bang" of domain combinations. As a consequence, these domain structures are on average slow folders today. Our results suggest that fast and efficient folding of domains shaped the universe of protein structure. This finding supports the hypothesis that optimization of the kinetic and thermodynamic accessibility of the native fold reduces protein aggregation propensities that hamper cellular functions.

  14. Evolutionary theory and the naturalist fallacy

    DEFF Research Database (Denmark)

    Grodal, Torben Kragh

    2008-01-01

    The article is an invited response to a target article by Joseph Carroll entitled "An evolutionary paradigm for literary study". It argues that the target article  misuse the fact that works of art are based on adaptations that were fitness-enhancing in the era of evolutionary adaptations to claim...... that great work of art are also automatically fitness-enhancing in the present day environment, at that there are simple correllations between whether a work of art has a high aesthetic value and whether it is fitness-enhancing or not.  Keywords :  Evolutionary aesthetics, film theory, literary theory...

  15. Evolutionary theory and the naturalist fallacy

    DEFF Research Database (Denmark)

    Grodal, Torben Kragh

    2008-01-01

    that great work of art are also automatically fitness-enhancing in the present day environment, at that there are simple correllations between whether a work of art has a high aesthetic value and whether it is fitness-enhancing or not.  Keywords :  Evolutionary aesthetics, film theory, literary theory......The article is an invited response to a target article by Joseph Carroll entitled "An evolutionary paradigm for literary study". It argues that the target article  misuse the fact that works of art are based on adaptations that were fitness-enhancing in the era of evolutionary adaptations to claim...

  16. Aspect-Oriented Programming

    NARCIS (Netherlands)

    Bergmans, Lodewijk; Videira Lopes, Cristina; Moreira, Ana; Demeyer, Serge

    1999-01-01

    Aspect-oriented programming is a promising idea that can improve the quality of software by reduce the problem of code tangling and improving the separation of concerns. At ECOOP'97, the first AOP workshop brought together a number of researchers interested in aspect-orientation. At ECOOP'98, during

  17. Lexical and Grammatical Aspect

    NARCIS (Netherlands)

    van Hout, Angeliek; Lidz, Jeffrey; Snyder, William; Pater, Joe

    The temporality of a given situation ‘out there in the world’ can be described in many ways. Tense and aspect offer the essential parameters. Lexical aspect characterizes event descriptions; a situation with a sleeping child can be referred to as a state of affairs (be asleep) or as a happening

  18. Smac mimetic triggers necroptosis in pancreatic carcinoma cells when caspase activation is blocked.

    Science.gov (United States)

    Hannes, Sabine; Abhari, Behnaz Ahangarian; Fulda, Simone

    2016-09-28

    Evasion of apoptosis represents a key mechanism of treatment resistance of pancreatic cancer (PC) and contributes to the poor prognosis of this cancer type. Here, we report that induction of necroptosis is an alternative strategy to trigger programmed cell death in apoptosis-resistant PC cells. We show that the second mitochondrial activator of caspases (Smac) mimetic BV6 that antagonizes inhibitor of apoptosis (IAP) proteins induces necroptosis in PC cells in which apoptosis is blocked by the caspase inhibitor zVAD.fmk. Intriguingly, BV6 switches autocrine/paracrine production of tumor necrosis factor (TNF)α by PC cells into a death signal and also acts in concert with exogenously supplied TNFα to trigger necroptosis, when caspase activation is simultaneously blocked. BV6 stimulates TNFα production and formation of the receptor-interacting protein (RIP)1/RIP3-containing necrosome complex in PC cells. Knockdown of TNF receptor 1 (TNFR1) protects PC cells from BV6- or BV6/TNFα-mediated cell death, demonstrating that TNFα autocrine/paracrine signaling by PC cells contributes to BV6-induced necroptosis. Importantly, genetic silencing of receptor interacting protein kinase 3 (RIPK3) or mixed lineage kinase domain-like protein (MLKL) significantly rescues PC cells from BV6- or BV6/TNFα-induced cell death. Similarly, pharmacological inhibition of RIP1, RIP3 or MLKL significantly reduces BV6- or BV6/TNFα-stimulated cell death. By demonstrating that Smac mimetics can bypass resistance to apoptosis by triggering necroptosis as an alternative form of programmed cell death, our findings have important implications for the design of new treatment concepts for PC. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  19. Caffeine inhibits erythrocyte membrane derangement by antioxidant activity and by blocking caspase 3 activation.

    Science.gov (United States)

    Tellone, Ester; Ficarra, Silvana; Russo, Annamaria; Bellocco, Ersilia; Barreca, Davide; Laganà, Giuseppina; Leuzzi, Ugo; Pirolli, Davide; De Rosa, Maria Cristina; Giardina, Bruno; Galtieri, Antonio

    2012-02-01

    The aim of this research was to investigate the effect of caffeine on band 3 (the anion exchanger protein), haemoglobin function, caspase 3 activation and glucose-6-phosphate metabolism during the oxygenation-deoxygenation cycle in human red blood cells. A particular attention has been given to the antioxidant activity by using in vitro antioxidant models. Caffeine crosses the erythrocyte membrane and interacts with the two extreme conformational states of haemoglobin (the T and the R-state within the framework of the simple two states allosteric model) with different binding affinities. By promoting the high affinity state (R-state), the caffeine-haemoglobin interaction does enhance the pentose phosphate pathway. This is of benefit for red blood cells since it leads to an increase of NADPH availability. Moreover, caffeine effect on band 3, mediated by haemoglobin, results in an extreme increase of the anion exchange, particularly in oxygenated erythrocytes. This enhances the transport of the endogenously produced CO(2) thereby avoiding the production of dangerous secondary radicals (carbonate and nitrogen dioxide) which are harmful to the cellular membrane. Furthermore caffeine destabilizes the haeme-protein interactions within the haemoglobin molecule and triggers the production of superoxide and met-haemoglobin. However this damaging effect is almost balanced by the surprising scavenger action of the alkaloid with respect to the hydroxyl radical. These experimental findings are supported by in silico docking and molecular dynamics studies and by what we may call the "caspase silence"; in fact, there is no evidence of any caspase 3 activity enhancement; this is likely due to the promotion of positive metabolic conditions which result in an increase of the cellular reducing power. Copyright © 2011 Elsevier Masson SAS. All rights reserved.

  20. Brain caspase-3 and intestinal FABP responses in preterm and term rats submitted to birth asphyxia

    Directory of Open Access Journals (Sweden)

    R.L. Figueira

    2016-01-01

    Full Text Available Neonatal asphyxia can cause irreversible injury of multiple organs resulting in hypoxic-ischemic encephalopathy and necrotizing enterocolitis (NEC. This injury is dependent on time, severity, and gestational age, once the preterm babies need ventilator support. Our aim was to assess the different brain and intestinal effects of ischemia and reperfusion in neonate rats after birth anoxia and mechanical ventilation. Preterm and term neonates were divided into 8 subgroups (n=12/group: 1 preterm control (PTC, 2 preterm ventilated (PTV, 3 preterm asphyxiated (PTA, 4 preterm asphyxiated and ventilated (PTAV, 5 term control (TC, 6 term ventilated (TV, 7 term asphyxiated (TA, and 8 term asphyxiated and ventilated (TAV. We measured body, brain, and intestine weights and respective ratios [(BW, (BrW, (IW, (BrW/BW and (IW/BW]. Histology analysis and damage grading were performed in the brain (cortex/hippocampus and intestine (jejunum/ileum tissues, as well as immunohistochemistry analysis for caspase-3 and intestinal fatty acid-binding protein (I-FABP. IW was lower in the TA than in the other terms (P<0.05, and the IW/BW ratio was lower in the TA than in the TAV (P<0.005. PTA, PTAV and TA presented high levels of brain damage. In histological intestinal analysis, PTAV and TAV had higher scores than the other groups. Caspase-3 was higher in PTAV (cortex and TA (cortex/hippocampus (P<0.005. I-FABP was higher in PTAV (P<0.005 and TA (ileum (P<0.05. I-FABP expression was increased in PTAV subgroup (P<0.0001. Brain and intestinal responses in neonatal rats caused by neonatal asphyxia, with or without mechanical ventilation, varied with gestational age, with increased expression of caspase-3 and I-FABP biomarkers.

  1. The Role of Protamine 2 Gene Expression and Caspase 9 Activity in Male Infertility.

    Science.gov (United States)

    Zalata, Adel A; Mokhtar, Naglaa; Atwa, Amany; Khaled, Mohamed; Shaker, Olfat G

    2016-03-01

    Approximately 15% of couples are affected by infertility with the man responsible in almost half of the cases. PRMs (protamines) confer a higher order of DNA packaging in sperm than that in somatic cells. Because of the critical roles of PRMs in spermatid differentiation, aberrations in PRM expression or changes in protein structure could be causes of certain types of idiopathic human male infertility. The aim of this study was to give insight into the role of PRM2 gene expression and caspase 9 activity in the pathogenesis of male infertility. The current study included 70 men with idiopathic infertility and 64 fertile men who attended the andrology outpatient clinic at Mansoura University Hospital. Semen sample analyses were done according to WHO recommendations. The acrosome reaction of spermatozoa recovered from each sample was assessed. Samples were separated using discontinuous gradient separation. From each semen sample mature sperm were separated from immature sperm. The resulting samples were divided into 2 parts, including one to determine caspase 9 activity and the other for RNA extraction and reverse transcriptase-polymerase chain reaction of PRM2 gene expression. The polymerase chain reaction product was electrophoresed on 2% agarose gel. PRM2 gene expression was significantly decreased in immature sperm extracted from the fertile and infertile groups. Caspase 9 activity was significantly increased in immature sperm extracted from both groups. Low levels of PRM2 may be associated with morphological abnormalities, initiation of the apoptotic pathway and decreasing sperm motility. PRM2 may be an important marker to better understand the key regulatory pathway of spermatogenesis and it may act as a crucial part of fertilization. Copyright © 2016 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

  2. Voltage dependent anion channel-1 regulates death receptor mediated apoptosis by enabling cleavage of caspase-8

    International Nuclear Information System (INIS)

    Chacko, Alex D; Liberante, Fabio; Paul, Ian; Longley, Daniel B; Fennell, Dean A

    2010-01-01

    Activation of the extrinsic apoptosis pathway by tumour necrosis factor related apoptosis inducing ligand (TRAIL) is a novel therapeutic strategy for treating cancer that is currently under clinical evaluation. Identification of molecular biomarkers of resistance is likely to play an important role in predicting clinical anti tumour activity. The involvement of the mitochondrial type 1 voltage dependent anion channel (VDAC1) in regulating apoptosis has been highly debated. To date, a functional role in regulating the extrinsic apoptosis pathway has not been formally excluded. We carried out stable and transient RNAi knockdowns of VDAC1 in non-small cell lung cancer cells, and stimulated the extrinsic apoptotic pathway principally by incubating cells with the death ligand TRAIL. We used in-vitro apoptotic and cell viability assays, as well as western blot for markers of apoptosis, to demonstrate that TRAIL-induced toxicity is VDAC1 dependant. Confocal microscopy and mitochondrial fractionation were used to determine the importance of mitochondria for caspase-8 activation. Here we show that either stable or transient knockdown of VDAC1 is sufficient to antagonize TRAIL mediated apoptosis in non-small cell lung cancer (NSCLC) cells. Specifically, VDAC1 is required for processing of procaspase-8 to its fully active p18 form at the mitochondria. Loss of VDAC1 does not alter mitochondrial sensitivity to exogenous caspase-8-cleaved BID induced mitochondrial depolarization, even though VDAC1 expression is essential for TRAIL dependent activation of the intrinsic apoptosis pathway. Furthermore, expression of exogenous VDAC1 restores the apoptotic response to TRAIL in cells in which endogenous VDAC1 has been selectively silenced. Expression of VDAC1 is required for full processing and activation of caspase-8 and supports a role for mitochondria in regulating apoptosis signaling via the death receptor pathway

  3. Doves and hawks in economics revisited: An evolutionary quantum game theory based analysis of financial crises

    Science.gov (United States)

    Hanauske, Matthias; Kunz, Jennifer; Bernius, Steffen; König, Wolfgang

    2010-11-01

    The last financial and economic crisis demonstrated the dysfunctional long-term effects of aggressive behaviour in financial markets. Yet, evolutionary game theory predicts that under the condition of strategic dependence a certain degree of aggressive behaviour remains within a given population of agents. However, as a consequence of the financial crisis, it would be desirable to change the “rules of the game” in a way that prevents the occurrence of any aggressive behaviour and thereby also the danger of market crashes. The paper picks up this aspect. Through the extension of the well-known hawk-dove game by a quantum approach, we can show that dependent on entanglement, evolutionary stable strategies also can emerge, which are not predicted by the classical evolutionary game theory and where the total economic population uses a non-aggressive quantum strategy.

  4. Training the Millennial learner through experiential evolutionary scaffolding: implications for clinical supervision in graduate education programs.

    Science.gov (United States)

    Venne, Vickie L; Coleman, Darrell

    2010-12-01

    They are the Millennials--Generation Y. Over the next few decades, they will be entering genetic counseling graduate training programs and the workforce. As a group, they are unlike previous youth generations in many ways, including the way they learn. Therefore, genetic counselors who teach and supervise need to understand the Millennials and explore new ways of teaching to ensure that the next cohort of genetic counselors has both skills and knowledge to represent our profession well. This paper will summarize the distinguishing traits of the Millennial generation as well as authentic learning and evolutionary scaffolding theories of learning that can enhance teaching and supervision. We will then use specific aspects of case preparation during clinical rotations to demonstrate how incorporating authentic learning theory into evolutionary scaffolding results in experiential evolutionary scaffolding, a method that potentially offers a more effective approach when teaching Millennials. We conclude with suggestions for future research.

  5. From descent to ascent--the human exception in the evolutionary synthesis.

    Science.gov (United States)

    Sommer, Marianne

    2010-01-01

    As the 'Darwin anniversary' (2009) has amply illustrated, Charles Darwin is seen as having forced a new understanding of self on humankind as a product of blind natural forces. However, mechanisms such as orthogenesis and the inheritance of acquired characteristics were maintained post-Origin to explain purposeful evolution. Only with the modern synthesis these mechanisms lost their validity, and Darwinian selection theory became the core of evolutionary biology. Thereafter, teleology was no longer an aspect of the natural world. This is how Theodosius Dobzhansky, Julian Huxley, Ernst Mayr, and George Gaylord Simpson told the history of evolutionary biology after Darwin throughout their lives. In the aftermath of the Darwin-year, it is worth taking another look: Was it in the evolutionary theories of the synthesis that humans finally became generally regarded as just another kind of living organism, subjected to the indifferent mechanisms of evolution and the whims of chance?

  6. Monomerization of cytosolic mature smac attenuates interaction with IAPs and potentiation of caspase activation.

    OpenAIRE

    Stephen P Burke; Jeffrey B Smith

    2010-01-01

    The four residues at the amino-terminus of mature Smac/DIABLO are an IAP binding motif (IBM). Upon exit from mitochondria, mature Smac interacts with inhibitor of apoptosis proteins (IAPs), abrogating caspase inhibition. We used the ubiquitin fusion model to express mature Smac in the cytosol. Transiently expressed mature Smac56-239 (called Smac56) and Smac60-239 (called Smac60), which lacks the IBM, interacted with X-linked inhibitor of apoptosis protein (XIAP). However, stable expression pr...

  7. Inactivation of cellular caspases by peptide-derived tryptophan and tyrosine peroxides

    DEFF Research Database (Denmark)

    Hampton, Mark B; Morgan, Philip E; Davies, Michael Jonathan

    2002-01-01

    Peroxides generated on peptides and proteins within cells, as a result of radical attack or reaction with singlet oxygen, are longer-lived than H(2)O(2) due to their poor removal by protective enzymes. These peroxides readily oxidize cysteine residues and can inactivate thiol-dependent enzymes. We...... show here that Trp- and Tyr-derived peptide peroxides, generated by singlet oxygen, inhibit caspase activity in the lysates of apoptotic Jurkat cells. N-Ac-Trp-OMe peroxide was the most effective inhibitor, and was 30-fold more effective than H(2)O(2) under identical conditions. As such, protein...

  8. Molluscan death effector domain (DED)-containing caspase-8 gene from disk abalone (Haliotis discus discus): molecular characterization and expression analysis.

    Science.gov (United States)

    Lee, Youngdeuk; De Zoysa, Mahanama; Whang, Ilson; Lee, Sukkyoung; Kim, Yucheol; Oh, Chulhong; Choi, Cheol Young; Yeo, Sang-Yeob; Lee, Jehee

    2011-02-01

    The caspase family represents aspartate-specific cysteine proteases that play key roles in apoptosis and immune signaling. In this study, we cloned the first death effector domain (DED)-containing molluscan caspase-8 gene from disk abalone (Haliotis discus discus), which is named as hdCaspase-8. The full-length hdCaspase was 2855 bp, with a 1908 bp open reading frame encoding 636 amino acids. The hdCaspase-8 had 72 kDa predicted molecular mass with an estimated isoelectric point (PI) of 6.0. The hdCaspase-8 amino acid sequence contained the characteristic feature of an N-terminal two DED, a C-terminal catalytic domain and the caspase family cysteine active site ⁵¹³KPKLFFLQACQG⁵²⁴. Phylogenetic analysis results showed that hdCaspase-8 is more similar to the invertebrate Tubifex tubifex (sludge worm) caspase-8. Real-time RT-PCR results showed that hdCaspase-8 constitutively and ubiquitously expressed in all tested tissue of unchallenged disk abalone. The basal expression level of hdCaspase-8 in gill tissue was higher than all other tested tissues. The hdCaspase-8 mRNA expression in gill and hemocytes was significantly up-regulated by exposure to bacteria (Vibrio alginolyticus, Vibrio parahemolyticus and Listeria monocytogenes) and VHSV (viral hemorrhagic septicemia virus), as compared to control animals. These results suggest that hdCaspase-8 may be involved in immune response reactions in disk abalone. Copyright © 2010 Elsevier Ltd. All rights reserved.

  9. [Evolutionary Concept Analysis of Spirituality].

    Science.gov (United States)

    Ko, Il Sun; Choi, So Young; Kim, Jin Sook

    2017-04-01

    This study was done to clarify attributes, antecedents, and consequences of spirituality. Rodgers's evolutionary concept analysis was used to analyze fifty seven studies from the literature related to spirituality as it appears in systematic literature reviews of theology, medicine, counseling & psychology, social welfare, and nursing. Spirituality was found to consist of two dimensions and eight attributes: 1) vertical dimension: 'intimacy and connectedness with God' and 'holy life and belief', 2) horizontal dimension: 'self-transcendence', 'meaning and purpose in life', 'self-integration', and 'self-creativity' in relationship with self, 'connectedness' and 'trust' in relationship with others·neighbors·nature. Antecedents of spirituality were socio-demographic, religious, psychological, and health related characteristics. Consequences of spirituality were positive and negative. Being positive included 'life centered on God' in vertical dimension, and among horizontal dimension 'joy', 'hope', 'wellness', 'inner peace', and 'self-actualization' in relationship with self, 'doing in love' and 'extended life toward neighbors and the world' in relationship with others·neighbors·nature. Being negative was defined as having 'guilt', 'inner conflict', 'loneliness', and 'spiritual distress'. Facilitators of spirituality were stressful life events and experiences. Spirituality is a multidimensional concept. Unchangeable attributes of spirituality are 'connectedness with God', 'self-transcendence', 'meaning of life' and 'connectedness with others·nature'. Unchangeable consequences of spirituality are 'joy' and 'hope'. The findings suggest that the dimensional framework of spirituality can be used to assess the current spiritual state of patients. Based on these results, the development of a Korean version of the scale measuring spirituality is recommended. © 2017 Korean Society of Nursing Science

  10. Evolutionary biology and life histories

    Directory of Open Access Journals (Sweden)

    Brown, C. R.

    2004-06-01

    Full Text Available The demographic processes that drive the spread of populations through environments and in turn determine the abundance of organisms are the same demographic processes that drive the spread of genes through populations and in turn determine gene frequencies and fitness. Conceptually, marked similarities exist in the dynamic processes underlying population ecology and those underlying evolutionary biology. Central to an understanding of both disciplines is life history and its component demographic rates, such as survival, fecundity, and age of first breeding, and biologists from both fields have a vested interest in good analytical machinery for the estimation and analysis of these demographic rates. In the EURING conferences, we have been striving since the mid 1980s to promote a quantitative understanding of demographic rates through interdisciplinary collaboration between ecologists and statisticians. From the ecological side, the principal impetus has come from population biology, and in particular from wildlife biology, but the importance of good quantitative insights into demographic processes has long been recognized by a number of evolutionary biologists (e.g., Nichols & Kendall, 1995; Clobert, 1995; Cooch et al., 2002. In organizing this session, we have aimed to create a forum for those committed to gaining the best possible understanding of evolutionary processes through the application of modern quantitative methods for the collection and interpretation of data on marked animal populations. Here we present a short overview of the material presented in the session on evolutionary biology and life histories. In a plenary talk, Brown & Brown (2004 explored how mark–recapture methods have allowed a better understanding of the evolution of group–living and alternative reproductive tactics in colonial cliff swallows (Petrochelidon pyrrhonota. By estimating the number of transient birds passing through colonies of different sizes, they

  11. [Evolutionary medicine: an emergent basic science].

    Science.gov (United States)

    Spotorno, Angel E

    2005-02-01

    Evolutionary Medicine is an emergent basic science that offers new and varied perspectives to the comprehension of human health. The application of classic evolutionary theories (descent with modification, and natural selection) to the human organism, to its pathogens, and their mutual co-evolution, provides new explanations about why we get sick, how we can prevent this, and how we can heal. Medicine has focused mainly on the proximate or immediate causes of diseases and the treatment of symptoms, and very little on its evolutionary or mediate causes. For instance, the present human genome and phenotypes are essentially paleolithic ones: they are not adapted to modern life style, thus favoring the so-called diseases of civilization (ie: ateroesclerosis, senescence, myopia, phobias, panic attacks, stress, reproductive cancers). With the evolutionary approach, post-modern medicine is detecting better the vulnerabilities, restrictions, biases, adaptations and maladaptations of human body, its actual diseases, and its preventions.

  12. 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 ...

  13. Mean-Potential Law in Evolutionary Games

    Science.gov (United States)

    Nałecz-Jawecki, Paweł; Miekisz, Jacek

    2018-01-01

    The Letter presents a novel way to connect random walks, stochastic differential equations, and evolutionary game theory. We introduce a new concept of a potential function for discrete-space stochastic systems. It is based on a correspondence between one-dimensional stochastic differential equations and random walks, which may be exact not only in the continuous limit but also in finite-state spaces. Our method is useful for computation of fixation probabilities in discrete stochastic dynamical systems with two absorbing states. We apply it to evolutionary games, formulating two simple and intuitive criteria for evolutionary stability of pure Nash equilibria in finite populations. In particular, we show that the 1 /3 law of evolutionary games, introduced by Nowak et al. [Nature, 2004], follows from a more general mean-potential law.

  14. Evolutionary medicine: its scope, interest and potential

    Science.gov (United States)

    Stearns, Stephen C.

    2012-01-01

    This review is aimed at readers seeking an introductory overview, teaching courses and interested in visionary ideas. It first describes the range of topics covered by evolutionary medicine, which include human genetic variation, mismatches to modernity, reproductive medicine, degenerative disease, host–pathogen interactions and insights from comparisons with other species. It then discusses priorities for translational research, basic research and health management. Its conclusions are that evolutionary thinking should not displace other approaches to medical science, such as molecular medicine and cell and developmental biology, but that evolutionary insights can combine with and complement established approaches to reduce suffering and save lives. Because we are on the cusp of so much new research and innovative insights, it is hard to estimate how much impact evolutionary thinking will have on medicine, but it is already clear that its potential is enormous. PMID:22933370

  15. The active evolutionary lives of echinoderm larvae.

    Science.gov (United States)

    Raff, R A; Byrne, M

    2006-09-01

    Echinoderms represent a researchable subset of a dynamic larval evolutionary cosmos. Evolution of echinoderm larvae has taken place over widely varying time scales from the origins of larvae of living classes in the early Palaeozoic, approximately 500 million years ago, to recent, rapid and large-scale changes that have occurred within living genera within a span of less than a million years to a few million years. It is these recent evolutionary events that offer a window into processes of larval evolution operating at a micro-evolutionary level of evolution of discrete developmental mechanisms. We review the evolution of the diverse larval forms of living echinoderms to outline the origins of echinoderm larval forms, their diversity among living echinoderms, molecular clocks and rates of larval evolution, and finally current studies on the roles of developmental regulatory mechanisms in the rapid and radical evolutionary changes observed between closely related congeneric species.

  16. A Philosophical Perspective on Evolutionary Systems Biology.

    Science.gov (United States)

    O'Malley, Maureen A; Soyer, Orkun S; Siegal, Mark L

    2015-03-01

    Evolutionary systems biology (ESB) is an emerging hybrid approach that integrates methods, models, and data from evolutionary and systems biology. Drawing on themes that arose at a cross-disciplinary meeting on ESB in 2013, we discuss in detail some of the explanatory friction that arises in the interaction between evolutionary and systems biology. These tensions appear because of different modeling approaches, diverse explanatory aims and strategies, and divergent views about the scope of the evolutionary synthesis. We locate these discussions in the context of long-running philosophical deliberations on explanation, modeling, and theoretical synthesis. We show how many of the issues central to ESB's progress can be understood as general philosophical problems. The benefits of addressing these philosophical issues feed back into philosophy too, because ESB provides excellent examples of scientific practice for the development of philosophy of science and philosophy of biology.

  17. Evolutionary optimization of production materials workflow processes

    DEFF Research Database (Denmark)

    Herbert, Luke Thomas; Hansen, Zaza Nadja Lee; Jacobsen, Peter

    2014-01-01

    We present an evolutionary optimisation technique for stochastic production processes, which is able to find improved production materials workflow processes with respect to arbitrary combinations of numerical quantities associated with the production process. Working from a core fragment...

  18. Litter feedbacks, evolutionary change and exotic plant

    NARCIS (Netherlands)

    Eppinga, M.B.; Kaproth, M.A.; Collins, A.R.; Molofsky, J.

    2011-01-01

    1. Understanding the mechanisms driving exotic plant invasions is important for designing successful invader control strategies. Previous studies have highlighted different invasion mechanisms, including alteration of nutrient cycles through plant–soil feedback and evolutionary change toward more

  19. A Hybrid Chaotic Quantum Evolutionary Algorithm

    DEFF Research Database (Denmark)

    Cai, Y.; Zhang, M.; Cai, H.

    2010-01-01

    and enhance the global search ability. A large number of tests show that the proposed algorithm has higher convergence speed and better optimizing ability than quantum evolutionary algorithm, real-coded quantum evolutionary algorithm and hybrid quantum genetic algorithm. Tests also show that when chaos......A hybrid chaotic quantum evolutionary algorithm is proposed to reduce amount of computation, speed up convergence and restrain premature phenomena of quantum evolutionary algorithm. The proposed algorithm adopts the chaotic initialization method to generate initial population which will form...... a perfect distribution in feasible solution space in advantage of randomicity and non-repetitive ergodicity of chaos, the simple quantum rotation gate to update non-optimal individuals of population to reduce amount of computation, and the hybrid chaotic search strategy to speed up its convergence...

  20. Deciphering morphology in Triatominae: the evolutionary signals.

    Science.gov (United States)

    Dujardin, J P; Costa, J; Bustamante, D; Jaramillo, N; Catalá, S

    2009-01-01

    Many species of Triatominae show evidence for morphological plasticity. Frequent taxonomic questions arose from this variability leading to disputes about describing new subspecies, species or even genera. We suggest this phenotypic flexibility is primarily an intraspecific feature, but with potential for evolutionary changes. We present arguments for a selection regime leading to the separation of species having low developmental canalization into morphologically distinct ecotypes. We suggest that these ecotypes, or morphs, or forms, may have evolutionary importance even if gene flow still exists between them. Thus, although we consider the morphological plasticity of Triatominae as an intraspecific trait, we defend the idea that it might represent a common evolutionary route to new species. Speciation processes in Triatominae could result from disruptive selection regimes combined with weak developmental canalization. Added to this basic pattern, accidental events could hasten evolutionary change. We suggest the heterosis as one of them.