Extended Synthesis (Evolution Theory)

from Wikipedia, the free encyclopedia

Advanced synthesis of evolutionary theory (Extended Evolutionary Synthesis, EES) is a term used by members of a group of originally 16 ( Altenberg-16 ), and then philosophers Biology establish further biologists and in 2008. The term expresses the opinion that the previous evolution theory (called synthetic evolution theory ) has to be expanded for various reasons. The ideas have matured from the long-standing criticism of the synthesis and the notion that this synthesis needs to be greatly expanded. Various contents of the extended synthesis are now used under this term in standard textbooks and manuals.

The opponents of the initiative criticized the fact that the term was superfluous, since the conventional theory had so far adopted and integrated all new discoveries. In October 2014, the journal Nature gave both sides the opportunity to publish a detailed statement.

Early history

In the 1950s, the British biologist CH Waddington called for an expansion of synthesis based on his work on epigenetics and genetic assimilation . An extended synthesis was also proposed by the Austrian zoologist Rupert Riedl , based on studies on evolvability . In 1978 the zoologist Michael JD White wrote about an extension of the Modern Synthesis based on his research on speciation .

In the 1980s, American paleontologists Stephen Jay Gould and Niles Eldredge argued for an expanded synthesis. This demand was justified with the idea of punctualism , an explanation of discontinuous rates of change and jumps in fossil rows, as well as the observation that great evolutionary changes take place in the selection of species. Ultimately, natural selection works on different levels, from genes to the organism in the entire species.

The ethologist and evolutionary biologist John Endler also pleaded in 1988 for a "newer synthesis" in which he pointed out evolutionary processes that were not taken into account.

From 1990, in the course of research results in the new discipline of evolutionary developmental biology, voices became louder calling for embryonic development with its change processes and mechanisms to be a core component of evolutionary theory. The most extensive work on this comes from the American Mary Jane West-Eberhard . In 2003, in a work of 800 pages, in which around 100 biologists are involved and which contains numerous empirical studies, it provides a comprehensive critique of standard theory and calls for a new framework for a unified theory of evolution that considers development, the environment and plasticity as causative factors Evolution takes up.

Key messages from 2010

From the point of view of the advocates of extended synthesis, the standard theory focuses exclusively on genetic inheritance and on processes that influence the frequency of alleles. According to this, natural selection is "the only explanation for adaptation". The proponents of the extended synthesis claim that the synthetic theory of evolution does not allow or does not deal with important topics for the explanation of evolution . They emphasize that their theory is not limited to weighting already known knowledge differently, but that the theory of evolution has to be updated in its basic structure, in its framework conditions or basic assumptions as well as in its prediction options. The theory of evolution is newly established in its causality. In a handbook on evolution, the ideas of the extended synthesis are included, which states that, among other things, through evolutionary developmental biology, “the original approach of neo-Darwinism has changed significantly and has led to a greater theoretical and methodological diversity in evolutionary biology. The theory of evolution has thereby become less adaptationistic and also more organism-oriented (and in this sense less gentristic). ”The essential new statements of the extended synthesis relate to the following research areas and topics:

Evolutionary development

From the new point of view, embryonic development is treated as a "black box" by the previous synthetic evolution theory. The emergence of phenotypic variation is not explained and taken for granted. The synthetic theory of evolution does not contain any theory of the origin of variation. It relies on the presence of random mutation in inheritance and its population genetic frequency. According to Kirschner / Gerhart and other evolution theorists, however, the theory of evolution needs three equally important pillars:

  1. A theory of natural selection
  2. A theory of inheritance
  3. A theory of phenotypic variation.

The extended synthesis provides the missing building block with the explanation of the origin of variation in the development.

Amundson writes: “For embryologists, the synthesis was far from complete. It had two related loopholes: the mistake of not dealing with development and the inability to study genetically the traits that characterize species and higher taxa. ”The extended synthesis also sees the epigenetic levels (cells, cell clusters, Environment) and see the development as a "complex epigenetic system".

Scientists who had drawn attention to the importance of development at an early stage, such as Conrad Hal Waddington , were not integrated into the synthetic theory of evolution. The research discipline EvoDevo is now becoming an important part of the Extended Synthesis. It provides causal-mechanistic explanations, while the synthetic theory of evolution, which focuses on population genetics, provides mathematical-statistical descriptive knowledge. The theoretical structure of the theory of evolution changes accordingly with the causal-mechanistic explanatory approach of EvoDevo and the detachment from the preponderance of population genetics .

Evolutionary developmental biology criticizes that neo-Darwinism has no "theory of the generative", that is, no theory about how ordered organismic structure can evolve (e.g. fingers, hair, blood vessels, etc.). As a consequence, the prevailing theory of evolution can only predict what will be preserved, but not what will appear evolutionary. Elsewhere it is said that selection has no innovative capacity; either it eliminates or it preserves what exists. The generative and ordering aspects of morphological evolution thus lie outside the theory of evolution.

Directed development

Biased development means that as a result of genetic or environmental variation, certain phenotypes are more likely than others. Directed development is seen as an important evolutionary process that facilitates evolution and directs it towards certain phenotypes. Certain developmental pathways produce such parallel evolution, known in standard theory as convergent evolution and attributed to natural selection. These directed phenotypes can no longer be explained with passive constraints , but with active, development-immanent processes.

An example of directed development is polydactyly . Here the frequencies of additional finger and toe numbers of the mutant follow a statistical distribution with a maximum. The shape of the head with a bulging forehead in certain cichlids is also directional and therefore remarkable because this shape occurs in different African lakes, in which the species are more distantly related than the species within a lake. Furthermore, the more than 100 different species of millipedes always have an odd number of pairs of legs, which is also based on development mechanisms. Directed development is a major source of evolvability in Extended Synthesis and for explaining its mechanisms, distribution and direction.

Developmental plasticity

Developmental plasticity or phenotypic plasticity is predominant according to the extended synthesis at all levels of biological organization. Plasticity is seen as a cause and not a consequence of phenotypic evolution. The authors, among them Mary Jane West-Eberhard , cite numerous examples in which plasticity enables the colonization of new environments, influences the connection of populations or contributes to temporal and spatial variation in selection. Although developmental plasticity is closely related to EvoDevo, the authors see it as a separate topic due to its causal property for evolution.

Including inheritance

The traditional theory is limited to genetic inheritance. Extended Synthesis sees both genetic and non-genetic inheritance, what it calls inclusive inheritance. According to this, inheritance contains all the causal mechanisms by which offspring resemble their parents. Phenotypes are not inherited, but rather reconstructed during development using EvoDevo mechanisms. Non-genetic inheritance mechanisms enable the emergence and spread of environmentally induced variations and innovations in evolution.

Environment as a cause of evolution

According to Pigliucci, ecology was also ignored by the synthetic theory of evolution. The synthetic theory of evolution refers to the Weismann barrier , according to which it is not possible that germ cells and thus DNA can be hereditary changed by environmental influences . However, modern evolutionary research now knows a large number of empirical studies, according to which the environment causally influences the hereditary development of variation and thus evolution and does not only appear in the form of selection and adaptation. These include the experiments by Conrad Hal Waddington on the wing wings . These experimentally and theoretically confirmed research results were further substantiated by Darwin's finches , the taming of silver foxes by Belyaev and other examples.

Complex genotype-phenotype relationship

From the perspective of extended synthesis, the synthetic theory of evolution assumes that there is a simple, deterministic relationship between genes and phenotypic characteristics. More recent research, however, shows that due to environmental influences during development ( phenotypic plasticity ) and due to the emergent capabilities of development as a complex system, one can no longer speak of a deterministic relationship. As West-Eberhard put it : “One can never say that the individual genome controls development. Development depends in every step on the pre-existing structure of the phenotype, a structure that is complexly determined by a long history of influences from both the genome and the environment. "

Internal factors of evolution

From the perspective of extended synthesis, the synthetic theory of evolution explains evolution primarily through the action of natural selection and thus biologically external. The extended synthesis, on the other hand, explains the origin of phenotypic variation causally through development and thus biologically internal. Thus, the extended synthesis raises the question of the "arrival of the fittest", while the synthesis is limited to the "survival of the fittest".

Spontaneous phenotypic variation

For the synthetic theory of evolution, evolutionary change takes place exclusively in gradualistic, smallest steps, which can accumulate to phenotypically larger variations over the course of many generations. In Julian Huxley's work The Modern Synthesis it says: “Every sharp step [of evolution] is immediately buffered. […] Final change must wait for further mutation. […] In any case, what mutates is the gene complex, and it can do this in a series of small irregular steps, so finely graduated as if they represented a continuous increase. ”Such a view gives natural selection“ the direction “About what arises adaptively . The evolutionary developmental biology and Advanced Synthesis contrast go spontaneous, makroevolutionärer from, phenotypic variation during development. It is initiated (but not controlled) by genetic mutation, but in most cases, according to West-Eberhard, by changing environmental influences. Environmental influences maintain variations in a population, and genetic assimilation only occurs later on . The Extended Synthesis adopts this concept of phenotypic variation from the theory of eased variation and from EvoDevo in general.

Niche construction

The theory of the niche construction of the British John Odling-Smee , as an essential pillar of the extended synthesis, explains how living beings created their own environment and how this environment in turn influences the evolution of these living beings. According to the theory, this applies to the spread of algae on earth and the associated oxygen production in the atmosphere. Numerous other examples include niche construction, including beavers and termites through to humans who create culture in whose environment their own evolution takes place. In addition to natural selection, niche construction is seen as its own evolutionary factor.

Partial theories

"Third way" between "Neo-Darwinism" and "Creationism"

Four members of the original Extended Synthesis from 2008 ( Altenberg-16 ), namely Eva Jablonka, Gerd B. Müller, Stuart A. Newman and John Odling-Smee, are also members of another initiative with similar goals: "The Third Way" . It was founded in May 2014 and consists of more than 50 members (2017), mostly professors from various biological disciplines. According to its own statement, it sees itself as the third way alongside neo-Darwinism and creationism . Creationism as an explanation for evolution is rejected as unscientific. They reject “neo-Darwinism”, the previous standard theory, because it regards natural selection as the only determining factor in evolution. ("Neo-Darwinists have elevated Natural Selection into a unique creative force").

The initiators of the Internet portal The Third Way are Raju Pookottil , Denis Noble and James A. Shapiro . Pookottil is an engineer and author of the book "Biological Emergence-Based Evolutionary Mechanism: How Species Direct Their Own Evolution" , which promotes a rebirth of the evolutionary theory of Lamarckism . Noble is a retired Oxford Professor and one of the pioneers in systems biology . From his point of view, all central assumptions of the synthetic theory of evolution have been refuted in such a way that they challenge a new synthesis. Shapiro is a microbiologist at the University of Chicago. Natural genetic engineering goes back to him , the idea that the genome has processes and mechanisms for its own evolutionary remodeling. Random mutations alone did not adequately explain the genetic processes in the overall evolutionary process.

Criticism and counter-criticism

In a joint statement in the journal Nature (2014), seven biologists expressed criticism of the term initiative. They summarized the concerns of the initiative and criticized the use of the term “extended synthesis” as superfluous. They welcomed the proponents' ideas as part of what the theory of evolution might become in the future. They agreed with the initiative's opinion that the following four phenomena are important for evolutionary biology: phenotypic plasticity, niche construction, including heredity and developmental bias, and they would do their own research in these areas. In their opinion, however, it is not necessary to introduce the new term "extended synthesis in the theory of evolution" for the processes mentioned.

The critics have the following comments on the four subject areas mentioned by the initiative:

The role of phenotypic plasticity in evolutionary change is so well documented that it does not need to be emphasized again. “The question of whether plasticity can control genetic variation as part of the adaptation process is less clear. Over 50 years ago, developmental biologist Conrad Waddington described a process he called genetic assimilation . New mutations can convert one plastic property into another, which subsequently develops without the specific cause. There are only a few examples of this outside of the laboratory. Whether this is due to the fact that this phenomenon has not yet been seriously considered or whether it is a real rarity in nature, we can only find out through further investigations. "

The new name niche construction does not change the fact that evolutionary biologists have been researching feedback mechanisms between organisms and their environment for more than a century.

So far there is no solid evidence that inherited, epigenetic modifications (part of so-called inclusive inheritance) play a major role in adaptation. “Not a single new feature is known that is based solely on epigenetic mechanisms and not also on its gene sequence. Both aspects should be examined more closely. "

Due to a lack of data, it is currently not possible to assess the role of “directed development” (developmental bias) in evolution. “Ultimately, however, it is not a question of the extent of the feature variation or the exact trigger mechanism. The only decisive factor is the inheritable differences in the characteristics, especially those with a selective advantage. "

The critics of the term initiative come to the conclusion that it can be discussed whether these phenomena have already been sufficiently taken into account. Alternatively, they argue that the theoretical foundations should be laid down and more empirical studies should be undertaken in order to find out the actual meaning of these phenomena.

The proponents of the extended synthesis declared in 2015 that the extended theory does not represent different weightings of what is already known, as interpreted by the critics, but that Laland uses its own theory with different framework conditions or basic assumptions, new interpretation of research results and new types of forecasting options elsewhere it is clear that the Extended Synthesis is about new causality in evolution. In addition to those who have appeared so far, other authors call for epigenetics to be included in the theory of evolution, specifically in extended synthesis.

Web links

literature

Basics

  • Jablonka, Eva & Lamb Marion J. (2005): Evolution in four dimensions. Genetic, Epigenetic, Behavioral and Symbolic Variation in the History of Life. WITH PreLangess.
  • Kirschner, Marc W. & Gerhart, John C. (2010): Facilitated Variation, in: Pigliucci, Massimo & Müller, Gerd (2010) Evolution - the Extended Synthesis . MIT Press
  • Kirschner, Marc W. & Gerhart, John C. (2007): The Solution to Darwin's Dilemma - How Evolution Creates Complex Life. Rowohlt. Orig. The Plausibility of Life (2005)
  • Laubichler MD, Renn J. 2015. Extended evolution: A conceptual framework for integrating regulatory networks and niche construction. J. Exp. Zool. (Mol. Dev. Evol.) 324B: 565-577. ( pdf )
  • Love, Alan C. (2010): Rethinking the Structure of Evolutionary Theory for an Extended Synthesis in Pigliucci / Müller (2010)
  • Müller, Gerd B. (2010): Epigenetic Innovation in: Pigliucci, Massimo & Müller, Gerd (2010): Evolution - the Extended Synthesis . MIT Press
  • Müller, Gerd B. (2009): Extending the Evolutionary Synthesis
  • Odling-Smee, John (2010): Niche inheritance. in Pigliucci / Müller (2010)
  • Pigliucci, Massimo & Müller, Gerd (2010): Evolution - the Extended Synthesis . MIT Press. (with articles from all participants of the Altenberg16 group).
  • Pigliucci, Massimo & Müller, Gerd (2010): Elements of an Evolutionary Synthesis, in Pugliucci / Müller 2010
  • West-Eberhard, Mary Jane (2003): Development Plastizity and Evolution. Oxford University Press.
  • Wilson, David Sloan (2010): Multilevel Selection and Major Transitions, in Pigliucci / Müller (2010)
  • Wilson, David Sloan (2007): Evolution for Everyone: How Darwin's Theory Can Change the Way We Think About Our Lives. New York: Delacorte Press.

deepening

  • Amundson, Ron (2005): The Changing Role of the Embryo in Evolutionary Thought The Routs of EvoDevo. Cambridge University Press
  • Callebaut, Werner (2010): The Dialectics of Dis / Unity in the Evolutionary Synthesis and its Extensions in Pigliucci / Müller 2010
  • Dupré, John (2009): Darwin's Legacy. Suhrkamp paperback science 1904
  • Douglas J. Futuyma: Can Modern Evolutionary Theory Explain Macroevolution? In Emanuele Serrelli, Nathalie Gontier (editors): Macroevolution. Explanation, Interpretation and Evidence. Springer 2015 ISBN 978-3-319-15045-1 ( pdf )
  • Gilbert, Scott F. & Epel, David (2009): Ecological Development Biology. Integrating Epigenetics, Medicine and Evolution. Sinauer Ass.
  • Jenner, Ronald A. (2008): EvoDevo's Identity - From Modell Organisms to Developmental Types in Minelli / Fusco 2008
  • Minelli, A. & Fusco, G. (Eds.) (2008): Evolving Pathways - Key Themes in Evolutionary Developmental Biology. Cambridge University Press
  • Newmann Stuart A., Forgacs, Gabor, Müller Gerd (2006): Before programs: The physical origination of multicellular forms
  • Nihjout, Frederic (2006): Researchers evolve a complex genetic trait in the labratory
  • Yuichiro Suzuki, H. Federic Nihjout: Genetic basis of adaptive evolution of a polyphenism by genetic accommodation . In: Journal of Evolutionary Biology . 21, No. 1, 2008, pp. 57-66. doi: 10.1111 / j.1420-9101.2007.01464.x
  • Pigliucci, Massimo (2008c): The Proper Role of Population Genetics in Modern Evolutionary Theory
  • Pigliucci, Massimo (2008b): Evolutionary Theory. The view from Altenberg
  • Richerson, J. & Boyd, R .: Not by Genes alone. How Culture transformed Human Evolution. University of Chicago Press

Individual evidence

  1. ↑ a b c d e f g h i j Kevin N. Laland, Tobias Uller, Marcus W. Feldman, Kim Sterelny, Gerd B. Müller, Armin Moczek, Eva Jablonka, John Odling-Smee. The extended evolutionary synthesis: its structure, assumptions and predictions. Proceedings of the Royal Society B: Biological Sciences 282 (1813). August 2015 DOI: 10.1098 / rspb.2015.1019
  2. ↑ a b c Pigliucci, Massimo & Müller Gerd B. (2010) Elements of an Extended Evolutionary Synthesis in Pigliucci / Müller (2010) p. 8.
  3. ^ A b Ron Amundson: The Changing Role of the Embryo in Evolutionary Thought The Routs of EvoDevo. 2005 p. 188.
  4. ↑ Caroll, Sean B. (o. Year, published 2008) Evo-Devo - The new image of evolution. Berlin. (Orig .: Endless Forms Most Beautiful, USA 2006)
  5. ^ Dupré, John (2009): Darwin's Legacy. Suhrkamp paperback no.1904
  6. ^ Jablonka, Eva & Lamb Marion J. (2005): Evolution in four Dimensions. Genetic, Epigenetic, Behavioral and Symbolic Variation in the History of Life. MIT Press
  7. ↑ Kirschner, Marc W. & Gerhart, John C. (2007): The solution to Darwin's dilemma - How evolution creates complex life. Rowohlt. Orig. The Plausibility of Life (2005)
  8. ↑ Müller-Wille, Staffan u. Rheinberger, Hans-Jörg (2009). The gene in the age of post-genomics. An epistemological inventory. Suhrkamp Edition Unseld.
  9. ^ A b West-Eberhard, Mary Jane (2003) Development Plastizity and Evolution. Oxford University Press. P. 29.
  10. ↑ Ulrich Kutschera. Evolutionary biology. UTB 4th edition 2015
  11. ↑ Philip Sarasin and Marianne Sommer (eds.). Evolution. An interdisciplinary manual. JB Metzler 2010.
  12. ↑ a b c d e K. Laland, T. Uller, M. Feldman, K. Sterelny, GB Müller, A. Moczek, E. Jablonka, J. Odling-Smee, GA Wray, HE Hoekstra, DJ Futuyma, RE Lenski , TF Mackay, D. Schluter, JE Strassmann: Does evolutionary theory need a rethink? In: Nature. Volume 514, Number 7521, October 2014, ISSN  1476-4687 , pp. 161-164, doi: 10.1038 / 514161a , PMID 25297418 . German translation
  13. ^ Adam S Wilkins, Waddington's Unfinished Critique of Neo-Darwinian Genetics: Then and Now . In: Biological Theory . 3, No. 3, 2008, pp. 224-232. doi : 10.1162 / biot.2008.3.3.224 .
  14. ↑ Massimo Pigliucci, et al: Phenotypic plasticity and evolution by genetic assimilation . In: Journal of Experimental Biology . 209, 2006, pp. 2362-2367. doi : 10.1242 / jeb.02070 .
  15. ^ Huang S. (2011). The molecular and mathematical basis of Waddington's epigenetic landscape: A framework for post-Darwinian biology? BioEssays 34: 149-157.
  16. ^ Wagner, Günter P; Laubichler; Manfred D. (2004). "Rupert Riedl and the Re-Synthesis of Evolutionary and Developmental Biology: Body Plans and Evolvability" ( Memento of the original dated December 8, 2015 in the Internet Archive ) Info: The archive link was inserted automatically and has not yet been checked. Please check the original and archive link according to the instructions and then remove this notice. . Journal of Experimental Zoology (Mol Dev Evol) 302B: 92-102. @1@ 2Template: Webachiv / IABot / www.yale.edu
  17. ↑ Parnell, Dennis R. (1978). Heralding a New Synthesis Modes of Speciation by MJD White . Systematic botany. Vol. 3, No. 1. p. 126.
  18. ↑ Gould, Stephen Jay. (1980). Is a New and General Theory of Evolution Emerging? Paleobiology. Vol. 6, No. 1. pp. 119-130.
  19. ↑ Stephen Jay Gould: Darwinism and the Expansion of Evolutionary Theory . In: Science . 216, No. 4544, 1982, pp. 380-387. doi : 10.1126 / science.7041256 .
  20. ↑ "A More Modern Synthesis" . American Scientist.
  21. ↑ Geerat J Vermeij: Unfinished Synthesis: Biological Hierarchies and Modern Evolutionary Thought by Niles Eldredge . In: The Quarterly Review of Biology . 62, No. 1, 1987, pp. 79-80. doi : 10.1086 / 415312 .
  22. ↑ Endler, John A; McLellan, Tracy. (1988). The Processes of Evolution: Toward a Newer Synthesis . Annual Review of Ecology and Systematics. Vol. 19, pp. 395-421. doi : 10.1146 / annurev.es.19.110188.002143 JSTOR 2097160
  23. ^ Mary Jane West-Eberhard. Developmental Plasticity and Evolution. Oxford University Press. 2003
  24. ↑ a b The World's Top Biologists Have Met to Discuss Whether We Should Update Evolution
  25. ↑ Ingo Brigandt: Beyond Neo-Darwinism? New developments in evolutionary biology in: Philip Sarasin and Marianne Sommer (eds.). Evolution. An interdisciplinary manual. JB Metzler 2010.
  26. ^ Ron Amundson: The Changing Role of the Embryo in Evolutionary Thought The Routs of EvoDevo. Cambridge University Press 2005.
  27. ^ Marc W. Kirschner, John C. Gerhart: Facilitated Variation in: Massimo Pigliucci, Gerd Müller: Evolution - the Extended Synthesis. MIT Press (2010), p. 276.
  28. ↑ a b c Denis Noble, Eva Jablonka, Michael J. Joyner, Gerd B. Müller, Stig W. Omholt: Evolution evolves: physiology returns to center stage. In: J Physiol. 592.11 (2014) pp. 2237-2244.
  29. ^ Love, Alan C. (2010) Rethinking the Structure of Evolutionary Theory for an Extended Synthesis in Pigliucci / Müller (2010)
  30. ^ Müller, Gerd B. (2010): Epigenetic Innovation in: Pigliucci, Massimo & Müller, Gerd (2010): Evolution - the Extended Synthesis . MIT Press
  31. ^ A b Gerd B. Müller & Stuart A. Newman. Origination of Organizational Form. Beyond the Gene in Developmental and Evolutionary Biology. MIT Press 2003
  32. ↑ Pigliucci, Massimo & Müller, Gerd (2010): Elements of an Evolutionary Synthesis in Pugliucci / Müller 2010 p. 8
  33. ↑ A. Wagner. Arrival of the Fittest: Natural Selection as an Incantation. Evolution News & Views November 17, 2014
  34. ↑ Julian Huxley. Evolution. The Modern Synthesis. The Definitive Edition. MIT Press 2010. p. 68
  35. ↑ Richerson, J. & Boyd, R. (2005) Not by Genes alone. How culture transformed human evolution. University of Chicago Press
  36. ↑ James Shapiro, Raju Pookottil, Denis Noble: The Third Way .
  37. ^ Raju Pookottil: Beem. Biological Emergence-Based Evolutionary Mechanism: How Species Direct Their Own Evolution . Troubador Publishing Ltd, 2013, ISBN 978-0-9575005-0-1 .
  38. ↑ Denis Noble. The Music of life, Biology Beyond Genes, Oxford University Press 2006
  39. ^ Profile of Denis Noble
  40. ↑ James A. Shapiro. Evolution. A View from the 21st Century. FT Press 2011
  41. ^ Profile of James A. Shapiro
  42. ↑ Aaron W. Schrey, Christina L. Richards, Victoria Meller, Vincent Sollars, Douglas M. Ruden: The Role of Epigenetics in Evolution: The Extended Synthesis. In: Genetics Research International. 2012, 2012, p. 1, doi : 10.1155 / 2012/286164 .