Organogênese de mamíferos em tempos imemoriais: Haeckel redivivus???

sábado, dezembro 03, 2016

Mammalian organogenesis in deep time: tools for teaching and outreach

Marcelo R. Sánchez-Villagra and Ingmar WerneburgEmail author

Evolution: Education and Outreach20169:11

DOI: 10.1186/s12052-016-0062-y© The Author(s) 2016

Received: 9 July 2016Accepted: 20 November 2016Published: 1 December 2016


Abstract

Mammals constitute a rich subject of study on evolution and development and provide model organisms for experimental investigations. They can serve to illustrate how ontogeny and phylogeny can be studied together and how the reconstruction of ancestors of our own evolutionary lineage can be approached. Likewise, mammals can be used to promote 'tree thinking' and can provide an organismal appreciation of evolutionary changes. This subject is suitable for the classroom and to the public at large given the interest and familiarity of people with mammals and their closest relatives. We present a simple exercise in which embryonic development is presented as a transformative process that can be observed, compared, and analyzed. In addition, we provide and discuss a freely available animation on organogenesis and life history evolution in mammals. An evolutionary tree can be the best tool to order and understand those transformations for different species. A simple exercise introduces the subject of changes in developmental timing or heterochrony and its importance in evolution. The developmental perspective is relevant in teaching and outreach efforts for the understanding of evolutionary theory today.

Keywords

Development Ontogeny Embryology Phylogeny Heterochrony Recapitulation Placentalia Human

Duas etapas de revisão amplificam a exatidão da tradução do código genético: mero acaso, fortuita necessidade ou design inteligente???

Two proofreading steps amplify the accuracy of genetic code translation

Ka-Weng Ieong a, Ülkü Uzun a,1, Maria Selmer a, and Måns Ehrenberg a,2

Author Affiliations

a Department of Cell and Molecular Biology, Uppsala University, Uppsala 75124, Sweden

Edited by Ada Yonath, Weizmann Institute of Science, Rehovot, Israel, and approved October 12, 2016 (received for review July 4, 2016)



Significance

We have discovered that two proofreading steps amplify the accuracy of genetic code reading, not one step, as hitherto believed. We have characterized the molecular basis of each one of these steps, paving the way for structural analysis in conjunction with structure-based standard free energy computations. Our work highlights the essential role of elongation factor Tu for accurate genetic code translation in both initial codon selection and proofreading. Our results have implications for the evolution of efficient and accurate genetic code reading through multistep proofreading, which attenuates the otherwise harmful effects of the obligatory tradeoff between efficiency and accuracy in substrate selection by enzymes.

Abstract

Aminoacyl-tRNAs (aa-tRNAs) are selected by the messenger RNA programmed ribosome in ternary complex with elongation factor Tu (EF-Tu) and GTP and then, again, in a proofreading step after GTP hydrolysis on EF-Tu. We use tRNA mutants with different affinities for EF-Tu to demonstrate that proofreading of aa-tRNAs occurs in two consecutive steps. First, aa-tRNAs in ternary complex with EF-Tu·GDP are selected in a step where the accuracy increases linearly with increasing aa-tRNA affinity to EF-Tu. Then, following dissociation of EF-Tu·GDP from the ribosome, the accuracy is further increased in a second and apparently EF-Tu−independent step. Our findings identify the molecular basis of proofreading in bacteria, highlight the pivotal role of EF-Tu for fast and accurate protein synthesis, and illustrate the importance of multistep substrate selection in intracellular processing of genetic information.

ribosome error correction fidelity EF-Tu ternary complex

Footnotes

1Present address: Department of Biochemistry, University of Oxford, Oxford OX1 3QU, United Kingdom.

2To whom correspondence should be addressed. Email: ehrenberg@xray.bmc.uu.se.

Author contributions: K.-W.I. and M.E. designed research; K.-W.I. and Ü.U. performed research; M.S. performed structural analysis; K.-W.I. and M.E. analyzed data; and K.-W.I. and M.E. wrote the paper.

The authors declare no conflict of interest.

This article is a PNAS Direct Submission.

This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1610917113/-/DCSupplemental.

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Os biólogos que querem revisar profundamente a teoria da evolução

quinta-feira, dezembro 01, 2016

Douglas Futuyma, a biologist at Stony Brook University, defends the “Modern Synthesis” of evolution at the Royal Society earlier this month.
Tom Parker / Quanta Magazine

The Biologists Who Want to Overhaul Evolution

A half-century’s worth of scientific discoveries since the last major update to evolutionary theory has some researchers pushing for a paradigm shift.



“I think it’s going quite well,” Laland said. “It hasn’t gone to fisticuffs yet.”

Laland is an evolutionary biologist who works at the University of St. Andrews in Scotland. On a chilly gray November day, he came down to London to co-host a meeting at the Royal Society called “New Trends in Evolutionary Biology.” A motley crew of biologists, anthropologists, doctors, computer scientists, and self-appointed visionaries packed the room. The Royal Society is housed in a stately building overlooking St. James’s Park. Today the only thing for Laland to see out of the tall meeting-room windows was scaffolding and gauzy tarps set up for renovation work. Inside, Laland hoped, another kind of renovation would be taking place.

In the mid-1900s, biologists updated Darwin’s theory of evolution with new insights from genetics and other fields. The result is often called the Modern Synthesis, and it has guided evolutionary biology for over 50 years. But in that time, scientists have learned a tremendous amount about how life works. They can sequence entire genomes. They can watch genes turn on and off in developing embryos. They can observe how animals and plants respond to changes in the environment.

As a result, Laland and a like-minded group of biologists argue that the Modern Synthesis needs an overhaul. It has to be recast as a new vision of evolution, which they’ve dubbed the Extended Evolutionary Synthesis. Other biologists have pushed back hard, saying there is little evidence that such a paradigm shift is warranted.

This meeting at the Royal Society was the first public conference where Laland and his colleagues could present their vision. But Laland had no interest in merely preaching to the converted, and so he and his fellow organizers also invited prominent evolutionary biologists who are skeptical about the Extended Evolutionary Synthesis.

Both sides offered their arguments and critiques in a civil way, but sometimes you could sense the tension in the room—the punctuations of tsk-tsks, eye-rolling, and partisan bursts of applause.

But no fisticuffs. At least not yet.

...

Read more here/Leia mais aqui: The Atlantic

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This blogger's commentary:

In the first chapter of the book “The Extended Synthesis” editors Gerd Müller and Massimo Pigliucci explained that the new synthesis (EES) overcomes the Modern Synthesis in three basic points:

Gradualism:

“The dynamics of biological systems illuminates the capacity of continuous selectional regimes to produce the nongradual phenotypic change frequently observed in the paleontological record.” (p. 13)

Externalism:

Instead of giving priority to all external factors and natural selection alone as the main cause of biological novelties the EES considers that “the specificity of its phenotypic outcome is provided by the developmental system it operates on. Hence the organisms themselves represent the determinants of selectable variations and innovation.” (p. 13)

Gene-centrism:

“Gene-centrism necessarily disappears in an extended account that provides for multicausal evolutionary factors acting on organismal systems´ properties, including the non programmed components of environment, development and inheritance.” (p. 14)

If one overcomes gradualism, the central role of natural selection and gene centrism in creating new phenotypic traits, as far as Darwinism is concerned, what have we got left? And what about information? I wish these scientific points were fully discussed on the RS meeting. A new general theory of evolution needs to replace the Modern Evolutionary Synthesis.

Biston betularia, ícone do fato, Fato, FATO da evolução nos livros didáticos, é EVIDÊNCIA CONTRA a evolução!

Letter

The industrial melanism mutation in British peppered moths is a transposable element

Arjen E. van’t Hof, Pascal Campagne, Daniel J. Rigden, Carl J. Yung, Jessica Lingley, Michael A. Quail, Neil Hall, Alistair C. Darby & Ilik J. Saccheri

Affiliations Contributions Corresponding author

Nature 534, 102–105 (02 June 2016) doi:10.1038/nature17951

Received 03 July 2015 Accepted 22 March 2016 Published online 01 June 2016


Discovering the mutational events that fuel adaptation to environmental change remains an important challenge for evolutionary biology. The classroom example of a visible evolutionary response is industrial melanism in the peppered moth (Biston betularia): the replacement, during the Industrial Revolution, of the common pale typica form by a previously unknown black (carbonaria) form, driven by the interaction between bird predation and coal pollution 1. The carbonaria locus has been coarsely localized to a 200-kilobase region, but the specific identity and nature of the sequence difference controlling the carbonaria–typica polymorphism, and the gene it influences, are unknown2. Here we show that the mutation event giving rise to industrial melanism in Britain was the insertion of a large, tandemly repeated, transposable element into the first intron of the gene cortex. Statistical inference based on the distribution of recombined carbonaria haplotypes indicates that this transposition event occurred around 1819, consistent with the historical record. We have begun to dissect the mode of action of the carbonaria transposable element by showing that it increases the abundance of a cortex transcript, the protein product of which plays an important role in cell-cycle regulation, during early wing disc development. Our findings fill a substantial knowledge gap in the iconic example of microevolutionary change, adding a further layer of insight into the mechanism of adaptation in response to natural selection. The discovery that the mutation itself is a transposable element will stimulate further debate about the importance of ‘jumping genes’ as a source of major phenotypic novelty 3.

Subject terms: Evolutionary genetics Gene expression

Subscription or payment needed/Requer assinatura ou pagamento: Nature

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Professores, pesquisadores e alunos de universidades públicas e privadas com acesso ao Portal de Periódicos CAPES/MEC podem  ler gratuitamente esta carta na Nature e mais 30.000 publicações científicas.

Por que nós precisamos de teorias científicas?

terça-feira, novembro 29, 2016

Progress in Biophysics and Molecular Biology

Volume 122, Issue 1, October 2016, Pages 4–10

From the Century of the Genome to the Century of the Organism: New Theoretical Approaches

Why do we need theories?

Giuseppe Longo a, b, , , Ana M. Soto a, b, 

a Centre Cavaillès, République des Savoirs, CNRS USR3608, Collège de France et Ecole Normale Supérieure, Paris, France

b Department of Integrative Physiology and Pathobiology, Tufts University School of Medicine, Boston, MA, USA

Received 3 March 2016, Revised 16 June 2016, Accepted 21 June 2016, Available online 4 July 2016


Abstract

Theories organize knowledge and construct objectivity by framing observations and experiments. The elaboration of theoretical principles is examined in the light of the rich interactions between physics and mathematics. These two disciplines share common principles of construction of concepts and of the proper objects of inquiry. Theory construction in physics relies on mathematical symmetries that preserve the key invariants observed and proposed by such theory; these invariants buttress the idea that the objects of physics are generic and thus interchangeable and they move along specific trajectories which are uniquely determined, in classical and relativistic physics.

In contrast to physics, biology is a historical science that centers on the changes that organisms experience while undergoing ontogenesis and phylogenesis. Biological objects, namely organisms, are not generic but specific; they are individuals. The incessant changes they undergo represent the breaking of symmetries, and thus the opposite of symmetry conservation, a central component of physical theories. This instability corresponds to the changes of the environment and the phenotypes.

Inspired by Galileo’s principle of inertia, the “default state” of inert matter, we propose a “default state” for biological dynamics following Darwin’s first principle, “descent with modification” that we transform into “proliferation with variation and motility” as a property that spans life, including cells in an organism. These dissimilarities between theories of the inert and of biology also apply to causality: biological causality is to be understood in relation to the distinctive role that constraints assume in this discipline. Consequently, the notion of cause will be reframed in a context where constraints to activity are seen as the core component of biological analyses. Finally, we assert that the radical materiality of life rules out distinctions such as “software vs. hardware.”

Keywords: 

Default state; Mathematical symmetries; Phase space; Biological organization

Corresponding author. Centre Cavaillès, République des Savoirs, CNRS USR3608, Collège de France et Ecole Normale Supérieure, 29 rue d’Ulm, 75005, Paris, France.

© 2016 Elsevier Ltd. All rights reserved.

Subscription or payment required/Requer assinatura ou pagamento:

Exames de tomografia computadorizada de alta precisão revelam "condicionadores de ar" internos nos bicos de aves

sexta-feira, novembro 25, 2016

The Auk 134(1):65-75. 2017 


Habitat-specific divergence of air conditioning structures in bird bills

Divergencia dependiente del hábitat en estructuras acondicionadoras del aire de los picos de las aves open access

Raymond M. Danner 1,a*, Eric R. Gulson-Castillo 2, Helen F. James 3, Sarah A. Dzielski 2, David C. Frank III 2, Eric T. Sibbald 2, and David W. Winkler 2

1Smithsonian Migratory Bird Center, Smithsonian Conservation Biology Institute, Washington, DC, USA

2Department of Ecology and Evolutionary Biology, Cornell University, Ithaca, New York, USA

3Department of Vertebrate Zoology, National Museum of Natural History, Smithsonian Institution, Washington, DC, USA

aDepartment of Biology and Marine Biology, University of North Carolina Wilmington, Wilmington, North Carolina, USA

*Corresponding author: dannerr@uncw.edu

Source/Fonte: E. Gulson-Castillo and E. Sibbald

ABSTRACT

We used high precision computed tomography (CT) and traditional radiography to study the nasal conchae, complex structures within the nasal cavity that condition air via countercurrent heat exchange. Air conditioning in the conchae assists thermoregulation and water balance, both of which pose challenges for many birds. We hypothesized that hot and water-limited environments would select for larger or more complex conchae to maximize moisture recapture during exhalation and in turn cause the evolution of deeper and wider bills. We provide the first intraspecific comparison of concha size and structure in birds based on CT scans of 15 individuals and radiographs of 39 individuals of 2 subspecies of Song Sparrow (Melospiza melodia) that inhabit climatically distinct habitats. CT scans revealed that middle and rostral conchae filled the nasal cavities and had larger surface areas in individuals with larger nasal cavities. The subspecies that inhabits hot and dry coastal dunes (M. m. atlantica) had relatively larger conchae and greater overlap of middle and rostral conchae than a nearby inland subspecies that inhabits moister environments (M. m. melodia). Radiographs revealed deeper and wider nasal cavities in the dune-endemic subspecies, further indicating they have larger conchae. Locations of maximum complexity of both conchae were more distal in the dune endemic subspecies. These anatomical differences suggest current or past divergent selection pressures on conchae; the larger conchae in the dune subspecies may allow greater water recapture while exhaling. The conchae and external bill are nested structures that were positively related in size and play functionally related roles in thermoregulation, therefore suggesting phenotypic integration. We hypothesize that the typically deeper and wider bill of the dune subspecies has evolved, at least in part, to accommodate larger conchae.

RESUMEN

Utilizamos tomografía computarizada (TC) de alta precisión y radiografía tradicional para estudiar los cornetes nasales, los cuales son estructuras complejas dentro de las fosas nasales que acondicionan el aire mediante el intercambio de calor a contracorriente. El acondicionamiento de aire en los cornetes nasales asiste a la termorregulación y al equilibrio hídrico, los cuales presentan retos para muchas aves. Hipotetizamos que ambientes cálidos y limitados de agua favorecerían cornetes más grandes o complejos para maximizar la retención de humedad durante la exhalación y, así, causar la evolución de picos más profundos y anchos. Presentamos la primera comparación intra-específica de tamaños y estructuras de cornetes en aves basándonos en las TC de 15 individuos y las radiografías de 39 individuos de dos subespecies de Melospiza melodia que vive en hábitats de climas distintos. Las TC revelaron que los cornetes llenaban las fosas nasales y tenían mayor área superficial en individuos con fosas nasales más grandes. La subespecie que habita en dunas costeras cálidas y secas (M. m. atlantica) tenía cornetes medios relativamente más grandes y mayor superposición entre los dos pares de cornetes que la subespecie que habita en ambientes cercanos más húmedos, tierra adentro (M. m. melodia). Las radiografías revelaron fosas nasales más profundas y anchas en la subespecie endémica de las dunas, lo cual indica aún más que tienen cornetes más grandes. Las localidades de máxima complejidad en ambos cornetes fueron más distales en la subespecie endémica de las dunas. Estas diferencias anatómicas sugieren que los cornetes experimentan o han experimentado fuerzas de selección divergentes: los cornetes más grandes de la subespecie que habita en dunas quizás permitan la retención de más agua durante la exhalación. Los cornetes y el exterior del pico son estructuras encajadas que estaban positivamente relacionadas en tamaño y tienen funciones relacionadas con la termoregulación, sugiriendo integración fenotípica. Hipotetizamos que los picos típicamente más profundos y anchos de la subespecie de las dunas han evolucionado, por lo menos en parte, para acomodar cornetes más grandes.

Palabras clave: cornetes nasales, conchas nasales, termorregulación, equilibrio hídrico, morfología del pico, Melospiza melodia, Tomografía Computerizada TC de alto contraste, rayos X

Received: May 30, 2016; Accepted: August 22, 2016; Published: November 9, 2016

Keywords: nasal conchae, turbinate, thermoregulation, water balance, bill morphology, Song Sparrow, contrast-enhanced CT scan, X-ray

© 2016 American Ornithologists' Union

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Arganazes cinzentos: quanto mais velhos, mais suas células se rejuvenescem!

Telomeres are elongated in older individuals in a hibernating rodent, the edible dormouse (Glis glis)

Franz Hoelzl, Steve Smith, Jessica S. Cornils, Denise Aydinonat, Claudia Bieber & Thomas Ruf

Scientific Reports 6, Article number: 36856 (2016)


Download Citation

Molecular ecology Senescence

Received: 26 February 2016 Accepted: 14 October 2016 Published online: 24 November 2016

Source/Fonte: Arkive.org


Abstract

Telomere shortening is thought to be an important biomarker for life history traits such as lifespan and aging, and can be indicative of genome integrity, survival probability and the risk of cancer development. In humans and other animals, telomeres almost always shorten with age, with more rapid telomere attrition in short-lived species. Here, we show that in the edible dormouse (Glis glis) telomere length significantly increases from an age of 6 to an age of 9 years. While this finding could be due to higher survival of individuals with longer telomeres, we also found, using longitudinal measurements, a positive effect of age on the rate of telomere elongation within older individuals. To our knowledge, no previous study has reported such an effect of age on telomere lengthening. We attribute this exceptional pattern to the peculiar life-history of this species, which skips reproduction in years with low food availability. Further, we show that this “sit tight” strategy in the timing of reproduction is associated with an increasing likelihood for an individual to reproduce as it ages. As reproduction could facilitate telomere attrition, this life-history strategy may have led to the evolution of increased somatic maintenance and telomere elongation with increasing age.

Acknowledgements

This study was financially supported by the Austrian Science Fund (FWF Grant no. P25023) and the state governments of Lower Austria and Vienna. We are grateful to Österreichische Bundesforste AG for their permission to access the study site and their general support for the project. We also thank Karin Lebl and Klaus Kürbisch for their help with collecting data on the reproductive state of free-living dormice, Boglárka Bálint for the assistance in the laboratory and Renate Hengsberger for her help with the literature search and formatting of the manuscript.

Author information

Affiliations

Department of Integrative Biology and Evolution, University of Veterinary Medicine, Vienna, Austria

Franz Hoelzl, Steve Smith, Jessica S. Cornils, Denise Aydinonat, Claudia Bieber & Thomas Ruf

Contributions

F.H. and T.R. designed the study, analysed the data, wrote the manuscript and produced the figures. F.H. and J.C. carried out the field work and extracted the DNA. F.H., D.A. and S.S. carried out the laboratory work and processed the raw data. C.B. provided data. All authors commented on drafts of the manuscript.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Franz Hoelzl.

FREE PDF GRATIS: Scientific Reports Sup. Info

Somente 50% do cromossomo é DNA: muito menos do que antes se sabia!

quinta-feira, novembro 24, 2016

3D-CLEM Reveals that a Major Portion of Mitotic Chromosomes Is Not Chromatin

Daniel G. Booth5, Alison J. Beckett, Oscar Molina, Itaru Samejima, Hiroshi Masumoto, Natalay Kouprina, Vladimir Larionov, Ian A. Prior, William C. Earnshaw 

5Lead Contact

Published Online: November 10, 2016

Open Access


Open access funded by Wellcome Trust

Article Info

Publication History

Published: November 10, 2016 Accepted: October 5, 2016

Received in revised form: August 24, 2016 Received: April 4, 2016

User License

Creative Commons Attribution (CC BY 4.0)


Highlights

• 3D-CLEM combines light and serial block-face scanning electron microscopy

• The complete architecture of all 46 human chromosomes has been defined

• A large portion of mitotic chromosomes is not composed of chromatin

• Chromosome volumes determined by light and electron microscopy differ dramatically

Summary

Recent studies have revealed the importance of Ki-67 and the chromosome periphery in chromosome structure and segregation, but little is known about this elusive chromosome compartment. Here we used correlative light and serial block-face scanning electron microscopy, which we term 3D-CLEM, to model the entire mitotic chromosome complement at ultra-structural resolution. Prophase chromosomes exhibit a highly irregular surface appearance with a volume smaller than metaphase chromosomes. This may be because of the absence of the periphery, which associates with chromosomes only after nucleolar disassembly later in prophase. Indeed, the nucleolar volume almost entirely accounts for the extra volume found in metaphase chromosomes. Analysis of wild-type and Ki-67-depleted chromosomes reveals that the periphery comprises 30%–47% of the entire chromosome volume and more than 33% of the protein mass of isolated mitotic chromosomes determined by quantitative proteomics. Thus, chromatin makes up a surprisingly small percentage of the total mass of metaphase chromosomes.

Keywords: 3D-CLEM, chromosome periphery, Ki-67, electron microscopy, CLEM

Received: April 4, 2016; Received in revised form: August 24, 2016; Accepted: October 5, 2016; Published: November 10, 2016

© 2016 The Author(s). Published by Elsevier Inc.

FREE PDF GRATIS: Molecular Cell

Uma visão de sistemas da assimilação genética de Waddington: Lamarck redivivus???

International Journal of Bioinformatics & Biological Systems (IJBBS) IJBBS-01-102

A Systems View of Waddington’s Genetic Assimilation

Nair A1*, Dearden PK2

1 Arthritis & Clinical Immunology Research Program, Oklahoma Medical Research Foundation, Oklahoma City 73104, Oklahoma, USA.

2 Laboratory for Evolution & Development, Biochemistry Department,University of Otago,Dunedin 9054, New Zealand.

*Corresponding Author

Ajay Nair
Arthritis & Clinical Immunology Research Program,
Oklahoma Medical Research Foundation,
Oklahoma City 73104, Oklahoma, USA.
Tel: 1 (405)985-6960
Email : ajay-nair@omrf.org

Received: January 11, 2016; Accepted: March 30, 2016; Published: April 13, 2016

Citation: Nair A, Dearden PK (2016) A Systems View of Waddington’s Genetic Assimilation. Int J Bioinform Biol Syst. 1(1), 10-17.

Copyright: Nair A© 2016. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution and reproduction in any medium, provided the original author and source are credited.

Source/Fonte: UNC Chapel Hill


Abstract

Lamarck believed that traits acquired during an organism’s lifetime could be passed onto the next generation. Although the idea of the inheritance of acquired characters was discarded due to lack of experimental evidence, Conrad H. Waddington realized its significance. In 1953, he showed that Drosophila melanogaster (wild-type) flies that were heat-shocked produced a Crossveinless (cve; disrupted posterior crossveins) trait. Through repeated selection of this trait with heat-shock, he not only increased its frequency in the population, but also found that individuals, from the untreated stock, showed the phenotype. This apparent inheritance of an acquired character is important to evolutionary theory, because it provides a mechanism whereby the environment may influence future evolutionary change. Despite the long history of this experiment, genetic assimilation remains elusive. The main aim of this work was to examine genetic assimilation and understand it as an evolutionary theory. Revisiting the experiment indicated that there is much that remains unclear. We have shown that production of cve is strain specific, with the white-eyed lines being vulnerable and the wild-type not. Though the frequency of the cve allele increased in every generation, there was a fitness cost for acquiring crossveinless. Assimilation of cve was found to be heritable but, unlike Waddington’s classic work, it did not tend towards fixation; appearing more like a transient, low penetrance effect.

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Mero acaso, fortuita necessidade ou design inteligente? Cérebros humanos têm um algoritmo básico capacitando a inteligência

quarta-feira, novembro 23, 2016

Front. Syst. Neurosci., 15 November 2016 | 


Brain Computation Is Organized via Power-of-Two-Based Permutation Logic

Kun Xie1,2†, Grace E. Fox1†, Jun Liu1,2†, Cheng Lyu3,4†, Jason C. Lee1†, Hui Kuang1†, Stephanie Jacobs1, Meng Li1,2, Tianming Liu3, Sen Song5 and Joe Z. Tsien1,2*

1Brain and Behavior Discovery Institute and Department of Neurology, Medical College of Georgia, Augusta University, Augusta, GA, USA

2The Brain Decoding Center, Banna Biomedical Research Institute, Yunnan Academy of Science and Technology, Yunnan, China

3Department of Computer Science and Brain Imaging Center, University of Georgia, Athens, GA, USA

4School of Automation, Northwestern Polytechnical University, Xi’an, China

5McGovern Institute for Brain Research and Center for Brain-Inspired Computing Research, Tsinghua University, Beijing, China


Abstract

There is considerable scientific interest in understanding how cell assemblies—the long-presumed computational motif—are organized so that the brain can generate intelligent cognition and flexible behavior. The Theory of Connectivity proposes that the origin of intelligence is rooted in a power-of-two-based permutation logic (N = 2i–1), producing specific-to-general cell-assembly architecture capable of generating specific perceptions and memories, as well as generalized knowledge and flexible actions. We show that this power-of-two-based permutation logic is widely used in cortical and subcortical circuits across animal species and is conserved for the processing of a variety of cognitive modalities including appetitive, emotional and social information. However, modulatory neurons, such as dopaminergic (DA) neurons, use a simpler logic despite their distinct subtypes. Interestingly, this specific-to-general permutation logic remained largely intact although NMDA receptors—the synaptic switch for learning and memory—were deleted throughout adulthood, suggesting that the logic is developmentally pre-configured. Moreover, this computational logic is implemented in the cortex via combining a random-connectivity strategy in superficial layers 2/3 with nonrandom organizations in deep layers 5/6. This randomness of layers 2/3 cliques—which preferentially encode specific and low-combinatorial features and project inter-cortically—is ideal for maximizing cross-modality novel pattern-extraction, pattern-discrimination and pattern-categorization using sparse code, consequently explaining why it requires hippocampal offline-consolidation. In contrast, the nonrandomness in layers 5/6—which consists of few specific cliques but a higher portion of more general cliques projecting mostly to subcortical systems—is ideal for feedback-control of motivation, emotion, consciousness and behaviors. These observations suggest that the brain’s basic computational algorithm is indeed organized by the power-of-two-based permutation logic. This simple mathematical logic can account for brain computation across the entire evolutionary spectrum, ranging from the simplest neural networks to the most complex.

A importância evolutiva das repetições em nossos genomas

terça-feira, novembro 22, 2016

TET-dependent regulation of retrotransposable elements in mouse embryonic stem cells

Lorenzo de la Rica, Özgen Deniz, Kevin C. L. Cheng, Christopher D. Todd, Cristina Cruz, Jonathan Houseley and Miguel R. BrancoEmail author

Genome Biology 201617:234

DOI: 10.1186/s13059-016-1096-8 © The Author(s). 2016

Received: 25 July 2016Accepted: 1 November 2016Published: 18 November 2016

Source/Fonte: Forbes

Abstract

Background

Ten-eleven translocation (TET) enzymes oxidise DNA methylation as part of an active demethylation pathway. Despite extensive research into the role of TETs in genome regulation, little is known about their effect on transposable elements (TEs), which make up nearly half of the mouse and human genomes. Epigenetic mechanisms controlling TEs have the potential to affect their mobility and to drive the co-adoption of TEs for the benefit of the host.

Results

We performed a detailed investigation of the role of TET enzymes in the regulation of TEs in mouse embryonic stem cells (ESCs). We find that TET1 and TET2 bind multiple TE classes that harbour a variety of epigenetic signatures indicative of different functional roles. TETs co-bind with pluripotency factors to enhancer-like TEs that interact with highly expressed genes in ESCs whose expression is partly maintained by TET2-mediated DNA demethylation. TETs and 5-hydroxymethylcytosine (5hmC) are also strongly enriched at the 5′ UTR of full-length, evolutionarily young LINE-1 elements, a pattern that is conserved in human ESCs. TETs drive LINE-1 demethylation, but surprisingly, LINE-1s are kept repressed through additional TET-dependent activities. We find that the SIN3A co-repressive complex binds to LINE-1s, ensuring their repression in a TET1-dependent manner.

Conclusions

Our data implicate TET enzymes in the evolutionary dynamics of TEs, both in the context of exaptation processes and of retrotransposition control. The dual role of TET action on LINE-1s may reflect the evolutionary battle between TEs and the host.

Keywords

Embryonic stem cells Retrotransposons LINE-1 DNA methylation Hydroxymethylation Ten-eleven translocation enzymes Enhancers

FREE PDF GRATIS: Genome Biology

Comitê educacional no Texas afirma: alunos do ensino médio não sabem lidar com evidências contrárias ao Darwinismo!

segunda-feira, novembro 21, 2016

Texas Committee: High Schoolers Can’t Handle Evidence Against Darwinism



By JONATHAN WITT Published on November 20, 2016 • 2 Comments

On Thursday, I testified in Austin, Texas about the latest skirmish over how evolution is taught in Texas public high schools. I want it taught, warts and all. Darwinists want it taught as airbrushed and unquestionable dogma.
The state school board meeting was called to consider initial steps to streamline the Texas Essential Knowledge and Skills (TEKS). Streamlining is fine, in principle. The problem is that some of the proposed changes to the evolution section water down four passages that call on students to learn about, analyze and evaluate some of the growing evidential challenges to modern evolutionary theory.
So, for instance, what are we to make of the sudden appearance of new species and fundamentally new body plans in the fossil record? Neo-Darwinism says these animal forms evolved very gradually as part of the evolutionary tree of life, but the pattern in the geological column paints a different picture. Shouldn’t biology students be able to exercise their critical thinking skills by wrestling with this conundrum? The majority on the biology committee weren’t keen on that idea. They struck the sudden appearance language from the TEKS and argued that high school students aren’t mature enough to hear about it and ask intelligent questions. Not “developmentally appropriate,” the committee report said.
And, besides, said Karyn Ard, the chair of the biology curriculum review committee, there’s not enough time to cover it during the school year. There’s too much other material they have to cover. Ditto the growing mystery surrounding the origin of the first life.
Since I substitute taught in the Austin Independent School District for a year before I started graduate school, I could sympathize with Ard when she emphasized the wide disparity in student ability and the challenge teachers face to cover all the assigned material adequately. At the same time, the very real effect of the committee’s streamlining is to get rid of just those areas that best expose kids to the growing evidential challenges facing evolution, while leaving behind all kinds of pro-Darwinian propaganda woven into the fabric of the leading high school biology textbooks.

Covering for Darwin

Significantly, the pro-Darwin Texas Freedom Network (TFN) has had it in for these four hot-button passages ever since the passages made their way into the TEKS a few years ago. So it’s no surprise that TFN is celebrating the proposed deletions.
Ard told the board that the biology committee’s motives were focused squarely on streamlining, that she wasn’t even aware of the TFN until recently, and that their proposed deletions were not in any way politically motivated. My first reaction was: Really? The committee just happened to water down precisely the four passages the pro-Darwin TFN named as public enemy number 1, and the committee includes a vocal Darwin defender, Ron Wetherington, but somehow it was never the committee’s intent to put a giant thumb on the scale for Darwin?

Wetherington himself testified a bit later and made it abundantly obvious that he’s had it in for these four passages since they first made it into the TEKS. Some able cross-examination from conservative state school board member Marty Rowley (Amarillo) further underscored this fact.
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Read more here/Leia mais aqui: The Stream

Além do DNA: Concluído mapa do epigenoma humano

sexta-feira, novembro 18, 2016

DNA Methylation Dynamics of Human Hematopoietic Stem Cell Differentiation

Matthias Farlik 1, 13, Florian Halbritter 1, 13, Fabian Müller 2, 3, 13, Fizzah A. Choudry 4, 5, Peter Ebert 2, 3, Johanna Klughammer 1, Samantha Farrow 4, 5, Antonella Santoro 6, Valerio Ciaurro 6, Anthony Mathur 7, Rakesh Uppal 7, Hendrik G. Stunnenberg 8, Willem H. Ouwehand 4, 5, 9, 10, Elisa Laurenti 4, 6, Thomas Lengauer 2, Mattia Frontini 4, 5, 9, Christoph Bock 1, 2, 11, 12, 14. 

1 CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, 1090 Vienna, Austria

2 Max Planck Institute for Informatics, Saarland Informatics Campus, 66123 Saarbrücken, Germany

3 Graduate School of Computer Science, Saarland University, 66123 Saarbrücken, Germany

4 Department of Haematology, University of Cambridge, Cambridge CB2 0PT, UK

5 National Health Service Blood and Transplant, Cambridge Biomedical Campus, Cambridge CB2 0PT, UK

6 Wellcome Trust-Medical Research Council Cambridge Stem Cell Institute, University of Cambridge, Clifford Allbutt Building, Hills Road, Cambridge CB2 0AH, UK

7 Department of Cardiology, Barts Heart Centre, St Bartholomew’s Hospital, Barts Health NHS Trust, London EC1A 7BE, UK

8 Faculty of Science, Department of Molecular Biology, Radboud University, 6525GA Nijmegen, the Netherlands

9 British Heart Foundation Centre of Excellence, Cambridge Biomedical Campus, Long Road, Cambridge CB2 0QQ, UK

10 Department of Human Genetics, The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1HH, UK

11 Department of Laboratory Medicine, Medical University of Vienna, 1090 Vienna, Austria

12 Ludwig Boltzmann Institute for Rare and Undiagnosed Diseases, 1090 Vienna, Austria

Received 19 February 2016, Revised 4 October 2016, Accepted 24 October 2016, Available online 17 November 2016

Published: November 17, 2016


Open Access funded by Wellcome Trust

Under a Creative Commons license

Source/Fonte: Christoph Bock/CeMM

Highlights

• Sequencing provides DNA methylation maps of hematopoietic stem and progenitor cells

• Methylation differs in HSCs from fetal liver, bone marrow, cord, and peripheral blood

• Myeloid and lymphoid progenitors are distinguished by enhancer-linked DNA methylation

• Machine learning enables data-driven reconstruction of the hematopoietic lineage

Summary

Hematopoietic stem cells give rise to all blood cells in a differentiation process that involves widespread epigenome remodeling. Here we present genome-wide reference maps of the associated DNA methylation dynamics. We used a meta-epigenomic approach that combines DNA methylation profiles across many small pools of cells and performed single-cell methylome sequencing to assess cell-to-cell heterogeneity. The resulting dataset identified characteristic differences between HSCs derived from fetal liver, cord blood, bone marrow, and peripheral blood. We also observed lineage-specific DNA methylation between myeloid and lymphoid progenitors, characterized immature multi-lymphoid progenitors, and detected progressive DNA methylation differences in maturing megakaryocytes. We linked these patterns to gene expression, histone modifications, and chromatin accessibility, and we used machine learning to derive a model of human hematopoietic differentiation directly from DNA methylation data. Our results contribute to a better understanding of human hematopoietic stem cell differentiation and provide a framework for studying blood-linked diseases.

FREE PDF GRATIS: Cell Stem Cell