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


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.”


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.

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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


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.


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


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


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.


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


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


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)


• 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


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


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.


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


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



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.


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.


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.


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.
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


• 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


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.


O tempo como propriedade geométrica do espaço

quinta-feira, novembro 17, 2016


Front. Phys., 17 November 2016 | http://dx.doi.org/10.3389/fphy.2016.00044

Time As a Geometric Property of Space

James M. Chappell1*, John G. Hartnett2, Nicolangelo Iannella3, Azhar Iqbal1 and Derek Abbott1

1School of Electrical and Electronic Engineering, University of Adelaide, Adelaide, SA, Australia

2School of Physical Sciences, Institute for Photonics and Advanced Sensing, University of Adelaide, Adelaide, SA, Australia

3School of Mathematical Sciences, University of Nottingham, London, UK


The proper description of time remains a key unsolved problem in science. Newton conceived of time as absolute and universal which “flows equably without relation to anything external.” In the nineteenth century, the four-dimensional algebraic structure of the quaternions developed by Hamilton, inspired him to suggest that he could provide a unified representation of space and time. With the publishing of Einstein's theory of special relativity these ideas then lead to the generally accepted Minkowski spacetime formulation of 1908. Minkowski, though, rejected the formalism of quaternions suggested by Hamilton and adopted an approach using four-vectors. The Minkowski framework is indeed found to provide a versatile formalism for describing the relationship between space and time in accordance with Einstein's relativistic principles, but nevertheless fails to provide more fundamental insights into the nature of time itself. In order to answer this question we begin by exploring the geometric properties of three-dimensional space that we model using Clifford geometric algebra, which is found to contain sufficient complexity to provide a natural description of spacetime. This description using Clifford algebra is found to provide a natural alternative to the Minkowski formulation as well as providing new insights into the nature of time. Our main result is that time is the scalar component of a Clifford space and can be viewed as an intrinsic geometric property of three-dimensional space without the need for the specific addition of a fourth dimension.

FREE PDF GRATIS: Frontiers in Physics

A importância dos miRNAs pode ser superestimada

The number of biologically relevant microRNA targets has been largely overestimated

Natalia Pinzón1, Blaise Li1, Laura Martinez1, Anna Sergeeva1,5, Jessy Presumey2,3,6, Florence Apparailly2,3,4 and Hervé Seitz1

- Author Affiliations

1Institut de Génétique Humaine, CNRS UPR 1142, 34396 Montpellier, France;

2INSERM, U1183, IRMB, University Hospital St Éloi, 34295 Montpellier, France;

3University of Medicine, 34060 Montpellier, France;

4Clinical Department for Osteoarticular Diseases, University Hospital Lapeyronie, 34295 Montpellier, France

- Author Notes

↵Present addresses: 5MSU, The Museum of Natural History, Moscow, Russia, 119991; 6Children's Hospital, Boston, MA 02115, USA

Corresponding author: herve.seitz@igh.cnrs.fr


According to the current view, each microRNA regulates hundreds of genes. Computational tools aim at identifying microRNA targets, usually selecting evolutionarily conserved microRNA binding sites. Here, we provide evidence that such predictions are often biologically irrelevant. Focusing on miR-223-guided repression, we observed that it is often smaller than inter-individual variability in gene expression among wild-type mice, suggesting that most predicted targets are functionally insensitive to that microRNA. Furthermore, we found that human haplo-insufficient genes tend to bear the most highly conserved microRNA binding sites. It thus appears that biological functionality of microRNA binding sites depends on the dose-sensitivity of their host gene and that, conversely, it is unlikely that every predicted microRNA target is dose-sensitive enough to be functionally regulated by microRNAs. We also observed that some mRNAs can efficiently titrate microRNAs, providing a reason for microRNA binding site conservation for inefficiently repressed targets. Finally, many conserved microRNA binding sites are conserved in a microRNA-independent fashion: Sequence elements may be conserved for other reasons, while being fortuitously complementary to microRNAs. Collectively, our data suggest that the role of microRNAs in normal and pathological conditions has been overestimated.


[Supplemental material is available for this article.]

Article published online before print. Article, supplemental material, and publication date are at http://www.genome.org/cgi/doi/10.1101/gr.205146.116.

Received February 4, 2016. Accepted October 6, 2016.

© 2016 Pinzón et al.; Published by Cold Spring Harbor Laboratory Press

This article is distributed exclusively by Cold Spring Harbor Laboratory Press for the first six months after the full-issue publication date (see http://genome.cshlp.org/site/misc/terms.xhtml). After six months, it is available under a Creative Commons License (Attribution-NonCommercial 4.0 International), as described at http://creativecommons.org/licenses/by-nc/4.0/.


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A energia escura poderá forçar o universo a se desfazer gradualmente

terça-feira, novembro 15, 2016

Cosmological perturbations in an effective and genuinely phantom dark energy Universe

Source/Fonte: Thomas Gray/Millennium Images, UK
We carry out an analysis of the cosmological perturbations in general relativity for three different models which are good candidates to describe the current acceleration of the Universe. These three set-ups are described classically by perfect fluids with a phantom nature and represent deviations from the most widely accepted 
CDM model. In addition, each of the models under study induce different future singularities or abrupt events known as (i) Big Rip, (ii) Little Rip and (iii) Little Sibling of the Big Rip. Only the first one is regarded as a true singularity since it occurs at a finite cosmic time. For this reason, we refer to the others as abrupt events. With the aim to find possible footprints of this scenario in the Universe matter distribution, we not only obtain the evolution of the cosmological scalar perturbations but also calculate the matter power spectrum for each model. Finally, we constrain observationally these models using several measurements of the growth rate function, more precisely 
, and compare our results with the observational ones reaching the conclusion that even if these three models are very similar at present there are small differences that could allow us to distinguish them.
Comments:18 pages, 4 figures, 1 table. RevTeX 4.1
Subjects:Cosmology and Nongalactic Astrophysics (astro-ph.CO); General Relativity and Quantum Cosmology (gr-qc); High Energy Physics - Phenomenology (hep-ph); High Energy Physics - Theory (hep-th)
Cite as:arXiv:1611.00392 [astro-ph.CO]
 (or arXiv:1611.00392v1 [astro-ph.CO] for this version)

Submission history

From: Mariam Bouhmadi-Lopez [view email
[v1] Tue, 1 Nov 2016 21:06:33 GMT (1843kb)


NOTA DESTE BLOGGER: Calma, gente! Os cientistas pensam que isso somente ocorrerá daqui a 100 bilhões de anos!