Apple lança seu primeiro artigo científico sobre Inteligência Artificial: mero acaso, fortuita necessidade ou design inteligente?

quarta-feira, dezembro 28, 2016

Learning from Simulated and Unsupervised Images through Adversarial Training

Ashish Shrivastava, Tomas Pfister, Oncel Tuzel, Josh Susskind, Wenda Wang, Russ Webb

(Submitted on 22 Dec 2016)

With recent progress in graphics, it has become more tractable to train models on synthetic images, potentially avoiding the need for expensive annotations. However, learning from synthetic images may not achieve the desired performance due to a gap between synthetic and real image distributions. To reduce this gap, we propose Simulated+Unsupervised (S+U) learning, where the task is to learn a model to improve the realism of a simulator's output using unlabeled real data, while preserving the annotation information from the simulator. We develop a method for S+U learning that uses an adversarial network similar to Generative Adversarial Networks (GANs), but with synthetic images as inputs instead of random vectors. We make several key modifications to the standard GAN algorithm to preserve annotations, avoid artifacts and stabilize training: (i) a 'self-regularization' term, (ii) a local adversarial loss, and (iii) updating the discriminator using a history of refined images. We show that this enables generation of highly realistic images, which we demonstrate both qualitatively and with a user study. We quantitatively evaluate the generated images by training models for gaze estimation and hand pose estimation. We show a significant improvement over using synthetic images, and achieve state-of-the-art results on the MPIIGaze dataset without any labeled real data.

Comments: Submitted for review to a conference on Nov 15, 2016

Subjects: Computer Vision and Pattern Recognition (cs.CV); Learning (cs.LG); Neural and Evolutionary Computing (cs.NE)

Cite as: arXiv:1612.07828 [cs.CV]

(or arXiv:1612.07828v1 [cs.CV] for this version)

Submission history

From: Ashish Shrivastava [view email

[v1] Thu, 22 Dec 2016 22:10:51 GMT (2012kb,D)


A Nomenklatura científica não ousa abordar o que está errado com a biologia evolucionária

segunda-feira, dezembro 26, 2016

Biology & Philosophy

pp 1–17

What’s wrong with evolutionary biology?


Authors and affiliations

John J. Welch1

Email author

1.Department of Genetics University of Cambridge Cambridge UK

Open AccessArticle

First Online: 20 December 2016

Cite this article as:

Welch, J.J. Biol Philos (2016). doi:10.1007/s10539-016-9557-8

Source/Fonte: New Scientist


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

Keywords: Adaptation Extended evolutionary synthesis Neo-Darwinism Inclusive fitness

I’ve been wondering why so many evolutionary biologists are unimpressed by my idea… and I think the problem goes back to Newton (advocate of the Extended Evolutionary Synthesis)

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Análises de redes em Biologia de Sistemas - novas estratégias em lidar com a complexidade biológica

Network Analyses in Systems Biology: New Strategies for Dealing with Biological Complexity

Sara Green,i Maria Şerban,ii Raphael Scholl,iii Nicholaos Jones,iv Ingo Brigandt,v and William Bechtelvi,1

Source/Fonte: VIZBI


The increasing application of network models to interpret biological systems raises a number of important methodological and epistemological questions. What novel insights can network analysis provide in biology? Are network approaches an extension of or in conflict with mechanistic research strategies? When and how can network and mechanistic approaches interact in productive ways? In this paper we address these questions by focusing on how biological networks are represented and analyzed in a diverse class of case studies. Our examples span from the investigation of organizational properties of biological networks using tools from graph theory to the application of dynamical systems theory to understand the behavior of complex biological systems. We show how network approaches support and extend traditional mechanistic strategies but also offer novel strategies for dealing with biological complexity.

Preprint version. The final version will be published in Synthese


A Física por detrás da Biologia de Sistemas

The Physics behind Systems Biology

Nicole E. RaddeEmail author and Marc-Thorsten Hütt

EPJ Nonlinear Biomedical Physics20164:7

DOI: 10.1140/epjnbp/s40366-016-0034-8 © The Author(s) 2016

Received: 6 June 2016Accepted: 14 July 2016Published: 12 August 2016

Source/Fonte: University of Aberdeen


Systems Biology is a young and rapidly evolving research field, which combines experimental techniques and mathematical modeling in order to achieve a mechanistic understanding of processes underlying the regulation and evolution of living systems.

Systems Biology is often associated with an Engineering approach: The purpose is to formulate a data-rich, detailed simulation model that allows to perform numerical (‘in silico’) experiments and then draw conclusions about the biological system. While methods from Engineering may be an appropriate approach to extending the scope of biological investigations to experimentally inaccessible realms and to supporting data-rich experimental work, it may not be the best strategy in a search for design principles of biological systems and the fundamental laws underlying Biology. [???]

Physics has a long tradition of characterizing and understanding emergent collective behaviors in systems of interacting units and searching for universal laws. Therefore, it is natural that many concepts used in Systems Biology have their roots in Physics. With an emphasis on Theoretical Physics, we will here review the ‘Physics core’ of Systems Biology, show how some success stories in Systems Biology can be traced back to concepts developed in Physics, and discuss how Systems Biology can further benefit from its Theoretical Physics foundation.

Keywords: Complex systems Statistical physics of networks Nonlinear dynamics Mathematical models Robustness Model inference

Biologia de sistemas como uma abordagem comparativa para entender a expressão complexa de gene em doenças neurológicas

Behav. Sci. 2013, 3(2), 253-272; doi:10.3390/bs3020253

Systems Biology as a Comparative Approach to Understand Complex Gene Expression in Neurological Diseases

Leticia Diaz-Beltran 1,3, Carlos Cano 2, Dennis P. Wall 3 and Francisco J. Esteban 1,3,* 

Systems Biology Unit, Department of Experimental Biology, University of Jaen, Campus Las Lagunillas s/n, Jaen, 23071, Spain

Department of Computer Science, University of Granada, Daniel Saucedo Aranda s/n, Granada, 18071, Spain

Center for Biomedical Informatics & Department of Pathology, Harvard Medical School, 10 Shattuck Street, Boston, MA 02115, USA

Author to whom correspondence should be addressed.

Received: 9 April 2013 / Revised: 8 May 2013 / Accepted: 16 May 2013 / Published: 21 May 2013


Systems biology interdisciplinary approaches have become an essential analytical tool that may yield novel and powerful insights about the nature of human health and disease. Complex disorders are known to be caused by the combination of genetic, environmental, immunological or neurological factors. Thus, to understand such disorders, it becomes necessary to address the study of this complexity from a novel perspective. Here, we present a review of integrative approaches that help to understand the underlying biological processes involved in the etiopathogenesis of neurological diseases, for example, those related to autism and autism spectrum disorders (ASD) endophenotypes. Furthermore, we highlight the role of systems biology in the discovery of new biomarkers or therapeutic targets in complex disorders, a key step in the development of personalized medicine, and we demonstrate the role of systems approaches in the design of classifiers that can shorten the time for behavioral diagnosis of autism. View Full-Text

Keywords: systems biology; neurological diseases; gene expression; autism; autism spectrum disorders; network analysis; protein-protein interactions; translational bioinformatics; behavioral diagnosis

This is an open access article distributed under the Creative Commons Attribution License (CC BY 3.0).

FREE PDF GRATIS: Behavioral Sciences

Bioinformática e biologia de sistemas

Molecular Oncology

Volume 6, Issue 2, April 2012, Pages 147–154

Personalized cancer medicine

Bioinformatics and systems biology

Prahlad T. Ram, , John Mendelsohn, Gordon B. Mills

Department of Systems Biology, Institute for Personalized Cancer Therapy, The University of Texas, MD Anderson Cancer Center, Houston, TX 77054, USA

Received 6 December 2011, Accepted 24 January 2012, Available online 17 February 2012

Under an Elsevier user license

Source/Fonte: CRC Press


Delivering personalized therapeutic options to cancer patients based on the genetic and molecular aberrations of the tumor offers great promise to improve the outcomes of cancer therapy. Significant progress in biotechnology has allowed the measurement of tens of thousands of “omic” data points across multiple levels (DNA, RNA protein, metabolomics) from a single tumor biopsy sample in a reasonable time frame for making clinical decisions. With this data in hand, the challenge from the bioinformatics and systems biology point of view is how does one convert data into information and knowledge that can improve the delivery of personalized therapy to the patient.


Systens biology; Personalized cancer therapy; Predictive model systems

FREE PDF GRATIS: Molecular Oncology

Darwin, olha o olho de novo: Convergência análoga de inputs sustentados e transitórios em caminhos paralelos liga e desliga para a computação do movimento retinal

Analogous Convergence of Sustained and Transient Inputs in Parallel On and Off Pathways for Retinal Motion Computation

Matthew J. Greene 6, Jinseop S. Kim 5,6, H. Sebastian Seung, 4

5Present address: Department of Structure and Function of Neural Networks, Korea Brain Research Institute, Daegu 700-300, Republic of Korea

6Co-first author

Published Online: February 18, 2016

Open Access


• We analyzed serial electron microscopic images of a mouse retina

• On starburst amacrine cells (SACs) and bipolar cells (BCs) were reconstructed

• We defined an additional On BC type in the course of classifying On BCs

• Sustained and transient BC types are wired to SAC dendrites at different distances


Visual motion information is computed by parallel On and Off pathways in the retina, which lead to On and Off types of starburst amacrine cells (SACs). The approximate mirror symmetry between this pair of cell types suggests that On and Off pathways might compute motion using analogous mechanisms. To test this idea, we reconstructed On SACs and On bipolar cells (BCs) from serial electron microscopic images of a mouse retina. We defined a new On BC type in the course of classifying On BCs. Through quantitative contact analysis, we found evidence that sustained and transient On BC types are wired to On SAC dendrites at different distances from the SAC soma, mirroring our previous wiring diagram for the Off BC-SAC circuit. Our finding is consistent with the hypothesis that On and Off pathways contain parallel correlation-type motion detectors.

This is an open access article under the CC BY license (

Received: September 25, 2015; Received in revised form: November 20, 2015; Accepted: January 23, 2016; Published: February 18, 2016

© 2016 The Authors. Published by Elsevier Inc.


Darwin, os neurônios no olho humano (que você sentia calafrios) são organizados para a correção de erros!!!

sábado, dezembro 24, 2016

Error-Robust Modes of the Retinal Population Code

Jason S. Prentice, Olivier Marre, Mark L. Ioffe, Adrianna R. Loback, Gašper Tkačik, Michael J. Berry II 

Published: November 17, 2016

Source/Fonte: Eyewire


Across the nervous system, certain population spiking patterns are observed far more frequently than others. A hypothesis about this structure is that these collective activity patterns function as population codewords–collective modes–carrying information distinct from that of any single cell. We investigate this phenomenon in recordings of ∼150 retinal ganglion cells, the retina’s output. We develop a novel statistical model that decomposes the population response into modes; it predicts the distribution of spiking activity in the ganglion cell population with high accuracy. We found that the modes represent localized features of the visual stimulus that are distinct from the features represented by single neurons. Modes form clusters of activity states that are readily discriminated from one another. When we repeated the same visual stimulus, we found that the same mode was robustly elicited. These results suggest that retinal ganglion cells’ collective signaling is endowed with a form of error-correcting code–a principle that may hold in brain areas beyond retina.

Author Summary

Neurons in most parts of the nervous system represent and process information in a collective fashion, yet the nature of this collective code is poorly understood. An important constraint placed on any such collective processing comes from the fact that individual neurons’ signaling is prone to corruption by noise. The information theory and engineering literatures have studied error-correcting codes that allow individual noise-prone coding units to “check” each other, forming an overall representation that is robust to errors. In this paper, we have analyzed the population code of one of the best-studied neural systems, the retina, and found that it is structured in a manner analogous to error-correcting schemes. Indeed, we found that the complex activity patterns over ~150 retinal ganglion cells, the output neurons of the retina, could be mapped onto collective code words, and that these code words represented precise visual information while suppressing noise. In order to analyze this coding scheme, we introduced a novel quantitative model of the retinal output that predicted neural activity patterns more accurately than existing state-of-the-art approaches

Citation: Prentice JS, Marre O, Ioffe ML, Loback AR, Tkačik G, Berry MJ II (2016) Error-Robust Modes of the Retinal Population Code. PLoS Comput Biol 12(11): e1005148. doi:10.1371/journal.pcbi.1005148

Editor: Ian H. Stevenson, University of Connecticut, UNITED STATES

Received: July 15, 2015; Accepted: September 15, 2016; Published: November 17, 2016

Copyright: © 2016 Prentice et al. 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.

Data Availability: All supporting data files are available from the Dryad database under doi:10.5061/dryad.1f1rc.

Funding: JSP was supported by a C.V. Starr Fellowship from the Starr Foundation ( GT was supported by Austrian Research Foundation ( grant FWF P25651. MJB received support from National Eye Institute ( grant EY 14196 and from the National Science Foundation grant 1504977. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Competing interests: The authors have declared that no competing interests exist.

FREE PDF GRATIS: PLoS Computational Biology

Biosemiotics: chamada para artigos sobre os aspectos semióticos da Síntese Ampliada/Estendida

quinta-feira, dezembro 22, 2016


For a Special Issue of the journal Biosemiotics: Semiotic Aspects of the Extended Synthesis.

The journal Biosemiotics (Springer) is preparing a special issue on “Semiotic Aspects of the Extended Synthesis” guest-edited by Andrew M. Winters. While the field of biosemiotics is concerned with the origin and development of natural semiotic systems, much of the discussion has been framed in terms of Darwinian frameworks, including the Modern Synthesis. Non-Darwinian views were held by Uexküll and, more recently, Darwinian views have been supplemented in important ways by Kull, Hoffmeyer, and Barbieri. Many biological phenomena, such as transgenerational epigenetic inheritance, have yet to be explained in terms of these evolutionary theories. In the 1980s, biologists aimed to develop an Extended Synthesis to build upon and replace parts of the Modern Synthesis to better accommodate and explain these observed phenomenon. Given recent discussions of the Extended Synthesis, this Special Issue aims to understand the extent to which biosemiotics is commensurate with burgeoning developments in contemporary biology by exploring how core features of biosemiotics are either consistent or at odds with those accommodated by the Extended Synthesis.

The Special Issue of “Semiotic Aspects of the Extended Synthesis” welcomes papers that analyze specific semiotic processes within the Extended Synthesis, assess the general tenability of understanding biosemiotics in terms of the Extended Synthesis, or explore the relationship between biosemiotics and the Extended Synthesis. Papers in the form of theoretical works, empirical findings, or metatheoretical considerations are welcome.

Some potential questions to be explored in this Special Issue include:

• How does the extended synthesis differ from Darwinian evolution and the modern synthesis in its impact on biosemiotics?

• Does niche construction involve the construction of signs?

• How does semiotics contribute to evolutionary-developmental biology?

• Do signs further enhance plasticity and accommodation?

• Are signs replicable?

• Do signs and semiotic systems evolve?

• Are signs capable of emerging and contributing to multilevel selection?

• To what extent are candidate signs (e.g., genes)involved in genomic evolution?

Technical Details and Timeline:

• Paper Proposals (Title and Abstract) Due January 31st, 2017

• Notification of Acceptance February 28th, 2017

• Paper Submissions Due September 30th, 2017

• Final Drafts Due January 31st, 2018

• Electronic Publication February 2018

• Print Version Issue #2 August 2018

• Papers should be no more than 7,000 words (minus abstract and references)

• Instructions for authors can be found at:

• Submit abstracts and contact the editor at

Interações focadas são importantes para a dinâmica de proteínas

quarta-feira, dezembro 21, 2016

Dramatic influence of patchy attractions on short-time protein diffusion under crowded conditions

Saskia Bucciarelli 1, Jin Suk Myung 1,2, Bela Farago 3, Shibananda Das 2, Gerard A. Vliegenthart 2, Olaf Holderer 4, Roland G. Winkler 2, Peter Schurtenberger 1, Gerhard Gompper 2 and Anna Stradner 1,5,*

- Author Affiliations

1Division of Physical Chemistry, Department of Chemistry, Lund University, Naturvetarvägen 16, SE-221 00 Lund, Sweden.

2Theoretical Soft Matter and Biophysics, Institute of Complex Systems and Institute for Advanced Simulation, Forschungszentrum Jülich, D-52425 Jülich, Germany.

3Institut Laue-Langevin (ILL), F-38042 Grenoble Cedex 9, France.

4Jülich Centre for Neutron Science (JCNS) at Heinz Maier-Leibnitz Zentrum (MLZ), Forschungszentrum Jülich GmbH, Lichtenbergstr. 1, D-85748 Garching, Germany.

5Department of Chemistry, University of Fribourg, Chemin du Musée 9, CH-1700 Fribourg, Switzerland.

↵*Corresponding author. Email:

Science Advances 07 Dec 2016:

Vol. 2, no. 12, e1601432


In the dense and crowded environment of the cell cytoplasm, an individual protein feels the presence of and interacts with all surrounding proteins. While we expect this to strongly influence the short-time diffusion coefficient Ds of proteins on length scales comparable to the nearest-neighbor distance, this quantity is difficult to assess experimentally. We demonstrate that quantitative information about Ds can be obtained from quasi-elastic neutron scattering experiments using the neutron spin echo technique. We choose two well-characterized and highly stable eye lens proteins, bovine α-crystallin and γB-crystallin, and measure their diffusion at concentrations comparable to those present in the eye lens. While diffusion slows down with increasing concentration for both proteins, we find marked variations that are directly linked to subtle differences in their interaction potentials. A comparison with computer simulations shows that anisotropic and patchy interactions play an essential role in determining the local short-time dynamics. Hence, our study clearly demonstrates the enormous effect that weak attractions can have on the short-time diffusion of proteins at concentrations comparable to those in the cellular cytosol.

Keywords Protein crowding short-time dynamics protein-protein interactions anisotropic interactions protein diffusion neutron spin echo technique hydrodynamic interactions computer simulations multiparticle collision dynamics

Copyright © 2016, The Authors

This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial license, which permits use, distribution, and reproduction in any medium, so long as the resultant use is not for commercial advantage and provided the original work is properly cited.

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Viés de publicação e a canonização de "fatos científicos" falsos

Research: Publication bias and the canonization of false facts

Silas Boye Nissen Tali Magidson Kevin Gross Carl T Bergstrom 

University of Copenhagen, Denmark; University of Washington, United States; North Carolina State University, United States

Published December 20, 2016

Cite as eLife 2016;5:e21451


Science is facing a “replication crisis” in which many experimental findings cannot be replicated and are likely to be false. Does this imply that many scientific facts are false as well? To find out, we explore the process by which a claim becomes fact. We model the community’s confidence in a claim as a Markov process with successive published results shifting the degree of belief. Publication bias in favor of positive findings influences the distribution of published results. We find that unless a sufficient fraction of negative results are published, false claims frequently can become canonized as fact. Data-dredging, p-hacking, and similar behaviors exacerbate the problem. Should negative results become easier to publish as a claim approaches acceptance as a fact, however, true and false claims would be more readily distinguished. To the degree that the model reflects the real world, there may be serious concerns about the validity of purported facts in some disciplines.


Revertendo a velhice: descoberta a Fonte da Juventude?

In Vivo Amelioration of Age-Associated Hallmarks by Partial Reprogramming

Alejandro Ocampo6, Pradeep Reddy6, Paloma Martinez-Redondo6, Aida Platero-Luengo, Fumiyuki Hatanaka, Tomoaki Hishida, Mo Li, David Lam, Masakazu Kurita, Ergin Beyret, Toshikazu Araoka, Eric Vazquez-Ferrer, David Donoso, Jose Luis Roman, Jinna Xu, Concepcion Rodriguez Esteban, Gabriel Nuñez, Estrella Nuñez Delicado, Josep M. Campistol, Isabel Guillen, Pedro Guillen, Juan Carlos Izpisua Belmonte7,

6Co-first author

7Lead Contact


• Partial reprogramming erases cellular markers of aging in mouse and human cells

• Induction of OSKM in progeria mice ameliorates signs of aging and extends lifespan

• In vivo reprogramming improves regeneration in 12-month-old wild-type mice


Aging is the major risk factor for many human diseases. In vitro studies have demonstrated that cellular reprogramming to pluripotency reverses cellular age, but alteration of the aging process through reprogramming has not been directly demonstrated in vivo. Here, we report that partial reprogramming by short-term cyclic expression of Oct4, Sox2, Klf4, and c-Myc (OSKM) ameliorates cellular and physiological hallmarks of aging and prolongs lifespan in a mouse model of premature aging. Similarly, expression of OSKM in vivo improves recovery from metabolic disease and muscle injury in older wild-type mice. The amelioration of age-associated phenotypes by epigenetic remodeling during cellular reprogramming highlights the role of epigenetic dysregulation as a driver of mammalian aging. Establishing in vivo platforms to modulate age-associated epigenetic marks may provide further insights into the biology of aging.

Keywords: aging, cellular reprogramming, lifespan, epigenetics

Received: August 19, 2016; Received in revised form: October 14, 2016; Accepted: November 28, 2016; Published: December 15, 2016

© 2016 Elsevier Inc.


Como se originaram as células complexas?

terça-feira, dezembro 20, 2016

The non-canonical mitochondrial inner membrane presequence translocase of trypanosomatids contains two essential rhomboid-like proteins

Anke Harsman, Silke Oeljeklaus, Christoph Wenger, Jonathan L. Huot, Bettina Warscheid & André Schneider

Nature Communications 7, Article number: 13707 (2016)

Download Citation

Mitochondria Protein translocation Proteomics

Received: 07 April 2016 Accepted: 24 October 2016 Published online: 19 December 2016

Source/Fonte: Biotechnology


Mitochondrial protein import is essential for all eukaryotes. Here we show that the early diverging eukaryote Trypanosoma brucei has a non-canonical inner membrane (IM) protein translocation machinery. Besides TbTim17, the single member of the Tim17/22/23 family in trypanosomes, the presequence translocase contains nine subunits that co-purify in reciprocal immunoprecipitations and with a presequence-containing substrate that is trapped in the translocation channel. Two of the newly discovered subunits are rhomboid-like proteins, which are essential for growth and mitochondrial protein import. Rhomboid-like proteins were proposed to form the protein translocation pore of the ER-associated degradation system, suggesting that they may contribute to pore formation in the presequence translocase of T. brucei. Pulldown of import-arrested mitochondrial carrier protein shows that the carrier translocase shares eight subunits with the presequence translocase. This indicates that T. brucei may have a single IM translocase that with compositional variations mediates import of presequence-containing and carrier proteins.


A.H. gratefully acknowledges a fellowship from the Peter und Traudl Engelhorn foundation. We thank B. Knapp for technical assistance in LC-MS analyses. Research in the group of B.W. was funded by the Deutsche Forschungsgemeinschaft and the Excellence Initiative of the German Federal and State Governments (EXC 294 BIOSS Centre for Biological Signalling Studies). Research in the laboratory of A.S. was supported by grant 138355 and in part by the NCCR ‘RNA & Disease’ both funded by the Swiss National Science Foundation. Deposition of the data to the ProteomeXchange Consortium was supported by the PRIDE Team, EBI.

Author information


Department of Chemistry and Biochemistry, University of Bern, Freiestrasse 3, Bern CH-3012, Switzerland

Anke Harsman, Christoph Wenger, Jonathan L. Huot & André Schneider

Department of Biochemistry and Functional Proteomics, Institute of Biology II, Faculty of Biology, University of Freiburg, Schänzlestraße 18, Freiburg 79104, Germany

Silke Oeljeklaus & Bettina Warscheid

BIOSS Centre for Biological Signalling Studies, University of Freiburg, Schänzlestraße 18, Freiburg 79104, Germany

Bettina Warscheid


A.H. and A.S. designed the experiments. A.H., C.W. and J.L.H. performed and analysed the experiments. Quantitative proteomic experiments were designed by S.O. and B.W. and SILAC-MS data were collected and analysed by S.O. A.S. and B.W. supervised the project. A.S. coordinated the entire project and obtained the main source of funding; A.H. and A.S. prepared and revised the manuscript with the input of S.O. and B.W.

Competing interests

The authors declare no competing financial interests.

Corresponding authors

Correspondence to Bettina Warscheid or André Schneider.

                           Excel Files 1, 2, 3, 4, 5, 6

RNA não codificante: o que é funcional e o que é lixo?


Front. Genet., 26 January 2015 |

Non-coding RNA: what is functional and what is junk?

Alexander F. Palazzo* and Eliza S. Lee

Department of Biochemistry, University of Toronto, Toronto, ON, Canada

Source/Fonte: Forbes


The genomes of large multicellular eukaryotes are mostly comprised of non-protein coding DNA. Although there has been much agreement that a small fraction of these genomes has important biological functions, there has been much debate as to whether the rest contributes to development and/or homeostasis. Much of the speculation has centered on the genomic regions that are transcribed into RNA at some low level. Unfortunately these RNAs have been arbitrarily assigned various names, such as “intergenic RNA,” “long non-coding RNAs” etc., which have led to some confusion in the field. Many researchers believe that these transcripts represent a vast, unchartered world of functional non-coding RNAs (ncRNAs), simply because they exist. However, there are reasons to question this Panglossian view because it ignores our current understanding of how evolution shapes eukaryotic genomes and how the gene expression machinery works in eukaryotic cells. Although there are undoubtedly many more functional ncRNAs yet to be discovered and characterized, it is also likely that many of these transcripts are simply junk. Here, we discuss how to determine whether any given ncRNA has a function. Importantly, we advocate that in the absence of any such data, the appropriate null hypothesis is that the RNA in question is junk.

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Evolução da resistência contra a manipulação de gene com o CRISPR / Cas9

segunda-feira, dezembro 19, 2016

Evolution of Resistance Against CRISPR/Cas9 Gene Drive

Robert L. Unckless, Andrew G. Clark, Philipp W. Messer

GENETICS Early online December 10, 2016; DOI: 10.1534/genetics.116.197285


CRISPR/Cas9 gene drive (CGD) promises a highly adaptable approach for spreading genetically engineered alleles throughout a species, even if those alleles impair reproductive success. CGD has been shown to be effective in laboratory crosses of insects, yet it remains unclear to what extent potential resistance mechanisms will affect the dynamics of this process in large natural populations. Here we develop a comprehensive population genetic framework for modeling CGD dynamics, which incorporates potential resistance mechanisms as well as random genetic drift. Using this framework, we calculate the probability that resistance against CGD evolves from standing genetic variation, de novo mutation of wildtype alleles, or cleavage-repair by nonhomologous end joining (NHEJ) -- a likely byproduct of CGD itself. We show that resistance to standard CGD approaches should evolve almost inevitably in most natural populations, unless repair of CGD-induced cleavage via NHEJ can be effectively suppressed, or resistance costs are on par with those of the driver. The key factor determining the probability that resistance evolves is the overall rate at which resistance alleles arise at the population level by mutation or NHEJ. By contrast, the conversion efficiency of the driver, its fitness cost, and its introduction frequency have only minor impact. Our results shed light on strategies that could facilitate the engineering of drivers with lower resistance potential, and motivate the possibility to embrace resistance as a possible mechanism for controlling a CGD approach. This study highlights the need for careful modeling of the population dynamics of CGD prior to the actual release of a driver construct into the wild.


Received October 27, 2016. Accepted December 1, 2016.

Copyright © 2016, The Genetics Society of America


Veja Darwin, resistência antibiótica sem antibióticos sintéticos há mais de 4 milhões de anos!

sexta-feira, dezembro 16, 2016

A diverse intrinsic antibiotic resistome from a cave bacterium

Andrew C. Pawlowski, Wenliang Wang, Kalinka Koteva, Hazel A. Barton, Andrew G. McArthur & Gerard D. Wright

Nature Communications 7, Article number: 13803 (2016)

Download Citation

Antimicrobial resistanceBacterial evolutionEnzymes

Received: 05 July 2016 Accepted: 01 November 2016 Published online: 08 December 2016

Paenibacillus vortex colony - Eshel Ben Jacob


Antibiotic resistance is ancient and widespread in environmental bacteria. These are therefore reservoirs of resistance elements and reflective of the natural history of antibiotics and resistance. In a previous study, we discovered that multi-drug resistance is common in bacteria isolated from Lechuguilla Cave, an underground ecosystem that has been isolated from the surface for over 4 Myr. Here we use whole-genome sequencing, functional genomics and biochemical assays to reveal the intrinsic resistome of Paenibacillus sp. LC231, a cave bacterial isolate that is resistant to most clinically used antibiotics. We systematically link resistance phenotype to genotype and in doing so, identify 18 chromosomal resistance elements, including five determinants without characterized homologues and three mechanisms not previously shown to be involved in antibiotic resistance. A resistome comparison across related surface Paenibacillus affirms the conservation of resistance over millions of years and establishes the longevity of these genes in this genus.

Additional information

How to cite this article: Pawlowski, A. C. et al. A diverse intrinsic antibiotic resistome from a cave bacterium. Nat. Commun. 7, 13803 doi: 10.1038/ncomms13803 (2016).

Publisher's note: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.


We thank members of the CARD team for input into antibiotic resistance sequence analysis. We also thank Nicholas Waglechner (McMaster University) for helpful discussions in generating the Paenibacillus species tree and Christine King (McMaster University) for genome sequencing and shearing genomic DNA. This research was funded by a Canadian Institutes of Health Research Grant (MT-13536), Natural Sciences and Engineering Research Council Grant (237480) and by a Canada Research Chair in Antibiotic Biochemistry (to G.D.W). A.G.M. holds a Cisco Research Chair in Bioinformatics, supported by Cisco Systems Canada, Inc.

Author information


Michael G. DeGroote Institute for Infectious Disease Research and the Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, Ontario, Canada L8S 4K1

Andrew C. Pawlowski, Wenliang Wang, Kalinka Koteva, Andrew G. McArthur & Gerard D. Wright

Department of Biology, University of Akron, Akron, Ohio 44325, USA

Hazel A. Barton


A.C.P. performed all experiments except for structural elucidation using NMR. W.W. assisted in acetyl-capreomycin purification and performed acetyl-capreomycin NMR experiments. K.K. assisted in purifying descladinose clarithromycin and structural characterization of inactivated bacitracin, and performed descladinose clarithromycin NMR experiments. A.G.M. assisted the antibiotic resistance sequence analysis. H.A.B. collected strains and provided growth parameters. A.C.P and G.D.W. designed research and wrote the paper with contributions from all authors.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Gerard D. Wright.