A cinesina gira de forma unidirecional e gera torque ao caminhar sobre microtúbulos: mero acaso, fortuita necessidade ou design inteligente?

quarta-feira, novembro 22, 2017

Kinesin rotates unidirectionally and generates torque while walking on microtubules

Avin Ramaiya a,1, Basudev Roy a,1,2, Michael Bugiel a, and Erik Schäffer a,

Author Affiliations

a Cellular Nanoscience, Center for Plant Molecular Biology, University of Tübingen, 72076 Tübingen, Germany

Edited by J. Richard McIntosh, University of Colorado, Boulder, CO, and approved August 22, 2017 (received for review April 26, 2017)

<iframe width="425" height="344" src="https://www.youtube.com/embed/y-uuk4Pr2i8" frameborder="0" allowfullscreen></iframe>

Significance

Given the importance of cytoskeletal motor proteins, we asked whether translational motors rotate while walking along their tracks. Using an optical tweezers-based approach, we simultaneously measured translation, force, rotation, and torque of a kinesin motor with molecular resolution. We found that the gait followed a rotary stepping mechanism that generates torque and spins cargo. Thus, during walking, the motor “tail (and organelle) will tend to wind up like the rubber band of a toy airplane,” as Joe Howard hypothesized in 1996. To determine the overall motor efficiency, our measurements also point to the importance of accounting for rotational work. Apart from other cytoskeletal motors, the technique may be applied to molecular machines such as DNA motors and rotary engines like the ATP synthase.

Abstract

Cytoskeletal motors drive many essential cellular processes. For example, kinesin-1 transports cargo in a step-wise manner along microtubules. To resolve rotations during stepping, we used optical tweezers combined with an optical microprotractor and torsion balance using highly birefringent microspheres to directly and simultaneously measure the translocation, rotation, force, and torque generated by individual kinesin-1 motors. While, at low adenosine 5′-triphosphate (ATP) concentrations, motors did not generate torque, we found that motors translocating along microtubules at saturating ATP concentrations rotated unidirectionally, producing significant torque on the probes. Accounting for the rotational work makes kinesin a highly efficient machine. These results imply that the motor’s gait follows a rotary hand-over-hand mechanism. Our method is generally applicable to study rotational and linear motion of molecular machines, and our findings have implications for kinesin-driven cellular processes.

kinesin optical tweezers polarization microscopy birefringence rotation

Footnotes

1A.R. and B.R. contributed equally to this work.

2Present address: Department of Physics, Indian Institute of Technology, Madras 600036, India.

3To whom correspondence should be addressed. Email: Erik.Schaeffer@uni-tuebingen.de.

Author contributions: E.S. designed research; A.R., B.R., and M.B. performed research; A.R., B.R., M.B., and E.S. analyzed data; and A.R., B.R., and E.S. 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.1706985114/-/DCSupplemental.

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Testando a hipótese neutra da evolução fenotípica

Testing the neutral hypothesis of phenotypic evolution

Wei-Chin Hoa, Yoshikazu Ohyab, and Jianzhi Zhanga,1 

Author Affiliations

a Department of Ecology and Evolutionary Biology, University of Michigan, Ann Arbor, MI 48109;

b Department of Integrated Biosciences, Graduate School of Frontier Sciences, University of Tokyo, Kashiwa, Chiba Prefecture 277-8562, Japan

Edited by Wen-Hsiung Li, Academia Sinica, Taipei, Taiwan, and approved October 6, 2017 (received for review June 29, 2017)

Source/Fonte: Amazon Books

Significance

Despite the universal recognition that adaptation by Darwinian selection can shape phenotypic variations within and between species, it remains unknown whether most phenotypic variations observed have adaptive values, in part because addressing this question requires examining a large, random set of traits while past studies were biased toward traits that are likely adaptive. Here, we study 210 yeast morphological traits chosen purely on the basis of experimental feasibility and expression levels of all yeast genes with reliable measurements. We find that morphological variations, but not expression variations, are largely adaptive, suggesting that different classes of phenotypic traits are subject to adaptive evolution to varying extents.

Abstract

Although evolution by natural selection is widely regarded as the most important principle of biology, it is unknown whether phenotypic variations within and between species are mostly adaptive or neutral due to the lack of relevant studies of large, unbiased samples of phenotypic traits. Here, we examine 210 yeast morphological traits chosen because of experimental feasibility irrespective of their potential adaptive values. Our analysis is based on the premise that, under neutrality, the rate of phenotypic evolution measured in the unit of mutational size declines as the trait becomes more important to fitness, analogous to the neutral paradigm that functional genes evolve more slowly than functionless pseudogenes. However, we find faster evolution of more important morphological traits within and between species, rejecting the neutral hypothesis. By contrast, an analysis of 3,466 gene expression traits fails to refute neutrality. Thus, at least in yeast, morphological evolution appears largely adaptive, but the same may not apply to other classes of phenotypes. Our neutrality test is applicable to other species, especially genetic model organisms, for which estimations of mutational size and trait importance are relatively straightforward.

adaptation gene expression morphology neutrality yeast

Footnotes

1To whom correspondence should be addressed. Email: jianzhi@umich.edu.

Author contributions: W.-C.H. and J.Z. designed research; W.-C.H. and Y.O. performed research; Y.O. contributed new reagents/analytic tools; W.-C.H. analyzed data; and W.-C.H. and J.Z. 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.1710351114/-/DCSupplemental.

Published under the PNAS license.

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Sobre a origem da construção biológica com um foco na multicelularidade: mero acaso, fortuita necessidade ou design inteligente?

On the origin of biological construction, with a focus on multicellularity

Jordi van Gestel a,b,c,d and Corina E. Tarnita e,

Author Affiliations

a Department of Evolutionary Biology and Environmental Studies, University of Zürich, 8057 Zürich, Switzerland;

b Swiss Institute of Bioinformatics, 1015 Lausanne, Switzerland;

c Department of Environmental Systems Science, ETH Zürich, 8092 Zürich, Switzerland;

d Department of Environmental Microbiology, Swiss Federal Institute of Aquatic Science and Technology (EAWAG), 8600 Dübendorf, Switzerland;

e Department of Ecology and Evolutionary Biology, Princeton University, Princeton, NJ 08544

Edited by Gene E. Robinson, University of Illinois at Urbana–Champaign, Urbana, IL, and approved September 1, 2017 (received for review April 9, 2017)


Abstract

Biology is marked by a hierarchical organization: all life consists of cells; in some cases, these cells assemble into groups, such as endosymbionts or multicellular organisms; in turn, multicellular organisms sometimes assemble into yet other groups, such as primate societies or ant colonies. The construction of new organizational layers results from hierarchical evolutionary transitions, in which biological units (e.g., cells) form groups that evolve into new units of biological organization (e.g., multicellular organisms). Despite considerable advances, there is no bottom-up, dynamical account of how, starting from the solitary ancestor, the first groups originate and subsequently evolve the organizing principles that qualify them as new units. Guided by six central questions, we propose an integrative bottom-up approach for studying the dynamics underlying hierarchical evolutionary transitions, which builds on and synthesizes existing knowledge. This approach highlights the crucial role of the ecology and development of the solitary ancestor in the emergence and subsequent evolution of groups, and it stresses the paramount importance of the life cycle: only by evaluating groups in the context of their life cycle can we unravel the evolutionary trajectory of hierarchical transitions. These insights also provide a starting point for understanding the types of subsequent organizational complexity. The central research questions outlined here naturally link existing research programs on biological construction (e.g., on cooperation, multilevel selection, self-organization, and development) and thereby help integrate knowledge stemming from diverse fields of biology.

major evolutionary transitions hierarchical evolutionary transitions bottom-up approach life cycle animal sociality

Footnotes

1To whom correspondence should be addressed. Email: ctarnita@princeton.edu.

Author contributions: J.v.G. and C.E.T. 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.1704631114/-/DCSupplemental.

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Captura de imagens a laser e profundo sequenciamento revelam os programas transcriptômicos regulando o início à diferenciação do pâncreas e fígado em embriões humanos

Laser Capture and Deep Sequencing Reveals the Transcriptomic Programmes Regulating the Onset of Pancreas and Liver Differentiation in Human Embryos

Rachel E. Jennings, Andrew A. Berry, David T. Gerrard, Stephen J. Wearne, James Strutt, Sarah Withey, Mariya Chhatriwala, Karen Piper Hanley, Ludovic Vallier, Nicoletta Bobola, Neil A. Hanley'Correspondence information about the author Neil A. HanleyEmail the author Neil A. Hanley

Published Online: October 19, 2017

Open Access

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Open access funded by Wellcome Trust

Article Info

Publication History

Published: October 19, 2017 Accepted: September 25, 2017

Received in revised form: September 22, 2017 Received: April 25, 2017

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Creative Commons Attribution (CC BY 4.0) How you can reuse Information Icon


Highlights

Transcriptomic signatures at the inception of human liver and pancreas development

• Limited conservation of pancreas-enriched gene expression between human and mouse

• Human PSC protocols imply a dorsal rather than a ventral pancreatic program

• New pancreatic transcription factors imputed by differential analysis

Summary

To interrogate the alternative fates of pancreas and liver in the earliest stages of human organogenesis, we developed laser capture, RNA amplification, and computational analysis of deep sequencing. Pancreas-enriched gene expression was less conserved between human and mouse than for liver. The dorsal pancreatic bud was enriched for components of Notch, Wnt, BMP, and FGF signaling, almost all genes known to cause pancreatic agenesis or hypoplasia, and over 30 unexplored transcription factors. SOX9 and RORA were imputed as key regulators in pancreas compared with EP300, HNF4A, and FOXA family members in liver. Analyses implied that current in vitro human stem cell differentiation follows a dorsal rather than a ventral pancreatic program and pointed to additional factors for hepatic differentiation. In summary, we provide the transcriptional codes regulating the start of human liver and pancreas development to facilitate stem cell research and clinical interpretation without inter-species extrapolation.

FREE PDF GRATIS: Stem Cell Reports

Dawkins disse que o design na natureza é ilusão, mas a engenharia inspirada nela é, de facto, a ciência do Design Inteligente!!!

Ultra-antireflective synthetic brochosomes

Shikuan Yang, Nan Sun, Birgitt Boschitsch Stogin, Jing Wang, Yu Huang & Tak-Sing Wong

Nature Communications 8, Article number: 1285 (2017)


Download Citation

Bioinspired materials Colloids Optical materials and structures

Received: 05 March 2017 Accepted: 14 September 2017

Published online: 03 November 2017




Abstract

Since the early discovery of the antireflection properties of insect compound eyes, new examples of natural antireflective coatings have been rare. Here, we report the fabrication and optical characterization of a biologically inspired antireflective surface that emulates the intricate surface architectures of leafhopper-produced brochosomes—soccer ball-like microscale granules with nanoscale indentations. Our method utilizes double-layer colloidal crystal templates in conjunction with site-specific electrochemical growth to create these structures, and is compatible with various materials including metals, metal oxides, and conductive polymers. These brochosome coatings (BCs) can be designed to exhibit strong omnidirectional antireflective performance of wavelengths from 250 to 2000 nm, comparable to the state-of-the-art antireflective coatings. Our results provide evidence for the use of brochosomes as a camouflage coating against predators of leafhoppers or their eggs. The discovery of the antireflective function of BCs may find applications in solar energy harvesting, imaging, and sensing devices.

Acknowledgements

We thank Josh Stapleton from Materials Characterization Laboratory and Leland Shawn Burghard at The Pennsylvania State University for the help with the optical measurements and the greenhouse management, respectively. We acknowledge funding support by the Defense Advanced Research Projects Agency Award# D14AP00042 (materials and optical characterizations), the National Science Foundation CAREER Award# 1351462 (materials fabrication), Start-Up Fund from The Pennsylvania State University, and Wormley Family Early Career Professorship. Stogin acknowledges support from the NSF Graduate Research Fellowship (Grant No.: DGE1255832). Publication of this article was funded in part by The Pennsylvania State University Libraries Open Access Publishing Fund. Part of the work was conducted at the Penn State node of the NSF-funded National Nanotechnology of Infrastructure Network.

Author information

Affiliations

Department of Mechanical and Nuclear Engineering, The Pennsylvania State University, University Park, PA, 16802, USA

Shikuan Yang, Nan Sun, Birgitt Boschitsch Stogin, Jing Wang, Yu Huang & Tak-Sing Wong

Materials Research Institute, The Pennsylvania State University, University Park, PA, 16802, USA

Shikuan Yang, Nan Sun, Birgitt Boschitsch Stogin, Jing Wang, Yu Huang & Tak-Sing Wong

Institute for Composites Science Innovation, School of Materials Science and Engineering, Zhejiang University, Hangzhou, 310027, China

Shikuan Yang

Department of Biomedical Engineering, The Pennsylvania State University, University Park, PA, 16802, USA

Tak-Sing Wong

Contributions

S.Y. and T.-S.W. designed the experiments. S.Y. carried out the materials fabrication, wetting, and optical characterizations. S.Y., N.S., B.B.S., J.W., and Y.H. conducted the data analysis. N.S. and J.W. performed vision simulations of various organisms and experimental verifications. S.Y., B.B.S., and T.-S.W. wrote the paper. All authors contributed to paper revision.

Competing interests

The authors declare no competing financial interests.

Corresponding authors

Correspondence to Shikuan Yang or Tak-Sing Wong.

Estrutura tridimensional do flagelo/cília eucariótico por tomografia crio-eletrônica: mero acaso, fortuita necessidade ou design inteligente?

segunda-feira, novembro 20, 2017

BIOPHYSICS

Vol. 9 (2013) p. 141-148

DOI: http://doi.org/10.2142/biophysics.9.141

Review Article

3D structure of eukaryotic flagella/cilia by cryo-electron tomography



Takashi Ishikawa1)

1) Laboratory of Biomolecular Research, Paul Scherrer Institute, Villigen PSI

Released on J-STAGE 2013/10/17 

Received 2013/07/09 Accepted 2013/09/25

Keywords: dynein, microtubule, cryo-EM, axoneme, motor protein

FREE PDF GRATIS: BioPhysics

Ajuste fino de cílios e flagelos móveis: a evolução das proteínas do motor de dineína de plantas aos seres humanos em alta resolução: mero acaso, fortuita necessidade ou design inteligente?

Fine-Tuning Motile Cilia and Flagella: Evolution of the Dynein Motor Proteins from Plants to Humans at High Resolution 

Martin Kollmar

Molecular Biology and Evolution, Volume 33, Issue 12, 1 December 2016, Pages 3249–3267, https://doi.org/10.1093/molbev/msw213

Published: 07 October 2016


Abstract

The flagellum is a key innovation linked to eukaryogenesis. It provides motility by regulated cycles of bending and bend propagation, which are thought to be controlled by a complex arrangement of seven distinct dyneins in repeated patterns of outer- (OAD) and inner-arm dynein (IAD) complexes. Electron tomography showed high similarity of this axonemal repeat pattern across ciliates, algae, and animals, but the diversity of dynein sequences across the eukaryotes has not yet comprehensively been resolved and correlated with structural data. To shed light on the evolution of the axoneme I performed an exhaustive analysis of dyneins using the available sequenced genome data. Evidence from motor domain phylogeny allowed expanding the current set of nine dynein subtypes by eight additional isoforms with, however, restricted taxonomic distributions. I confirmed the presence of the nine dyneins in all eukaryotic super-groups indicating their origin predating the last eukaryotic common ancestor. The comparison of the N-terminal tail domains revealed a most likely axonemal dynein origin of the new classes, a group of chimeric dyneins in plants/algae and Stramenopiles, and the unique domain architecture and origin of the outermost OADs present in green algae and ciliates but not animals. The correlation of sequence and structural data suggests the single-headed class-8 and class-9 dyneins to localize to the distal end of the axonemal repeat and the class-7 dyneins filling the region up to the proximal heterodimeric IAD. Tracing dynein gene duplications across the eukaryotes indicated ongoing diversification and fine-tuning of flagellar functions in extant taxa and species.

axoneme, cilium, flagellum, dynein, last eukaryotic common ancestor.

Issue Section: Discoveries

FREE PDF GRATIS: Mol Biol Evol

A tomografia crio-eletrônica revela características conservadas de microtúbulos duplos em flagelos: mero acaso, fortuita necessidade ou design inteligente?

Cryo-electron tomography reveals conserved features of doublet microtubules in flagella

Daniela Nicastro a,1, Xiaofeng Fu a,b, Thomas Heuser a, Alan Tso a, Mary E. Porter c, and Richard W. Linck c 

Author Affiliations

Edited by J. Richard McIntosh, University of Colorado, Boulder, CO, and approved August 24, 2011 (received for review May 3, 2011)

Fig. 1. Cryo-ET provides an overview of the 3D structure of DMTs. Tomographic slices (A and B) and isosurface renderings (D–F) of averaged axonemal repeats from Chlamydomonas pseudo-WT (pWT; Table 1) show cross-sectional (A and D), longitudinal (B), and oblique (E and F) views of the DMT. The red lines in A indicate the cutting plane of the slice shown in B. In the surface renderings, only the DMT core is shown, whereas all peripheral structures [e.g., inner or outer dynein arm (IDA or ODA, respectively)] were removed but their positions are indicated in A (surface rendering overview with associated structures is shown in Fig. S1). PF numbers [according to Linck and Stephens (16)] are colored pink in the A-tubule (At) and dark blue in the B-tubule (Bt). In B, prominent left-handed helical lines with an 8-nm axial periodicity are apparent, probably corresponding to the helical lattice of tubulin subunits (28, 49). The IJ and trimeric outer junction (OJ) have distinct structures. Colored arrowheads point to MIP1 (light blue), MIP2 (red), MIP3 (yellow), and MIP4 (orange). DMT cross-sections are viewed from a proximal orientation (flagellar base) toward a distal (flagellar tip) orientation, and in the longitudinal view, the left side is proximal. The DMT orientations, labels, and colors shown here are used consistently in all subsequent figures unless otherwise noted and are valid for all panels. (C) Resolution of the DMT averages used in this study ranged from 3.3 to 3.9 nm (0.5 criterion of the Fourier shell correlation method). More details are provided in Table 1. (Scale bar: 10 nm.)

Abstract

The axoneme forms the essential and conserved core of cilia and flagella. We have used cryo-electron tomography of Chlamydomonas and sea urchin flagella to answer long-standing questions and to provide information about the structure of axonemal doublet microtubules (DMTs). Solving an ongoing controversy, we show that B-tubules of DMTs contain exactly 10 protofilaments (PFs) and that the inner junction (IJ) and outer junction between the A- and B-tubules are fundamentally different. The outer junction, crucial for the initiation of doublet formation, appears to be formed by close interactions between the tubulin subunits of three PFs with unusual tubulin interfaces; other investigators have reported that this junction is weakened by mutations affecting posttranslational modifications of tubulin. The IJ consists of an axially periodic ladder-like structure connecting tubulin PFs of the A- and B-tubules. The recently discovered microtubule inner proteins (MIPs) on the inside of the A- and B-tubules are more complex than previously thought. They are composed of alternating small and large subunits with periodicities of 16 and/or 48 nm. MIP3 forms arches connecting B-tubule PFs, contrary to an earlier report that MIP3 forms the IJ. Finally, the “beak” structures within the B-tubules of Chlamydomonas DMT1, DMT5, and DMT6 are clearly composed of a longitudinal band of proteins repeating with a periodicity of 16 nm. These findings, discussed in relation to genetic and biochemical data, provide a critical foundation for future work on the molecular assembly and stability of the axoneme, as well as its function in motility and sensory transduction.

microtubule stability cilia axoneme ciliopathies cytoskeleton

Footnotes

1To whom correspondence should be addressed. E-mail: nicastro@brandeis.edu.

Author contributions: D.N. designed research; D.N., X.F., T.H., and A.T. performed research; M.E.P. contributed new reagents/analytic tools; D.N., X.F., T.H., and R.W.L. analyzed data; and D.N. and R.W.L. wrote the paper.

The authors declare no conflict of interest.

This article is a PNAS Direct Submission.

See Author Summary on page 17249.

This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1106178108/-/DCSupplemental.

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Análise estrutural tridimensional de flagelo/cilia eucariótico por tomografia eletro-crio.

J. Synchrotron Rad. (2011). 18, 2-5

Three-dimensional structural analysis of eukaryotic flagella/cilia by electron cryo-tomography


K. H. Bui, G. Pigino and T. Ishikawa


Figure 1 Structure of a flagellum and its components in various dimensions. The appropriate method for structural analysis at each scale is shown on the right. (a) Chlamydomonas cell with two flagella (5–10 µm length, 0.25 µm diameter). (b) Cross section [at the red dotted circle in (a)] of a flagellum. ODA: outer dynein arms. IDA: inner dynein arms. RS: radial spokes. (c) One microtubule doublet is extracted [red dotted circle in (b)], rotated and enlarged. (d) Schematic diagram of one dynein heavy chain [enclosed by the red dotted line in (c)]. (e) Atomic structure of the microtubule binding domain at the tip of the coiled-coil stalk.

Abstract

Electron cryo-tomography is a potential approach to analyzing the three-dimensional conformation of frozen hydrated biological macromolecules using electron microscopy. Since projections of each individual object illuminated from different orientations are merged, electron tomography is capable of structural analysis of such heterogeneous environments as in vivo or with polymorphism, although radiation damage and the missing wedge are severe problems. Here, recent results on the structure of eukaryotic flagella, which is an ATP-driven bending organelle, from green algae Chlamydomonas are presented. Tomographic analysis reveals asymmetric molecular arrangements, especially that of the dynein motor proteins, in flagella, giving insight into the mechanism of planar asymmetric bending motion. Methodological challenges to obtaining higher-resolution structures from this technique are also discussed.

Keywords: dynein; flagella; axoneme; tomography; cryo-EM.

FREE PDF GRATIS: J Sinchroton Rad.

Foi a evolução pulsada que modelou os tamanhos dos planos corporais dos vertebrados

Pulsed evolution shaped modern vertebrate body sizes

Michael J. Landis a and Joshua G. Schraiber b,c,

Author Affiliations

Edited by Neil H. Shubin, The University of Chicago, Chicago, IL, and approved October 6, 2017 (received for review June 18, 2017)


Fig. 1.
Model selection profiles for 66 vertebrate clades. Clade colors indicate their order: black, fish; purple, amphibians; green, reptiles; blue, birds; and red, mammals. Each clade was fitted to seven models, classified into four groups: incremental change (BM), incremental stationarity (OU), explosive change (EB), and pulsed change (JN, NIG, BM+JN, BM+NIG). AICc weights were computed using only the best-fitting model within each class. A model class is selected only if its AICc weight is twice as large than that of any other model class (circles indicate selection counts: 12 incremental change, 1 incremental stationarity, 9 explosive change, 21 pulsed change, 23 ambiguous). Alternative model classifications are provided in SI Appendix.

Significance

The diversity of forms found among animals on Earth is striking. Despite decades of study, it has been difficult to reconcile the patterns of diversity seen between closely related species with those observed when studying single species on ecological timescales. We propose a set of models, called Lévy processes, to attempt to reconcile rapid evolution between species with the relatively stable distributions of phenotypes seen within species. These models, which have been successfully used to model stock market data, allow for long periods of stasis followed by bursts of rapid change. We find that many vertebrate groups are well fitted by Lévy models compared with models for which traits evolve toward a stationary optimum or evolve in an incremental and wandering manner.

Abstract

The relative importance of different modes of evolution in shaping phenotypic diversity remains a hotly debated question. Fossil data suggest that stasis may be a common mode of evolution, while modern data suggest some lineages experience very fast rates of evolution. One way to reconcile these observations is to imagine that evolution proceeds in pulses, rather than in increments, on geological timescales. To test this hypothesis, we developed a maximum-likelihood framework for fitting Lévy processes to comparative morphological data. This class of stochastic processes includes both an incremental and a pulsed component. We found that a plurality of modern vertebrate clades examined are best fitted by pulsed processes over models of incremental change, stationarity, and adaptive radiation. When we compare our results to theoretical expectations of the rate and speed of regime shifts for models that detail fitness landscape dynamics, we find that our quantitative results are broadly compatible with both microevolutionary models and observations from the fossil record.

macroevolution Levy process pulsed evolution adaptive landscape

Footnotes

1To whom correspondence should be addressed. Email: joshua.schraiber@temple.edu.

Author contributions: M.J.L. and J.G.S. designed research, performed research, analyzed data, and 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.1710920114/-/DCSupplemental.

Copyright © 2017 the Author(s). Published by PNAS.

This open access article is distributed under Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND).


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Delimitando a velocidade da gravidade com as observações de ondas gravitacionais

Bounding the Speed of Gravity with Gravitational Wave Observations

Neil Cornish, Diego Blas, and Germano Nardini
Phys. Rev. Lett. 119, 161102 – Published 18 October 2017



Abstract

The time delay between gravitational wave signals arriving at widely separated detectors can be used to place upper and lower bounds on the speed of gravitational wave propagation. Using a Bayesian approach that combines the first three gravitational wave detections reported by the LIGO Scientific and Virgo Collaborations we constrain the gravitational waves propagation speed 
cgw
 to the 90% credible interval 
0.55c<cgw<1.42c
, where 
c
 is the speed of light in vacuum. These bounds will improve as more detections are made and as more detectors join the worldwide network. Of order 20 detections by the two LIGO detectors will constrain the speed of gravity to within 20% of the speed of light, while just five detections by the LIGO-Virgo-Kagra network will constrain the speed of gravity to within 1% of the speed of light.

Received 19 July 2017



Published by the American Physical Society under the terms of the Creative Commons Attribution 4.0 International license. Further distribution of this work must maintain attribution to the author(s) and the published article’s title, journal citation, and DOI.

Published by the American Physical Society

Physics Subject Headings (PhySH)
Research Areas
Alternative gravity theories Gravitational waves Gravitation, Cosmology & Astrophysics

FREE PDF GRATIS: Physical Review Letters

Só a Nomenklatura científica e a Galera dos meninos e meninas de Darwin acreditam no mito da ciência se corrigir a si mesma!

sábado, novembro 18, 2017

Correcting the “self-correcting” mythos of science

Douglas Allchin *

Source/Fonte: PLoS Blog


Abstract: 

In standard characterizations, science is self-correcting. Scientists examine each other’s work skeptically, try to replicate important discoveries, and thereby expose latent errors. Thus, while science is tentative, it also seems to have a system for correcting whatever mistakes arise. It powerfully explains and justifies the authority of science. Self-correction thus often serves emblematically in promoting science as a superior form of knowledge. But errors can and do occur. Some errors remain uncorrected for long periods. I present five sets of historical observations that indicate a need to rethink the widespread mythos of self-correction. First, some errors persist for decades, wholly undetected. Second, many errors seem corrected by independent happenstance, not by any methodical appraisal. Third, some errors have been “corrected” in a cascade of successive errors that did not effectively remedy the ultimate source of the error. Fourth, some errors have fostered further serious errors without the first error being noticed. Finally, some corrections to erroneous theories have themselves been rejected when initially presented. In all these cases, scientists failed to identify and correct the errors in a timely manner, or according to any uniform self-correcting mechanism. These historical perspectives underscore that error correction in science requires epistemic work. We need deeper understanding of errors, through the emerging field of error analytics.

Keywords: scientific error; self-correction; error cascade; compounded error; error analytics


* The Minnesota Center for the Philosophy of Science and STEM Education Center.
University of Minnesota, Minneapolis, MN, U.S.A, ZIP 55455. 
E-mail: allch001@umn.edu

Custo mutagênico de ribonucleotídeos no DNA bacteriano

sexta-feira, novembro 17, 2017

Mutagenic cost of ribonucleotides in bacterial DNA

Jeremy W. Schroeder a,1,2, Justin R. Randall a,1, William G. Hirst a, Michael E. O’Donnell b,3, and Lyle A. Simmons a,

Author Affiliations

Contributed by Michael E. O’Donnell, September 18, 2017 (sent for review June 19, 2017; reviewed by Martin Marinus and Roger Woodgate)



Significance

DNA polymerases frequently incorporate ribonucleotides in place of deoxyribonucleotides during genome replication. RNase HII is responsible for initiating the removal of ribonucleotide errors across all three domains of life. Ribonucleotides that persist in genomic DNA due to defects in RNase HII result in strand breaks, mutagenesis, and neurodevelopmental disease in humans. Here, we define the proteins important for ribonucleotide excision repair in Bacillus subtilis and use genome-wide mutational profiling to determine the mutagenic cost of ribonucleotides in RNase HII-deficient cells. We show that the absence of RNase HII yields error-prone ribonucleotide correction via a pathway that relies on an essential DNA polymerase. We further demonstrate that error-prone ribonucleotide removal causes sequence context-dependent GC → AT transitions on the lagging strand.

Abstract

Replicative DNA polymerases misincorporate ribonucleoside triphosphates (rNTPs) into DNA approximately once every 2,000 base pairs synthesized. Ribonucleotide excision repair (RER) removes ribonucleoside monophosphates (rNMPs) from genomic DNA, replacing the error with the appropriate deoxyribonucleoside triphosphate (dNTP). Ribonucleotides represent a major threat to genome integrity with the potential to cause strand breaks. Furthermore, it has been shown in the bacterium Bacillus subtilis that loss of RER increases spontaneous mutagenesis. Despite the high rNTP error rate and the effect on genome integrity, the mechanism underlying mutagenesis in RER-deficient bacterial cells remains unknown. We performed mutation accumulation lines and genome-wide mutational profiling of B. subtilis lacking RNase HII, the enzyme that incises at single rNMP residues initiating RER. We show that loss of RER in B. subtilis causes strand- and sequence-context–dependent GC → AT transitions. Using purified proteins, we show that the replicative polymerase DnaE is mutagenic within the sequence context identified in RER-deficient cells. We also found that DnaE does not perform strand displacement synthesis. Given the use of nucleotide excision repair (NER) as a backup pathway for RER in RNase HII-deficient cells and the known mutagenic profile of DnaE, we propose that misincorporated ribonucleotides are removed by NER followed by error-prone resynthesis with DnaE.

ribonucleotide excision repair DNA polymerase mutagenesis RNase HII

Footnotes

1J.W.S. and J.R.R. contributed equally to this work.

2Present address: Department of Bacteriology, University of Wisconsin, Madison, WI 53706.

3To whom correspondence may be addressed. Email: odonnel@mail.rockefeller.edu or lasimm@umich.edu.

Author contributions: J.W.S., J.R.R., W.G.H., and L.A.S. designed research; J.W.S., J.R.R., W.G.H., and L.A.S. performed research; J.W.S. and J.R.R. contributed new reagents/analytic tools; J.W.S., J.R.R., W.G.H., M.E.O., and L.A.S. analyzed data; and J.W.S., J.R.R., M.E.O., and L.A.S. wrote the paper.

Reviewers: M.M., University of Massachusetts Medical School; and R.W., National Institute of Child Health and Human Development, National Institutes of Health.

The authors declare no conflict of interest.

Data deposition: The sequences reported in this paper have been deposited in the Sequence Read Archive database (accession no. SRP117359).

This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1710995114/-/DCSupplemental.

Copyright © 2017 the Author(s). Published by PNAS.

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A evolução heterocrônica explica o novo formato corporal de um celacanto do Triássico da Suiça

Heterochronic evolution explains novel body shape in a Triassic coelacanth from Switzerland

Lionel Cavin, Bastien Mennecart, Christian Obrist, Loïc Costeur & Heinz Furrer

Scientific Reports 7, Article number: 13695 (2017)


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Embryonic induction Evolution Ichthyology Palaeontology

Received: 05 June 2017 Accepted: 02 October 2017

Published online: 20 October 2017



Phylogenetic relationships of Foreyia maxkuhni gen. et sp. nov. and developmental origin of the derived characters.

Abstract

A bizarre latimeriid coelacanth fish from the Middle Triassic of Switzerland shows skeletal features deviating from the uniform anatomy of coelacanths. The new form is closely related to a modern-looking coelacanth found in the same locality and differences between both are attributed to heterochronic evolution. Most of the modified osteological structures in the new coelacanth have their developmental origin in the skull/trunk interface region in the embryo. Change in the expression of developmental patterning genes, specifically the Pax1/9 genes, may explain a rapid evolution at the origin of the new coelacanth. This species broadens the morphological disparity range within the lineage of these ‘living fossils’ and exemplifies a case of rapid heterochronic evolution likely trigged by minor changes in gene expression.

Acknowledgements

The Palaeontological Institute and Museum, University of Zürich (PIMUZ) enabled H.F. to conduct systematic prospecting and numerous excavations near Davos. The government of Canton Graubünden, the municipality of Davos, and the Bündner Naturmuseum in Chur gave permission for the excavations and financial support. Max Kuhn (Uster) provided generous financial support for the preparation of the specimens by C.O. B.M. and L.Ca. also thank the Département de la culture et du sport de la Ville de Genève for a financial support for computer facilities, and Philippe Wagneur (Natural History Museum of Geneva) for assistance to produce the CT scan movie. We thank Anne Kemp (Griffith University) and Mélanie Debiais-Thibaud (University of Montpellier) for discussion. This paper is a contribution to the project “Evolutionary pace in the coelacanth clade: New evidence from the Triassic of Switzerland” supported by the Swiss National Science Foundation (200021-172700) by L.Ca.

Author information

Affiliations

Department of Geology and Palaeontology, Muséum d’Histoire Naturelle, CP6434, 1211, Geneva, 6, Switzerland

Lionel Cavin

Naturhistorisches Museum Basel, Augustinergasse 2, 4001, Basel, Switzerland

Bastien Mennecart & Loïc Costeur

Erliackerweg 8, 4462, Rickenbach, BL, Switzerland

Christian Obrist

Paläontologisches Institut und Museum der Universität Zürich, Karl Schmid-Strasse 4, 8006, Zurich, Switzerland

Heinz Furrer

Contributions

L.Ca. wrote the description of the new taxon, collected and analyzed the phylogenetic and ontogenetic data, and wrote the corresponding parts of the manuscript. C.O. collected specimens PIMUZ A/I 4620 and PIMUZ A/I 4372, and prepared them. H.F. analyzed the stratigraphic data in the field, and wrote the corresponding methods and results. B.M. and L.Co. performed the CT scan analysis and interpreted the images. L.Ca. and H.F. obtained funding for fieldwork and data analysis. All authors contributed to write the last version of the text.

Competing Interests

The authors declare that they have no competing interests.

Corresponding author

Correspondence to Lionel Cavin.