Quando rápido é melhor: fundamentos e mecanismos de enovelamento de proteínas de acessos ultrarrápidos

sábado, maio 27, 2017

When fast is better: protein folding fundamentals and mechanisms from ultrafast approaches

Victor Muñoz, Michele Cerminara

Biochemical Journal Aug 30, 2016, 473 (17) 2545-2559; 


Protein folding research stalled for decades because conventional experiments indicated that proteins fold slowly and in single strokes, whereas theory predicted a complex interplay between dynamics and energetics resulting in myriad microscopic pathways. Ultrafast kinetic methods turned the field upside down by providing the means to probe fundamental aspects of folding, test theoretical predictions and benchmark simulations. Accordingly, experimentalists could measure the timescales for all relevant folding motions, determine the folding speed limit and confirm that folding barriers are entropic bottlenecks. Moreover, a catalogue of proteins that fold extremely fast (microseconds) could be identified. Such fast-folding proteins cross shallow free energy barriers or fold downhill, and thus unfold with minimal co-operativity (gradually). A new generation of thermodynamic methods has exploited this property to map folding landscapes, interaction networks and mechanisms at nearly atomic resolution. In parallel, modern molecular dynamics simulations have finally reached the timescales required to watch fast-folding proteins fold and unfold in silico. All of these findings have buttressed the fundamentals of protein folding predicted by theory, and are now offering the first glimpses at the underlying mechanisms. Fast folding appears to also have functional implications as recent results connect downhill folding with intrinsically disordered proteins, their complex binding modes and ability to moonlight. These connections suggest that the coupling between downhill (un)folding and binding enables such protein domains to operate analogically as conformational rheostats.

FREE PDF GRATIS: Biochemical Journal



Notem na figura de enovelamento de proteínas o formato da Estrela de Davi.

Rápido enovelamento e lento desenovelamento de uma proteína pré-cambriana ressurgida.

PNAS,  vol. 114 no. 21 

Adela M. Candel,  E4122–E4123. 
doi: 10.1073/pnas.1703227114
Fast folding and slow unfolding of a resurrected Precambrian protein

Adela M. Candel a, M. Luisa Romero-Romero a,1, Gloria Gamiz-Arco a, Beatriz Ibarra-Molero a, and Jose M. Sanchez-Ruiz a,2

Author Affiliations

a Departamento de Quimica Fisica, Facultad de Ciencias, Universidad de Granada, Granada 18071, Spain

Tzul et al. (1) report different unfolding rates and similar folding rates for a number of thioredoxins. The authors interpret this result as evidence of the principle of minimal frustration. Their study includes several resurrected Precambrian thioredoxins that we have previously prepared and characterized (25).
We agree that the principle of minimal frustration is essential to understand protein evolution. However, approximate folding-rate invariance is easily explained without invoking this principle. Thioredoxin kinetic stability relies on a transition state that is substantially unstructured (56). Therefore, mutations that changed unfolding rates to tune kinetic stability during evolution likely had much less effect on folding rates, as implied by the well-known principles of ϕ-value analysis (7).
Moreover, our experimental results are not consistent with folding-rate invariance being a general feature of thioredoxins. Fig. 1 shows folding–unfolding rates for the modern Escherichia coli thioredoxin and a resurrected Precambrian thioredoxin. The unfolding of the ancestral protein is ∼three orders-of-magnitude slower than the unfolding of the modern protein, indicating enhanced kinetic stability. However, in clear …
2To whom correspondence should be addressed. Email: sanchezr@ugr.es.
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A forma geral da regra de Hamilton não faz predições e nem pode ser testada empiricamente!

The general form of Hamilton’s rule makes no predictions and cannot be tested empirically

Martin A. Nowak a,b,c, Alex McAvoy a, Benjamin Allen a,d, and Edward O. Wilson e,1

Author Affiliations

aProgram for Evolutionary Dynamics, Harvard University, Cambridge, MA 02138;

bDepartment of Mathematics, Harvard University, Cambridge, MA 02138;

cDepartment of Organismic and Evolutionary Biology, Harvard University, Cambridge, MA 02138;

dDepartment of Mathematics, Emmanuel College, Boston, MA 02115;

eMuseum of Comparative Zoology, Harvard University, Cambridge, MA 02138

Contributed by Edward O. Wilson, April 13, 2017 (sent for review February 2, 2017; reviewed by Michael Doebeli and Jan Rychtar)


Hamilton’s rule is a well-known concept in evolutionary biology. It is usually perceived as a statement that makes predictions about natural selection in situations where interactions occur between genetic relatives. Here, we examine what has been called the “exact and general” formulation of Hamilton’s rule. We show that in this formulation, which is widely endorsed by proponents of inclusive fitness theory, Hamilton’s rule does not make any prediction and cannot be tested empirically. This formulation of Hamilton’s rule is not a consequence of natural selection and not even a statement specifically about biology. We give simple and transparent expressions for the quantities of benefit, cost, and relatedness that appear in Hamilton’s rule, which reveal that these quantities depend on the data that are to be predicted.


Hamilton’s rule asserts that a trait is favored by natural selection if the benefit to others, [Math Processing Error]B, multiplied by relatedness, [Math Processing Error]R, exceeds the cost to self, [Math Processing Error]C. Specifically, Hamilton’s rule states that the change in average trait value in a population is proportional to [Math Processing Error]BR−C. This rule is commonly believed to be a natural law making important predictions in biology, and its influence has spread from evolutionary biology to other fields including the social sciences. Whereas many feel that Hamilton’s rule provides valuable intuition, there is disagreement even among experts as to how the quantities [Math Processing Error]B, [Math Processing Error]R, and [Math Processing Error]C should be defined for a given system. Here, we investigate a widely endorsed formulation of Hamilton’s rule, which is said to be as general as natural selection itself. We show that, in this formulation, Hamilton’s rule does not make predictions and cannot be tested empirically. It turns out that the parameters [Math Processing Error]B and [Math Processing Error]C depend on the change in average trait value and therefore cannot predict that change. In this formulation, which has been called “exact and general” by its proponents, Hamilton’s rule can “predict” only the data that have already been given.

evolution cooperation kin selection sociobiology


1To whom correspondence should be addressed. Email: ewilson@oeb.harvard.edu.

Author contributions: M.A.N., A.M., B.A., and E.O.W. designed research, performed research, analyzed data, and wrote the paper.

Reviewers: M.D., University of British Columbia; and J.R., The University of North Carolina at Greensboro.

The authors declare no conflict of interest.

Freely available online through the PNAS open access option.


O custo energético na "construção" de um vírus

Energetic cost of building a virus

Gita Mahmoudabadia, Ron Milob, and Rob Phillipsa,c,1

Author Affiliations

aDepartment of Bioengineering, California Institute of Technology, Pasadena, CA 91125;

bDepartment of Plant and Environmental Sciences, Weizmann Institute of Science, Rehovot 7610001, Israel;

cDepartment of Applied Physics, California Institute of Technology, Pasadena, CA 91125

Edited by Ned S. Wingreen, Princeton University, Princeton, NJ, and accepted by Editorial Board Member Curtis G. Callan Jr. April 19, 2017 (received for review January 30, 2017)"


Human hepegivirus 1 has parts of both hepatitis C virus (above) and human pegivirus.


Viruses rely entirely on their host as an energy source. Despite numerous experimental studies that demonstrate the capability of viruses to rewire and undermine their host’s metabolism, we still largely lack a quantitative understanding of an infection’s energetics. However, the energetics of a viral infection is at the center of broader evolutionary and physical questions in virology. By enumerating the energetic costs of different viral processes, we open the door to quantitative predictions about viral evolution. For example, we predict that, for the majority of viruses, translation will serve as the dominant cost of building a virus, and that selection, rather than drift, will govern the fate of new genetic elements within viral genomes.


Viruses are incapable of autonomous energy production. Although many experimental studies make it clear that viruses are parasitic entities that hijack the molecular resources of the host, a detailed estimate for the energetic cost of viral synthesis is largely lacking. To quantify the energetic cost of viruses to their hosts, we enumerated the costs associated with two very distinct but representative DNA and RNA viruses, namely, T4 and influenza. We found that, for these viruses, translation of viral proteins is the most energetically expensive process. Interestingly, the costs of building a T4 phage and a single influenza virus are nearly the same. Due to influenza’s higher burst size, however, the overall cost of a T4 phage infection is only 2–3% of the cost of an influenza infection. The costs of these infections relative to their host’s estimated energy budget during the infection reveal that a T4 infection consumes about a third of its host’s energy budget, whereas an influenza infection consumes only ≈ 1%. Building on our estimates for T4, we show how the energetic costs of double-stranded DNA phages scale with the capsid size, revealing that the dominant cost of building a virus can switch from translation to genome replication above a critical size. Last, using our predictions for the energetic cost of viruses, we provide estimates for the strengths of selection and genetic drift acting on newly incorporated genetic elements in viral genomes, under conditions of energy limitation.

viral energetics viral evolution T4 influenza cellular energetics


1To whom correspondence should be addressed. Email: phillips@pboc.caltech.edu.

Author contributions: G.M., R.M., and R.P. designed research, performed research, analyzed data, and wrote the paper.

The authors declare no conflict of interest.

This article is a PNAS Direct Submission. N.S.W. is a guest editor invited by the Editorial Board.

This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1701670114/-/DCSupplemental.

Freely available online through the PNAS open access option.


A modelagem integrativa da evolução do gene e do genoma enraíza a árvore da vida da Archaea.

Integrative modeling of gene and genome evolution roots the archaeal tree of life

Tom A. Williams a,b,1, Gergely J. Szöllősi c,2, Anja Spang d,2, Peter G. Foster e, Sarah E. Heaps b,f, Bastien Boussau g, Thijs J. G. Ettema d, and T. Martin Embley b

Author Affiliations

aSchool of Earth Sciences, University of Bristol, Bristol BS8 1TQ, United Kingdom;

bInstitute for Cell and Molecular Biosciences, Newcastle University, Newcastle upon Tyne NE2 4HH, United Kingdom;

cMTA-ELTE Lendület Evolutionary Genomics Research Group, 1117 Budapest, Hungary;

dDepartment of Cell and Molecular Biology, Science for Life Laboratory, Uppsala University, SE-75123 Uppsala, Sweden;

eDepartment of Life Sciences, Natural History Museum, London SW7 5BD, United Kingdom;

fSchool of Mathematics & Statistics, Newcastle University, Newcastle upon Tyne NE1 7RU, United Kingdom;

gUniv Lyon, Université Lyon 1, CNRS, Laboratoire de Biométrie et Biologie Evolutive UMR5558, F-69622 Villeurbanne, France

Edited by W. Ford Doolittle, Dalhousie University, Halifax, Canada, and approved April 24, 2017 (received for review November 7, 2016)


The Archaea represent a primary domain of cellular life, play major roles in modern-day biogeochemical cycles, and are central to debates about the origin of eukaryotic cells. However, understanding their origins and evolutionary history is challenging because of the immense time spans involved. Here we apply a new approach that harnesses the information in patterns of gene family evolution to find the root of the archaeal tree and to resolve the metabolism of the earliest archaeal cells. Our approach robustly distinguishes between published rooting hypotheses, suggests that the first Archaea were anaerobes that may have fixed carbon via the Wood–Ljungdahl pathway, and quantifies the cumulative impact of horizontal transfer on archaeal genome evolution.


A root for the archaeal tree is essential for reconstructing the metabolism and ecology of early cells and for testing hypotheses that propose that the eukaryotic nuclear lineage originated from within the Archaea; however, published studies based on outgroup rooting disagree regarding the position of the archaeal root. Here we constructed a consensus unrooted archaeal topology using protein concatenation and a multigene supertree method based on 3,242 single gene trees, and then rooted this tree using a recently developed model of genome evolution. This model uses evidence from gene duplications, horizontal transfers, and gene losses contained in 31,236 archaeal gene families to identify the most likely root for the tree. Our analyses support the monophyly of DPANN (Diapherotrites, Parvarchaeota, Aenigmarchaeota, Nanoarchaeota, Nanohaloarchaea), a recently discovered cosmopolitan and genetically diverse lineage, and, in contrast to previous work, place the tree root between DPANN and all other Archaea. The sister group to DPANN comprises the Euryarchaeota and the TACK Archaea, including Lokiarchaeum, which our analyses suggest are monophyletic sister lineages. Metabolic reconstructions on the rooted tree suggest that early Archaea were anaerobes that may have had the ability to reduce CO2 to acetate via the Wood–Ljungdahl pathway. In contrast to proposals suggesting that genome reduction has been the predominant mode of archaeal evolution, our analyses infer a relatively small-genomed archaeal ancestor that subsequently increased in complexity via gene duplication and horizontal gene transfer.

evolution phylogenetics Archaea


1To whom correspondence should be addressed. Email: tom.a.williams@bristol.ac.uk.

2G.J.S. and A.S. contributed equally to this work.

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

The authors declare no conflict of interest.

This article is a PNAS Direct Submission.

This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1618463114/-/DCSupplemental.

Freely available online through the PNAS open access option.


As compensações da mutação genética conduzem à evolução paralela

Environment determines evolutionary trajectory in a constrained phenotypic space

David T Fraebel Harry Mickalide Diane Schnitkey Jason Merritt Thomas E Kuhlman Seppe Kuehn 

University of Illinois at Urbana-Champaign, United States

Published March 27, 2017

Cite as eLife 2017;6:e24669

Source/Fonte: The Economist


Constraints on phenotypic variation limit the capacity of organisms to adapt to the multiple selection pressures encountered in natural environments. To better understand evolutionary dynamics in this context, we select Escherichia coli for faster migration through a porous environment, a process which depends on both motility and growth. We find that a trade-off between swimming speed and growth rate constrains the evolution of faster migration. Evolving faster migration in rich medium results in slow growth and fast swimming, while evolution in minimal medium results in fast growth and slow swimming. In each condition parallel genomic evolution drives adaptation through different mutations. We show that the trade-off is mediated by antagonistic pleiotropy through mutations that affect negative regulation. A model of the evolutionary process shows that the genetic capacity of an organism to vary traits can qualitatively depend on its environment, which in turn alters its evolutionary trajectory.

eLife digest

In nature organisms face many challenges, and species adapt to their environment by changing heritable traits over the course of many generations. How organisms adapt is often limited by trade-offs, in which improving one trait can only come at the expense of another.

In the laboratory, scientists use well-controlled environments to study how populations adapt to specific challenges without interference from their natural habitat. Most experiments, however, only look at simple challenges and do not take into account that organisms in the wild face many pressures at the same time. Fraebel et al. wanted to know what happens when an organism’s performance depends on two traits that are restricted by a trade-off. The experiments used populations of the bacterium Escherichia coli, which can go through hundreds of generations in a week, providing ample opportunity to study mutations and their impact on heritable traits.

Through a combination of mathematical modeling and experiments, Fraebel et al. found that the environment is crucial for determining how bacteria adapt when their swimming speed and population growth rate are restricted by a trade-off. When nutrients are plentiful, E. coli populations evolve to spread faster by swimming more quickly despite growing more slowly. Yet, if nutrients are scarcer, the bacteria evolve to spread faster by growing more quickly despite swimming more slowly. In each scenario, the experiments identified single mutations that changed both swimming speed and growth rate by modifying regulatory activity in the cell.

A better understanding of how an organism’s genetic architecture, its environment and trade-offs are connected may help identify the traits that are most easily changed by mutations. The ultimate goal would be to be able to predict evolutionary responses to complex selection pressures.


A profunda ignorância dos cientistas sobre a origem dos sexos

Sex chromosome evolution: historical insights and future perspectives

Jessica K. Abbott, Anna K. Nordén, Bengt Hansson

Published 3 May 2017.DOI: 10.1098/rspb.2016.2806


Many separate-sexed organisms have sex chromosomes controlling sex determination. Sex chromosomes often have reduced recombination, specialized (frequently sex-specific) gene content, dosage compensation and heteromorphic size. Research on sex determination and sex chromosome evolution has increased over the past decade and is today a very active field. However, some areas within the field have not received as much attention as others. We therefore believe that a historic overview of key findings and empirical discoveries will put current thinking into context and help us better understand where to go next. Here, we present a timeline of important conceptual and analytical models, as well as empirical studies that have advanced the field and changed our understanding of the evolution of sex chromosomes. Finally, we highlight gaps in our knowledge so far and propose some specific areas within the field that we recommend a greater focus on in the future, including the role of ecology in sex chromosome evolution and new multilocus models of sex chromosome divergence.

Authors' contributions

A.K.N., B.H. and J.K.A. all contributed to developing the ideas presented here and wrote the manuscript together. A.K.N. created figure 1 and J.K.A. created table 1.

Competing interests

We declare we have no competing interests.


This work has been supported by ERC-StG-2015-678148 (to J.K.A.) and VR-2014-5222 (to B.H.).


The authors thank two anonymous reviewers for constructive feedback on an earlier version of the manuscript.

Received January 12, 2017.
Accepted April 4, 2017.
© 2017 The Authors.

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Published by the Royal Society under the terms of the Creative Commons Attribution License http://creativecommons.org/licenses/by/4.0/, which permits unrestricted use, provided the original author and source are credited.


Cientistas editam estocasticamente as sinapses das planárias que dirigem a forma do corpo

Long-Term, Stochastic Editing of Regenerative Anatomy via Targeting Endogenous Bioelectric Gradients

Fallon Durant, Junji Morokuma, Christopher Fields, Katherine Williams, Dany Spencer Adams, Michael Levin

Open Access

Article Info

Publication History

Editor: Stanislav Shvartsman.

Accepted: April 14, 2017 Received: January 20, 2017

User License

Creative Commons Attribution – NonCommercial – No Derivs (CC BY-NC-ND 4.0)

Source/Fonte: Biophysical Journal


We show that regenerating planarians’ normal anterior-posterior pattern can be permanently rewritten by a brief perturbation of endogenous bioelectrical networks. Temporary modulation of regenerative bioelectric dynamics in amputated trunk fragments of planaria stochastically results in a constant ratio of regenerates with two heads to regenerates with normal morphology. Remarkably, this is shown to be due not to partial penetrance of treatment, but a profound yet hidden alteration to the animals’ patterning circuitry. Subsequent amputations of the morphologically normal regenerates in water result in the same ratio of double-headed to normal morphology, revealing a cryptic phenotype that is not apparent unless the animals are cut. These animals do not differ from wild-type worms in histology, expression of key polarity genes, or neoblast distribution. Instead, the altered regenerative bodyplan is stored in seemingly normal planaria via global patterns of cellular resting potential. This gradient is functionally instructive, and represents a multistable, epigenetic anatomical switch: experimental reversals of bioelectric state reset subsequent regenerative morphology back to wild-type. Hence, bioelectric properties can stably override genome-default target morphology, and provide a tractable control point for investigating cryptic phenotypes and the stochasticity of large-scale epigenetic controls.

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Primeira evidência empírica de androgênese ocorrendo naturalmente em vertebrados!

First empirical evidence of naturally occurring androgenesis in vertebrates

Miguel Morgado-Santos, Sara Carona, Luís Vicente, Maria João Collares-Pereira

Published 24 May 2017.DOI: 10.1098/rsos.170200


Androgenesis among vertebrates is considered a rare phenomenon, with some cases reported so far, but linked to experiments involving gamete manipulation (artificial androgenesis). Herein, we report the first empirical evidence of the natural occurrence of spontaneous androgenesis in a vertebrate, the Squalius alburnoides allopolyploid complex. A genetically screened random sample of a natural population was allowed to reproduce in an isolated pond without any human interference, and the viable offspring obtained was later analysed for paternity. Both nuclear and mitochondrial markers showed that the only allodiploid fish found among all the allotriploid offspring was androgenetically produced by an allodiploid male. This specimen had no female nuclear genomic input, and the sequence of the mitochondrial fragment examined differed from that of the male progenitor, matching one of the parental females available in the pond, probably the mother. The possible role of androgenesis in the reproductive dynamics of this highly successful vertebrate complex is discussed.

Authors' contributions

Conception and design: M.M.-S., L.V. and M.J.C.-P. Acquisition of data: M.M.-S. and S.C. Analysis and interpretation of data: M.M.-S., S.C. and M.J.C.-P. Drafting the article: M.M.-S. Revising the article critically: S.C. and M.J.C.-P. Final approval of the version to be published: M.M.-S., S.C., L.V. and M.J.C.-P.

Competing interests

We have no competing interests.


This work was supported by Portuguese National Funds, through Fundação para a Ciência e a Tecnologia (FCT) (project nos UID/BIA/00329/2013, PEstOE/BIA/UI0329/2014; grant no. SFRH/BD/65154/2009).


We thank I. Cowx for language revision and comments to an earlier version, M. A. Aboim for help with microsatellite genotyping, and the anonymous reviewers for their insightful recommendations. We also thank the ICNF for authorizing fish sampling and use in experimental trials.


Electronic supplementary material is available online at https://dx.doi.org/10.6084/m9.figshare.c.3780131.

Received March 3, 2017.
Accepted April 27, 2017.

© 2017 The Authors.

Published by the Royal Society under the terms of the Creative Commons Attribution License http://creativecommons.org/licenses/by/4.0/, which permits unrestricted use, provided the original author and source are credited.

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O cronograma da evolução

sexta-feira, maio 26, 2017

The timetable of evolution

Andrew H. Knoll1,* and Martin A. Nowak2

1Department of Organismic and Evolutionary Biology, Harvard University, Cambridge, MA 02138, USA.

2Program for Evolutionary Dynamics, Department of Organismic and Evolutionary Biology, Department of Mathematics, Harvard University, Cambridge, MA 02138, USA.

↵*Corresponding author. Email: aknoll@oeb.harvard.edu

+ See all authors and affiliations

Science Advances 17 May 2017:

Vol. 3, no. 5, e1603076


The integration of fossils, phylogeny, and geochronology has resulted in an increasingly well-resolved timetable of evolution. Life appears to have taken root before the earliest known minimally metamorphosed sedimentary rocks were deposited, but for a billion years or more, evolution played out beneath an essentially anoxic atmosphere. Oxygen concentrations in the atmosphere and surface oceans first rose in the Great Oxygenation Event (GOE) 2.4 billion years ago, and a second increase beginning in the later Neoproterozoic Era [Neoproterozoic Oxygenation Event (NOE)] established the redox profile of modern oceans. The GOE facilitated the emergence of eukaryotes, whereas the NOE is associated with large and complex multicellular organisms. Thus, the GOE and NOE are fundamental pacemakers for evolution. On the time scale of Earth’s entire 4 billion–year history, the evolutionary dynamics of the planet’s biosphere appears to be fast, and the pace of evolution is largely determined by physical changes of the planet. However, in Phanerozoic ecosystems, interactions between new functions enabled by the accumulation of characters in a complex regulatory environment and changing biological components of effective environments appear to have an important influence on the timing of evolutionary innovations. On the much shorter time scale of transient environmental perturbations, such as those associated with mass extinctions, rates of genetic accommodation may have been limiting for life.

Keywords evolution Earth history geochronology evolutionary theory

Copyright © 2017, 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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A biomecânica por trás da osteofagia extrema em Tyrannosaurus rex: 8.500-34.500 Newtons

The Biomechanics Behind Extreme Osteophagy in Tyrannosaurus rex

Paul M. Gignac & Gregory M. Erickson

Scientific Reports 7, Article number: 2012 (2017)

Download Citation

Biomechanics Palaeontology

Received: 25 November 2016 Accepted: 07 April 2017

Published online: 17 May 2017


Most carnivorous mammals can pulverize skeletal elements by generating tooth pressures between occluding teeth that exceed cortical bone shear strength, thereby permitting access to marrow and phosphatic salts. Conversely, carnivorous reptiles have non-occluding dentitions that engender negligible bone damage during feeding. As a result, most reptilian predators can only consume bones in their entirety. Nevertheless, North American tyrannosaurids, including the giant (13 metres [m]) theropod dinosaur Tyrannosaurus rex stand out for habitually biting deeply into bones, pulverizing and digesting them. How this mammal-like capacity was possible, absent dental occlusion, is unknown. Here we analyzed T. rex feeding behaviour from trace evidence, estimated bite forces and tooth pressures, and studied tooth-bone contacts to provide the answer. We show that bone pulverization was made possible through a combination of: (1) prodigious bite forces (8,526–34,522 newtons [N]) and tooth pressures (718–2,974 megapascals [MPa]) promoting crack propagation in bones, (2) tooth form and dental arcade configurations that concentrated shear stresses, and (3) repetitive, localized biting. Collectively, these capacities and behaviors allowed T. rex to finely fragment bones and more fully exploit large dinosaur carcasses for sustenance relative to competing carnivores.


We thank P. Larson and staff at the BHI, P. Makovicky and the FMNH, M. Norell, C. Mehling, and the AMNH, and K. Cramer at CarmikeTM Cinemas (which temporarily exhibited BHI 4100) for access to specimens; A. Andersen and Virtual Surfaces, Inc. for allowing us access to surface-scan files of BHI 3033; D. Kay and S. Kuhn-Hendricks for assistance in specimen measurements; J. Brueggen and K. Vliet for assistance accessing citations; K. Chin for early discussions about this subject; M. Hill and H. Towbin for technical assistance with CT scanning; H. O’Brien and A. Watanabe for assistance with 3-D rendering software. PMG was supported by the National Science Foundation (no. 1450850) and Oklahoma State University Center for Health Sciences. GME was supported by a grant from the Committee for Research and Exploration of the National Geographic Society (no. 7026–01) and Florida State University.

Author information


Department of Anatomy and Cell Biology, Oklahoma State University Center for Health Sciences, Tulsa, Oklahoma, 74107-1898, USA

Paul M. Gignac

Department of Biological Science, Florida State University, Tallahassee, Florida, 32306-4295, USA

Gregory M. Erickson


P.M.G. and G.M.E. designed the study and collected the data. P.M.G. performed the biomechanical analyses and developed the figures. P.M.G. and G.M.E. wrote the paper. The authors have no conflicting financial interests in the content or techniques discussed in this manuscript.

Competing Interests

The authors declare that they have no competing interests.

Corresponding author

Correspondence to Paul M. Gignac.

Darwin, o berço da humanidade está se mudando de mala e cuia para a Europa!

quinta-feira, maio 25, 2017

Potential hominin affinities of Graecopithecus from the Late Miocene of Europe

Jochen Fuss, Nikolai Spassov, David R. Begun, Madelaine Böhme 


The split of our own clade from the Panini is undocumented in the fossil record. To fill this gap we investigated the dentognathic morphology of Graecopithecus freybergi from Pyrgos Vassilissis (Greece) and cf. Graecopithecus sp. from Azmaka (Bulgaria), using new μCT and 3D reconstructions of the two known specimens. Pyrgos Vassilissis and Azmaka are currently dated to the early Messinian at 7.175 Ma and 7.24 Ma. Mainly based on its external preservation and the previously vague dating, Graecopithecus is often referred to as nomen dubium. The examination of its previously unknown dental root and pulp canal morphology confirms the taxonomic distinction from the significantly older northern Greek hominine Ouranopithecus. Furthermore, it shows features that point to a possible phylogenetic affinity with hominins. G. freybergi uniquely shares p4 partial root fusion and a possible canine root reduction with this tribe and therefore, provides intriguing evidence of what could be the oldest known hominin.

Citation: Fuss J, Spassov N, Begun DR, Böhme M (2017) Potential hominin affinities of Graecopithecus from the Late Miocene of Europe. PLoS ONE 12(5): e0177127. https://doi.org/10.1371/journal.pone.0177127

Editor: Roberto Macchiarelli, Université de Poitiers, FRANCE

Received: December 22, 2016; Accepted: April 21, 2017; Published: May 22, 2017

Copyright: © 2017 Fuss 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 relevant data are within the paper and its Supporting Information files.

Funding: We acknowledge funding from the German Science Foundation DFG (grant Bo 1550/19-1 to MB). 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.


Ovários de camundongos impressos em 3D produzem proles saudáveis

quarta-feira, maio 24, 2017

A bioprosthetic ovary created using 3D printed microporous scaffolds restores ovarian function in sterilized mice

Monica M. Laronda, Alexandra L. Rutz, Shuo Xiao, Kelly A. Whelan, Francesca E. Duncan, Eric W. Roth, Teresa K. Woodruff & Ramille N. Shah

Nature Communications 8, Article number: 15261 (2017)

Download Citation

Biomaterials Preclinical research Translational research

Received: 09 February 2017 Accepted: 14 March 2017

Published online:16 May 2017

Source/Fonte: Technology Networks


Emerging additive manufacturing techniques enable investigation of the effects of pore geometry on cell behavior and function. Here, we 3D print microporous hydrogel scaffolds to test how varying pore geometry, accomplished by manipulating the advancing angle between printed layers, affects the survival of ovarian follicles. 30° and 60° scaffolds provide corners that surround follicles on multiple sides while 90° scaffolds have an open porosity that limits follicle–scaffold interaction. As the amount of scaffold interaction increases, follicle spreading is limited and survival increases. Follicle-seeded scaffolds become highly vascularized and ovarian function is fully restored when implanted in surgically sterilized mice. Moreover, pups are born through natural mating and thrive through maternal lactation. These findings present an in vivo functional ovarian implant designed with 3D printing, and indicate that scaffold pore architecture is a critical variable in additively manufactured scaffold design for functional tissue engineering.


M.M.L. and A.L.R. contributed equally to this work. The authors would like to thank Keisha Barreto (NU) of the Reproductive Science Histology Core, Center for Reproductive Science, Lindsay Reustle (KUMC) for her technical contribution on HMGB1 immunohistochemistry and Dr. Constadina Arvanitis (NU) of the Center of Advanced Microscopy. The authors would also like to thank Prof. Wesley Burghardt for use of his lab’s rheometer and his advisement on rheological data. This work was supported by the Watkins Chair of Obstetrics and Gynecology (TKW), the National Institutes of Health National Center for Translational Research in Reproduction and Infertility (NCTRI) Center for Reproductive Health After Disease (P50HD076188, T.K.W., M.M.L., Pilot FED), the UH3TR001207 (NCATS, NICHD, NIEHS, OWHR, NIH Common Fund, TKW), NIH 1K01DK099454-01 (R.N.S.), the Burroughs Wellcome Fund Career Award at the Scientific Interface (M.M.L.), and the NSF Graduate Research Fellowship Program (A.L.R., DGE-1324585). The University of Virginia Center for Research in Reproduction Ligand Assay and Analysis Core is supported by the Eunice Kennedy Shriver NICHD/NIH (NCTRI) Grant P50-HD28934. Imaging work was performed at the Northwestern University Center for Advanced Microscopy generously supported by NCI CCSG P30 CA060553 awarded to the Robert H Lurie Comprehensive Cancer Center. This work made use of the EPIC facility of the NUANCE Center at Northwestern University, which has received support from the Soft and Hybrid Nanotechnology Experimental (SHyNE) Resource (NSF NNCI-1542205); the MRSEC program (NSF DMR-1121262) at the Materials Research Center; the International Institute for Nanotechnology (IIN); the Keck Foundation; and the State of Illinois, through the IIN.

Author information

Author notes

Monica M. Laronda & Alexandra L. Rutz

These authors contributed equally to this work.


Division of Reproductive Biology in Medicine, Department of Obstetrics and Gynecology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611, USA

Monica M. Laronda, Shuo Xiao, Kelly A. Whelan, Francesca E. Duncan & Teresa K. Woodruff

Center for Reproductive Science, Northwestern University, Chicago, Illinois 60611, USA

Monica M. Laronda, Shuo Xiao, Kelly A. Whelan, Francesca E. Duncan & Teresa K. Woodruff

Oncofertility Consortium, Northwestern University, Chicago, Illinois 60611, USA

Monica M. Laronda, Shuo Xiao, Kelly A. Whelan, Francesca E. Duncan & Teresa K. Woodruff

Simpson Querrey Institute for BioNanotechnology, Northwestern University, Chicago, Illinois 60611, USA

Alexandra L. Rutz & Ramille N. Shah

Department of Biomedical Engineering, Northwestern University, Evanston, Illinois 60208, USA

Alexandra L. Rutz & Ramille N. Shah

Department of Anatomy and Cell Biology, University of Kansas Medical Center, Kansas City, Kansas 66160, USA

Francesca E. Duncan

Northwestern University Atomic and Nanoscale Characterization Experimental Center, Northwestern University, Evanston, Illinois 60208, USA

Eric W. Roth

Department of Materials Science and Engineering, Northwestern University, Evanston, Illinois 60208, USA

Ramille N. Shah

Department of Surgery, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611, USA

Ramille N. Shah


M.M.L., A.L.R., T.K.W. and R.N.S. wrote this manuscript. T.K.W. envisioned the bioprosthetic ovary and A.L.R. and R.N.S. designed the 3D printing scaffolds. A.L.R. conceptualized and developed the ink and performed printing and material analyses. T.K.W., M.M.L. and K.A.W. designed the in vitro and in vivo ovarian follicle experiments. M.M.L. and K.A.W. performed all mouse experiments, including follicle culture and surgeries, and histological analysis of follicle culture and surgical tissue sections. F.E.D. determined the appropriate stroma cell marker for the ovary and analysed those histological samples. S.X. performed the MII egg staining. A.L.R. designed 3D analyses of scaffold–follicle interactions and performed immunostaining and confocal imaging of follicles seeded within 3D printed scaffolds. E.W.R. performed SEM imaging. M.M.L., A.L.R., S.X., T.K.W. and R.N.S. contributed to experimental design and interpretation.

Competing interests

M.M.L., A.L.R., R.N.S. and T.K.W. have filed an international Patent Application #PCT/US16/15398 titled in 2016. The remaining authors declare no competing financial interests.

Corresponding author

Correspondence to Ramille N. Shah.