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

sábado, maio 27, 2017

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

Abstract

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


Abstract

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.

Funding

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).

Acknowledgements

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.

Footnotes

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



Abstract

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



Abstract

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.

Acknowledgements

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

Affiliations

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

Contributions

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 




Abstract

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.

FREE PDF GRATIS: PLoS One

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


Abstract

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.

Acknowledgements

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.

Affiliations

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

Contributions

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.

Darwin, ensinar genética primeiro pode melhorar o ensino de sua teoria da evolução. Será Projeto ENCODE???

Teaching genetics prior to teaching evolution improves evolution understanding but not acceptance

Rebecca Mead, Momna Hejmadi, Laurence D. Hurst 




Abstract

What is the best way to teach evolution? As microevolution may be configured as a branch of genetics, it being a short conceptual leap from understanding the concepts of mutation and alleles (i.e., genetics) to allele frequency change (i.e., evolution), we hypothesised that learning genetics prior to evolution might improve student understanding of evolution. In the UK, genetics and evolution are typically taught to 14- to 16-y-old secondary school students as separate topics with few links, in no particular order and sometimes with a large time span between. Here, then, we report the results of a large trial into teaching order of evolution and genetics. We modified extant questionnaires to ascertain students’ understanding of evolution and genetics along with acceptance of evolution. Students were assessed prior to teaching, immediately post teaching and again after several months. Teachers were not instructed what to teach, just to teach in a given order. Regardless of order, teaching increased understanding and acceptance, with robust signs of longer-term retention. Importantly, teaching genetics before teaching evolution has a significant (p < 0.001) impact on improving evolution understanding by 7% in questionnaire scores beyond the increase seen for those taught in the inverse order. For lower ability students, an improvement in evolution understanding was seen only if genetics was taught first. Teaching genetics first additionally had positive effects on genetics understanding, by increasing knowledge. These results suggest a simple, minimally disruptive, zero-cost intervention to improve evolution understanding: teach genetics first. This same alteration does not, however, result in a significantly increased acceptance of evolution, which reflects a weak correlation between knowledge and acceptance of evolution. Qualitative focus group data highlights the role of authority figures in determination of acceptance.

Author summary

What is the best way to teach evolution? We hypothesised that if students know the fundamental concepts of genetics, then this might help them understand evolution better. To evaluate this, we performed a large trial in which pupils in United Kingdom secondary schools were either taught genetics and then evolution or evolution and then genetics. We found that the students being taught genetics first had a 5%–10% improvement in their understanding of evolution, above that shown in the group taught evolution first. The change was seen in both higher- and foundation-ability classes. Indeed, in the foundation classes the genetics-first approach was the only approach that enabled an increase in evolution understanding. Teaching genetics first comes at no cost to genetics understanding (and may even improve it). However, the genetics-first approach was no different from the evolution-first approach in helping the acceptance of evolution. Qualitative follow-up studies indicated a major role for authority figures in determining acceptance, potentially explaining the weak correlation between understanding and acceptance. These results suggest a simple, minimally disruptive, zero-cost intervention to improve evolution understanding: teach genetics first.


Citation: Mead R, Hejmadi M, Hurst LD (2017) Teaching genetics prior to teaching evolution improves evolution understanding but not acceptance. PLoS Biol 15(5): e2002255. https://doi.org/10.1371/journal.pbio.2002255

Academic Editor: Mary Tyler, University of Maine, United States of America
Received: February 16, 2017; Accepted: April 11, 2017; Published: May 23, 2017

Copyright: © 2017 Mead 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 (S1 Data).

Funding: Evolution Education Trust. The funder 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.

Abbreviations: GCSE, General Certificate of Education; GLAI, Genetics Literacy Assessment Instrument; GM, genetically modified; MATE, Measure of Acceptance of the Theory of Evolution

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+++++

P.S. 24/05/2017:

Ensinem genética aos alunos antes de ensinar a teoria da evolução. Ensinem especialmente as descobertas do Projeto Encode:

“If the human genome is indeed devoid of junk DNA as implied by the ENCODE Project, then a long, undirected evolutionary process cannot explain the human genome,” said ENCODE opponent Dan Graur at the 2013 meeting of the Society of Molecular Biology and Evolution in Chicago. “If, on the other hand, organisms are designed, then all DNA, or as much as possible, is expected to exhibit function. If ENCODE is right, then evolution is wrong.”

Se as descobertas do Projeto ENCODE estiverem certas, então a [teoria da] evolução está errada!!!

Fui, nem sei por que, esperando que essa recomendação de ensinar primeiro a genética aos alunos os ajudem a compreender as falácias da teoria da evolução no contexto de justificação teórica!

Por que existe algo em vez de nada? Uma investigação lógica

Erkenntnis

June 2017, Volume 82, Issue 3, pp 531–559

Why is There Something Rather Than Nothing? A Logical Investigation

Authors

Authors and affiliations

Jan Heylen 1

Email author

View author's OrcID profile

1.Centre for Logic and Analytic Philosophy, Institute of PhilosophyKU LeuvenLeuvenBelgium

Original Research

First Online: 20 July 2016


Cite this article as:

Heylen, J. Erkenn (2017) 82: 531. doi: 10.1007/s10670-016-9831-9

283 Downloads



Abstract

From Leibniz to Krauss philosophers and scientists have raised the question as to why there is something rather than nothing (henceforth, the Question). Why-questions request a type of explanation and this is often thought to include a deductive component. With classical logic in the background only trivial answers are forthcoming. With free logics in the background, be they of the negative, positive or neutral variety, only question-begging answers are to be expected. The same conclusion is reached for the modal version of the Question, namely ‘Why is there something contingent rather than nothing contingent?’ (except that possibility of answers with neutral free logic in the background is not explored). The categorial version of the Question, namely ‘Why is there something concrete rather than nothing concrete?’, is also discussed. The conclusion is reached that deductive explanations are question-begging, whether one works with classical logic or positive or negative free logic. I also look skeptically at the prospects of giving causal-counterfactual or probabilistic answers to the Question, although the discussion of the options is less comprehensive and the conclusions are more tentative. The meta-question, viz. ‘Should we not stop asking the Question’, is accordingly tentatively answered affirmatively.

+++++

Previous versions of this paper have been presented at the Fifth Graduate Student Conference (27 March 2015, Leuven), the SePPhia Seminar (1 April, 2015), the Congress for Logic, Methodology and Philosophy of Science (7 August 2015, Helsinki), and the CEFISES Seminar in Louvain-la-Neuve (13 January 2016). I would like to thank the audiences for their comments and questions. Furthermore, I would like to thank the anonymous reviewers for their useful reports.

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Darwin, a engenharia da estabilidade das proteínas é de precisão atômica: mero acaso, fortuita necessidade ou design inteligente?

terça-feira, maio 23, 2017

Engineering protein stability with atomic precision in a monomeric miniprotein

Emily G Baker, Christopher Williams, Kieran L Hudson, Gail J Bartlett, Jack W Heal, Kathryn L Porter Goff, Richard B Sessions, Matthew P Crump & Derek N Woolfson
AffiliationsContributionsCorresponding authors
Nature Chemical Biology (2017) doi:10.1038/nchembio.2380
Received 20 September 2016 Accepted 27 February 2017 Published online 22 May 2017

Source/Fonte: Emily G. Baker et al.

Abstract 

Miniproteins simplify the protein-folding problem, allowing the dissection of forces that stabilize protein structures. Here we describe PPα-Tyr, a designed peptide comprising an α-helix buttressed by a polyproline II helix. PPα-Tyr is water soluble and monomeric, and it unfolds cooperatively with a midpoint unfolding temperature (TM) of 39 °C. NMR structures of PPα-Tyr reveal proline residues docked between tyrosine side chains, as designed. The stability of PPα is sensitive to modifications in the aromatic residues: replacing tyrosine with phenylalanine, i.e., changing three solvent-exposed hydroxyl groups to protons, reduces the TM to 20 °C. We attribute this result to the loss of CH–π interactions between the aromatic and proline rings, which we probe by substituting the aromatic residues with nonproteinogenic side chains. In analyses of natural protein structures, we find a preference for proline–tyrosine interactions over other proline-containing pairs, and observe abundant CH–π interactions in biologically important complexes between proline-rich ligands and SH3 and similar domains.

Subscription or payment needed/Requer assinatura ou pagamento:

Nature Chemical Biology

Cientistas, publiquem mais casas de tijolos do que mansões de palha: MAIS EVIDÊNCIAS!!!

Publish houses of brick, not mansions of straw

Papers need to include fewer claims and more proof to make the scientific literature more reliable, warns William G. Kaelin Jr.



I worry about sloppiness in biomedical research: too many published results are true only under narrow conditions, or cannot be reproduced at all. The causes are diverse, but what I see as the biggest culprit is hardly discussed. Like the proverbial boiled frog that failed to leap from a slowly warming pot of water, biomedical researchers are stuck in a system in which the amount of data and number of claims in individual papers has gradually risen over decades. Moreover, the goal of a paper seems to have shifted from validating specific conclusions to making the broadest possible assertions. The danger is that papers are increasingly like grand mansions of straw, rather than sturdy houses of brick.

The papers leading to my 2016 Lasker prize (with Gregg Semenza and Peter Ratcliffe, for discovering how cells sense oxygen) were published more than a decade ago. Most would be considered quaint, preliminary and barely publishable today. One — showing that a tumour-suppressor protein was required for oxygen signalling — would today be criticized for failing to include a clear mechanism and animal experiments (O. Iliopoulos et al. Proc. Natl Acad. Sci. USA 93,10595–10599; 1996). Another, showing that the protein’s main target underwent an oxygen-dependent modification, was almost rejected because we hadn’t identified the enzyme responsible (M. Ivan et al. Science 292, 464–468; 2001). Fortunately, an experienced editor intervened, arguing that publication would open the search for the enzyme to other groups; such reprieves seem less common today.

What is driving today’s ‘claims inflation’? One factor is the emphasis that funding agencies place on impact and translation. Another is that technological advances have made it easier to generate data, which can be accommodated in online supplements. Both factors encourage reviewers and editors to demand extra experiments that are derivative, tangential to the main conclusion or aimed at increasing impact. And it has always taken more courage to accept a paper than to reject it with suggestions for more experiments. That can create perverse incentives by linking acceptance to a pre­ordained result. I fear that reviewers are especially inclined to ask for more when funding is tight, as it is now.

...

FREE PDF GRATIS: Nature

Por que nós precisamos de teorias na ciência?

Why do we need theories?

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

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

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



Abstract

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

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

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

Keywords: default state, mathematical symmetries, phase space, biological organization

Mais complexidade, Darwin: quase a metade do que está no cromossomo ainda é mistério!!!

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

Daniel G. Booth 5, Alison J. Beckett, Oscar Molina, Itaru Samejima, Hiroshi Masumoto, Natalay Kouprina, Vladimir Larionov, Ian A. Prior, William C. Earnshaw' 

5 Lead Contact

Published Online: November 10, 2016

Open Access


Open access funded by Wellcome Trust

Article Info

Publication History

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

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

User License

Creative Commons Attribution (CC BY 4.0)

Source/Fonte: Sergei Nivens


Highlights

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

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

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

• Chromosome volumes determined by light and electron microscopy differ dramatically

Summary

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

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Usar a quantidade de RNA mensageiro (mRNA) como um representante da abundância de proteínas pode ser arriscado

Post-transcriptional regulation across human tissues

Alexander Franks, Edoardo Airoldi, Nikolai Slavov 



Abstract

Transcriptional and post-transcriptional regulation shape tissue-type-specific proteomes, but their relative contributions remain contested. Estimates of the factors determining protein levels in human tissues do not distinguish between (i) the factors determining the variability between the abundances of different proteins, i.e., mean-level-variability and, (ii) the factors determining the physiological variability of the same protein across different tissue types, i.e., across-tissues variability. We sought to estimate the contribution of transcript levels to these two orthogonal sources of variability, and found that scaled mRNA levels can account for most of the mean-level-variability but not necessarily for across-tissues variability. The reliable quantification of the latter estimate is limited by substantial measurement noise. However, protein-to-mRNA ratios exhibit substantial across-tissues variability that is functionally concerted and reproducible across different datasets, suggesting extensive post-transcriptional regulation. These results caution against estimating protein fold-changes from mRNA fold-changes between different cell-types, and highlight the contribution of post-transcriptional regulation to shaping tissue-type-specific proteomes.

Author Summary

The identity of human tissues depends on their protein levels. Are tissue protein levels set largely by corresponding mRNA levels or by other (post-transcriptional) regulatory mechanisms? We revisit this question based on statistical analysis of mRNA and protein levels measured across human tissues. We find that for any one gene, its protein levels across tissues are poorly predicted by its mRNA levels, suggesting tissue-specific post-transcriptional regulation. In contrast, the overall protein levels are well predicted by scaled mRNA levels. We show how these speciously contradictory findings are consistent with each other and represent the two sides of Simpson’s paradox.

Citation: Franks A, Airoldi E, Slavov N (2017) Post-transcriptional regulation across human tissues. PLoS Comput Biol 13(5): e1005535. https://doi.org/10.1371/journal.pcbi.1005535

Editor: Christine Vogel, NYU, UNITED STATES

Received: December 19, 2016; Accepted: April 26, 2017; Published: May 8, 2017

Copyright: © 2017 Franks 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: Data and code are available from https://github.com/afranks86/tissue-ptr and from https://web.northeastern.edu/slavovlab/2016_PTR/.

Funding: This work was partially funded by a SPARC grant from the Broad Institute to NS and EA (https://www.broadinstitute.org/), the Washington Research Foundation Fund for Innovation in Data-Intensive Discovery (wrf.washington.edu/) and the Moore/Sloan Data Science Environments Project at the University of Washington (msdse.org/), and NIGMS of the NIH under Award Number DP2GM123497 (https://www.nigms.nih.gov/). 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.

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