Os cromossomos podem ser atados

sábado, outubro 21, 2017

Polymers 2017, 9(8), 317; doi:10.3390/polym9080317

Are There Knots in Chromosomes?

Jonathan T. Siebert 1, Alexey N. Kivel 1, Liam P. Atkinson 2, Tim J. Stevens 3, Ernest D. Laue 2 and Peter Virnau 1,* 

1 Department of Physics, Johannes Gutenberg University Mainz, Staudinger Weg 9, 55128 Mainz, Germany

2 Department of Biochemistry, University of Cambridge, 80 Tennis Court Road, Cambridge CB2 1GA, UK

3 MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge Biomedical Campus, Cambridge CB2 0QH, UK

* Author to whom correspondence should be addressed.

Received: 30 June 2017 / Revised: 24 July 2017 / Accepted: 25 July 2017 / Published: 2 August 2017

(This article belongs to the Special Issue Knotted and Catenated Polymers)

Researchers at Mainz University found two knots in chromosome 14, here indicated by the solid lines. The blue and red dots mark the beginning and end of the chromosome. The coloring used in the image is designed to help with orientation only.
Credit: Ill./ ©: Jonathan Siebert, JGU

Abstract

Recent developments have for the first time allowed the determination of three-dimensional structures of individual chromosomes and genomes in nuclei of single haploid mouse embryonic stem (ES) cells based on Hi–C chromosome conformation contact data. Although these first structures have a relatively low resolution, they provide the first experimental data that can be used to study chromosome and intact genome folding. Here we further analyze these structures and provide the first evidence that G1 phase chromosomes are knotted, consistent with the fact that plots of contact probability vs sequence separation show a power law dependence that is intermediate between that of a fractal globule and an equilibrium structure. View Full-Text

Keywords: knots; chromosomes; chromosome territories; DNA; fractal globule

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

FREE PDF GRATIS: Polymers 11.3 MBs.

Ainda é grande o fosso de representatividade feminina em publicações científicas

Women are underrepresented in computational biology: An analysis of the scholarly literature in biology, computer science and computational biology

Kevin S. Bonham , Melanie I. Stefan


Source/Fonte: Harvard Medical School


Abstract

While women are generally underrepresented in STEM fields, there are noticeable differences between fields. For instance, the gender ratio in biology is more balanced than in computer science. We were interested in how this difference is reflected in the interdisciplinary field of computational/quantitative biology. To this end, we examined the proportion of female authors in publications from the PubMed and arXiv databases. There are fewer female authors on research papers in computational biology, as compared to biology in general. This is true across authorship position, year, and journal impact factor. A comparison with arXiv shows that quantitative biology papers have a higher ratio of female authors than computer science papers, placing computational biology in between its two parent fields in terms of gender representation. Both in biology and in computational biology, a female last author increases the probability of other authors on the paper being female, pointing to a potential role of female PIs in influencing the gender balance.

Author summary

There are fewer women than men working in Science, Technology, Engineering and Mathematics (STEM). However, some fields within STEM are more gender-balanced than others. For instance, biology has a relatively high proportion of women, whereas there are few women in computer science. But what about computational biology? As an interdisciplinary STEM field, would its gender balance be close to one of its “parent” fields, or in between the two? To investigate this question, we examined authorship data from databases of scholarly publications in biology, computational biology, and computer science. We found that computational biology lies in between computer science and biology, as far as female representation goes. This is independent of other factors, e.g. year of publication. This suggests that computational biology might provide an environment that is more conducive to female participation that other areas of computer science. Across all three fields, we also found that if the last author on a publication—usually the person leading the study—is a women, then there will also be more women in other authorship positions. This suggests that having women in leadership positions might be beneficial for overall gender balance, though our data do not allow us to uncover the underlying mechanism.

Citation: Bonham KS, Stefan MI (2017) Women are underrepresented in computational biology: An analysis of the scholarly literature in biology, computer science and computational biology. PLoS Comput Biol13(10): e1005134. https://doi.org/10.1371/journal.pcbi.1005134

Editor: Carl T. Bergstrom, University of Washington, UNITED STATES

Received: December 7, 2016; Accepted: July 7, 2017; Published: October 12, 2017

Copyright: © 2017 Bonham, Stefan. 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: Publication and author information for the manuscripts analyzed are archived on zenodo.org http://doi.org/10.5281/zenodo.58990 http://doi.org/10.5281/zenodo.60088 Code to analyze the data are available on github and archived at zenodo.org. http://doi.org/10.5281/zenodo.60090 Gender inferences for first names were supplied by Gender-API.com. An example dataset of 1000 names and associated data is included as supplementary data. For more information, contact Markus Perl at contact@gender-api.com.

Funding: The authors received no specific funding for this work.

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

FREE PDF GRATIS: PLoS Computational Biology

A teoria do equilíbrio da seleção de mutação foi confirmada???

quarta-feira, outubro 18, 2017

The population genetics of human disease: The case of recessive, lethal mutations

Carlos Eduardo G. Amorim , Ziyue Gao, Zachary Baker, José Francisco Diesel, Yuval B. Simons, Imran S. Haque, Joseph Pickrell , Molly Przeworski 

Published: September 28, 2017 https://doi.org/10.1371/journal.pgen.1006915

Source/Fonte: Genetics


Abstract

Do the frequencies of disease mutations in human populations reflect a simple balance between mutation and purifying selection? What other factors shape the prevalence of disease mutations? To begin to answer these questions, we focused on one of the simplest cases: recessive mutations that alone cause lethal diseases or complete sterility. To this end, we generated a hand-curated set of 417 Mendelian mutations in 32 genes reported to cause a recessive, lethal Mendelian disease. We then considered analytic models of mutation-selection balance in infinite and finite populations of constant sizes and simulations of purifying selection in a more realistic demographic setting, and tested how well these models fit allele frequencies estimated from 33,370 individuals of European ancestry. In doing so, we distinguished between CpG transitions, which occur at a substantially elevated rate, and three other mutation types. Intriguingly, the observed frequency for CpG transitions is slightly higher than expectation but close, whereas the frequencies observed for the three other mutation types are an order of magnitude higher than expected, with a bigger deviation from expectation seen for less mutable types. This discrepancy is even larger when subtle fitness effects in heterozygotes or lethal compound heterozygotes are taken into account. In principle, higher than expected frequencies of disease mutations could be due to widespread errors in reporting causal variants, compensation by other mutations, or balancing selection. It is unclear why these factors would have a greater impact on disease mutations that occur at lower rates, however. We argue instead that the unexpectedly high frequency of disease mutations and the relationship to the mutation rate likely reflect an ascertainment bias: of all the mutations that cause recessive lethal diseases, those that by chance have reached higher frequencies are more likely to have been identified and thus to have been included in this study. Beyond the specific application, this study highlights the parameters likely to be important in shaping the frequencies of Mendelian disease alleles.

Author summary

What determines the frequencies of disease mutations in human populations? To begin to answer this question, we focus on one of the simplest cases: mutations that cause completely recessive, lethal Mendelian diseases. We first review theory about what to expect from mutation and selection in a population of finite size and generate predictions based on simulations using a plausible demographic scenario of recent human evolution. For a highly mutable type of mutation, transitions at CpG sites, we find that the predictions are close to the observed frequencies of recessive lethal disease mutations. For less mutable types, however, predictions substantially under-estimate the observed frequency. We discuss possible explanations for the discrepancy and point to a complication that, to our knowledge, is not widely appreciated: that there exists ascertainment bias in disease mutation discovery. Specifically, we suggest that alleles that have been identified to date are likely the ones that by chance have reached higher frequencies and are thus more likely to have been mapped. More generally, our study highlights the factors that influence the frequencies of Mendelian disease alleles.

Citation: Amorim CEG, Gao Z, Baker Z, Diesel JF, Simons YB, Haque IS, et al. (2017) The population genetics of human disease: The case of recessive, lethal mutations. PLoS Genet13(9): e1006915. https://doi.org/10.1371/journal.pgen.1006915

Editor: Philipp W. Messer, Cornell University, UNITED STATES

Received: December 4, 2016; Accepted: July 9, 2017; Published: September 28, 2017

Copyright: © 2017 Amorim 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 and code from gitHub (https://github.com/cegamorim/PopGenHumDisease; https://github.com/sellalab/ForwardSimulator).

Funding: CEGA was partially funded by a Science Without Borders fellowship from CAPES foundation (BEX 8279/11-0) and Conselho Nacional de Desenvolvimento Científico e Tecnológico (PDE 201145/2015-4), Brazil. ZG was partially supported by a postdoctoral fellowship funded by Stanford Center for Computational, Evolutionary and Human Genomics. JFD was funded by a Science Without Borders fellowship from CAPES foundation (88888.038761/2013-00). YBS was supported by NIH grant GM115889. The work was partially supported by a Research Initiative in Science and Engineering grant from Columbia University and NIGMS grants (GM121372) to JKP and MP. The computing in this project was supported by two National Institutes of Health instrumentation grants (S10OD012351 and S10OD021764) received by the Department of Systems Biology at Columbia University. 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 Genetics

Pesquisadores retiram pigmento original, beta queratina e proteínas musculares de fóssil de tartaruga marinha jovem datado de 54 MYA

Biochemistry and adaptive colouration of an exceptionally preserved juvenile fossil sea turtle

Johan Lindgren, Takeo Kuriyama, Henrik Madsen, Peter Sjövall, Wenxia Zheng, Per Uvdal, Anders Engdahl, Alison E. Moyer, Johan A. Gren, Naoki Kamezaki, Shintaro Ueno & Mary H. Schweitzer

Scientific Reports 7, Article number: 13324 (2017)


Download Citation

Biogeochemistry Molecular biology Palaeontology

Received: 17 May 2017 Accepted: 19 September 2017 Published online: 17 October 2017

Holotype of Tasbacka danica. (a) Photograph of the fossil. Fo, fontanelle (the light colour is a result of sediment infill); Hyo, hyoplastron; Hyp, hypoplastron; Ne, neural; Nu, nuchal; Pe, peripheral; Py, pygal. Arrowheads indicate neural nodes. (b) Detail of the carapace with the sampled area demarcated by a circle. Co, costal; Hu, humerus; Sc, scapula. (c) Higher magnification image showing marginal scutes (arrowheads), pigmentations on bones (arrows), and a brown-black film covering the fontanelles (stars).

Abstract

The holotype (MHM-K2) of the Eocene cheloniine Tasbacka danica is arguably one of the best preserved juvenile fossil sea turtles on record. Notwithstanding compactional flattening, the specimen is virtually intact, comprising a fully articulated skeleton exposed in dorsal view. MHM-K2 also preserves, with great fidelity, soft tissue traces visible as a sharply delineated carbon film around the bones and marginal scutes along the edge of the carapace. Here we show that the extraordinary preservation of the type of T. danica goes beyond gross morphology to include ultrastructural details and labile molecular components of the once-living animal. Haemoglobin-derived compounds, eumelanic pigments and proteinaceous materials retaining the immunological characteristics of sauropsid-specific β-keratin and tropomyosin were detected in tissues containing remnant melanosomes and decayed keratin plates. The preserved organics represent condensed remains of the cornified epidermis and, likely also, deeper anatomical features, and provide direct chemical evidence that adaptive melanism – a biological means used by extant sea turtle hatchlings to elevate metabolic and growth rates – had evolved 54 million years ago.

Acknowledgements

Ola Gustafsson assisted during the TEM analyses. James Parham provided information on sea turtle anatomy, whereas Edwin Cadena provided samples of an extant analogue for controls. This research was supported through a Grant for Distinguished Young Researchers (award number 642-2014-3773; Swedish Research Council) to J.L. Part of this work was performed at the Analytical Instrumentation Facility at North Carolina State University, which is supported by the State of North Carolina and National Science Foundation (award number ECCS-1542015). Further support was provided through a National Science Foundation INSPIRE grant (award number EAR-1344198) to M.H.S. and W.Z., and the National Science Foundation Graduate Research Fellowship Program (award number DGE-1252376) to A.E.M.

Author information

Affiliations

Department of Geology, Lund University, 223 62, Lund, Sweden

Johan Lindgren, Takeo Kuriyama, Johan A. Gren & Mary H. Schweitzer

Institute of Natural and Environmental Sciences, University of Hyogo, 669 3842, Hyogo, Japan

Takeo Kuriyama

Wildlife Management Research Center, 669 3842, Hyogo, Japan

Takeo Kuriyama

Mo-clay Museum, 7900, Nykøbing Mors, Denmark

Henrik Madsen

RISE Research Institutes of Sweden, Chemistry and Materials, 501 15, Borås, Sweden

Peter Sjövall

Department of Biological Sciences, North Carolina State University, Raleigh, NC, 27695, USA

Wenxia Zheng, Alison E. Moyer & Mary H. Schweitzer

North Carolina Museum of Natural Sciences, Raleigh, NC, 27601, USA

Wenxia Zheng & Mary H. Schweitzer

Chemical Physics, Department of Chemistry, Lund University, 221 00, Lund, Sweden

Per Uvdal

MAX-IV laboratory, Lund University, 221 00, Lund, Sweden

Anders Engdahl

Department of Biosphere-Geosphere Science, Okayama University of Science, 700 005, Okayama, Japan

Naoki Kamezaki

Department of Ecosystem Studies, University of Tokyo, 113 8657, Tokyo, Japan

Shintaro Ueno

Contributions

J.L. designed the research. J.L., M.H.S. and P.S. wrote the manuscript with input from all other authors. H.M. collected and prepared MHM-K2. T.K., J.L., P.S., and J.A.G. carried out the FEG-SEM and TEM analyses, M.H.S. and W.Z. performed the immunohistochemical investigation, P.S. and J.L. conducted the ToF-SIMS experiments, and P.U., A.E. and J.L. recorded the IR microspectroscopic measurements. A.E.M. developed the chicken feather antibodies used in this study, whereas N.K. and S.U. provided reference materials.

Competing Interests

The authors declare that they have no competing interests.

Corresponding author

Correspondence to Johan Lindgren.

Supressão da liberdade acadêmica - uma 'crise global'

terça-feira, outubro 17, 2017



Suppression of academic freedom a ‘global crisis’

BY MARIA BURKE16 OCTOBER 2017 Source: SHUTTERSTOCK

Universities around the world under attack as states and groups seek to silence free thought 

Attacks on academics and students are occurring with such alarming frequency and in so many places around the world that it is now a ‘global crisis’, according to a new report by the US charity Scholars at Risk (SAR).

‘What has become increasingly clear this year is an anti-democratic fear of universities as spaces in which everyone is free to think, question and share ideas,’ comments Robert Quinn, SAR’s executive director. Under authoritarian regimes and in areas of conflict, higher education communities are often a focal point for violence and coercion. The common motivation is to control or silence inquiry and discourse.

It is a human rights crisis, since it represents an attack on the fundamental right to freedom of opinion and expression

MARTIN CHALFIE, 2008 CHEMISTRY NOBEL LAUREATE

Quinn wants the report to serve ‘as a clarion call’ for action. He urges states, leaders and civil society to recognise publicly that this is a problem and to reaffirm their commitment to academic freedom and the principle that everyone should be free to think, question and share ideas.

SAR’s report Free to Think 2017 summarises a year of data collected by SAR’s monitoring project; it includes 257 reported attacks in 35 countries. ‘Attacks’ include killings, violence and disappearances; wrongful prosecution and imprisonment; loss of position and expulsion from study; improper travel restrictions; and other severe or systemic issues including, for example, university closures or military occupation of a campus.

There is a growing trend that, in societies experiencing armed conflict or extremism, higher education communities are perceived as symbols of state authority or sources of potential opposition to radical ideologies. Attacks are generally intended to punish or deter inquiry, or even expression, on unpopular topics. During the past year, SAR found evidence of large-scale violent attacks on campuses in Pakistan, Nigeria and Syria, while targeted killings of individuals were reported in Pakistan, Nigeria and Sierra Leone.
...

Read more here/Leia mais aqui: Chemistry World

Free to Think 2017 FREE PDF GRATIS: Scholars at Risk

As galhas de plantas e a evolução: como mais de 12.000 fatos estão matando uma belíssima hipótese - o Darwinismo

sexta-feira, outubro 13, 2017

Wolf-Ekkehard Lönnig

7 September 2017

(with a few slight additions on the following days and a postscript on plant galls and the fossil record a week later)

Plant Galls and Evolution


How More than Twelve Thousand 1 Ugly Facts are Slaying a Beautiful Hypothesis: Darwinism 2

[T]he great tragedy of Science – the slaying of a beautiful hypothesis by an ugly fact. [But] Science commits suicidewhen it adopts a creed.

Thomas Henry Huxley

If it could be proved that any part of the structure of any one species had been formed for the exclusive good of another species, it would annihilate my theory, for such could not have been produced through natural selection

Charles Darwin

Even those strongly skeptical about teleological interpretations cannot contest the fact that plant galls are constructions promoting a parasite thus benefiting a foreign organism, devices which already by this support are detrimental to the host plant.”

Ernst Küster 3

The problem which plant galls present for the selection theory has often been neglected. ... [The dilemma] is not slight, since the expediency of galls throws up very serious difficulties for the selection principle.

Erich Becher 4

FREE PDF GRATIS: W. E. Lönnig

Por princípios físicos da evolução biológica

Towards physical principles of biological evolution

Mikhail I Katsnelson, Yuri I. Wolf, Eugene V. Koonin



Abstract

Biological systems reach organizational complexity that far exceeds the complexity of any known inanimate objects. Biological entities undoubtedly obey the laws of quantum physics and statistical mechanics. However, is modern physics sufficient to adequately describe, model and explain the evolution of biological complexity? Detailed parallels have been drawn between statistical thermodynamics and the population-genetic theory of biological evolution. Based on these parallels, we outline new perspectives on biological innovation and major transitions in evolution, and introduce a biological equivalent of thermodynamic potential that reflects the innovation propensity of an evolving population. Deep analogies have been suggested to also exist between the properties of biological entities and processes, and those of frustrated states in physics, such as glasses. Such systems are characterized by frustration whereby local state with minimal free energy conflict with the global minimum, resulting in emergent phenomena. We extend such analogies by examining frustration-type phenomena, such as conflicts between different levels of selection, in biological evolution. These frustration effects appear to drive the evolution of biological complexity. We further address evolution in multidimensional fitness landscapes from the point of view of percolation theory and suggest that percolation at level above the critical threshold dictates the tree-like evolution of complex organisms. Taken together, these multiple connections between fundamental processes in physics and biology imply that construction of a meaningful physical theory of biological evolution might not be a futile effort. However, it is unrealistic to expect that such a theory can be created in one scoop; if it ever comes to being, this can only happen through integration of multiple physical models of evolutionary processes. Furthermore, the existing framework of theoretical physics is unlikely to suffice for adequate modeling of the biological level of complexity, and new developments within physics itself are likely to be required.

Copyright 

The copyright holder for this preprint is the author/funder. This article is a US Government work. It is not subject to copyright under 17 USC 105 and is also made available for use under a CC0 license.

FREE PDF GRATIS: bioRxiv

Darwin, mais complexidade: um complexo molecular de eliminação de lixo tem um papel na embalagem do genoma!

quarta-feira, outubro 11, 2017

The 19S proteasome is directly involved in the regulation of heterochromatin spreading in fission yeast

Hogyu David Seo1, Yoonjung Choi1, Minhoo Kim1, Keunsoo Kang2, Takeshi Urano3 and Daeyoup Lee1*

- Author Affiliations

1 Korea Advanced Institute of Science and Technology, Korea, Republic of;

2 Dankook University, Korea, Republic of;

3 Shimane University, Japan

↵* Corresponding author; email: daeyoup@kaist.ac.kr

Author contributions: H.D.S. and D.L. conceived and designed the project; H.D.S. performed most of the experiments and data analyses with input from D.L.; Y.C. performed the sRNA-seq experiments and analyses; M.K took part in the random mutagenesis; K.K. contributed to the bioinformatic analysis; T.U. provided the anti-H3K9me2 antibody; H.D.S. and D.L. drafted the manuscript; and all authors contributed to revising the manuscript and gave final approval for its publication.


Abstract

Cumulative evidence suggests that non-proteolytic functions of the proteasome are involved in transcriptional regulation, mRNA export and ubiquitin-dependent histone modification, and thereby modulate the intracellular levels of regulatory proteins implicated in controlling key cellular functions. To date, the non-proteolytic roles of the proteasome have been mainly investigated in euchromatin; their effects on heterochromatin are largely unknown. Here, using fission yeast as a model, we randomly mutagenized the subunits of the 19S proteasome subcomplex, and sought to uncover a direct role of the proteasome in heterochromatin regulation. We identified a non-proteolytic allele, rpt4-1. Experiments performed using rpt4-1 cells revealed that the proteasome is involved in the regulation of heterochromatin spreading to prevent its uncontrolled invasion into neighboring euchromatin regions. Intriguingly, the phenotype of the non-proteolytic rpt4-1 mutant resembled that of epe1Δ cells, which lack the Epe1 protein that counteracts heterochromatin spreading. Both mutants exhibited variegated gene-silencing phenotypes across yeast colonies, spreading of heterochromatin, bypassing of the requirement for RNAi in heterochromatin formation at the outer repeat region (otr), and upregulation of RNA polymerase II. Further analysis revealed Mst2, another factor that antagonizes heterochromatin spreading, may function redundantly with Rpt4. These observations suggest that the 19S proteasome may be involved in modulating the activities of Epe1 and Mst2. In conclusion, our findings indicate that the proteasome appears to have a heterochromatin-regulating function that is independent of its canonical function in proteolysis.

chromatin regulation epigenetics heterochromatin proteasome RNA interference (RNAi) 19S RP Epe1 RNAi heterochromatin spreading non-proteolytic function

Received April 11, 2017. Accepted August 7, 2017.

Copyright © 2017, The American Society for Biochemistry and Molecular Biology

EXTRA! EXTRA! EXTRA! Porque alguns darwinistas não querem uma nova teoria geral da evolução

terça-feira, outubro 10, 2017

Why we don’t want another “Synthesis”

Arlin Stoltzfus ORCID ID profile

Biology Direct 201712:23

https://doi.org/10.1186/s13062-017-0194-1 © The Author(s) 2017 ReadCube 

Received: 27 July 2017 Accepted: 18 September 2017 Published: 2 October 2017


Abstract

High-level debates in evolutionary biology often treat the Modern Synthesis as a framework of population genetics, or as an intellectual lineage with a changing distribution of beliefs. Unfortunately, these flexible notions, used to negotiate decades of innovations, are now thoroughly detached from their historical roots in the original Modern Synthesis (OMS), a falsifiable scientific theory. The OMS held that evolution can be adequately understood as a process of smooth adaptive change by shifting the frequencies of small-effect alleles at many loci simultaneously, without the direct involvement of new mutations. This shifting gene frequencies theory was designed to support a Darwinian view in which the course of evolution is governed by selection, and to exclude a mutation-driven view in which the timing and character of evolutionary change may reflect the timing and character of events of mutation. The OMS is not the foundation of current thinking, but a special case of a broader conception that includes (among other things) a mutation-driven view introduced by biochemists in the 1960s, and now widely invoked. This innovation is evident in mathematical models relating the rate of evolution directly to the rate of mutation, which emerged in 1969, and now represent a major branch of theory with many applications. In evo-devo, mutationist thinking is reflected by a concern for the “arrival of the fittest”. Though evolutionary biology is not governed by any master theory, and incorporates views excluded from the OMS, the recognition of these changes has been hindered by woolly conceptions of theories, and by historical accounts, common in the evolutionary literature, that misrepresent the disputes that defined the OMS.

Reviewers: This article was reviewed by W. Ford Doolittle, Eugene Koonin and J. Peter Gogarten.

Keywords

Modern Synthesis Evolutionary theory Darwinism Synthesis Historiography Mutation-driven evolution

FREE PDF GRATIS: Biology Direct

Darwin iria gostar: a origem do mundo RNA - o destino das nucleobases em pequenas lagoas quentes

quarta-feira, outubro 04, 2017

Origin of the RNA world: The fate of nucleobases in warm little ponds

Ben K. D. Pearce a,b,1, Ralph E. Pudritz a,b,c,d, Dmitry A. Semenov c, and Thomas K. Henning c  

Author Affiliations

a Origins Institute, McMaster University, Hamilton, ON L8S 4M1, Canada;

b Department of Physics and Astronomy, McMaster University, Hamilton, ON L8S 4M1, Canada;

c Planet and Star Formation Department, Max Planck Institute for Astronomy, 69117 Heidelberg, Germany;

d Institute for Theoretical Astrophysics, Center for Astronomy Heidelberg, 69120 Heidelberg, Germany

Edited by Donald E. Canfield, Institute of Biology and Nordic Center for Earth Evolution, University of Southern Denmark, Odense M., Denmark, and approved August 28, 2017 (received for review June 7, 2017)

Source/Fonte: Springer Link

Abstract

Significance

There are currently two competing hypotheses for the site at which an RNA world emerged: hydrothermal vents in the deep ocean and warm little ponds. Because the former lacks wet and dry cycles, which are well known to promote polymerization (in this case, of nucleotides into RNA), we construct a comprehensive model for the origin of RNA in the latter sites. Our model advances the story and timeline of the RNA world by constraining the source of biomolecules, the environmental conditions, the timescales of reaction, and the emergence of first RNA polymers.

Abstract

Before the origin of simple cellular life, the building blocks of RNA (nucleotides) had to form and polymerize in favorable environments on early Earth. At this time, meteorites and interplanetary dust particles delivered organics such as nucleobases (the characteristic molecules of nucleotides) to warm little ponds whose wet–dry cycles promoted rapid polymerization. We build a comprehensive numerical model for the evolution of nucleobases in warm little ponds leading to the emergence of the first nucleotides and RNA. We couple Earth’s early evolution with complex prebiotic chemistry in these environments. We find that RNA polymers must have emerged very quickly after the deposition of meteorites (less than a few years). Their constituent nucleobases were primarily meteoritic in origin and not from interplanetary dust particles. Ponds appeared as continents rose out of the early global ocean, but this increasing availability of “targets” for meteorites was offset by declining meteorite bombardment rates. Moreover, the rapid losses of nucleobases to pond seepage during wet periods, and to UV photodissociation during dry periods, mean that the synthesis of nucleotides and their polymerization into RNA occurred in just one to a few wet–dry cycles. Under these conditions, RNA polymers likely appeared before 4.17 billion years ago.

life origins astrobiology planetary science meteoritics RNA world

Footnotes

1To whom correspondence should be addressed. Email: pearcbe@mcmaster.ca.

Author contributions: B.K.D.P., R.E.P., D.A.S., and T.K.H. designed research; B.K.D.P. performed research; B.K.D.P. and R.E.P. analyzed data; and B.K.D.P., R.E.P., D.A.S., and T.K.H. 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.1710339114/-/DCSupplemental.

+++++

Professores, pesquisadores e alunos de universidades públicas e privadas com acesso ao Portal Periódicos CAPES/MEC podem ler gratuitamente este artigo do PNAS e mais 33.000 publicações científicas.

Uma ribozima de transcriptase reversa vai salvar o mundo RNA???

A reverse transcriptase ribozyme

Gerald F Joyce, Biswajit Samanta

The Salk Institute, United States

SHORT REPORT Sep 26, 2017

CITE AS: eLife 2017;6:e31153 DOI: 10.7554/eLife.31153



Abstract

A highly evolved RNA polymerase ribozyme was found to also be capable of functioning as a reverse transcriptase, an activity that has never been demonstrated before for RNA. This activity is thought to have been crucial for the transition from RNA to DNA genomes during the early history of life on Earth, when it similarly could have arisen as a secondary function of an RNA-dependent RNA polymerase. The reverse transcriptase ribozyme can incorporate all four dNTPs and can generate products containing up to 32 deoxynucleotides. It is likely that this activity could be improved through evolution, ultimately enabling the synthesis of complete DNA genomes. DNA is much more stable compared to RNA and thus provides a larger and more secure repository for genetic information.

Article and author information

Author details

Gerald F Joyce

The Salk Institute, La Jolla, United States

For correspondence gjoyce@salk.edu

Competing interests The authors declare that no competing interests exist.

ORCID icon 0000-0003-0603-2874

Biswajit Samanta

The Salk Institute, La Jolla, United States

Competing interests The authors declare that no competing interests exist.

Funding

National Aeronautics and Space Administration (NNX14AK15G)

Gerald F Joyce

Simons Foundation (287624)

Gerald F Joyce

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

Andrew D Ellington, Reviewing Editor, University of Texas at Austin, United States

Publication history

Received: August 10, 2017 Accepted: September 26, 2017

Accepted Manuscript published: September 26, 2017 (version 1)

Copyright

© 2017, Joyce & Samanta

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

FREE PDF GRATIS: eLIFE Sup. Info. Zip File

Darwin, mais design: mecânica cromossômica "guia" a montagem nuclear

Cell Volume 170, Issue 5, 24 August 2017, Pages 956-972.e23

Article

DNA Cross-Bridging Shapes a Single Nucleus from a Set of Mitotic Chromosomes ReadCube 

MatthiasSamwer1 Maximilian W.G.Schneider1 RudolfHoefler1 Philipp S.Schmalhorst2 Julian G.Jude3 JohannesZuber3 Daniel W.Gerlich14

1 Institute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA), Vienna Biocenter (VBC), 1030 Vienna, Austria

2 Institute of Science and Technology Austria (IST Austria), 3400 Klosterneuburg, Austria

3 Research Institute of Molecular Pathology (IMP), Vienna Biocenter (VBC), 1030 Vienna, Austria

Received 2 March 2017, Revised 12 June 2017, Accepted 24 July 2017, Available online 25 August 2017.

Published: August 24, 2017




Open Access funded by European Research Council

Under a Creative Commons licenseopen access

Highlights

• Spindle-independent mechanism based on BAF shapes single nucleus in mitotic exit

• BAF transiently cross-bridges anaphase chromosomes to prevent nuclear fragmentation

• BAF forms a dense DNA network at the chromosome ensemble surface

• Network mesh size restricts membrane access and thereby guides the nuclear envelope

Summary

Eukaryotic cells store their chromosomes in a single nucleus. This is important to maintain genomic integrity, as chromosomes packaged into separate nuclei (micronuclei) are prone to massive DNA damage. During mitosis, higher eukaryotes disassemble their nucleus and release individualized chromosomes for segregation. How numerous chromosomes subsequently reform a single nucleus has remained unclear. Using image-based screening of human cells, we identified barrier-to-autointegration factor (BAF) as a key factor guiding membranes to form a single nucleus. Unexpectedly, nuclear assembly does not require BAF’s association with inner nuclear membrane proteins but instead relies on BAF’s ability to bridge distant DNA sites. Live-cell imaging and in vitro reconstitution showed that BAF enriches around the mitotic chromosome ensemble to induce a densely cross-bridged chromatin layer that is mechanically stiff and limits membranes to the surface. Our study reveals that BAF-mediated changes in chromosome mechanics underlie nuclear assembly with broad implications for proper genome function.

Keywords

mitosis nuclear assembly chromosomes nuclear envelope micronuclei chromothripsis barrier-to-autointegration factor BAF DNA cross-bridging

FREE PDF GRATIS: Cell

Um dinossauro tridimensionalmente blindado excepcionalmente preservado revela insights sobre a coloração e a dinâmica predador-rapina do Cretáceo

terça-feira, outubro 03, 2017

An Exceptionally Preserved Three-Dimensional Armored Dinosaur Reveals Insights into Coloration and Cretaceous Predator-Prey Dynamics

Caleb M. Brown6, Donald M. Henderson, Jakob Vinther, Ian Fletcher, Ainara Sistiaga, Jorsua Herrera, Roger E. Summons

6Lead Contact

Published Online: August 03, 2017

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Publication History

Published: August 3, 2017 

Accepted: June 27, 2017 Received in revised form: May 16, 2017

Received: March 6, 2017

User License

Creative Commons Attribution – NonCommercial – NoDerivs (CC BY-NC-ND 4.0)

Photographs of the Holotype of Borealopelta markmitchelli, TMP 2011.033.0001

Highlights

• A new armored dinosaur is described based on an exceptionally preserved specimen

• Abundant in situ osteoderms with keratinous sheaths and scales are preserved

• Reddish-brown coloration and crypsis in the form of countershading are indicated

Crypsis indicates strong predation pressure on this large, heavily armored dinosaur

Summary

Predator-prey dynamics are an important evolutionary driver of escalating predation mode and efficiency, and commensurate responses of prey [1, 2, 3]. Among these strategies, camouflage is important for visual concealment, with countershading the most universally observed [4, 5, 6]. Extant terrestrial herbivores free of significant predation pressure, due to large size or isolation, do not exhibit countershading. Modern predator-prey dynamics may not be directly applicable to those of the Mesozoic due to the dominance of very large, visually oriented theropod dinosaurs [7]. Despite thyreophoran dinosaurs’ possessing extensive dermal armor, some of the most extreme examples of anti-predator structures [8, 9], little direct evidence of predation on these and other dinosaur megaherbivores has been documented. Here we describe a new, exquisitely three-dimensionally preserved nodosaurid ankylosaur, Borealopelta markmitchelli gen. et sp. nov., from the Early Cretaceous of Alberta, which preserves integumentary structures as organic layers, including continuous fields of epidermal scales and intact horn sheaths capping the body armor. We identify melanin in the organic residues through mass spectroscopic analyses and observe lighter pigmentation of the large parascapular spines, consistent with display, and a pattern of countershading across the body. With an estimated body mass exceeding 1,300 kg, B. markmitchelli was much larger than modern terrestrial mammals that either are countershaded or experience significant predation pressure as adults. Presence of countershading suggests predation pressure strong enough to select for concealment in this megaherbivore despite possession of massive dorsal and lateral armor, illustrating a significant dichotomy between Mesozoic predator-prey dynamics and those of modern terrestrial systems.

FREE PDF GRATIS: Current Biology

Mais complexidade, Darwin: Os efeitos do superenrolamento do DNA na formação de quadriplexos G

The effects of DNA supercoiling on G-quadruplex formation 

Doreen A.T. Sekibo Keith R. Fox

Nucleic Acids Research, gkx856, https://doi.org/10.1093/nar/gkx856

Published: 28 September 2017 

Article history Received: 16 February 2017 Revision Received: 10 September 2017

Accepted: 13 September 2017


Abstract

Guanine-rich DNAs can fold into four-stranded structures that contain stacks of G-quartets. Bioinformatics studies have revealed that G-rich sequences with the potential to adopt these structures are unevenly distributed throughout genomes, and are especially found in gene promoter regions. With the exception of the single-stranded telomeric DNA, all genomic G-rich sequences will always be present along with their C-rich complements, and quadruplex formation will be in competition with the corresponding Watson–Crick duplex. Quadruplex formation must therefore first require local dissociation (melting) of the duplex strands. Since negative supercoiling is known to facilitate the formation of alternative DNA structures, we have investigated G-quadruplex formation within negatively supercoiled DNA plasmids. Plasmids containing multiple copies of (G3T)n and (G3T4)n repeats, were probed with dimethylsulphate, potassium permanganate and S1 nuclease. While dimethylsulphate footprinting revealed some evidence for G-quadruplex formation in (G3T)n sequences, this was not affected by supercoiling, and permanganate failed to detect exposed thymines in the loop regions. (G3T4)n sequences were not protected from DMS and showed no reaction with permanganate. Similarly, both S1 nuclease and 2D gel electrophoresis of DNA topoisomers did not detect any supercoil-dependent structural transitions. These results suggest that negative supercoiling alone is not sufficient to drive G-quadruplex formation.

Topic: plasmids aspergillus nuclease s1 dna dna, superhelical diffuse mesangial sclerosis

Issue Section: Chemical Biology and Nucleic Acid Chemistry

Mais complexidade, Darwin: A modelagem de precisão transcricional sugere duas etapas de revisão pela polimerase do RNA

Transcriptional accuracy modeling suggests two-step proofreading by RNA polymerase 

Harriet Mellenius Måns Ehrenberg

Nucleic Acids Research, gkx849, https://doi.org/10.1093/nar/gkx849

Published: 28 September 2017 

Article history

Received: 04 August 2016 Revision Received: 10 September 2017

Accepted: 22 September 2017

Source/Fonte: Nucleic Acids Research


Abstract

We suggest a novel two-step proofreading mechanism with two sequential rounds of proofreading selection in mRNA transcription. It is based on the previous experimental observations that the proofreading RNA polymerase cleaves off transcript fragments of at least 2 nt and that transcript elongation after a nucleotide misincorporation is anomalously slow. Taking these results into account, we extend the description of the accuracy of template guided nucleotide selection beyond previous models of RNA polymerase-dependent DNA transcription. The model derives the accuracy of initial and proofreading base selection from experimentally estimated nearest-neighbor parameters. It is also used to estimate the small accuracy enhancement of polymerase revisiting of previous positions following transcript cleavage.

Issue Section: COMPUTATIONAL BIOLOGY

FREE PDF GRATIS: Nucleic Acids Research

Novo livro de Nicholas Maxwell - Karl Popper, Science and Enlightment

segunda-feira, outubro 02, 2017

UCL PRESS

Karl Popper, Science and Enlightenment

Nicholas Maxwell | September 2017

Format: 234x156mm 
Open Access PDF
ISBN: 978‑1‑78735‑039‑7
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Hardback
ISBN: 978‑1‑78735‑040‑3
£40.00

Paperback
ISBN: 978‑1‑78735‑041‑0
£20.00

epub
ISBN: 978‑1‑78735‑038‑0
£5.99

Pages: 370

About the book

Here is an idea that just might save the world. It is that science, properly understood, provides us with the methodological key to the salvation of humanity. A version of this idea can be found in the works of Karl Popper. Famously, Popper argued that science cannot verify theories but can only refute them, and this is how science makes progress. Scientists are forced to think up something better, and it is this, according to Popper, that drives science forward.

But Nicholas Maxwell finds a flaw in this line of argument. Physicists only ever accept theories that are unified – theories that depict the same laws applying to the range of phenomena to which the theory applies – even though many other empirically more successful disunified theories are always available. This means that science makes a questionable assumption about the universe, namely that all disunified theories are false. Without some such presupposition as this, the whole empirical method of science breaks down.

By proposing a new conception of scientific methodology, which can be applied to all worthwhile human endeavours with problematic aims, Maxwell argues for a revolution in academic inquiry to help humanity make progress towards a better, more civilized and enlightened world. 

About the author

Nicholas Maxwell has devoted much of his working life to arguing that we need to bring about a revolution in academia so that it seeks and promotes wisdom and does not just acquire knowledge. He has published eight books on this theme, including How Universities Can Help Create a Wiser World (2014) and In Praise of Natural Philosophy (2017). For 30 years he taught philosophy of science at University College London, where he is now Emeritus Reader. For more about his work, see www.ucl.ac.uk/from-knowledge-to-wisdom.

Lentes bifocais de um olho complexo de larvas

quinta-feira, setembro 28, 2017

A Complex Lens for a Complex Eye

Aaron L. Stahl Regina S. Baucom Tiffany A. Cook Elke K. Buschbeck

Integrative and Comparative Biology, icx116, https://doi.org/10.1093/icb/icx116

Published: 02 September 2017

Source/Fonte: Current Biology

Abstract

A key innovation for high resolution eyes is a sophisticated lens that precisely focuses light onto photoreceptors. The eyes of holometabolous larvae range from very simple eyes that merely detect light to eyes that are capable of high spatial resolution. Particularly interesting are the bifocal lenses of Thermonectus marmoratus larvae, which differentially focus light on spectrally-distinct retinas. While functional aspects of insect lenses have been relatively well studied, little work has explored their molecular makeup, especially in regard to more complex eye types. To investigate this question, we took a transcriptomic and proteomic approach to identify the major proteins contributing to the principal bifocal lenses of T. marmoratus larvae. Mass spectrometry revealed 10 major lens proteins. Six of these share sequence homology with cuticular proteins, a large class of proteins that are also major components of corneal lenses from adult compound eyes of Drosophila melanogaster and Anopheles gambiae. Two proteins were identified as house-keeping genes and the final two lack any sequence homologies to known genes. Overall the composition seems to follow a pattern of co-opting transparent and optically dense proteins, similar to what has been described for other animal lenses. To identify cells responsible for the secretion of specific lens proteins, we performed in situ hybridization studies and found some expression differences between distal and proximal corneagenous cells. Since the distal cells likely give rise to the periphery and the proximal cells to the center of the lens, our findings highlight a possible mechanism for establishing structural differences that are in line with the bifocal nature of these lenses. A better understanding of lens composition provides insights into the evolution of proper focusing, which is an important step in the transition between low-resolution and high-resolution eyes.

Issue Section: Low Spatial Resolution Vision

© The Author 2017. Published by Oxford University Press on behalf of the Society for Integrative and Comparative Biology. All rights reserved. For permissions please email: journals.permissions@oup.com.

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