Divisão celular requer nível equilibrado de RNA não codificante para estabilidade cromossômica: mero acaso, fortuita necessidade ou design inteligente?

sábado, maio 25, 2019

Point centromere activity requires an optimal level of centromeric noncoding RNA

Yick Hin Ling and Karen Wing Yee Yuen

PNAS March 26, 2019 116 (13) 6270-6279; first published March 8, 2019 https://doi.org/10.1073/pnas.1821384116

Edited by Douglas Koshland, University of California, Berkeley, CA, and approved February 5, 2019 (received for review December 21, 2018)

Fig. 5.
Fig. 5 Knockdown of total cenRNAs reduces mitotic stability of minichromosome.

Significance

Budding yeast harbors a simple point centromere, which is originally believed to be sequence dependent without much epigenetic regulation and is transcription incompatible, as inserting a strong promoter upstream inactivates the centromere completely. Here, we demonstrate that an optimal level centromeric noncoding RNA is required for budding yeast centromere activity. Centromeric transcription is induced in S phase, coinciding with the assembly of new centromeric proteins. Too much or too little centromeric noncoding RNA leads to centromere malfunction. Overexpression of centromeric noncoding RNA reduces the protein levels and chromatin localization of inner centromere and kinetochore proteins, such as CENP-A, CENP-C, and the chromosome passenger complex. This work shows that point centromere is epigenetically regulated by noncoding RNA.

Abstract

In budding yeast, which possesses simple point centromeres, we discovered that all of its centromeres express long noncoding RNAs (cenRNAs), especially in S phase. Induction of cenRNAs coincides with CENP-ACse4 loading time and is dependent on DNA replication. Centromeric transcription is repressed by centromere-binding factor Cbf1 and histone H2A variant H2A.ZHtz1. Deletion of CBF1 and H2A.ZHTZ1 results in an up-regulation of cenRNAs; an increased loss of a minichromosome; elevated aneuploidy; a down-regulation of the protein levels of centromeric proteins CENP-ACse4, CENP-A chaperone HJURPScm3, CENP-CMif2, SurvivinBir1, and INCENPSli15; and a reduced chromatin localization of CENP-ACse4, CENP-CMif2, and Aurora BIpl1. When the RNA interference system was introduced to knock down all cenRNAs from the endogenous chromosomes, but not the cenRNA from the circular minichromosome, an increase in minichromosome loss was still observed, suggesting that cenRNA functions in trans to regulate centromere activity. CenRNA knockdown partially alleviates minichromosome loss in cbf1Δ, htz1Δ, and cbf1Δ htz1Δ in a dose-dependent manner, demonstrating that cenRNA level is tightly regulated to epigenetically control point centromere function.

centromeric transcription long noncoding RNA centromere-binding factor Cbf1 histone H2A variant Htz1 chromosome instability

FREE PDF GRATIS: PNAS Sup. Info

Além de fabricar proteínas, ribossomos regulam a expressão de genes humanos

Translation affects mRNA stability in a codon-dependent manner in human cells


Qiushuang Wu, Santiago Gerardo Medina, Gopal Kushawah, Michelle Lynn DeVore, Luciana A Castellano, Jacqelyn M Hand, Matthew Wright, Ariel Alejandro Bazzini  

Stowers Institute for Medical Research, United States

RESEARCH ARTICLE Apr 23, 2019

Upstream regulator and downstream effect for codon optimality tRNA level, tRNA charged ratio, amino acid, and translational level might contribute to regulates the regulatory identity and/or strength of each codon to affect gene expression, by influencing the speed of translation elongation.

Abstract

mRNA translation decodes nucleotide into amino acid sequences. However, translation has also been shown to affect mRNA stability depending on codon composition in model organisms, although universality of this mechanism remains unclear. Here, using three independent approaches to measure exogenous and endogenous mRNA decay, we define which codons are associated with stable or unstable mRNAs in human cells. We demonstrate that the regulatory information affecting mRNA stability is encoded in codons and not in nucleotides. Stabilizing codons tend to be associated with higher tRNA levels and higher charged/total tRNA ratios. While mRNAs enriched in destabilizing codons tend to possess shorter poly(A)-tails, the poly(A)-tail is not required for the codon-mediated mRNA stability. This mechanism depends on translation; however, the number of ribosome loads into a mRNA modulates the codon-mediated effects on gene expression. This work provides definitive evidence that translation strongly affects mRNA stability in a codon-dependent manner in human cells.

https://doi.org/10.7554/eLife.45396.001

eLife digest

Proteins are made by joining together building blocks called amino acids into strings. The proteins are ‘translated’ from genetic sequences called mRNA molecules. These sequences can be thought of as series of ‘letters’, which are read in groups of three known as codons. Molecules called tRNAs recognize the codons and add the matching amino acids to the end of the protein. Each tRNA can recognize one or several codons, and the levels of different tRNAs inside the cell vary.

There are 61 codons that code for amino acids, but only 20 amino acids. This means that some codons produce the same amino acid. Despite this, there is evidence to suggest that not all of the codons that produce the same amino acid are exactly equivalent. In bacteria, yeast and zebrafish, some codons seem to make the mRNA molecule more stable, and others make it less stable. This might help the cell to control how many proteins it makes. It was not clear whether the same is true for humans.

To find out, Wu et al. used three separate methods to examine mRNA stability in four types of human cell. Overall, the results revealed that some codons help to stabilize the mRNA, while others make the mRNA molecule break down faster. The effect seems to depend on the supply of tRNAs that have a charged amino acid; mRNA molecules were more likely to self-destruct in cells that contained codons with low levels of the tRNA molecules.

Wu et al. also found that conditions in the cell can alter how strongly the codons affect mRNA stability. For example, a cell that has been infected by a virus reduces translation. Under these conditions, the identity of the codons in the mRNA has less effect on the stability of the mRNA molecule.

Changes to protein production happen in many diseases. Understanding what controls these changes could help to reveal more about our fundamental biology, and what happens when it goes wrong.

https://doi.org/10.7554/eLife.45396.002

FREE PDF GRATIS: eLIFE

Karl Popper, Ciência e Iluminação

terça-feira, maio 14, 2019





Karl Popper, Science and Enlightenment
Nicholas Maxwell 

ISBN: 9781787350397

Publication: September 26, 2017
 
Description
 
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. 

Praise for Karl Popper, Science and Enightenment
 ‘Maxwell has provided general philosophy of science with a book that is notably clear, earnestly written, passionate, and stunningly stimulating… a book with a panoply of exciting ideas and some relevance for almost anyone working in academia.'
Metapsychology Online Reviews 


Publication details

Format: Open Access PDF
390 Pages
ISBN: 9781787350397
Publication: September 26, 2017

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.

Table of contents

Prologue: An idea to help save the world

Introduction

1. Karl Raimund Popper

2. Popper, Kuhn, Lakatos and aim-oriented empiricism

3. Einstein, aim-oriented empiricism, and the discovery of special and general relativity 

4. Non-empirical requirements scientific theories must satisfy: simplicity, unity, explanation, beauty

5. Scientific metaphysics

6. Comprehensibility rather than beauty

7. A mug’s game? Solving the problem of induction with metaphysical presuppositions

8. Does probabilism solve the great quantum mystery?

9. Science, reason, knowledge and wisdom: a critique of specialism

10. Karl Popper and the Enlightenment Programme 

FREE PDF GRATIS: UCL PRESS
 


O que é vida?

segunda-feira, maio 13, 2019

Journal of Biomolecular Structure and Dynamics 
Volume 29, 2011 - Issue 2

Vocabulary of Definitions of Life Suggests a Definition

Edward N. Trifonov

Pages 259-266 | Received 17 Mar 2011, Published online: 11 Jul 2012



Abstract

Analysis of the vocabulary of 123 tabulated definitions of life reveals nine groups of defining terms (definientia) of which the groups (self-)reproduction and evolution (variation) appear as the minimal set for a concise and inclusive definition: Life is self-reproduction with variations.

Key words: Consensus,  Definientia , Evolution, Origin of life, Self-reproduction, Variations, Vocabulary

Os evolucionistas sabem há muito tempo que Haeckel fraudou, mas o que vale é que prova a teoria da evolução!

Theory in Biosciences

May 2019, Volume 138, Issue 1, pp 9–29 

Ernst Haeckel’s contribution to Evo-Devo and scientific debate: a re-evaluation of Haeckel’s controversial illustrations in US textbooks in response to creationist accusations

Elizabeth Watts, Georgy S. Levit, Uwe Hossfeld

Original Article
First Online: 13 March 2019

Haeckel's fraud

True stages - Richardson et al, Science 1998
Abstract

As Blackwell (Am Biol Teach 69:135–136, 2007) pointed out, multiple authors have attempted to discredit Haeckel, stating that modern embryological studies have shown that Haeckel’s drawings are stylized or embellished. More importantly, though, it has been shown that the discussion within the scientific community concerning Haeckel’s drawings and the question of whether embryonic similarities are convergent or conserved have been extrapolated outside the science community in an attempt to discredit Darwin and evolutionary theory in general (Behe in Science 281:347–351, 1998; Blackwell in Am Biol Teach 69:135–136, 2007; Pickett et al. in Am Biol Teach 67:275, 2005; Wells in Am Biol Teach 61:345–349, 1999; Icons of evolution: science or myth? Why much of what we teach about evolution is wrong. Regnery Publishing, Washington, 2002). In this paper, we address the controversy surrounding Haeckel and his work in order to clarify the line between the shortcomings and the benefits of his research and illustrations. Specifically, we show that while his illustrations were not perfect anatomical representations, they were useful educational visualizations and did serve an important role in furthering studies in embryology.

Keywords Haeckel Visualization Creationism Evolution Science education Textbooks 

This article is a contribution to the Special Issue Ernst Haeckel (1834–1919): The German Darwin and his impact on modern biology—Guest Editors: U. Hossfeld, G. S. Levit, U. Kutschera.

FREE PDF GRATIS: Theory in Biosciences

Pesquisa Acadêmica no Século 21: Mantendo a Integridade Científica em um Clima de Incentivos Perversos e Hipercompetição

Academic Research in the 21st Century: Maintaining Scientific Integrity in a Climate of Perverse Incentives and Hypercompetition

Marc A. Edwards and Siddhartha Roy

Published Online:1 Jan 2017 https://doi.org/10.1089/ees.2016.0223



Abstract

Over the last 50 years, we argue that incentives for academic scientists have become increasingly perverse in terms of competition for research funding, development of quantitative metrics to measure performance, and a changing business model for higher education itself. Furthermore, decreased discretionary funding at the federal and state level is creating a hypercompetitive environment between government agencies (e.g., EPA, NIH, CDC), for scientists in these agencies, and for academics seeking funding from all sources—the combination of perverse incentives and decreased funding increases pressures that can lead to unethical behavior. If a critical mass of scientists become untrustworthy, a tipping point is possible in which the scientific enterprise itself becomes inherently corrupt and public trust is lost, risking a new dark age with devastating consequences to humanity. Academia and federal agencies should better support science as a public good, and incentivize altruistic and ethical outcomes, while de-emphasizing output.

Um guia sucinto para escrever uma boa revisão paritária

A quick guide to writing a solid peer review

Kimberly A. Nicholas  Wendy S. Gordon

First published: 12 July 2011 https://doi.org/10.1029/2011EO280001

Source/Fonte: Wiley


Abstract

[1] Scientific integrity and consensus rely on the peer review process, a defining feature of scientific discourse that subjects the literature forming the foundation of credible knowledge in a scientific field to rigorous scrutiny. However, there is surprisingly little training in graduate school on how to develop this essential skill [Zimmerman et al., 2011] or discussion of best practices to ensure that reviewers at all levels efficiently provide the most useful review. Even more challenging for the novice peer reviewer is that journals also vary widely in their review guidelines. Nonetheless, the goals of peer review are crystal clear: to ensure the accuracy and improve the quality of published literature through constructive criticism. To make the peer review process as efficient and productive as possible, you may want to consider a few useful approaches to tackling major steps throughout your review, from contemplating a review request and reading and assessing the manuscript to writing the review and interacting with the journal's editors (see Figure 1). These tips are particularly relevant for graduate students or other first‐time reviewers, but they may also be useful to experienced reviewers and to journal editors seeking to enhance their publication's processes.

FREE PDF GRATIS: EOS

David Gelernter (Yale University): desistindo de Darwin!

sexta-feira, maio 10, 2019

Giving up Darwin

By: David Gelernter

Posted: May 1, 2019

This article appeared in: Volume XIX, Number 2, Spring 2019



Darwinian evolution is a brilliant and beautiful scientific theory. Once it was a daring guess. Today it is basic to the credo that defines the modern worldview. Accepting the theory as settled truth—no more subject to debate than the earth being round or the sky blue or force being mass times acceleration—certifies that you are devoutly orthodox in your scientific views; which in turn is an essential first step towards being taken seriously in any part of modern intellectual life. But what if Darwin was wrong?

Like so many others, I grew up with Darwin’s theory, and had always believed it was true. I had heard doubts over the years from well-informed, sometimes brilliant people, but I had my hands full cultivating my garden, and it was easier to let biology take care of itself. But in recent years, reading and discussion have shut that road down for good.

This is sad. It is no victory of any sort for religion. It is a defeat for human ingenuity. It means one less beautiful idea in our world, and one more hugely difficult and important problem back on mankind’s to-do list. But we each need to make our peace with the facts, and not try to make life on earth simpler than it really is.

Charles Darwin explained monumental change by making one basic assumption—all life-forms descend from a common ancestor—and adding two simple processes anyone can understand: random, heritable variation and natural selection. Out of these simple ingredients, conceived to be operating blindly over hundreds of millions of years, he conjured up change that seems like the deliberate unfolding of a grand plan, designed and carried out with superhuman genius. Could nature really have pulled out of its hat the invention of life, of increasingly sophisticated life-forms and, ultimately, the unique-in-the-cosmos (so far as we know) human mind—given no strategy but trial and error? The mindless accumulation of small changes? It is an astounding idea. Yet Darwin’s brilliant and lovely theory explains how it could have happened.

Its beauty is important. Beauty is often a telltale sign of truth. Beauty is our guide to the intellectual universe—walking beside us through the uncharted wilderness, pointing us in the right direction, keeping us on track—most of the time.

Demolishing a Worldview

There’s no reason to doubt that Darwin successfully explained the small adjustments by which an organism adapts to local circumstances: changes to fur density or wing style or beak shape. Yet there are many reasons to doubt whether he can answer the hard questions and explain the big picture—not the fine-tuning of existing species but the emergence of new ones. The origin of species is exactly what Darwin cannot explain.

Stephen Meyer’s thoughtful and meticulous Darwin’s Doubt (2013) convinced me that Darwin has failed. He cannot answer the big question. Two other books are also essential: The Deniable Darwin and Other Essays (2009), by David Berlinski, and Debating Darwin’s Doubt (2015), an anthology edited by David Klinghoffer, which collects some of the arguments Meyer’s book stirred up. These three form a fateful battle group that most people would rather ignore. Bringing to bear the work of many dozen scientists over many decades, Meyer, who after a stint as a geophysicist in Dallas earned a Ph.D. in History and Philosophy of Science from Cambridge and now directs the Discovery Institute’s Center for Science and Culture, disassembles the theory of evolution piece by piece. Darwin’s Doubt is one of the most important books in a generation. Few open-minded people will finish it with their faith in Darwin intact.

Meyer doesn’t only demolish Darwin; he defends a replacement theory, intelligent design (I.D.). Although I can’t accept intelligent design as Meyer presents it, he does show that it is a plain case of the emperor’s new clothes: it says aloud what anyone who ponders biology must think, at some point, while sifting possible answers to hard questions. Intelligent design as Meyer explains it never uses religious arguments, draws religious conclusions, or refers to religion in any way. It does underline an obvious but important truth: Darwin’s mission was exactly to explain the flagrant appearance of design in nature.

The religion is all on the other side. Meyer and other proponents of I.D. are the dispassionate intellectuals making orderly scientific arguments. Some I.D.-haters have shown themselves willing to use any argument—fair or not, true or not, ad hominem or not—to keep this dangerous idea locked in a box forever. They remind us of the extent to which Darwinism is no longer just a scientific theory but the basis of a worldview, and an emergency replacement religion for the many troubled souls who need one.

As for Biblical religion, it forces its way into the discussion although Meyer didn’t invite it, and neither did Darwin. Some have always been bothered by the harm Darwin is said to have done religion. His theory has been thought by some naïfs (fundamentalists as well as intellectuals) to have shown or alleged that the Bible is wrong, and Judeo-Christian religion bunk. But this view assumes a childishly primitive reading of Scripture. Anyone can see that there are two different creation stories in Genesis, one based on seven days, the other on the Garden of Eden. When the Bible gives us two different versions of one story, it stands to reason that the facts on which they disagree are without basic religious significance. The facts on which they agree are the ones that matter: God created the universe, and put man there for a reason. Darwin has nothing to say on these or any other key religious issues.

Fundamentalists and intellectuals might go on arguing these things forever. But normal people will want to come to grips with Meyer and the downfall of a beautiful idea. I will mention several of his arguments, one of them in (just a bit of) detail. This is one of the most important intellectual issues of modern times, and every thinking person has the right and duty to judge for himself.

Looking for Evidence

Darwin himself had reservations about his theory, shared by some of the most important biologists of his time. And the problems that worried him have only grown more substantial over the decades. In the famous “Cambrian explosion” of around half a billion years ago, a striking variety of new organisms—including the first-ever animals—pop up suddenly in the fossil record over a mere 70-odd million years. This great outburst followed many hundreds of millions of years of slow growth and scanty fossils, mainly of single-celled organisms, dating back to the origins of life roughly three and half billion years ago.

Darwin’s theory predicts that new life forms evolve gradually from old ones in a constantly branching, spreading tree of life. Those brave new Cambrian creatures must therefore have had Precambrian predecessors, similar but not quite as fancy and sophisticated. They could not have all blown out suddenly, like a bunch of geysers. Each must have had a closely related predecessor, which must have had its own predecessors: Darwinian evolution is gradual, step-by-step. All those predecessors must have come together, further back, into a series of branches leading down to the (long ago) trunk.

But those predecessors of the Cambrian creatures are missing. Darwin himself was disturbed by their absence from the fossil record. He believed they would turn up eventually. Some of his contemporaries (such as the eminent Harvard biologist Louis Agassiz) held that the fossil record was clear enough already, and showed that Darwin’s theory was wrong. Perhaps only a few sites had been searched for fossils, but they had been searched straight down. The Cambrian explosion had been unearthed, and beneath those Cambrian creatures their Precambrian predecessors should have been waiting—and weren’t. In fact, the fossil record as a whole lacked the upward-branching structure Darwin predicted.

The trunk was supposed to branch into many different species, each species giving rise to many genera, and towards the top of the tree you would find so much diversity that you could distinguish separate phyla—the large divisions (sponges, mosses, mollusks, chordates, and so on) that comprise the kingdoms of animals, plants, and several others—take your pick. But, as Berlinski points out, the fossil record shows the opposite: “representatives of separate phyla appearing first followed by lower-level diversification on those basic themes.” In general, “most species enter the evolutionary order fully formed and then depart unchanged.” The incremental development of new species is largely not there. Those missing pre-Cambrian organisms have still not turned up. (Although fossils are subject to interpretation, and some biologists place pre-Cambrian life-forms closer than others to the new-fangled Cambrian creatures.)

Some researchers have guessed that those missing Precambrian precursors were too small or too soft-bodied to have made good fossils. Meyer notes that fossil traces of ancient bacteria and single-celled algae have been discovered: smallness per se doesn’t mean that an organism can’t leave fossil traces—although the existence of fossils depends on the surroundings in which the organism lived, and the history of the relevant rock during the ages since it died. The story is similar for soft-bodied organisms. Hard-bodied forms are more likely to be fossilized than soft-bodied ones, but many fossils of soft-bodied organisms and body parts do exist. Precambrian fossil deposits have been discovered in which tiny, soft-bodied embryo sponges are preserved—but no predecessors to the celebrity organisms of the Cambrian explosion.

This sort of negative evidence can’t ever be conclusive. But the ever-expanding fossil archives don’t look good for Darwin, who made clear and concrete predictions that have (so far) been falsified—according to many reputable paleontologists, anyway. When does the clock run out on those predictions? Never. But any thoughtful person must ask himself whether scientists today are looking for evidence that bears on Darwin, or looking to explain away evidence that contradicts him. There are some of each. Scientists are only human, and their thinking (like everyone else’s) is colored by emotion.
...


David Gelernter is professor of computer science at Yale University, chief scientist at Mirror Worlds Technologies, and member of the National Council of the Arts.


FREE PDF GRATIS: CRB

Mecânica Quântica Emergente - Perspectivas do Centenário de David Bohm

Emergent Quantum Mechanics - David Bohm Centennial Perspectives

Topics of the Special Issue:

Interpretations of Quantum Mechanics
Nonlocality and Violation of Bell Inequalities
Quantum Probabilities and Contextuality
Quantum Causality and Ontology
Information Measures in Quantum Theory
Quantum Observation and the Physics of the Experimenter Agent
Nonlinear Methods applied to Quantum Theory
Self-organization and Quantum Emergence
Hidden Variable Theories and Relativity
Emergent Space-time
ISBN 978-3-03897-616-5 (Pbk);
ISBN 978-3-03897-617-2 (PDF);
© 2019 by the authors; CC BY-NC-ND licence

Jan Walleczek, Gerhard Grössing, Paavo Pylkkänen and Basil Hiley (Eds.)
Pages: 544
Published: April 2019
  
Emergent quantum mechanics (EmQM) explores the possibility of an ontology for quantum mechanics. The resurgence of interest in realist approaches to quantum mechanics challenges the standard textbook view, which represents an operationalist approach. The possibility of an ontological, i.e., realist, quantum mechanics was first introduced with the original de Broglie–Bohm theory, which has also been developed in another context as Bohmian mechanics. This book features expert contributions which were invited as part of the David Bohm Centennial symposium of the EmQM conference series. Questions directing the EmQM research agenda are: Is reality intrinsically random or fundamentally interconnected? Is the universe local or nonlocal? Might a radically new conception of reality include a form of quantum causality or quantum ontology? What is the role of the experimenter agent in ontological quantum mechanics? The book features research examining ontological propositions also that are not based on the Bohm-type nonlocality. These include, for example, local, yet time-symmetric, ontologies, such as quantum models based upon retrocausality. The book offers thirty-two contributions which are organized into seven categories to provide orientation as is outlined in the Editorial contribution in the beginning of the book.

This book is a printed edition of the Special Issue Emergent Quantum Mechanics – David Bohm Centennial Perspectives that was published in Entropy.


FREE PDF GRATIS: Entropy

Pode o vírus gigante Medusa ajudar explicar a evolução da complexidade da vida?

quinta-feira, maio 09, 2019

Medusavirus, a Novel Large DNA Virus Discovered from Hot Spring Water

Genki Yoshikawa, Romain Blanc-Mathieu, Chihong Song, Yoko Kayama, Tomohiro Mochizuki, Kazuyoshi Murata, Hiroyuki Ogata, Masaharu Takemura
Joanna L. Shisler, Editor


Resultado de imagem para Medusavirus
A new giant virus may help scientists better understand the emergence of complex life.
Credit: © Tokyo University of Science

ABSTRACT

Recent discoveries of new large DNA viruses reveal high diversity in their morphologies, genetic repertoires, and replication strategies. Here, we report the novel features of medusavirus, a large DNA virus newly isolated from hot spring water in Japan. Medusavirus, with a diameter of 260 nm, shows a T=277 icosahedral capsid with unique spherical-headed spikes on its surface. It has a 381-kb genome encoding 461 putative proteins, 86 of which have their closest homologs in Acanthamoeba, whereas 279 (61%) are orphan genes. The virus lacks the genes encoding DNA topoisomerase II and RNA polymerase, showing that DNA replication takes place in the host nucleus, whereas the progeny virions are assembled in the cytoplasm. Furthermore, the medusavirus genome harbored genes for all five types of histones (H1, H2A, H2B, H3, and H4) and one DNA polymerase, which are phylogenetically placed at the root of the eukaryotic clades. In contrast, the host amoeba encoded many medusavirus homologs, including the major capsid protein. These facts strongly suggested that amoebae are indeed the most promising natural hosts of medusavirus, and that lateral gene transfers have taken place repeatedly and bidirectionally between the virus and its host since the early stage of their coevolution. Medusavirus reflects the traces of direct evolutionary interactions between the virus and eukaryotic hosts, which may be caused by sharing the DNA replication compartment and by evolutionarily long lasting virus-host relationships. Based on its unique morphological characteristics and phylogenomic relationships with other known large DNA viruses, we propose that medusavirus represents a new family, Medusaviridae.

IMPORTANCE 

We have isolated a new nucleocytoplasmic large DNA virus (NCLDV) from hot spring water in Japan, named medusavirus. This new NCLDV is phylogenetically placed at the root of the eukaryotic clades based on the phylogenies of several key genes, including that encoding DNA polymerase, and its genome surprisingly encodes the full set of histone homologs. Furthermore, its laboratory host, Acanthamoeba castellanii, encodes many medusavirus homologs in its genome, including the major capsid protein, suggesting that the amoeba is the genuine natural host from ancient times of this newly described virus and that lateral gene transfers have repeatedly occurred between the virus and amoeba. These results suggest that medusavirus is a unique NCLDV preserving ancient footprints of evolutionary interactions with its hosts, thus providing clues to elucidate the evolution of NCLDVs, eukaryotes, and virus-host interaction. Based on the dissimilarities with other known NCLDVs, we propose that medusavirus represents a new viral family, Medusaviridae.

FREE PDF GRATIS: Journal of Virology

Stuart Kauffman 'falou e disse': uma nova física é necessária para investigar as origens da vida

A World Beyond Physics: The Emergence and Evolution of Life Stuart A. Kauffman Oxford University Press (2019)

A protocell (artificial cell) dividing to produce two daughter cells.
An artist’s impression of early ‘protocells’ proliferating.Credit: Henning Dalhoff/Science Photo Library

Among the great scientific puzzles of our time is how life emerged from inorganic matter. Scientists have probed it since the 1920s, when biochemists Alexsandr Oparin and J. B. S. Haldane (separately) investigated the properties of droplets rich in organic molecules that existed in a ‘prebiotic soup’ on the primitive Earth (see T. Hyman and C. Brangwynne Nature 491, 524–525; 2012). Each hypothesized that organic compounds underwent reactions leading to more complex molecules, and eventually to the first life forms.

What was missing then, as now, is a concrete theory for the physics of what life is, testable against experiment — which is likely to be more universal than the chemistry of life on Earth. Decades after Oparin and Haldane, Erwin Schrödinger’s 1944 book What Is Life? (see P. Ball Nature 560, 548–550; 2018) attempted to lay conceptual foundations for such a theory. Yet, more than 70 years and two generations of physicists later, researchers still ponder whether the answers lie in unknown physics. No one has led the charge on these questions quite like Stuart Kauffman.

In the 1980s and 1990s, Kauffman — a complex-systems researcher — developed a highly influential theory for life’s origins, based on molecules that reproduce only collectively, called autocatalytic sets. He posited that if a chemical soup of polymers was sufficiently diverse, these sets would emerge spontaneously as a phase transition — that is, a significant change in state or function, akin to the shift from solid to liquid. The sets function holistically, mutually catalysing the formation of all their molecular members. (His inspiration was advances in the mathematics of networks by Paul Erdős and Alfréd Rényi, who had demonstrated how phase transitions occur in random networks as connectivity is increased.) Now, in A World Beyond Physics, Kauffman elaborates.

His key insight is motivated by what he calls “the nonergodic world” — that of objects more complex than atoms. Most atoms are simple, so all their possible states can exist over a reasonable period of time. Once they start interacting to form molecules, the number of possible states becomes mind-bogglingly massive. Only a tiny number of proteins that are modestly complex — say, 200 amino acids long — have emerged over the entire history of the Universe. Generating all 20020 of the possibilities would take aeons. Given such limitations, how does what does exist ever come into being?

This is where Kauffman expands on his autocatalytic-sets theory, introducing concepts such as closure, in which processes are linked so that each drives the next in a closed cycle. He posits that autocatalysing sets (of RNA, peptides or both) encapsulated in a sphere of lipid molecules could form self-reproducing protocells. And he speculates that these protocells could evolve. Thus, each new biological innovation begets a new functional niche fostering yet more innovation. You cannot predict what will exist, he argues, because the function of everything biology generates will depend on what came before, and what other things exist now, with an ever-expanding set of what is possible next.

Because of this, Kauffman provocatively concludes, there is no mathematical law that could describe the evolving diversity and abundance of life in the biosphere. He writes: “we do not know the relevant variables prior to their emergence in evolution.” At best, he argues, any ‘laws of life’ that do exist will describe statistical distributions of aspects of that evolution. For instance, they might predict the distribution of extinctions. Life’s emergence might rest on the foundations of physics, “but it is not derivable from them”, Kauffman argues.
...

FREE PDF GRATIS: Nature

Em meio a explosão de dados genômicos, cientistas descobrem proliferação de erros

Front. Microbiol., 28 February 2019 | https://doi.org/10.3389/fmicb.2019.00383

Whole Proteome Clustering of 2,307 Proteobacterial Genomes Reveals Conserved Proteins and Significant Annotation Issues

Svetlana Lockwood1, Kelly A. Brayton1,2,3, Jeff A. Daily4 and Shira L. Broschat1,2,3*

1 School of Electrical Engineering and Computer Science, Washington State University, Pullman, WA, United States

2 Department of Veterinary Microbiology and Pathology, Washington State University, Pullman, WA, United States

3 Paul G. Allen School for Global Animal Health, Washington State University, Pullman, WA, United States

4 Pacific Northwest National Laboratory, Richland, WA, United States

NextCODE Reloads With $240M, Eyes IPO, As Genomic Data Demand Grows
Source/Fonte: Exome

Abstract

We clustered 8.76 M protein sequences deduced from 2,307 completely sequenced Proteobacterial genomes resulting in 707,311 clusters of one or more sequences of which 224,442 ranged in size from 2 to 2,894 sequences. To our knowledge this is the first study of this scale. We were surprised to find that no single cluster contained a representative sequence from all the organisms in the study. Given the minimal genome concept, we expected to find a shared set of proteins. To determine why the clusters did not have universal representation we chose four essential proteins, the chaperonin GroEL, DNA dependent RNA polymerase subunits beta and beta′ (RpoB/RpoB′), and DNA polymerase I (PolA), representing fundamental cellular functions, and examined their cluster distribution. We found these proteins to be remarkably conserved with certain caveats. Although the groEL gene was universally conserved in all the organisms in the study, the protein was not represented in all the deduced proteomes. The genes for RpoB and RpoB′ were missing from two genomes and merged in 88, and the sequences were sufficiently divergent that they formed separate clusters for 18 RpoB proteins (seven clusters) and 14 RpoB′ proteins (three clusters). For PolA, 52 organisms lacked an identifiable sequence, and seven sequences were sufficiently divergent that they formed five separate clusters. Interestingly, organisms lacking an identifiable PolA and those with divergent RpoB/RpoB′ were predominantly endosymbionts. Furthermore, we present a range of examples of annotation issues that caused the deduced proteins to be incorrectly represented in the proteome. These annotation issues made our task of determining protein conservation more difficult than expected and also represent a significant obstacle for high-throughput analyses.

Nova análise nega afirmação controversa sobre a origem da humanidade via A. sediba



Temporal evidence shows Australopithecus sediba is unlikely to be the ancestor of Homo

Andrew Du* and Zeresenay Alemseged

Department of Organismal Biology and Anatomy, The University of Chicago, Chicago, IL 60637, USA.

↵*Corresponding author. Email: andrewdu@uchicago.edu

Science Advances 08 May 2019:Vol. 5, no. 5, eaav9038


Fossil casts of Australopithecus afarensis (left), Homo habilis (center), and Australopithecus sediba (right).
Fossil casts of Australopithecus afarensis (left), Homo habilis (center), and Australopithecus sediba (right). Image: Matt Wood, UChicago

Abstract

Understanding the emergence of the genus Homo is a pressing problem in the study of human origins. Australopithecus sediba has recently been proposed as the ancestral species of Homo, although it postdates earliest Homo by 800,000 years. Here, we use probability models to demonstrate that observing an ancestor’s fossil horizon that is at least 800,000 years younger than the descendant’s fossil horizon is unlikely (about 0.09% on average). We corroborate these results by searching the literature and finding that within pairs of purported hominin ancestor–descendant species, in only one case did the first-discovered fossil in the ancestor postdate that from the descendant, and the age difference between these fossils was much less than the difference observed between A. sediba and earliest Homo. Together, these results suggest it is highly unlikely that A. sediba is ancestral to Homo, and the most viable candidate ancestral species remains Australopithecus afarensis.

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Metabiota - um site sobre epidemias no mundo inteiro

sexta-feira, abril 19, 2019

Resultado de imagem para Metabiota
Um site rastreador sobre epidemias no mundo inteiro.


Origem do RNA codificante a partir de sequência aleatória de RNA

quarta-feira, abril 17, 2019

Origin of Coding RNA from Random-Sequence RNA

Gaspar Banfalvi

Published Online:5 Mar 2019 https://doi.org/10.1089/dna.2018.4389


FIG. 1. Ribose, the best fitting pentose in the nucleotide structure.

Abstract

D-ribose and D-arabinose differ only by the steric orientation of their C2-OH groups. The initial reactions and emergence of RNA depended on the position, reactivity, and flexibility of the C2-OH moiety in the ribose molecule. The steric relationship of the C2- and C3-OH groups favored the selection of ribose, ribonucleotide, and RNA synthesis and excluded the possibility of xenonucleic acid-based life on Earth. This brief review provides a hypothesis based on the absence of nucleotides and enzymes under prebiotic conditions and on the polymerization of ribose 5-phosphate units leading to the polarized formation of the ribose-phosphate backbone. The strong covalent bond formation in the sugar-phosphate backbone was followed by the somewhat less reactive interaction between ribose and nucleobase and supplemented by even weaker hydrogen-bonded and stacking interactions. This hypothesis proposes a scheme how prebiotic random-sequence RNA was formed under abiotic conditions and hydrolyzed to oligomers and nucleotides. The term random-sequence prebiotic RNA refers to nucleobases attached randomly to the ribose-phosphate backbone and not to cellular RNA sequences as proteins and cells did not probably exist at the time of abiotic RNA formation. It is hypothesized that RNA generated under abiotic conditions containing random nucleobases was hydrolyzed to nucleotides that served as a pool for the selected synthesis of genetic RNA.

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Nova hipótese da origem da vida: concentrações de óxido de nitrogênio em águas naturais na Terra Primeva

sábado, abril 13, 2019

Geochemistry, Geophysics, Geosystems

Nitrogen Oxide Concentrations in Natural Waters on Early Earth

Sukrit Ranjan  Zoe R. Todd  Paul B. Rimmer  Dimitar D. Sasselov  Andrew R. Babbin

First published: 12 April 2019 https://doi.org/10.1029/2018GC008082

This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as doi: 10.1029/2018gc008082

Resultado de imagem para early earth images


Abstract


A key challenge in origins‐of‐life studies is estimating the abundances of species relevant to the chemical pathways proposed to have contributed to the emergence of life on early Earth. Dissolved nitrogen oxide anions (NOurn:x-wiley:ggge:media:ggge21866:ggge21866-math-0001), in particular nitrate (NOurn:x-wiley:ggge:media:ggge21866:ggge21866-math-0002) and nitrite (NOurn:x-wiley:ggge:media:ggge21866:ggge21866-math-0003), have been invoked in diverse origins‐of‐life chemistry, from the oligomerization of RNA to the emergence of protometabolism. Recent work has calculated the supply of NOurn:x-wiley:ggge:media:ggge21866:ggge21866-math-0018 from the prebiotic atmosphere to the ocean, and reported steady‐state [NOurn:x-wiley:ggge:media:ggge21866:ggge21866-math-0005] to be high across all plausible parameter space. These findings rest on the assumption that NOurn:x-wiley:ggge:media:ggge21866:ggge21866-math-0004 is stable in natural waters unless processed at a hydrothermal vent. Here, we show that NOurn:x-wiley:ggge:media:ggge21866:ggge21866-math-0006 is unstable in the reducing environment of early Earth. Sinks due to UV photolysis and reactions with reduced iron (urn:x-wiley:ggge:media:ggge21866:ggge21866-math-0019) suppress [NOurn:x-wiley:ggge:media:ggge21866:ggge21866-math-0007] by several orders of magnitude relative to past predictions. For pH= 6.5 ‐ 8 and T=0‐50°C, we find that it is most probable that [NOurn:x-wiley:ggge:media:ggge21866:ggge21866-math-0008]<1 alt="urn:x-wiley:ggge:media:ggge21866:ggge21866-math-0020" class="section_image" img="" nbsp="" src="https://wol-prod-cdn.literatumonline.com/cms/attachment/2a0116a6-29d1-44f7-b669-6d2697d1616e/ggge21866-math-0020.png" style="border-style: none; box-sizing: border-box; max-width: 100%; vertical-align: middle;">M in the prebiotic ocean. On the other hand, prebiotic ponds with favorable drainage characteristics may have sustained [NOurn:x-wiley:ggge:media:ggge21866:ggge21866-math-0009]≥1μM. As on modern Earth, most NOurn:x-wiley:ggge:media:ggge21866:ggge21866-math-0010 on prebiotic Earth should have been present as NO urn:x-wiley:ggge:media:ggge21866:ggge21866-math-0011, due to its much greater stability. These findings inform the kind of prebiotic chemistries that would have been possible on early Earth. We discuss the implications for proposed prebiotic chemistries, and highlight the need for further studies of NOurn:x-wiley:ggge:media:ggge21866:ggge21866-math-0012 kinetics to reduce the considerable uncertainties in predicting [NOurn:x-wiley:ggge:media:ggge21866:ggge21866-math-0013] on early Earth.

Pele de dinossauro do Cretáceo perfeitamente preservada encontrada na Coreia

quinta-feira, abril 11, 2019

Exquisitely-preserved, high-definition skin traces in diminutive theropod tracks from the Cretaceous of Korea

Kyung Soo Kim, Martin G. Lockley, Jong Deock Lim & Lida Xing 

Scientific Reports volume 9, Article number: 2039 (2019)

Figure 4
Fig. 4

Abstract

Small theropod tracks, ichnogenus Minisauripus, from the Jinju Formation (Cretaceous) of Korea reveal exquisitely preserved skin texture impressions. This is the first report for any dinosaur of skin traces that cover entire footprints, and every footprint in a trackway. Special sedimentological conditions allowed footprint registration without smearing of skin texture patterns which consist of densely-packed, reticulate arrays of small (<0 .5="" also="" and="" as="" avian="" birds="" both="" casts="" china="" cretaceous="" different="" essentially="" foot="" for="" from="" had="" impressions="" is="" latter="" lower="" mm="" morphologies.="" nbsp="" of="" oldest="" polygons="" preserved="" quite="" replicas.="" report="" reported="" resembles="" skin="" span="" texture="" that="" the="" theropods="" this="" two="" which="">Minisauripus from Korea predating five reports from the Haman Formation of inferred Albian age. Minisauripus is now known from six Korean and three Chinese localities, all from the Lower Cretaceous. This gives a total sample of ~ 95 tracks representing ~ 54 trackways. With 80% of tracks <3 .0="" cm="" long="" nbsp="" span="">Minisauripus is pivotal in debates over whether small tracks represent small species, as the database suggests, or juveniles of large species. 

Acknowledgements

We thank the School of Biological Sciences, the University of Queensland, Brisbane for help with statistical analyses done in Supplementary Information.

Author information

Affiliations

Department of Science Education, Chinju National University of Education, 3 Jinnyangho-ro 369beon-gil, Jinju-si, Gyeongnam, 52673, Korea
Kyung Soo Kim

Dinosaur Trackers Research Group, University of Colorado Denver, P.O. Box 173364, Denver, CO, 80217, USA
Martin G. Lockley

Cultural Heritage Administration, Government Complex-Daejeon, 189, Cheongsa-ro, Seo-gu, Daejon, 35208, Korea
Jong Deock Lim

School of the Earth Sciences and Resources, China University of Geosciences, Beijing, 100083, China
Lida Xing

Contributions

K.-S.K. found, collected and photographed specimens K.-S.K., M.G.L. and J.-D.L. examined field site, measured specimens and prepared manuscript and figures. L.X. examined comparative material and helped with bibliographic research and database organization.

Competing Interests

The authors declare no competing interests.

Corresponding author

Correspondence to Martin G. Lockley.

Rights and permissions

Creative Commons BY

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

About this article

Publication history

Received 28 September 2018 Accepted 03 January 2019

Published 14 February 2019

DOI


Subjects Palaeontology Solid Earth sciences

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Insights estruturais sobre características únicas da reciclagem de ribossomos mitocondriais humanos

quarta-feira, abril 10, 2019

Structural insights into unique features of the human mitochondrial ribosome recycling

Ravi K. Koripella, Manjuli R. Sharma, Paul Risteff, Pooja Keshavan, and Rajendra K. Agrawal

PNAS published ahead of print April 8, 2019 


Edited by Yale E. Goldman, Pennsylvania Muscle Institute, University of Pennsylvania, Philadelphia, PA, and approved March 15, 2019 (received for review September 11, 2018)

Image result for human mitochondrial ribosome recycling

Significance

The human mitochondrial ribosome (mitoribosome) recycling factor (RRFmt) is known to play essential roles in mitochondrial physiology, including protein synthesis, and it has been implicated in human genetic diseases. The RRFmt is among the few protein molecules that carry their N-terminal signal peptide sequence into the mitochondrial matrix that is required for RRFmt’s interaction with the mitoribosome. In this study, we present a cryo-electron microscopic structure of the human mitoribosome in complex with the RRFmt. The structure reveals hitherto unknown features of RRFmt and its interactions with the functionally important regions of the ribosomal RNA that constitute the peptidyl-transferase center and that are linked to the GTPase-associated center of the mitoribosome, shedding light on the mechanism of ribosome recycling in mitochondria.

Abstract

Mammalian mitochondrial ribosomes (mitoribosomes) are responsible for synthesizing proteins that are essential for oxidative phosphorylation (ATP generation). Despite their common ancestry with bacteria, the composition and structure of the human mitoribosome and its translational factors are significantly different from those of their bacterial counterparts. The mammalian mitoribosome recycling factor (RRFmt) carries a mito-specific N terminus extension (NTE), which is necessary for the function of RRFmt. Here we present a 3.9-Å resolution cryo-electron microscopic (cryo-EM) structure of the human 55S mitoribosome-RRFmt complex, which reveals α-helix and loop structures for the NTE that makes multiple mito-specific interactions with functionally critical regions of the mitoribosome. These include ribosomal RNA segments that constitute the peptidyl transferase center (PTC) and those that connect PTC with the GTPase-associated center and with mitoribosomal proteins L16 and L27. Our structure reveals the presence of a tRNA in the pe/E position and a rotation of the small mitoribosomal subunit on RRFmt binding. In addition, we observe an interaction between the pe/E tRNA and a mito-specific protein, mL64. These findings help understand the unique features of mitoribosome recycling.

human mitochondrial RRFmito-specific sequence55S–RRFmt complexcryo-EM structuremito-specific interactions

Footnotes

↵1Present address: Charles River Laboratories Inc., Durham, NC 27703.

↵2To whom correspondence should be addressed. Email: Rajendra.Agrawal@health.ny.gov.
Author contributions: R.K.A. designed research; R.K.K., M.R.S., P.R., and P.K. performed research; R.K.K., M.R.S., and R.K.A. analyzed data; and R.K.K., M.R.S., and R.K.A. wrote the paper.

The authors declare no conflict of interest.

This article is a PNAS Direct Submission.

Data deposition: The cryo-EM maps and atomic coordinates have been deposited in the Electron Microscopy and PDB Data Bank (www.wwpdb.org) under accession codes EMD-0514 and PDB ID 6NU2, respectively, for the RRFmt-bound 55S mitoribosome (Complex I) and EMD-0515 and PDB ID 6NU3, respectively, for the unbound 55S mitoribosome (Complex II).

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Copyright © 2019 the Author(s). Published by PNAS.

Pesquisadores repensam a ancestralidade de células complexas

Researchers Rethink the Ancestry of Complex Cells
New studies revise ideas about the symbiosis that gave mitochondria to cells and about whether the last common ancestor of all eukaryotes was one cell or many.

Research into the origins of the complex cells called eukaryotes typically tries to trace lineages of the organisms back to a single ancestral cell. But now scientists are considering whether that common “ancestor” might really be an entire population of diverse cells.

DVDP for Quanta Magazine

Our planet formed a little over 4.5 billion years ago, and if the most recent estimates are correct, it wasn’t long before life arose. Not much is known about how that happened because it’s maddeningly difficult to investigate. It’s also proved tough to study what happened next, during the first billions of years of evolution that followed, when the main domains of life emerged.

A particularly vexing mystery is the rise of the eukaryotes, cells with well-defined internal compartments, or organelles, which are present only in animals, plants, fungi and some microbes like protists — our evolutionary kin. The earliest eukaryotes left no clear fossils as clues, so researchers are forced to deduce what they were like by comparing the structural and molecular details of later ones and inferring their evolutionary relationships.

Right now is “an incredibly exciting time” for such research, said Michelle Leger, a postdoctoral fellow at the Institute of Evolutionary Biology in Barcelona, Spain. With modern genetic sequencing technologies, scientists can read the entire genomes of diverse life forms, and as microbial life is revealed in ever-increasing detail, new species and other taxonomic groups are coming to light. With that wealth of data, researchers are tracing lineages of organisms backward through time. “We’re trying to approach the problem from so many sides,” she said. “That’s pushing us closer to the first eukaryotes.”


This paramecium, a single-cell protozoan microbe, has a nucleus, mitochondria and other organelles that are hallmarks of eukaryotic cells.

Michael Abbey/Science Source

And those first eukaryotes may depart significantly from what most scientists expected, if some recent findings are any indication. Earlier this month, one team presented evidence that a signature event in eukaryote evolution — the development of the organelles called mitochondria — might have unfolded quite differently than was theorized. Meanwhile, other researchers have suggested that the earliest “ancestor” of all eukaryotes might not have been a single cell at all, but rather a mixed population of cells that avidly swapped DNA. The difference is subtle, but it might be important for understanding the evolution and diversity of the eukaryotes we see today.

The Ancestral Eukaryotes

The very first cells — the first life forms on this planet — were prokaryotes, but they were not all alike. Even early on, two very distinct lineages emerged, the archaea and the bacteria. The archaea might have been the first to thrive because even now they can survive in extreme environments like hot vents and super-saline pools. But it’s also possible that archaea and bacteria split from the first cells at the same time and began to diversify independently from the start. Figuring out definitively when and how the split occurred is probably impossible given how much time has passed; fossil evidence is nonexistent, and organisms from both branches have swapped genes extensively through horizontal gene transfer (as opposed to the “vertical” transfer of genes down through generations), which complicates analyses of their genomic history.

What we do know is that the story of eukaryotes began when some rogue archaeal cell split from the rest and founded what was long considered an entirely new domain of life. “First and fundamentally we are a very strange kind of archaea,” said Maureen O’Malley, a philosopher of biology affiliated with the University of Bordeaux and the University of Sydney.
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