A plasticidade fenotípica inicia o viés de desenvolvimento?

quinta-feira, agosto 22, 2019

Does phenotypic plasticity initiate developmental bias?

Kevin J. Parsons Kirsty McWhinnie Natalie Pilakouta Lynsey Walker

First published: 26 July 2019


The generation of variation is paramount for the action of natural selection. Although biologists are now moving beyond the idea that random mutation provides the sole source of variation for adaptive evolution, we still assume that variation occurs randomly. In this review, we discuss an alternative view for how phenotypic plasticity, which has become well accepted as a source of phenotypic variation within evolutionary biology, can generate nonrandom variation. Although phenotypic plasticity is often defined as a property of a genotype, we argue that it needs to be considered more explicitly as a property of developmental systems involving more than the genotype. We provide examples of where plasticity could be initiating developmental bias, either through direct active responses to similar stimuli across populations or as the result of programmed variation within developmental systems. Such biased variation can echo past adaptations that reflect the evolutionary history of a lineage but can also serve to initiate evolution when environments change. Such adaptive programs can remain latent for millions of years and allow development to harbor an array of complex adaptations that can initiate new bouts of evolution. Specifically, we address how ideas such as the flexible stem hypothesis and cryptic genetic variation overlap, how modularity among traits can direct the outcomes of plasticity, and how the structure of developmental signaling pathways is limited to a few outcomes. We highlight key questions throughout and conclude by providing suggestions for future research that can address how plasticity initiates and harbors developmental bias.

FREE PDF GRATIS: Evolution and Development



“Although biologists are now moving beyond the idea that random mutation provides the sole source of variation for adaptive evolution, we still assume that variation occurs randomly...Darwin's idea that variation is generated randomly has largely been taken for granted rather than tested, representing a fundamental gap in our understanding of evolution.”

Desafios matemáticos à teoria da evolução - Berlinski, Meyer, e Gelernter

segunda-feira, julho 22, 2019

Origem da vida: tempo esgotado!

sexta-feira, julho 19, 2019

Time Out

Image result for james tour 

This essay comprises an argument, but it also contains an appeal to the OOL community. The history of science suggests that on occasion what is required for research to flourish is not further research—at least to the extent that further research involves doing the same thing. This is one of those times.

Needed for Life

Four molecules are needed for life: nucleotides, carbohydrates, proteins, and lipids. Nucleotides are composed of a trimeric nucleobase-carbohydrate-phosphate combination, and once polymerized, constitute DNA and RNA. Five different nucleobases comprise the entire alphabet for DNA and RNA. The nucleotides and their subsequent DNA and RNA structures are homochiral, yielding one of two possible enantiomers. Amino acids are most often homochiral. When amino acids are polymerized, they form proteins and enzymes. Proteins and enzymes also display a tertiary homochirality. Lipids are dipolar molecules with a polar water-soluble head and a non-polar water-insoluble tail. They, too, are most often homochiral. Cells use carbohydrates for energy, and carbohydrates, along with proteins, are identification-receptors. Carbohydrates are also homochiral, and their polymeric forms take on tertiary homochiral shapes. OOL researchers have spent a great deal of time trying to make these four classes of molecules, but with scant success.

Constructing the molecules necessary for life from their prebiotic precursors represents one goal of OOL research; putting them together, another. Some of synthetic chemistry is pedestrian, and some ingenious. Fundamental questions remain unaddressed. Claims that these structures could be prepared under prebiotic conditions in high enantiomeric purity using inorganic templates, or any presumed templates, have never been realized. The carbohydrates, amino acids, lipids, and other compounds within each of these classes require specific methods in order to control their regiochemistry and stereochemistry. The differences in reaction rates often require chiral systems acting upon chiral molecules. If this were possible under prebiotic conditions, it is odd that it cannot be replicated by synthetic chemists.

They have, after all, had 67 years to try.

Synthetic Hyperbole

Consider the class of experiments that deal with the assembly of chemicals into what are referred to as protocells—“a self-organized, endogenously ordered, spherical collection of lipids proposed as a stepping-stone to the origin of life.”2 In 2017, a team from the Origins of Life Initiative at Harvard University performed a type of polymerization reaction in water known as the reversible addition–fragmentation chain transfer.3 This reaction type is not seen in nature, and neither are the monomers that figure in the experiment. Still, this is standard chemistry. Polymers are made by a controlled radical polymerization reaction, where two different monomer types are added sequentially to a chain bearing both a hydrophobic and a hydrophilic block. Researchers observed polymeric vesicles forming during polymerization—interesting, but not extraordinary. The vesicles grew to bursting as researchers kept the radical chain growing through ultraviolet light activation. There is, in this, nothing surprising: the forces between the growing vesicle and the surrounding water dictate a critical growth volume before the vesicle ruptures.

The claims should have ended there.

Here is how the work was portrayed in the published article:
The observed net oscillatory vesicle population grows in a manner that reminds one of some elementary modes of sustainable (while there is available “food”!) population growth seen among living systems. The data supports an interpretation in terms of a micron scale self-assembled molecular system capable of embodying and mimicking some aspects of “simple” extant life, including self-assembly from a homogenous but active chemical medium, membrane formation, metabolism, a primitive form of self-replication, and hints of elementary system selection due to a spontaneous light triggered Marangoni instability [provoked by surface tension gradients].4
These claims were then rephrased and presented to the public by the Harvard Gazette:
A Harvard researcher seeking a model for the earliest cells has created a system that self-assembles from a chemical soup into cell-like structures that grow, move in response to light, replicate, and exhibit signs of rudimentary evolutionary selection [emphasis added].5
This degree of hyperbole is excessive.6 Nothing in this experiment had growing cell-like structures with replication, or that exhibited aspects of evolutionary selection.

Teams from the University of California and the University of New South Wales recently conducted lipid bilayer assembly experiments, publishing a summary of their work in 2017.7 They combined nucleotides and lipids in water to form lamellae, with the nucleotides sandwiched between the layers. Nucleotides are trimers of nucleobase-carbohydrate-phosphate, and, in this case, both nucleotides and lipids were purchased in pure homochiral form. Both teams then demonstrated that a condensation polymerization of the nucleotides can take place within the lamella upon dehydration. Polymerization takes place by means of a reaction between pre-loaded phosphate and the purchased stereo-defined alcohol moiety found on a neighboring nucleotide. Similar reactions, they conjectured, may have occurred at the edge of hydrothermal fields, volcanic landmasses providing the necessary heat for reactions.

The chemistry that figures in these experiments is unremarkable. Bear in mind that derivatives were all pre-loaded. To provide the essential concentrations for the reactions, researchers removed the water, thus driving the intermolecular reactions to form oligomers that resembled nucleic acids. The problem with condensation polymerization is obvious: any alcohol can compete for the reactive electrophilic site. In the case under consideration, researchers added no other alcohols. They were scrupulous, but the system was stacked. Condensation polymerization reactions need to be very pure, free of competing nucleophilic and electrophilic components. Witness the Carothers equation, which defines degrees of polymerization based upon monomer purity.8 If there happened to be amino acids or carbohydrates mixed with the nucleotides, they would terminate or interrupt the growth of the oligonucleotides. What is more, the researchers did not confirm the integrity of the structures they claimed to have derived. If carefully analyzed, these structures would likely have shown attacks from unintended hydroxyl sites. Since their sequences are essentially random, short oligonucleotides are not realistic precursors to RNA. An alphabet soup is not a precursor to a poem. The authors go on to suggest that the lamella sandwiching oligonucleotides eventually break off to form lipid bilayer vesicles. These contain the oligonucleotide-within-vesicle constructs, which they call protocells. The conversion of planar lamella into multilamellar vesicles as they hydrate is well established, but shearing forces are generally required to form the requisite lipid bilayer vesicle. For this reason, yields were likely to be low.9 It is hard to imagine finding highly purified homochiral nucleotides trapped in a pure lipid lamella on the prebiotic earth.

But set all that aside. These vesicles bear almost no resemblance to cellular lipid bilayers. Lipid bilayer balls are not cellular lipid bilayers. One would never know this from reading the authors’ account. “Then, in the gel phase,” they write, “protocells pack together in a system called a progenote and exchange sets of polymers, selecting those that enhance survival during many cycles.”10 Chemicals, of course, are indifferent to their survival. No mechanism is described to demonstrate how protocells would bear different sets of polymers or exchange polymers among them. Terms from biology have generally been misappropriated in a way that makes no chemical sense. This is not an isolated or incidental defect. It reappears when the authors write that “[t]he best-adapted protocells spread to other pools or streams, moving by wind and water…”11 Best-adapted? Microbial communities apparently “evolve into a primitive metabolism required by the earliest forms of life.” Molecules do not evolve, and nothing is being metabolized. Condensation polymerization is a simple chemical reaction based upon the addition of nucleophiles to electrophiles with loss of water. Such a reaction is never referred to as a form of metabolism within synthetic chemistry.

Terminology is one thing, non-sequiturs quite another. “After much trial and error,” the authors write, “one protocell assembles the complicated molecular machinery that enables it to divide into daughter cells. This paves the way for the first living microbial community.” How is the molecular machinery made? They do not say. The mechanisms needed for cellular division are complex, requiring cascades of precisely functioning enzymes. There is nothing between what the authors demonstrate and what they claim to have established, and nothing they propose “paves the way for the first living microbial community.”


Você não deve confiar em experimentos que afirmam a existência de universos paralelos

quarta-feira, julho 17, 2019

You Must Not Trust Experiments That Claim The Existence Of Parallel Universes

Ethan Siegel Contributor
Starts With A Bang Contributor Group Science 

The Universe is out there, waiting for you to discover it.

A representation of the different parallel "worlds" that might exist in other pockets of the multiverse, or anyplace else that theoretical physicists can concoct. Public domain

Is there another Universe out there? The Universe we know and inhabit, the one that began at the start of the hot Big Bang, might not be the only one out there. Perhaps one was created at the same time as ours was, but where time runs backwards instead of forwards. Perhaps there are an infinite number of parallel Universes out there, spawned by an eternally inflating Universe. Or, as has been in the media lately, perhaps there's literally a mirror Universe out there, where the particles we know of are replaced with an exotic version of themselves: mirror matter. 

Most scenarios involving parallel Universes like this are untestable, as we're restricted to living in our own Universe, disconnected from any others. Yet if one particular idea is right, there might be an experimental signature awaiting our investigations. But even if it yields positive results, you shouldn't trust it. Here's why. 

Whenever you have an experimental or observational result you cannot explain with your current theories, you have to take note of it. Robust measurements that defy the expectations of our predictions might turn out to be nothing — they might go away with more, improved data — or they might simply be errors. This has famously been the case many times, even recently, such as with
In all these cases, there was either an error with the way the team did the analysis or attributed the signal's components, an error in the experimental setup, or the observed effect was simply a random statistical fluctuation.
This happens. However, sometimes there are results that really do appear to be puzzles: the experiments shouldn't turn out the way they did if the Universe works the way we think it does. These results often turn out to be omens that we're about to discover new physics, but they also frequently turn out to be red herrings that lead nowhere. Even worse, they can turn out to be duds, where they only appear to be interesting because someone, somewhere, made an error.

Maquinaria de replicação de DNA capturada em detalhes a nível atômico: mero acaso, fortuita necessidade ou design inteligente?

segunda-feira, julho 15, 2019

DNA translocation mechanism of the MCM complex and implications for replication initiation

Martin Meagher, Leslie B. Epling & Eric J. Enemark 

Nature Communications volume 10, Article number: 3117 (2019) 

Fig. 8
Proposed MCM:DNA aspects of replication initiation. 


The DNA translocation activity of the minichromosome maintenance (MCM) complex powers DNA strand separation of the replication forks of eukaryotes and archaea. Here we illustrate an atomic level mechanism for this activity with a crystal structure of an archaeal MCM hexamer bound to single-stranded DNA and nucleotide cofactors. Sequence conservation indicates this rotary mechanism is fully possible for all eukaryotes and archaea. The structure definitively demonstrates the ring orients during translocation with the N-terminal domain leading, indicating that the translocation activity could also provide the physical basis of replication initiation where a double-hexamer idly encircling double-stranded DNA transforms to single-hexamers that encircle only one strand. In this mechanism, each strand binds to the N-terminal tier of one hexamer and the AAA+ tier of the other hexamer such that one ring pulls on the other, aligning equivalent interfaces to enable each hexamer to pull its translocation strand outside of the opposing hexamer.

Principais etapas iniciais para a origem da vida ocorrem sob variedade de condições

terça-feira, julho 09, 2019

Nitrogen heterocycles form peptide nucleic acid precursors in complex prebiotic mixtures

Laura E. Rodriguez, Christopher H. House, Karen E. Smith, Melissa R. Roberts & Michael P. Callahan 

Scientific Reports volume 9, Article number: 9281 (2019)

Fig. 5: Nitrogen heterocycles form peptide nucleic acid precursors in complex prebiotic mixtures


The ability to store information is believed to have been crucial for the origin and evolution of life; however, little is known about the genetic polymers relevant to abiogenesis. Nitrogen heterocycles (N-heterocycles) are plausible components of such polymers as they may have been readily available on early Earth and are the means by which the extant genetic macromolecules RNA and DNA store information. Here, we report the reactivity of numerous N-heterocycles in highly complex mixtures, which were generated using a Miller-Urey spark discharge apparatus with either a reducing or neutral atmosphere, to investigate how N-heterocycles are modified under plausible prebiotic conditions. High throughput mass spectrometry was used to identify N-heterocycle adducts. Additionally, tandem mass spectrometry and nuclear magnetic resonance spectroscopy were used to elucidate reaction pathways for select reactions. Remarkably, we found that the majority of N-heterocycles, including the canonical nucleobases, gain short carbonyl side chains in our complex mixtures via a Strecker-like synthesis or Michael addition. These types of N-heterocycle adducts are subunits of the proposed RNA precursor, peptide nucleic acids (PNAs). The ease with which these carbonylated heterocycles form under both reducing and neutral atmospheres is suggestive that PNAs could be prebiotically feasible on early Earth.

FREE PDF GRATIS: Scientific Reports Sup. Info.

Mutações: O engano da evolução X-Men

segunda-feira, julho 08, 2019

#ScienceUprising #RevoltaDaCiencia

Darwin, mais complexidade: microscopia de super resolução ilumina as associações entre os cromossomos

quinta-feira, julho 04, 2019

Superresolution microscopy reveals linkages between ribosomal DNA on heterologous chromosomes 

Tamara A. Potapova, Jay R. Unruh, Zulin Yu, Giulia Rancati, Hua Li, Martha R. Stampfer, Jennifer L. Gerton 

DOI: 10.1083/jcb.201810166 | Published July 3, 2019

The spatial organization of the genome is enigmatic. Direct evidence of physical contacts between chromosomes and their visualization at nanoscale resolution has been limited. We used superresolution microscopy to demonstrate that ribosomal DNA (rDNA) can form linkages between chromosomes. We observed rDNA linkages in many different human cell types and demonstrated their resolution in anaphase. rDNA linkages are coated by the transcription factor UBF and their formation depends on UBF, indicating that they regularly occur between transcriptionally active loci. Overexpression of c-Myc increases rDNA transcription and the frequency of rDNA linkages, further suggesting that their formation depends on active transcription. Linkages persist in the absence of cohesion, but inhibition of topoisomerase II prevents their resolution in anaphase. We propose that linkages are topological intertwines occurring between transcriptionally active rDNA loci spatially colocated in the same nucleolar compartment. Our findings suggest that active DNA loci engage in physical interchromosomal connections that are an integral and pervasive feature of genome organization.
FREE PDF GRATIS: Journal of Cell Biology

Origem da vida: requer inteligência

segunda-feira, julho 01, 2019

#ScienceUprising #RevoltaDaCiencia

Darwin, Hitler, e a avaliação moderna da vida humana - Dr. Richard Weikart

sábado, junho 29, 2019

Richard Weikart, Professor of Modern European History, California State University Stanislaus,

Por que a liberdade acadêmica é tão importante?

É por isso que a liberdade intelectual é tão importante. Permite que os acadêmicos expressem suas opiniões sem medo de represálias. Permite que um Charles Darwin se liberte das restrições do criacionismo. Ele permite que um Albert Einstein se liberte das restrições da física newtoniana. Ele permite que a raça humana questione a sabedoria convencional na busca incessante de conhecimento e verdade. E isso, em sua essência, é o que é o ensino superior. Sugerir outra coisa é ignorar por que as universidades foram criadas e por que os acadêmicos com foco crítico permanecem no centro de tudo que o ensino universitário pretende oferecer. Juiz Salvatore Vasta

That is why intellectual freedom is so important. It allows academics to express their opinions without fear of reprisals. It allows a Charles Darwin to break free of the constraints of creationism. It allows an Albert Einstein to break free of the constraints of Newtonian physics. It allows the human race to question conventional wisdom in the never-ending search for knowledge and truth. And that, at its core, is what higher learning is about. To suggest otherwise is to ignore why universities were created and why critically focussed academics remain central to all that university teaching claims to offer. Judge Salvatore Vasta

Darwin, as evidências estão desfocando os limites da vida

sexta-feira, junho 28, 2019

Blurring Life’s Boundaries

Darwinian theory is based on the idea that heredity flows vertically, parent to offspring, and that life’s history has branched like a tree. Now we know otherwise: that the ‘tree’ of life isn’t that simple.

Carl Tsevis

By David Quammen

Since the late 1970s, there have come three big surprises about what we humans are and about how life on our planet has evolved.

The first of those three surprises involves a whole category of life, previously unsuspected and now known as the archaea. (They look like bacteria through a microscope, but their DNA reveals they are shockingly different.) Another is a mode of hereditary change that was also unsuspected, now called horizontal gene transfer. (Heredity was supposed to move only vertically, from parents to offspring.) The third is a revelation, or anyway a strong likelihood, about our own deepest ancestry. (It seems now that our lineage traces to the archaea.) So we ourselves probably come from creatures that, as recently as forty years ago, were unknown to exist.

One of the most disorienting results of these developments is a new challenge to the concept of “species.” Biologists have long recognized that the boundaries of one species may blur into another—by the process of hybridism, for instance. And the notion of species is especially insecure in the realm of bacteria and archaea. But the discovery that horizontal gene transfer (HGT) has occurred naturally, many times, even in the lineages of animals and plants, has brought the categorical reality of a species into greater question than ever. That’s even true for us humans—we are composite individuals, mosaics.

It’s not just that—as you may have read in magazine articles—your human body contains at least as many bacterial cells as it does human cells. (This doesn’t even count all the nonbacterial microbes—the virus particles, fungal cells, archaea, and other teeny passengers inhabiting our guts, mouths, nostrils, and other bodily surfaces.) That’s the microbiome. Each of us is an ecosystem.

I’m talking about something else, a bigger and more shocking discovery that has come from the revolution in a field called molecular phylogenetics. (That phrase sounds fancy and technical, but it means merely the use of molecular information, such as DNA or RNA sequences, in discerning how one creature is related to another.) The discovery was that sizeable chunks of the genomes of all kinds of animals, including us, have been acquired by horizontal transfer from bacteria or other alien species.

How could that be possible? How could genes move sideways, between species, not just vertically along ancestral lineages? The mechanisms are complex, but one label that fits most of them is “infective heredity.”  DNA can be carried across boundaries, from one genome to another, by infective agents such as bacteria and viruses. Such horizontal gene transfer, like sex, has been a source of freshening innovation in otherwise discrete lineages, including ours—and it is still occurring.

This is an aspect of evolution that was unimagined by Charles Darwin. Evolution is trickier, far more intricate, than we had realized. The tree of life is more tangled.

READ MORE HERE: Anthropocene Magazine

SETI Institute: Where is the Origin of Life on Earth?/Onde está origem da vida na Terra?

terça-feira, junho 25, 2019


To answer the iconic question “Are We Alone?”, scientists around the world are also attempting to understand the origin of life. There are many pieces to the puzzle of how life began and many ways to put them together into a big picture. Some of the pieces are firmly established by the laws of chemistry and physics. Others are conjectures about what Earth was like four billion years ago, based on extrapolations of what we know from observing Earth today. However, there are still major gaps in our knowledge and these are necessarily filled in by best guesses.

We invited talented scientists to discuss their different opinions about the origin of life and the site of life’s origin. Most of them will agree that liquid water was necessary, but if we had a time machine and went back in time, would we find life first in a hydrothermal submarine setting in sea water or a fresh water site associated with emerging land masses?

Biologist David Deamer, a Research Professor of Biomolecular Engineering at the University of California, Santa Cruz, and multi-disciplinary scientist Bruce Damer, Associate Researcher in the Department of Biomolecular Engineering at UC Santa Cruz, will describe their most recent work, which infers that hydrothermal pools are the most plausible site for the origin of life. Both biologists have been collaborating since 2016 on a full conception of the Terrestrial Origin of Life Hypothesis.

Lynn Rothschild, Senior Scientist at NASA’s Ames Research Center and Adjunct Professor of Molecular Biology, Cell Biology, and Biochemistry at Brown University, who is an astrobiologist/ synthetic biologist specializing in molecular approaches to evolution, particularly in microbes and the application of synthetic biology to NASA's missions, will provide an evolutionary biologist’s perspective on the subject.

Ajuste fino: Você não é insignificante!

#ScienceUprising #RevoltaDaCiencia

Cientistas olham para dentro de células de 1 bilhão de anos

segunda-feira, junho 24, 2019

1 billion-year-old cell contents preserved in monazite and xenotime 

David Wacey, Eva Sirantoine, Martin Saunders & Paul Strother

Scientific Reports volume 9, Article number: 9068 (2019)


Exceptional microfossil preservation, whereby sub-cellular details of an organism are conserved, remains extremely rare in the Precambrian rock record. We here report the first occurrence of exceptional cellular preservation by the rare earth element (REE) phosphates monazite and xenotime. This occurs in ~1 billion-year-old lake sediments where REEs were likely concentrated by local erosion and drainage into a closed lacustrine basin. Monazite and xenotime preferentially occur inside planktonic cells where they preserve spheroidal masses of plasmolyzed cell contents, and occasionally also membranous fragments. They have not been observed associated with cell walls or sheaths, which are instead preserved by clay minerals or francolite. REE phosphates are interpreted to be the earliest minerals precipitated in these cells after death, with their loci controlled by the micro-scale availability of inorganic phosphate (Pi) and REEs, probably sourced from polyphosphate granules within the cells. The strong affinity of REEs for phosphate and the insolubility of these minerals once formed means that REE phosphates have the potential for rapid preservation of cellular morphology after death and durability in the rock record. Hence, authigenic REE phosphates provide a promising new target in the search for the preservation of intra-cellular components of fossilised microorganisms.
FREE PDF GRATIS: Scientific Reports Sup. Info.

A Revolta da Ciência - Episódio 3 - O DNA é um código: quem o codificou???

segunda-feira, junho 17, 2019

#ScienceUprising #RevoltaDaCiencia

Gases tóxicos em zona habitável podem dificultar o surgimento de vida extraterrestre

A Limited Habitable Zone for Complex Life

Edward W. Schwieterman1,2,3,4,5, Christopher T. Reinhard3,4,6, Stephanie L. Olson3,7, Chester E. Harman4,8,9, and Timothy W. Lyons1,3,4

Published 2019 June 10 • © 2019. The American Astronomical Society.

The Astrophysical Journal, Volume 878, Number 1

Trappist 1
No safe zone: do high carbon monoxide levels preclude the existence of life in the Trappist-1 system? (Courtesy: NASA/JPL-Caltech) Source/Fonte


The habitable zone (HZ) is commonly defined as the range of distances from a host star within which liquid water, a key requirement for life, may exist on a planet's surface. Substantially more CO2 than present in Earth's modern atmosphere is required to maintain clement temperatures for most of the HZ, with several bars required at the outer edge. However, most complex aerobic life on Earth is limited by CO2 concentrations of just fractions of a bar. At the same time, most exoplanets in the traditional HZ reside in proximity to M dwarfs, which are more numerous than Sun-like G dwarfs but are predicted to promote greater abundances of gases that can be toxic in the atmospheres of orbiting planets, such as carbon monoxide (CO). Here we show that the HZ for complex aerobic life is likely limited relative to that for microbial life. We use a 1D radiative-convective climate and photochemical models to circumscribe a Habitable Zone for Complex Life (HZCL) based on known toxicity limits for a range of organisms as a proof of concept. We find that for CO2 tolerances of 0.01, 0.1, and 1 bar, the HZCL is only 21%, 32%, and 50% as wide as the conventional HZ for a Sun-like star, and that CO concentrations may limit some complex life throughout the entire HZ of the coolest M dwarfs. These results cast new light on the likely distribution of complex life in the universe and have important ramifications for the search for exoplanet biosignatures and technosignatures.

FREE PDF GRATIS: The Astrophysical Journal

The Fourth Paradigm: Data-Intensive Scientific Discovery

quinta-feira, junho 13, 2019

The Fourth Paradigm: Data-Intensive Scientific Discovery

Increasingly, scientific breakthroughs will be powered by advanced computing capabilities that help researchers manipulate and explore massive datasets.

The speed at which any given scientific discipline advances will depend on how well its researchers collaborate with one another, and with technologists, in areas of eScience such as databases, workflow management, visualization, and cloud computing technologies.

In The Fourth Paradigm: Data-Intensive Scientific Discovery, the collection of essays expands on the vision of pioneering computer scientist Jim Gray for a new, fourth paradigm of discovery based on data-intensive science and offers insights into how it can be fully realized.

Critical praise for The Fourth Paradigm

“The individual essays—and The Fourth Paradigm as a whole—give readers a glimpse of the horizon for 21st-century research and, at their best, a peek at what lies beyond. It’s a journey well worth taking.”

— James P. Collins
School of Life Sciences, Arizona State University

Um mapa topográfico microscópico de complexidade da função celular: mero acaso, fortuita necessidade ou design inteligente?

Direct visualization of the E. coli Sec translocase engaging precursor proteins in lipid bilayers

Raghavendar Reddy Sanganna Gari1,*, Kanokporn Chattrakun1, Brendan P. Marsh1,†, Chunfeng Mao2, Nagaraju Chada1,‡, Linda L. Randall2 and Gavin M. King1,2,§

1Department of Physics and Astronomy, University of Missouri, Columbia, MO 65211, USA.

2Department of Biochemistry, University of Missouri, Columbia, MO 65211, USA.

↵§Corresponding author. Email: kinggm@missouri.edu

↵* Present address: Department of Anesthesiology, Weill Cornell Medicine, New York, NY 10065, USA.

↵† Present address: Department of Applied Physics, Stanford University, Stanford, CA 94305, USA.

↵‡ Present address: Department of Biology, Johns Hopkins University, 3400 N. Charles Street, Baltimore, MD 21218, USA.

Science Advances 12 Jun 2019: Vol. 5, no. 6, eaav9404

Fig. 6 Precursor-dependent model of translocase activity.


Escherichia coli exports proteins via a translocase comprising SecA and the translocon, SecYEG. Structural changes of active translocases underlie general secretory system function, yet directly visualizing dynamics has been challenging. We imaged active translocases in lipid bilayers as a function of precursor protein species, nucleotide species, and stage of translocation using atomic force microscopy (AFM). Starting from nearly identical initial states, SecA more readily dissociated from SecYEG when engaged with the precursor of outer membrane protein A as compared to the precursor of galactose-binding protein. For the SecA that remained bound to the translocon, the quaternary structure varied with nucleotide, populating SecA2 primarily with adenosine diphosphate (ADP) and adenosine triphosphate, and the SecA monomer with the transition state analog ADP-AlF3. Conformations of translocases exhibited precursor-dependent differences on the AFM imaging time scale. The data, acquired under near-native conditions, suggest that the translocation process varies with precursor species.

FREE PDF GRATIS: Science Advances

Como a célula se protege: mero acaso, fortuita necessidade ou design inteligente?

quarta-feira, junho 12, 2019

Nuclear Pre-snRNA Export Is an Essential Quality Assurance Mechanism for Functional Spliceosomes

Daniel Becker, Anna Greta Hirsch, Lysann Bender, Thomas Lingner, Gabriela Salinas, Heike Krebber

Open Access DOI: https://doi.org/10.1016/j.celrep.2019.05.031
Figure thumbnail fx1


• All yeast snRNAs, including U6, shuttle into the cytoplasm

• Export is mediated by Mex67 and Xpo1, and re-import requires Mtr10 and Cse1

• snRNA export prevents an incorporation of immature snRNAs into spliceosomes

• Spliceosomal assembly with immature snRNAs results in genome-wide splicing defects

Removal of introns from pre-mRNAs is an essential step in eukaryotic gene expression, mediated by spliceosomes that contain snRNAs as key components. Although snRNAs are transcribed in the nucleus and function in the same compartment, all except U6 shuttle to the cytoplasm. Surprisingly, the physiological relevance for shuttling is unclear, in particular because the snRNAs in Saccharomyces cerevisiae were reported to remain nuclear. Here, we show that all yeast pre-snRNAs including U6 undergo a stepwise maturation process after nuclear export by Mex67 and Xpo1. Sm- and Lsm-ring attachment occurs in the cytoplasm and is important for the snRNA re-import, mediated by Cse1 and Mtr10. Finally, nuclear pre-snRNA cleavage and trimethylation of the 5′-cap finalizes shuttling. Importantly, preventing pre-snRNAs from being exported or processed results in faulty spliceosome assembly and subsequent genome-wide splicing defects. Thus, pre-snRNA export is obligatory for functional splicing and resembles an essential evolutionarily conserved quality assurance step.

A Revolta da Ciência - Episódio 2 - A Mente: O Inescapável

segunda-feira, junho 10, 2019

#ScienceUprising #RevoltaDaCiencia

Como são regulados os ciclos de divisão celular: mero acaso, fortuita necessidade ou design inteligente?

sexta-feira, junho 07, 2019

Two Distinct E2F Transcriptional Modules Drive Cell Cycles and Differentiation

Maria C. Cuitiño, Thierry Pécot, Daokun Sun, Michael C. Ostrowski, Michele Pagano, Gustavo Leone

Open Access Published:May 23, 2019


• E2F expression during cell division, differentiation, and quiescence is measured in vivo

• E2F3A, E2F8, and E2F4 accumulate sequentially in the nucleus of cycling cells

• E2F3A-4 nuclear accumulation controls gene expression during cell-cycle exit

• Deep learning tools are applied to nuclear segmentation of complex mammalian tissues


Orchestrating cell-cycle-dependent mRNA oscillations is critical to cell proliferation in multicellular organisms. Even though our understanding of cell-cycle-regulated transcription has improved significantly over the last three decades, the mechanisms remain untested in vivo. Unbiased transcriptomic profiling of G0, G1-S, and S-G2-M sorted cells from FUCCI mouse embryos suggested a central role for E2Fs in the control of cell-cycle-dependent gene expression. The analysis of gene expression and E2F-tagged knockin mice with tissue imaging and deep-learning tools suggested that post-transcriptional mechanisms universally coordinate the nuclear accumulation of E2F activators (E2F3A) and canonical (E2F4) and atypical (E2F8) repressors during the cell cycle in vivo. In summary, we mapped the spatiotemporal expression of sentinel E2F activators and canonical and atypical repressors at the single-cell level in vivo and propose that two distinct E2F modules relay the control of gene expression in cells actively cycling (E2F3A-8-4) and exiting the cycle (E2F3A-4) during mammalian development.


Darwin, a tradução de genes é mais complexa do que esperada

Multi-Color Single-Molecule Imaging Uncovers Extensive Heterogeneity in mRNA Decoding

Sanne Boersma3 Deepak Khuperkar3 Bram M.P. Verhagen Jonathan B. Grimm Luke D. Lavis Marvin E. Tanenbaum4
Published:June 06, 2019 DOI: https://doi.org/10.1016/j.cell.2019.05.001


• Development of MoonTag, a fluorescence labeling system to visualize translation

• Combining MoonTag and SunTag enables visualization of translational heterogeneity

• mRNAs from a single gene vary in initiation frequency at different start sites

• Ribosomes take many different “paths” along the 5′ UTR of a single mRNA molecule


mRNA translation is a key step in decoding genetic information. Genetic decoding is surprisingly heterogeneous because multiple distinct polypeptides can be synthesized from a single mRNA sequence. To study translational heterogeneity, we developed the MoonTag, a fluorescence labeling system to visualize translation of single mRNAs. When combined with the orthogonal SunTag system, the MoonTag enables dual readouts of translation, greatly expanding the possibilities to interrogate complex translational heterogeneity. By placing MoonTag and SunTag sequences in different translation reading frames, each driven by distinct translation start sites, start site selection of individual ribosomes can be visualized in real time. We find that start site selection is largely stochastic but that the probability of using a particular start site differs among mRNA molecules and can be dynamically regulated over time. This study provides key insights into translation start site selection heterogeneity and provides a powerful toolbox to visualize complex translation dynamics.

A Revolta da Ciência contra a Ciência Fake e o Materialismo Entorpecente

terça-feira, junho 04, 2019

#ScienceUprising #RevoltaDaCiencia

Nullius in verba: a maioria dos artigos em química retraídos das publicações científicas por problemas sérios!

segunda-feira, junho 03, 2019

Correcting the Scientific Record: Retraction Practices in Chemistry and Materials Science

François-Xavier Coudert

Cite This: Chem. Mater.201931103593-3598

Publication Date:May 28, 2019


Copyright © 2019 American Chemical Society

Peer-reviewed articles, published by scholarly journals, currently form the cornerstone of the modern scholarly publication system and guarantee the dissemination of research findings through the worldwide, ever-increasing community of researchers. Collectively these published works, stamped with the seal of approval of a review by the authors’ peers, form the scientific record—the record of knowledge accumulated by mankind. It is the duty of every scholar to add knowledge to this record by publishing but also to ensure the integrity of the existing works by critically assessing them: before publication, acting as a reviewer or editor, and post-publication, by building upon existing works, improving them, and checking their reproducibility.

The means of post-publication peer review of articles, which was once limited to formally published comments (“Comment on...”), journal clubs and conference coffee breaks, are rapidly expanding through the use of Internet and social media. Discussion of published papers regularly takes place on Twitter and through blog posts and preprints, as well as in structured discussions: comments on the webpage on published papers (e.g., PLOS Oneand Frontiers journals), indexing servers (PubMed Commons, now closed(1)), or dedicated websites (such as PubPeer(2)). Critique of published articles is a necessary and healthy part of the advancement of science. Sometimes, it can lead to the identification of serious flaws in the data or authors’ analysis, so that the findings or the conclusions published cannot be trusted anymore. In such cases, the paper may be corrected or retracted, i.e., expunged from the scientific record.

COPE, the Committee on Publication Ethics, publishes a series of guidelines (policies and practices) that are considered the industry standard in publishing ethics. The areas covered include the handling of allegations of misconduct, complaints and appeals, data issues and reproducibility, and standards of authorship, as well as post-publication corrections and the retraction of papers. COPE guidelines give clear insights into the difference in nature between corrections and retractions.(3) Articles should be corrected if “a small portion of an otherwise reliable publication proves to be misleading (especially because of honest error)”. On the other hand, “journal editors should consider retracting a publication if:

they have clear evidence that the findings are unreliable, either as a result of misconduct (e.g., data fabrication) or honest error (e.g. miscalculation or experimental error),

the findings have previously been published elsewhere without proper crossreferencing, permission or justification (i.e. cases of redundant publication),

it constitutes plagiarism,

it reports unethical research.”Retractions thus ensure that the literature is corrected, alerting readers to the fact that a publication contains erroneous or unreliable data, and give clear insight into the nature of the issues.

Despite the healthy role of retractions in preserving the scientific record, and while erroneous data can be the result of a good faith mistake, there is definitely a stigma associated with the retraction of a paper. COPE guidelines state that “The main purpose of retractions is to correct the literature and ensure its integrity rather than to punish authors who misbehave”,(3) but previous work has shown a notable resistance to admitting error in scientific papers.(4) The term retraction is too often associated with research misconduct, giving it a negative connotation for authors.(5) This is particularly true in a highly competitive environment, where academics are driven to publish often and produce high-impact papers: Jin et al. showed that retractions have a negative effect on citations for early career researchers.(6,7) The same argument can also be made for the publishers, who may fear a dent in the reputation of the journal. Thus, none of the actors involved have any direct incentive to retract a paper.

In this context, and while the number of retractions is rising,(8,9) there is relatively little information available about retractions and retracted papers, beyond the retraction notices infrequently published by journals. There is no central repository or authoritative database that can be easily queried—although the Retraction Watch website, which covers the topic of retractions and publication ethics in general, has been collating such a database.(10)Previous systematic studies have focused on retractions in specific fields, and in particular in medicine(11−13)—with the notable exception of a study by Grieneisen et al. that spanned several fields of research.(14) In order to better understand the existing practices for article retraction in the chemical sciences, I have performed a systematic survey of 331 papers retracted in 2017 and 2018 and their retraction notices, publicly available on the journals’ websites. This article looks at the statistics of retractions, their distribution per country, and the occurrence of multiple retractions. I also provide a classification of the reasons behind the retractions and the distribution of their occurrence.

FREE PDF GRATIS: ACS Chemistry Materials Sup. Info. 1, Sup. Info. 2.

A insurreição da ciência - 3 de junho-8 de julho de 2019

sábado, junho 01, 2019

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.


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.


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


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


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.


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.


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.