Convite para o abandono da significância estatística em pesquisas científicas

sábado, março 31, 2018

Abandon Statistical Significance

Blakeley B. McShane, David Gal, Andrew Gelman, Christian Robert, Jennifer L. Tackett

(Submitted on 22 Sep 2017)

In science publishing and many areas of research, the status quo is a lexicographic decision rule in which any result is first required to have a p-value that surpasses the 0.05 threshold and only then is consideration--often scant--given to such factors as prior and related evidence, plausibility of mechanism, study design and data quality, real world costs and benefits, novelty of finding, and other factors that vary by research domain. There have been recent proposals to change the p-value threshold, but instead we recommend abandoning the null hypothesis significance testing paradigm entirely, leaving p-values as just one of many pieces of information with no privileged role in scientific publication and decision making. We argue that this radical approach is both practical and sensible.

Subjects: Methodology (stat.ME)

MSC classes: 97K70

Cite as: arXiv:1709.07588 [stat.ME]

(or arXiv:1709.07588v1 [stat.ME] for this version)

Submission history

From: Andrew Gelman [view email] 

[v1] Fri, 22 Sep 2017 03:59:24 GMT (15kb)


Falem mal, mas continuem falando da teoria do Design Inteligente

Revista Científica General José María Córdova

ISSN: 1900-6586
ISSN electrónico: 2500-7645 (En línea)

Escuela Militar de Cadetes General José María Córdova
Calle 80 N° 38-00

Teléfono: 3770850 Ext. 1104

Correo electrónico:

La evolución del diseño inteligente: entre religión y ciencia

Enrique Sandino Vargas, Marta Caccamo, Sumaya Hashim, Oskar Eng


Este trabajo evalúa el diseño inteligente (DI) como una pseudociencia. La ciencia ha incorporado muchas definiciones; asimismo la pseudociencia. Ambas han sido discutidas en diversos ámbitos. En lo que atañe a la esfera política, están caracterizados por una pluralidad de conflictos de visiones en discusión. No existe una sola filosofía de la ciencia, y en consecuencia tampoco una sola metodología de la ciencia. Los criterios de demarcación no son una cuestión clara. Esto se torna problemático al evaluar el diseño inteligente. El diseño, en particular, tal como lo conciben los científicos que consideran que no hay razones para incluirlo en el campo científico en su pretensión de que carece de cientificidad. Lo que hacemos aquí es seleccionar un conjunto de definiciones de pseudociencia y ver si el DI satisface los criterios de demarcación. Dado que nuestra unidad de análisis es el DI, se plantea la pregunta si el diseño inteligente es una pseudociencia, o si se puede caracterizar el diseño inteligente como una o varias formas de pseudociencia.

Palabras clave

criterios de demarcación; diseño inteligente; naturalismo; pseudociencia; método científico

Texto completo: PDF


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Um amigo destacou dois parágrafos deste artigo:

"The ID assumption is normative in that from its utterance; it requires the inference that anything, which is unexplainable by the naturalistic argument,
is designed. The scientific assumption is agnostic; it does not attribute all to evolution, it remains open-minded. In this sense, ID is pseudoscientific in that it fails to remain open-minded despite its lack of evidence and logical coherence."

Isso parece dizer que o DI é um argumento Designer das Lacunas, em vez de uma inferência a partir da complexidade especificada... e minimiza o modo que o Darwinismo atribui tudo à evolução.

Todavia, eles admitem:

"To the extent that both evolutionism and ID are based on unverifiable a priori metaphysical assumptions, on this level, ID remains comparably legitimate as the Darwinist argument. We cannot stake the assumptions of either paradigm against the other’s and claim that one is superior, as they are not comparable. In this sense, both ID and Darwinism remain sciences, legitimate under the axiom of their own a priori assumptions of the world and its creation."

Há anos salientamos que quaisquer críticas à TDI são, por tabela, críticas feitas à teoria da evolução de Darwin através da seleção natural e n mecanismos evolucionários (de A a Z, vai que um falhe...), pois sendo teorias de longo alcance histórico, a TDI e a Teoria da Evolução são metodologicamente idênticas!

Fui, nem sei por que pensando: Falem mal, mas falem da TDI...

Apresentação científica: usando práticas de sala de aula baseadas em evidência para apresentações científicas de conferência eficientes

quarta-feira, março 28, 2018

Scientific Presenting: Using Evidence-Based Classroom Practices to Deliver Effective Conference Presentations.


Amy Prunuske
University of Minnesota Medical School

Shannon B Seidel
San Francisco State University

Lisa A Corwin
Biology Department, Pacific Lutheran University, Tacoma, WA 98447

CBE Life Sci Educ 2018 ;17(1)


Scientists and educators travel great distances, spend significant time, and dedicate substantial financial resources to present at conferences. This highlights the value placed on conference interactions. Despite the importance of conferences, very little has been studied about what is learned from the presentations and how presenters can effectively achieve their goals. This essay identifies several challenges presenters face when giving conference presentations and discusses how presenters can use the tenets of scientific teaching to meet these challenges. We ask presenters the following questions:These questions target three broad goals that stem from the scientific teaching framework and that we propose are of great importance at conferences: learning, equity, and improvement. Using a backward design approach, we discuss how the lens of scientific teaching and the use of specific active-learning strategies can enhance presentations, improve their utility, and ensure that a presentation is broadly accessible to all audience members.


EXTRA! EXTRA! EXTRA! Mudança paradigmática radical na teoria da evolução

Processes and patterns of interaction as units of selection: An introduction to ITSNTS thinking

W. Ford Doolittle and S. Andrew Inkpen

PNAS March 26, 2018. 201722232; published ahead of print March 26, 2018.

Edited by Douglas Futuyma, Stony Brook University, Stony Brook, NY, and approved March 7, 2018 (received for review December 22, 2017)


Many practicing biologists accept that nothing in their discipline makes sense except in the light of evolution, and that natural selection is evolution’s principal sense-maker. But what natural selection actually is (a force or a statistical outcome, for example) and the levels of the biological hierarchy (genes, organisms, species, or even ecosystems) at which it operates directly are still actively disputed among philosophers and theoretical biologists. Most formulations of evolution by natural selection emphasize the differential reproduction of entities at one or the other of these levels. Some also recognize differential persistence, but in either case the focus is on lineages of material things: even species can be thought of as spatiotemporally restricted, if dispersed, physical beings. Few consider—as “units of selection” in their own right—the processes implemented by genes, cells, species, or communities. “It’s the song not the singer” (ITSNTS) theory does that, also claiming that evolution by natural selection of processes is more easily understood and explained as differential persistence than as differential reproduction. ITSNTS was formulated as a response to the observation that the collective functions of microbial communities (the songs) are more stably conserved and ecologically relevant than are the taxa that implement them (the singers). It aims to serve as a useful corrective to claims that “holobionts” (microbes and their animal or plant hosts) are aggregate “units of selection,” claims that often conflate meanings of that latter term. But ITSNS also seems broadly applicable, for example, to the evolution of global biogeochemical cycles and the definition of ecosystem function.

evolution natural selection process persistence microbiome


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



Sem dúvida uma grande e embaraçosa mudança na Síntese Evolutiva Moderna, atual moribunda teoria da evolução que não quer ser substituída pela Síntese Evolutiva Ampliada/Estendida lançada em agosto de 2015.

Pelo abstract eles  parecem dizer que todas as unidades de seleção devem ser consideradas - genes, células, organismos, espécies, e  comunidades. E aqui este blogger vai ser bem irônico - por que não adicionar os planetas, sistemas solares, galáxias, universos, e até os imaginários multiversos! Vai que um desses inúmeros processos evolutivos falhe...

Fui, nem sei por que, mas pensando nos epiciclos ptolomaicos!

Pano rápido! Darwin kaput desde 1859, mas a Nomenklatura científica teima em não enterrar esse defunto epistemológico por razões puramente ideológicas!

Tendões são irredutivelmente complexos???

segunda-feira, março 26, 2018

In tendons, differing physiological requirements lead to functionally distinct nanostructures

Andrew S. Quigley, Stéphane Bancelin, Dylan Deska-Gauthier, François Légaré, Laurent Kreplak & Samuel P. Veres

Scientific Reports Volume 8, Article number: 4409 (2018)

Download Citation

Biomedical engineering Tendons Tissues

Received: 02 October 2017 Accepted: 28 February 2018

Published online: 13 March 2018


The collagen-based tissues of animals are hierarchical structures: even tendon, the simplest collagenous tissue, has seven to eight levels of hierarchy. Tailoring tissue structure to match physiological function can occur at many different levels. We wanted to know if the control of tissue architecture to achieve function extends down to the nanoscale level of the individual, cable-like collagen fibrils. Using tendons from young adult bovine forelimbs, we performed stress-strain experiments on single collagen fibrils extracted from tendons with positional function, and tendons with energy storing function. Collagen fibrils from the two tendon types, which have known differences in intermolecular crosslinking, showed numerous differences in their responses to elongation. Unlike those from positional tendons, fibrils from energy storing tendons showed high strain stiffening and resistance to disruption in both molecular packing and conformation, helping to explain how these high stress tissues withstand millions of loading cycles with little reparative remodeling. Functional differences in load-bearing tissues are accompanied by important differences in nanoscale collagen fibril structure.


This work was supported by grants to SPV and LK from the Natural Sciences and Engineering Research Council of Canada (NSERC).

Author information


Department of Physics and Atmospheric Science, Dalhousie University, Halifax, Canada

Andrew S. Quigley & Laurent Kreplak

Institut National de la Recherche Scientifique, Centre Énergie, Matériaux, Télécommunication, Varennes, Canada

Stéphane Bancelin & François Légaré

Department of Medical Neuroscience, Dalhousie University, Halifax, Canada

Dylan Deska-Gauthier

School of Biomedical Engineering, Dalhousie University, Halifax, Canada

Laurent Kreplak & Samuel P. Veres

Division of Engineering, Saint Mary’s University, Halifax, Canada

Samuel P. Veres


S.P.V. and L.K. conceived the study; A.S.Q. performed the A.F.M. work and data analysis; S.B. performed the S.H.G. work and analysis under the supervision of F.L.; D.D.G. performed the confocal microscopy; all authors contributed to the writing of the manuscript.

Competing Interests

The authors declare no competing interests.

Corresponding authors

Correspondence to Laurent Kreplak or Samuel P. Veres.

FREE PDF GRATIS: Scientific Reports Sup. Info.

Como a genética está mudando nossa compreensão de 'raça'.

Sunday Review

How Genetics Is Changing Our Understanding of ‘Race’

Gray Matter


Credit Angie Wang

In 1942, the anthropologist Ashley Montagu published “Man’s Most Dangerous Myth: The Fallacy of Race,” an influential book that argued that race is a social concept with no genetic basis. A classic example often cited is the inconsistent definition of “black.” In the United States, historically, a person is “black” if he has any sub-Saharan African ancestry; in Brazil, a person is not “black” if he is known to have any European ancestry. If “black” refers to different people in different contexts, how can there be any genetic basis to it?

Beginning in 1972, genetic findings began to be incorporated into this argument. That year, the geneticist Richard Lewontin published an important study of variation in protein types in blood. He grouped the human populations he analyzed into seven “races” — West Eurasians, Africans, East Asians, South Asians, Native Americans, Oceanians and Australians — and found that around 85 percent of variation in the protein types could be accounted for by variation within populations and “races,” and only 15 percent by variation across them. To the extent that there was variation among humans, he concluded, most of it was because of “differences between individuals.”

In this way, a consensus was established that among human populations there are no differences large enough to support the concept of “biological race.” Instead, it was argued, race is a “social construct,” a way of categorizing people that changes over time and across countries.

It is true that race is a social construct. It is also true, as Dr. Lewontin wrote, that human populations “are remarkably similar to each other” from a genetic point of view.

But over the years this consensus has morphed, seemingly without questioning, into an orthodoxy. The orthodoxy maintains that the average genetic differences among people grouped according to today’s racial terms are so trivial when it comes to any meaningful biological traits that those differences can be ignored.

READ MORE HERE: The New York Times

Esqueçam o "gene egoísta", agora é o ribossomo egoísta como elo perdido na evolução da vida!

Journal of Theoretical Biology

Volume 367, 21 February 2015, Pages 130-158

The ribosome as a missing link in the evolution of life

Author MeredithRoot-Bernstein a1 RobertRoot-Bernstein b

School of Geography and the Environment, Oxford University, South Parks Road, Oxford, Oxfordshire OX1 3QY, United Kingdom

Department of Physiology, Michigan State University, East Lansing, MI 48824, USA

Received 15 July 2014, Revised 15 November 2014, Accepted 20 November 2014, Available online 10 December 2014. Get rights and content

Under a Creative Commons license open access


• Hypothesize that ribosome was self-replicating intermediate between compositional or RNA-world and cellular life.

• rRNA contains genetic information encoding self-replication machinery: all 20 tRNAs and active sites of key ribosomal proteins.

• Statistical analyses demonstrate rRNA-encodings are very unlikely to have occurred by chance.

• Contradicts view of rRNA as purely structural suggesting instead that rRNA, mRNA and tRNA had common ribosomal ancestor.

• Suggest that DNA and cells evolved to protect and optimize pre-existing ribosome functions.


Many steps in the evolution of cellular life are still mysterious. We suggest that the ribosome may represent one important missing link between compositional (or metabolism-first), RNA-world (or genes-first) and cellular (last universal common ancestor) approaches to the evolution of cells. We present evidence that the entire set of transfer RNAs for all twenty amino acids are encoded in both the 16S and 23S rRNAs of Escherichia coli K12; that nucleotide sequences that could encode key fragments of ribosomal proteins, polymerases, ligases, synthetases, and phosphatases are to be found in each of the six possible reading frames of the 16S and 23S rRNAs; and that every sequence of bases in rRNA has information encoding more than one of these functions in addition to acting as a structural component of the ribosome. Ribosomal RNA, in short, is not just a structural scaffold for proteins, but the vestigial remnant of a primordial genome that may have encoded a self-organizing, self-replicating, auto-catalytic intermediary between macromolecules and cellular life.

Ribosomal RNA Transfer RNA Messenger RNA Protein synthesis RNA world

Desafiando os paradigmas dominantes em Física

Journal of Scientific Exploration, Vol. 18, No. 3, pp. 421–438, 2004

Challenging Dominant Physics Paradigms


Departamento de Física,
Universidad de Alcal, 28871 Alcal de Henares, Madrid, España (Spain)


Science, Technology and Society, University of Wollongong, NSW 2522, Australia


There are many well-qualified scientists who question long established physics theories even when paradigms are not in crisis. Challenging scientific orthodoxy is difficult because most scientists are educated and work within current paradigms and have little career incentive to examine unconventional ideas. Dissidence is a strategic site for learning about the dynamics of science. Dozens of well-qualified scientists who challenge dominant physics paradigms were contacted to determine how they try to overcome resistance to their ideas. Some such challengers obtain funding in the usual ways; others tap unconventional sources or use their own funds. For publishing, many challengers use alternative journals and attend conferences dedicated to alternative viewpoints; publishing on the web is of special importance. Only a few physics dissidents come under attack, probably because they have not achieved enough prominence to be seen as a threat. Physics could benefit from greater openness to challenges; one way to promote thisis to expose students to unconventional views.

Keywords: physics— paradigms— challengers— alternatives— orthodoxy

A informação biológica, causalidade e especificidade - uma relação íntima

quinta-feira, março 22, 2018

Biological Information, causality and specificity – an intimate relationship

Stotz, Karola and Griffiths, Paul E. (2017) Biological Information, causality and specificity – an intimate relationship. [Preprint]

Source/Fonte: Evolution News


In this chapter we examine the relationship between biological information, the key biological concept of specificity, and recent philosophical work on causation. We begin by showing how talk of information in the molecular biosciences grew out of efforts to understand the sources of biological specificity. We then introduce the idea of ‘causal specificity’ from recent work on causation in philosophy, and our own, information theoretic measure of causal specificity. Biological specificity, we argue, is simply the causal specificity of certain biological processes. This, we suggest, means that causal relationships in biology are ‘informational’ relationships simply when they are highly specific relationships. Biological information can be identified with the storage, transmission and exercise of biological specificity. It has been argued that causal relationships should not be regarded as informational relationship unless they are ‘arbitrary’. We argue that, whilst arbitrariness is an important feature of many causal relationships in living systems, it should not be used in this way to delimit biological information. Finally, we argue that biological specificity, and hence biological information, is not confined to nucleic acids but distributed among a wide range of entities and processes.


E quando a verdade é desconsiderada... pobre ciência!


April 2018, Volume 83, Issue 2, pp 253–263 | Cite as

Bayesian Convergence and the Fair-Balance Paradox

Authors and affiliations

Bengt Autzen1

Email author

View author's OrcID profile

1.Department of Philosophy University of Bristol Bristol UK

Open Access Original Research

First Online: 28 February 2017


The paper discusses Bayesian convergence when the truth is excluded from the analysis by means of a simple coin-tossing example. In the fair-balance paradox a fair coin is tossed repeatedly. A Bayesian agent, however, holds the a priori view that the coin is either biased towards heads or towards tails. As a result the truth (i.e., the coin is fair) is ignored by the agent. In this scenario the Bayesian approach tends to confirm a false model as the data size goes to infinity. I argue that the fair-balance paradox reveals an unattractive feature of the Bayesian approach to scientific inference and explore a modification of the paradox.


A ciência nem sempre se autocorrige!

Foundations of Science

August 2016, Volume 21, Issue 3, pp 477–492 | Cite as

Science Is Not Always “Self-Correcting”

Fact–Value Conflation and the Study of Intelligence

Authors and affiliations

Nathan Cofnas1

Email author

Source/Fonte: PLoS Blog


First Online: 01 February 2015


Some prominent scientists and philosophers have stated openly that moral and political considerations should influence whether we accept or promulgate scientific theories. This widespread view has significantly influenced the development, and public perception, of intelligence research. Theories related to group differences in intelligence are often rejected a priori on explicitly moral grounds. Thus the idea, frequently expressed by commentators on science, that science is “self-correcting”—that hypotheses are simply abandoned when they are undermined by empirical evidence—may not be correct in all contexts. In this paper, documentation spanning from the early 1970s to the present is collected, which reveals the influence of scientists’ moral and political commitments on the study of intelligence. It is suggested that misrepresenting findings in science to achieve desirable social goals will ultimately harm both science and society.


Epistemology Fact–value distinction Intelligence research Science and morality


Dominando o caos: calculando a probabilidade em sistemas complexos

quarta-feira, março 21, 2018

Entropy-based generating Markov partitions for complex systems featured

Chaos 28, 033611 (2018);

Nicolás Rubido1, Celso Grebogi2, and Murilo S. Baptista2


1Instituto de Física de Facultad de Ciencias (IFFC), Universidad de la República (UdelaR), Iguá 4225, Montevideo, Uruguay

2Institute for Complex Systems and Mathematical Biology (ICSMB), King's College, University of Aberdeen (UoA), AB24 3UE Aberdeen, United Kingdom

Source/Fonte: Nicolás Rubido


Finding the correct encoding for a generic dynamical system's trajectory is a complicated task: the symbolic sequence needs to preserve the invariant properties from the system's trajectory. In theory, the solution to this problem is found when a Generating Markov Partition (GMP) is obtained, which is only defined once the unstable and stable manifolds are known with infinite precision and for all times. However, these manifolds usually form highly convoluted Euclidean sets, are a priori unknown, and, as it happens in any real-world experiment, measurements are made with finite resolution and over a finite time-span. The task gets even more complicated if the system is a network composed of interacting dynamical units, namely, a high-dimensional complex system. Here, we tackle this task and solve it by defining a method to approximately construct GMPs for any complex system's finite-resolution and finite-time trajectory. We critically test our method on networks of coupled maps, encoding their trajectories into symbolic sequences. We show that these sequences are optimal because they minimise the information loss and also any spurious information added. Consequently, our method allows us to approximately calculate the invariant probability measures of complex systems from the observed data. Thus, we can efficiently define complexity measures that are applicable to a wide range of complex phenomena, such as the characterisation of brain activity from electroencephalogram signals measured at different brain regions or the characterisation of climate variability from temperature anomalies measured at different Earth regions.

The use of measures from the Information Theory for complex systems' analysis requires the estimation of probabilities. In practice, these probabilities need to be derived from finite data-sets, namely, electroencephalogram (EEG) signals coming from different brain regions, electrocardiogram (EKG) signals coming from the heart, or temperature anomalies coming from different Earth regions. Respectively, the complex systems in these cases are the brain, the heart, and the Earth climate—all being systems composed of many dynamically interacting components. The main reason behind using measures from the Information Theory to analyse complex systems is that these measures help to better understand and predict their behaviour and functioning. However, calculating probabilities from observed data is never straightforward; in particular, up-to-now, we lack practical ways to define them without losing useful (or adding meaningless) information in the process. In order to minimise these spurious additions or losses, we propose here a method to derive these probabilities optimally. Our method makes an entropy-based encoding of the measured signals, thus, transforming them into easy-to-handle symbolic sequences containing most of the relevant information about the system dynamics. Consequently, we can find the Information Theory measures, or any other spatio-temporal average, when we seek analysing a complex system.


'Nova' forma de vida explica a evolução das células???

terça-feira, março 20, 2018

Converting Escherichia coli into an archaebacterium with a hybrid heterochiral membrane

Antonella Caforio, Melvin F. Siliakus, Marten Exterkate, Samta Jain, Varsha R. Jumde, Ruben L. H. Andringa, Servé W. M. Kengen, Adriaan J. Minnaard, Arnold J. M. Driessen and John van der Oost

PNAS March 19, 2018. 201721604; published ahead of print March 19, 2018.  

Edited by Eugene V. Koonin, National Institutes of Health, Bethesda, MD, and approved February 27, 2018 (received for review December 12, 2017).



Escherichia coli has been engineered toward an archaebacterium with an unprecedented high level of archaeal ether phospholipids. The obtained cells stably maintain a mixed heterochiral membrane. This finding challenges theories that assume that intrinsic instability of mixed membranes led to the “lipid divide” and the subsequent differentiation of bacteria and archaea. Furthermore, this study paves the way for future membrane engineering of industrial production organisms with improved robustness.


One of the main differences between bacteria and archaea concerns their membrane composition. Whereas bacterial membranes are made up of glycerol-3-phosphate ester lipids, archaeal membranes are composed of glycerol-1-phosphate ether lipids. Here, we report the construction of a stable hybrid heterochiral membrane through lipid engineering of the bacterium Escherichia coli. By boosting isoprenoid biosynthesis and heterologous expression of archaeal ether lipid biosynthesis genes, we obtained a viable E. coli strain of which the membranes contain archaeal lipids with the expected stereochemistry. It has been found that the archaeal lipid biosynthesis enzymes are relatively promiscuous with respect to their glycerol phosphate backbone and that E. coli has the unexpected potential to generate glycerol-1-phosphate. The unprecedented level of 20–30% archaeal lipids in a bacterial cell has allowed for analyzing the effect on the mixed-membrane cell’s phenotype. Interestingly, growth rates are unchanged, whereas the robustness of cells with a hybrid heterochiral membrane appeared slightly increased. The implications of these findings for evolutionary scenarios are discussed.

lipid biosynthesis ether lipids hybrid membranes bacteria archaea


A ciência está realmente enfrentando uma crise de replicabilidade das pesquisas, e nós precisamos disso?

Opinion: Is science really facing a reproducibility crisis, and do we need it to?

Daniele Fanelli

PNAS March 12, 2018. 201708272; published ahead of print March 12, 2018. 

Edited by David B. Allison, Indiana University Bloomington, Bloomington, IN, and accepted by Editorial Board Member Susan T. Fiske November 3, 2017 (received for review June 30, 2017)


Efforts to improve the reproducibility and integrity of science are typically justified by a narrative of crisis, according to which most published results are unreliable due to growing problems with research and publication practices. This article provides an overview of recent evidence suggesting that this narrative is mistaken, and argues that a narrative of epochal changes and empowerment of scientists would be more accurate, inspiring, and compelling.

reproducible research crisis integrity bias misconduct


Como as células se protegem contra o stress mecânico: mero acaso, fortuita necessidade ou design inteligente?

sábado, março 17, 2018

Voltage gating of mechanosensitive PIEZO channels

Mirko Moroni, M. Rocio Servin-Vences, Raluca Fleischer, Oscar Sánchez-Carranza & Gary R. Lewin

Nature Communications volume 9, Article number: 1096 (2018)


Download Citation

Ion channels in the nervous system Ion transport Mechanisms of disease Peripheral vascular disease Permeation and transport

Received: 17 August 2017 Accepted: 19 February 2018

Published online: 15 March 2018

Source/Fonte: Ardem Patapoutian


Mechanosensitive PIEZO ion channels are evolutionarily conserved proteins whose presence is critical for normal physiology in multicellular organisms. Here we show that, in addition to mechanical stimuli, PIEZO channels are also powerfully modulated by voltage and can even switch to a purely voltage-gated mode. Mutations that cause human diseases, such as xerocytosis, profoundly shift voltage sensitivity of PIEZO1 channels toward the resting membrane potential and strongly promote voltage gating. Voltage modulation may be explained by the presence of an inactivation gate in the pore, the opening of which is promoted by outward permeation. Older invertebrate (fly) and vertebrate (fish) PIEZO proteins are also voltage sensitive, but voltage gating is a much more prominent feature of these older channels. We propose that the voltage sensitivity of PIEZO channels is a deep property co-opted to add a regulatory mechanism for PIEZO activation in widely different cellular contexts.


We thank Prof. Thomas Baukrowitz for initial comments on the manuscript. Liana Kozitzki for technical assistance. This work was supported by an Alexander von Humboldt fellowship to M.M. and a Deutsche Forschungsgemeinschaft Collaborative Research Grant to G.R.L. (Project A9 SFB 958).

Author information


Department of Neuroscience, Max-Delbrück Center for Molecular Medicine, Robert-Rössle Straße 10, D-13092, Berlin, Germany

Mirko Moroni, M. Rocio Servin-Vences, Raluca Fleischer, Oscar Sánchez-Carranza & Gary R. Lewin

Excellence Cluster Neurocure, Charité Universitätsmedizin, 10117, Berlin, Germany

Gary R. Lewin


Conceptualization: M.M. and G.R.L. Methodology: M.M. Investigation: M.M., M.R.S.-V., R.F., O.S.-C. Writing: M.M. and G.R.L. Visualization: M.M., M.R.S.-V and R.F. Supervision: M.M. and G.R.L. Project administration: M.M. Funding acquisition: G.R.L.

Competing interests

The authors declare no competing interests.

Corresponding authors

Correspondence to Mirko Moroni or Gary R. Lewin.

Nossos ancestrais "transaram" duas vezes com os Denisovans

quinta-feira, março 15, 2018

Analysis of Human Sequence Data Reveals Two Pulses of Archaic Denisovan Admixture

Sharon R. Browning5, Brian L. Browning, Ying Zhou, Serena Tucci, Joshua M. Akey

5Lead Contact

Publication stage: In Press Corrected Proof

Article Info

Publication History

Published: March 15, 2018 Accepted: February 12, 2018

Received in revised form: November 21, 2017 Received: October 4, 2017


•Asian genomes carry introgressed DNA from Denisovans and Neanderthals

•East Asians show evidence of introgression from two distinct Denisovan populations

•South Asians and Oceanians carry introgression from one Denisovan population


Anatomically modern humans interbred with Neanderthals and with a related archaic population known as Denisovans. Genomes of several Neanderthals and one Denisovan have been sequenced, and these reference genomes have been used to detect introgressed genetic material in present-day human genomes. Segments of introgression also can be detected without use of reference genomes, and doing so can be advantageous for finding introgressed segments that are less closely related to the sequenced archaic genomes. We apply a new reference-free method for detecting archaic introgression to 5,639 whole-genome sequences from Eurasia and Oceania. We find Denisovan ancestry in populations from East and South Asia and Papuans. Denisovan ancestry comprises two components with differing similarity to the sequenced Altai Denisovan individual. This indicates that at least two distinct instances of Denisovan admixture into modern humans occurred, involving Denisovan populations that had different levels of relatedness to the sequenced Altai Denisovan.