Isso é vida: redes comunicadoras de RNA de vírus e células em interação contínua

quinta-feira, março 21, 2019

That is life: communicating RNA networks from viruses and cells in continuous interaction

Luis P. Villarreal  Guenther Witzany

First published: 13 March 2019 https://doi.org/10.1111/nyas.14040


Source/Fonte: Guenther Witzany

Abstract

All the conserved detailed results of evolution stored in DNA must be read, transcribed, and translated via an RNA‐mediated process. This is required for the development and growth of each individual cell. Thus, all known living organisms fundamentally depend on these RNA‐mediated processes. In most cases, they are interconnected with other RNAs and their associated protein complexes and function in a strictly coordinated hierarchy of temporal and spatial steps (i.e., an RNA network). Clearly, all cellular life as we know it could not function without these key agents of DNA replication, namely rRNA, tRNA, and mRNA. Thus, any definition of life that lacks RNA functions and their networks misses an essential requirement for RNA agents that inherently regulate and coordinate (communicate to) cells, tissues, organs, and organisms. The precellular evolution of RNAs occurred at the core of the emergence of cellular life and the question remained of how both precellular and cellular levels are interconnected historically and functionally. RNA networks and RNA communication can interconnect these levels. With the reemergence of virology in evolution, it became clear that communicating viruses and subviral infectious genetic parasites are bridging these two levels by invading, integrating, coadapting, exapting, and recombining constituent parts in host genomes for cellular requirements in gene regulation and coordination aims. Therefore, a 21st century understanding of life is of an inherently social process based on communicating RNA networks, in which viruses and cells continuously interact.

A célula quantificada: mero acaso, fortuita necessidade ou design inteligente?

Molecular Biology of the Cell Vol. 25, No. 22 Perspectives Free Access

The quantified cell

Avi Flamholz, Rob Phillips, and Ron Milo

Doug Kellogg, Monitoring Editor Jennifer Lippincott-Schwartz, Guest Editor
Published Online:13 Oct 2017 https://doi.org/10.1091/mbc.e14-09-1347

FIGURE 1: Which is larger, mRNA or the protein for which it codes? When we ask, most peoples' instinct is to say that proteins are larger. As seen in this figure, the opposite is overwhelmingly the case. The mRNA for actin is more massive and has a larger geometric size than the actin monomers for which it codes because the mass of a codon of mRNA is an order of magnitude greater than that of the average amino acid.

Abstract

The microscopic world of a cell can be as alien to our human-centered intuition as the confinement of quarks within protons or the event horizon of a black hole. We are prone to thinking by analogy—Golgi cisternae stack like pancakes, red blood cells look like donuts—but very little in our human experience is truly comparable to the immensely crowded, membrane-subdivided interior of a eukaryotic cell or the intricately layered structures of a mammalian tissue. So in our daily efforts to understand how cells work, we are faced with a challenge: how do we develop intuition that works at the microscopic scale?

I have deeply regretted that I did not proceed far enough at least to understand something of the great leading principles of mathematics, for men thus endowed seem to have an extra sense.

—Charles Darwin, Autobiography

In aiming to build better intuition for the alien world of cells, it is useful to first imagine how we would introduce our modern human society to curious aliens. If and when we meet an alien, we plan to come prepared with copies of the most recent census—chock full of numbers, charts, and summary statistics. Numbers will tell our alien friend when we will likely marry, how many children we will have, and what will most likely cause our deaths. They will also report how many hours we spend commuting to work and watching TV and what we eat when we do those things. Just as quantitative data clearly describe the behavior of human populations, numbers offer a clear path to understanding the alien world of cells. Yet there is still so much to be learned—our current cellular census is woefully incomplete. We biologists should improve the cellular census and document the budgets of cells so that we can leverage the incredible capacity of numbers to describe biological systems and generate testable predictions about them.

Applying this quantitative approach to biology is inherently difficult because life is dynamic and diverse. For example, when we ask our fellow biologists how many copies of their favorite protein are found in a particular cell line, they often answer that “it depends.” And indeed it does depend—on the carbon source, the presence of different signaling molecules, and the temperature in the lab that day. Sometimes, after a long day in lab, it may seem like “it depends” also on the whims of mercurial and vengeful gods. But we want to make the case that it is nonetheless important to supply a number. To see why, let's examine how intuitively we process dynamic ranges of values in a more familiar scenario.

How much does a car cost? You would certainly be right to say that the price depends on the make, the model, and the dealer. But that answer conveys no information. You might also tell us that the Honda Civic you want costs $12,895 at the dealership downtown. But that is only that one Honda—the answer is too precise to be informative about other cars. Finally, you might tell us that a car costs about $10,000. This number is not so accurate—a cheap car might be $8000 and a more expensive one $40,000—but it is a very useful estimate. We would probably have a similar discussion about the cost of a TV, only scaled down by an order of magnitude. Like a car, the cost of a TV also depends. If all we knew was that “it depends,” without a rough estimate of the price, it would be difficult for us to choose a free car over a free TV as a game show contestant. But everyone knows you should choose the car because a car costs ≈$10,000 and a TV costs ≈$1000. Luckily, we carry with us such intuition-building order-of-magnitude estimates as we forage through the modern jungle.

Moving to the world of cell biology, we can test our intuition by asking, Which is heavier, a protein or the mRNA that codes for it? Even after years of studying and manipulating DNA, RNA, and protein in our labs, we may not be prepared for this question. Equipped with a few numbers, however, we can answer the question easily and begin to renovate our intuition. Natural amino acids vary somewhat in their molecular mass, but their average mass is ≈100 Da or about threefold less than a nucleotide (weighing ≈300 Da; for full reference to the primary literature Google “BNID 104886,” the BioNumbers ID for this particular quantity). Because the genetic code uses three nucleotides to encode each amino acid, we quickly conclude that an mRNA has a mass about ninefold greater than the protein it encodes (without even accounting for the mass of untranslated regions of mRNA). In contrast to the usual cartoon representations of the central dogma, which can obscure the relative sizes of molecular components, Figure 1 is drawn to scale. If more of our models and textbook figures respected quantitative properties like size and concentration, we might have developed a better intuitive grasp of these properties (for an example of a situation in which paying attention to the relative sizes of proteins was vital see Davis and van der Merwe, 2006; James and Vale, 2012).

Bactéria ejeta parte do flagelo para continuar viva!

γ-proteobacteria eject their polar flagella under nutrient depletion, retaining flagellar motor relic structures

Josie L. Ferreira, Forson Z. Gao, Florian M. Rossmann, Andrea Nans, Susanne Brenzinger, Rohola Hosseini, Amanda Wilson, Ariane Briegel, Kai M. Thormann, Peter B. Rosenthal, Morgan Beeby 



Abstract

Bacteria switch only intermittently to motile planktonic lifestyles under favorable conditions. Under chronic nutrient deprivation, however, bacteria orchestrate a switch to stationary phase, conserving energy by altering metabolism and stopping motility. About two-thirds of bacteria use flagella to swim, but how bacteria deactivate this large molecular machine remains unclear. Here, we describe the previously unreported ejection of polar motors by γ-proteobacteria. We show that these bacteria eject their flagella at the base of the flagellar hook when nutrients are depleted, leaving a relic of a former flagellar motor in the outer membrane. Subtomogram averages of the full motor and relic reveal that this is an active process, as a plug protein appears in the relic, likely to prevent leakage across their outer membrane; furthermore, we show that ejection is triggered only under nutritional depletion and is independent of the filament as a possible mechanosensor. We show that filament ejection is a widespread phenomenon demonstrated by the appearance of relic structures in diverse γ-proteobacteria including Plesiomonas shigelloides, Vibrio cholerae, Vibrio fischeri, Shewanella putrefaciens, and Pseudomonas aeruginosa. While the molecular details remain to be determined, our results demonstrate a novel mechanism for bacteria to halt costly motility when nutrients become scarce.

Author summary

In the face of starvation, bacteria must minimize their energy use. Here, we describe our unexpected finding that some bacteria take the drastic measure of ejecting their flagella in response to nutrient deficiency. Bacteria continually assemble flagella as propellers—unrelated to eukaryotic flagella—rotated by rotary motors embedded in the cell; continual rotation and assembly can consume up to 3% of a bacterium’s energy. Using electron cryo-tomography, a technique that provides high-resolution 3D images of intact bacteria, we were surprised to find partial flagellar motors in bacterial cells that were rare when nutrients were abundant but became common when nutrients were scarce. A variety of clues led us to hypothesize that these structures were relics of motors whose flagella had been ejected, which we confirmed using a genetic approach. Curiously, flagellar relics—which would otherwise be open portals through which the contents of the bacterial periplasm could leak—were plugged by an unidentified protein, presumably as a preservation measure. We speculate that flagellar ejection saves the bacterium from the costs of continuously assembling and rotating its flagella, as a last-ditch survival attempt. Our work provides a striking example of evolution arriving at a functional yet unintuitive solution to a problem.

FREE PDF GRATIS: PLoS Biology

Citation: Ferreira JL, Gao FZ, Rossmann FM, Nans A, Brenzinger S, Hosseini R, et al. (2019) γ-proteobacteria eject their polar flagella under nutrient depletion, retaining flagellar motor relic structures. PLoS Biol 17(3): e3000165. https://doi.org/10.1371/journal.pbio.3000165

Academic Editor: Daniel B. Kearns, Indiana University, UNITED STATES

Received: July 25, 2018; Accepted: February 8, 2019; Published: March 19, 2019

Copyright: © 2019 Ferreira et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Data Availability: Subtomogram averages are available on EMDB (Motor: EMDB-4570. Relic: EMDB-4569).

Funding: This work was supported by a Medical Research Council grant MR/P019374/1 to MB, a Medical Research Council PhD Doctoral Training Partnership award grant number MR/K501281/1 to JLF, a Research fellowship of the German Research Foundation (DFG project number 385257318) to FMR, Grant TRR174 "Prokaryotic Cell Biology" from German Research Foundation (DFG) to KMT, Netherlands Organisation for Scientific Research (NWO) BBOL.737.016.004 to AB, a German Academy of Sciences Leopoldina (Fellowship Programme LPDS 2017-01) to SB, and NIH (AM, grants R01-GM051350 and R35-GM118108) to PBR. PBR is also supported by the Francis Crick Institute, which receives its core funding from Cancer Research UK (FC001143), the UK Medical Research Council (FC001143), and the Wellcome Trust (FC001143). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

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

Abbreviations: CCCP, Carbonyl cyanide m-chlorophenyl hydrazone; c-di-GMP, cyclic di-GMP; CFU, colony-forming unit; ECT, electron cryo-tomography; EM, electron microscopy; FSC, Fourier Shell Correlation; OD, optical density; SEC, general secretory pathway; WT, wild-type

O desempenho, propósito, função, objetivo e direção da termodinâmica da transferência de calor

Thermodynamics of heating

Adrian Bejan


Source/Fonte: NASA

Abstract

Heat transfer is a mature science, and so is thermodynamics. They are almost 200 years old having developed largely independently until the 1980s. Maturity comes from the usefulness and success of the thermal sciences. This review uses the thermodynamics of heat transfer to focus on aspects that are usually not discussed in physics: performance, purpose, function, objective and direction of evolutionary design. The article illustrates the unity of the thermal sciences discipline (heat transfer +thermodynamics + constructal law), and uses the opportunity to correct a few recent interpretations of the thermodynamics of heat transfer regarding dissipative engines and energy storage.

1. Introduction

Heat transfer happens. It is natural because temperature differences and gradients are everywhere. In the devices conceived by humans, just like in the design of the animal body, heat transfer is present because the bigger entity (device, animal, human and machine specimen) represents a design with purpose, with direction of change and evolution.

In science, ‘purpose’ is not mentioned, yet, many scientific words and concepts account for the same irrefutable aspect of reality, for example: performance, function, objective, cause, self-organization, self-optimization, cost, good, better, easy and difficult. This multitude of terms makes it difficult to address ‘performance’ in a fundamental way. Here are a few examples.

To the biologist who studies the design of the fur of a warm-blooded animal, performance is the animal's ability to thrive in a cold environment, which depends on the performance of its fur as a thermal insulation. To the manufacturer of a heat exchanger, performance is the cost of materials, labour and fuel used during manufacturing, which have everything to do with the performance of the whole heat exchanger as a facilitator of heat transfer. To the designer of a large-scale steam-turbine power plant, in addition to the total cost, performance is the overall energy conversion efficiency of the whole plant, which is a global measure to which contributes the functioning of each of the heat exchangers through which the steam flows [1–18].

All these interpretations belong together in a most useful and tutorial way if approached from the most fundamental point of view available in science: thermodynamics. Heat transfer is one kind of energy transfer between two systems (the system and its environment), and this kind has ‘performance’ that distinguishes it unmistakably from the performance of the other kind of energy transfer, which is work transfer. Performance is why heat transfer is eminently not the same as work transfer.

The objective of this article is to trace the path of the concept of performance from its fundamental place in thermodynamics to the many and diverse counterparts of performance that are recognized in other scientific undertakings. Along the way, we will discover opportunities to correct some of the erroneous interpretations of heat transfer performance that continue to propagate in the current literature.

FREE PDF GRATIS: Proc. R. Soc. A.

Sabine Hossenfelder 'falou e disse' - a ciência tem um problema e sugere como resolver.

quarta-feira, março 20, 2019

Science has a problem. Here is how you can help.

[I have gotten numerous requests by people who want to share Appendix C of my book. The content is copyrighted, of course, but my publisher kindly agreed that I can make it publicly available. You may use this text for non-commercial purposes, so long as you add the copyright disclaimer, see bottom of post.]

Both bottom-up and top-down measures are necessary to improve the current situation. This is an interdisciplinary problem whose solution requires input from the sociology of science, philosophy, psychology, and – most importantly – the practicing scientists themselves. Details differ by research area. One size does not fit all. Here is what you can do to help. 

As a scientist: 

Learn about social and cognitive biases: Become aware of what they are and under which circumstances they are likely to occur. Tell your colleagues.

Prevent social and cognitive biases: If you organize conferences, encourage speakers to not only list motivations but also shortcomings. Don’t forget to discuss “known problems.” Invite researchers from competing programs. If you review papers, make sure open questions are adequately mentioned and discussed. Flag marketing as scientifically inadequate. Don’t discount research just because it’s not presented excitingly enough or because few people work on it.

Beware the influence of media and social networks: What you read and what your friends talk about affects your interests. Be careful what you let into your head. If you consider a topic for future research, factor in that you might have been influenced by how often you have heard others speak about it positively.

Build a culture of criticism: Ignoring bad ideas doesn’t make them go away, they will still eat up funding. Read other researchers’ work and make your criticism publicly available. Don’t chide colleagues for criticizing others or think of them as unproductive or aggressive. Killing ideas is a necessary part of science. Think of it as community service.

Say no: If a policy affects your objectivity, for example because it makes continued funding dependent on the popularity of your research results, point out that it interferes with good scientific conduct and should be amended. If your university praises its productivity by paper counts and you feel that this promotes quantity over quality, say that you disapprove of such statements.

As a higher ed administrator, science policy maker, journal editor, representative of funding body: 

Do your own thing: Don’t export decisions to others. Don’t judge scientists by how many grants they won or how popular their research is – these are judgements by others who themselves relied on others. Make up your own mind, carry responsibility. If you must use measures, create your own. Better still, ask scientists to come up with their own measures.

Use clear guidelines: If you have to rely on external reviewers, formulate recommendations for how to counteract biases to the extent possible. Reviewers should not base their judgment on the popularity of a research area or the person. If a reviewer’s continued funding depends on the well-being of a certain research area, they have a conflict of interest and should not review papers in their own area. That will be a problem because this conflict of interest is presently everywhere. See next 3 points to alleviate it.

Make commitments: You have to get over the idea that all science can be done by postdocs on 2-year fellowships. Tenure was institutionalized for a reason and that reason is still valid. If that means fewer people, then so be it. You can either produce loads of papers that nobody will care about 10 years from now, or you can be the seed of ideas that will still be talked about in 1000 years. Take your pick. Short-term funding means short-term thinking.

Encourage a change of field: Scientists have a natural tendency to stick to what they know already. If the promise of a research area declines, they need a way to get out, otherwise you’ll end up investing money into dying fields. Therefore, offer reeducation support, 1-2 year grants that allow scientists to learn the basics of a new field and to establish contacts. During that period they should not be expected to produce papers or give conference talks.

Hire full-time reviewers: Create safe positions for scientists specialized in providing objective reviews in certain fields. These reviewers should not themselves work in the field and have no personal incentive to take sides. Try to reach agreements with other institutions on the number of such positions.

Support the publication of criticism and negative results: Criticism of other people’s work or negative results are presently underappreciated. But these contributions are absolutely essential for the scientific method to work. Find ways to encourage the publication of such communication, for example by dedicated special issues.

Offer courses on social and cognitive biases: This should be mandatory for anybody who works in academic research. We are part of communities and we have to learn about the associated pitfalls. Sit together with people from the social sciences, psychology, and the philosophy of science, and come up with proposals for lectures on the topic.

Allow a division of labor by specialization in task: Nobody is good at everything, so don’t expect scientists to be. Some are good reviewers, some are good mentors, some are good leaders, and some are skilled at science communication. Allow them to shine in what they’re good at and make best use of it, but don’t require the person who spends their evenings in student Q&A to also bring in loads of grant money. Offer them specific titles, degrees, or honors.

As a science writer or member of the public, ask questions: 

You’re used to asking about conflicts of interest due to funding from industry. But you should also ask about conflicts of interest due to short-term grants or employment. Does the scientists’ future funding depend on producing the results they just told you about?

Likewise, you should ask if the scientists’ chance of continuing their research depends on their work being popular among their colleagues. Does their present position offer adequate protection from peer pressure?

And finally, like you are used to scrutinize statistics you should also ask whether the scientists have taken means to address their cognitive biases. Have they provided a balanced account of pros and cons or have they just advertised their own research?

You will find that for almost all research in the foundations of physics the answer to at least one of these questions is no. This means you can’t trust these scientists’ conclusions. Sad but true. 





Reprinted from Lost In Math by Sabine Hossenfelder. Copyright © 2018. Available from Basic Books, an imprint of Perseus Books, a division of PBG Publishing, LLC, a subsidiary of Hachette Book Group, Inc.


Origem da vida? Resolvam primeiro o paradoxo do interatomo de Levinthal

terça-feira, março 19, 2019

The Levinthal paradox of the interactome

Peter Tompa George D. Rose

First published: 10 October 2011



The number of possible interactomes increases exponentially with proteome size. The number of possible different states (patterns of pairwise interactions) of the interactome increases exponentially with the number of its constituent proteins. In the simple case of four proteins (A), the number of possible different arrangements is only three. Five proteins (B) may already engage in 15 different pairwise interactions. The first pair (red‐blue, red‐purple, red‐yellow, red‐green) is connected by a solid line, followed by any of three possible secondary pairs (with connections indicated by dotted lines), plus three remaining possibilities (not illustrated) in which the first protein (red) is unpaired. The theoretical number for n proteins is n!/2n/2 × n/2! (cf. text and Supporting Information), which for a realistic interactome of 4500 proteins gives 107200 different possibilities.

Abstract

The central biological question of the 21st century is: how does a viable cell emerge from the bewildering combinatorial complexity of its molecular components? Here, we estimate the combinatorics of self‐assembling the protein constituents of a yeast cell, a number so vast that the functional interactome could only have emerged by iterative hierarchic assembly of its component sub‐assemblies. A protein can undergo both reversible denaturation and hierarchic self‐assembly spontaneously, but a functioning interactome must expend energy to achieve viability. Consequently, it is implausible that a completely “denatured” cell could be reversibly renatured spontaneously, like a protein. Instead, new cells are generated by the division of pre‐existing cells, an unbroken chain of renewal tracking back through contingent conditions and evolving responses to the origin of life on the prebiotic earth. We surmise that this non‐deterministic temporal continuum could not be reconstructed de novo under present conditions.

FREE PDF GRATIS: Protein Science Sup. Info.

Físicos revertem o tempo em pequenas partículas dentro de um computador quântico

sábado, março 16, 2019

Arrow of time and its reversal on the IBM quantum computer

G. B. Lesovik, I. A. Sadovskyy, M. V. Suslov, A. V. Lebedev & V. M. Vinokur 

Scientific Reportsvolume 9, Article number: 4396 (2019) 

Source/Fonte: Wired

Abstract

Uncovering the origin of the “arrow of time” remains a fundamental scientific challenge. Within the framework of statistical physics, this problem was inextricably associated with the Second Law of Thermodynamics, which declares that entropy growth proceeds from the system’s entanglement with the environment. This poses a question of whether it is possible to develop protocols for circumventing the irreversibility of time and if so to practically implement these protocols. Here we show that, while in nature the complex conjugation needed for time reversal may appear exponentially improbable, one can design a quantum algorithm that includes complex conjugation and thus reverses a given quantum state. Using this algorithm on an IBM quantum computer enables us to experimentally demonstrate a backward time dynamics for an electron scattered on a two-level impurity.

FREE PDF GRATIS: Scientific Reports Sup. Info.

Investigação bioinformática exploratória revela a IMPORTÂNCIA do DNA “lixo” no desenvolvimento embrionário inicial

quinta-feira, março 14, 2019

Exploratory bioinformatics investigation reveals importance of “junk” DNA in early embryo development

Steven Xijin Ge

BMC Genomics201718:200


Received: 13 October 2016 Accepted: 7 February 2017 Published: 23 February 2017



Abstract

Background

Instead of testing predefined hypotheses, the goal of exploratory data analysis (EDA) is to find what data can tell us. Following this strategy, we re-analyzed a large body of genomic data to study the complex gene regulation in mouse pre-implantation development (PD).

Results

Starting with a single-cell RNA-seq dataset consisting of 259 mouse embryonic cells derived from zygote to blastocyst stages, we reconstructed the temporal and spatial gene expression pattern during PD. The dynamics of gene expression can be partially explained by the enrichment of transposable elements in gene promoters and the similarity of expression profiles with those of corresponding transposons. Long Terminal Repeats (LTRs) are associated with transient, strong induction of many nearby genes at the 2-4 cell stages, probably by providing binding sites for Obox and other homeobox factors. B1 and B2 SINEs (Short Interspersed Nuclear Elements) are correlated with the upregulation of thousands of nearby genes during zygotic genome activation. Such enhancer-like effects are also found for human Alu and bovine tRNA SINEs. SINEs also seem to be predictive of gene expression in embryonic stem cells (ESCs), raising the possibility that they may also be involved in regulating pluripotency. We also identified many potential transcription factors underlying PD and discussed the evolutionary necessity of transposons in enhancing genetic diversity, especially for species with longer generation time.

Conclusions

Together with other recent studies, our results provide further evidence that many transposable elements may play a role in establishing the expression landscape in early embryos. It also demonstrates that exploratory bioinformatics investigation can pinpoint developmental pathways for further study, and serve as a strategy to generate novel insights from big genomic data.

Keywords Single-cell RNA-seq Exploratory data analysis Pre-implantation development Early embryogenesis Transposons Repetitive DNA Background

FREE PDF GRATIS: BMC Genomics

A biologia e a evolução da fala: por que só os seres humanos falam?

The Biology and Evolution of Speech: A Comparative Analysis
Annual Review of Linguistics

Vol. 4:255-279 (Volume publication date January 2018) 


W. Tecumseh Fitch

Department of Cognitive Biology, University of Vienna, Vienna 1090, Austria

Copyright © 2018 by W. Tecumseh Fitch. This work is licensed under a Creative Commons Attribution-ShareAlike 4.0 (CC-BY) International License, which permits unrestricted use, distribution, and reproduction in any medium and any derivative work is made available under the same, similar, or a compatible license. See credit lines of images or other third-party material in this article for license information.


Abstract

I analyze the biological underpinnings of human speech from a comparative perspective. By first identifying mechanisms that are evolutionarily derived relative to other primates, we obtain members of the faculty of language, derived components (FLD). Understanding when and why these evolved is central to understanding the evolution of speech. There is little evidence for human-specific mechanisms in auditory perception, and the hypothesis that speech perception is “special” is poorly supported by comparative data. Regarding speech production, human peripheral vocal anatomy includes several derived characteristics (permanently descended larynx, loss of air sacs), but their importance has been overestimated. In contrast, the central neural mechanisms underlying speech production involve crucial derived characteristics (direct monosynaptic connections from motor cortex to laryngeal motor neurons, derived intracortical dorsal circuitry between auditory and motor regions). Paleo-DNA from fossil hominins provides an exciting new opportunity to determine when these derived speech production mechanisms arose during evolution.

Keywords human evolution, speech perception, speech production, evolution of language, monosynaptic connections, paleo-DNA

A matemática que diz às células o que elas são: mero acaso, fortuita necessidade ou design inteligente?

MATHEMATICAL BIOLOGY

The Math That Tells Cells What They Are

During development, cells seem to decode their fate through optimal information processing, which could hint at a more general principle of life.



Cells in embryos need to make their way across a “developmental landscape” to their eventual fate. New findings bear on how they may do this so efficiently.

Adrian du Buisson for Quanta Magazine

In 1891, when the German biologist Hans Driesch split two-cell sea urchin embryos in half, he found that each of the separated cells then gave rise to its own complete, albeit smaller, larva. Somehow, the halves “knew” to change their entire developmental program: At that stage, the blueprint for what they would become had apparently not yet been drawn out, at least not in ink.

Since then, scientists have been trying to understand what goes into making this blueprint, and how instructive it is. (Driesch himself, frustrated at his inability to come up with a solution, threw up his hands and left the field entirely.) It’s now known that some form of positional information makes genes variously switch on and off throughout the embryo, giving cells distinct identities based on their location. But the signals carrying that information seem to fluctuate wildly and chaotically — the opposite of what you might expect for an important guiding influence.

“The [embryo] is a noisy environment,” said Robert Brewster, a systems biologist at the University of Massachusetts Medical School. “But somehow it comes together to give you a reproducible, crisp body plan.”

I don’t think optimization is an aesthetic or philosophical idea. It’s a very concrete idea.

William Bialek, Princeton University

The same precision and reproducibility emerge from a sea of noise again and again in a range of cellular processes. That mounting evidence is leading some biologists to a bold hypothesis: that where information is concerned, cells might often find solutions to life’s challenges that are not just good but optimal — that cells extract as much useful information from their complex surroundings as is theoretically possible. Questions about optimal decoding, according to Aleksandra Walczak, a biophysicist at the École Normale Supérieure in Paris, “are everywhere in biology.”

Biologists haven’t traditionally cast analyses of living systems as optimization problems because the complexity of those systems makes them hard to quantify, and because it can be difficult to discern what would be getting optimized. Moreover, while evolutionary theory suggests that evolving systems can improve over time, nothing guarantees that they should be driven to an optimal level.

Yet when researchers have been able to appropriately determine what cells are doing, many have been surprised to see clear indications of optimization. Hints have turned up in how the brain responds to external stimuli and how microbes respond to chemicals in their environments. Now some of the best evidence has emerged from a new study of fly larva development, reported recently in Cell.

Cells That Understand Statistics

For decades, scientists have been studying fruit fly larvae for clues about how development unfolds. Some details became apparent early on: A cascade of genetic signals establishes a pattern along the larva’s head-to-tail axis. Signaling molecules called morphogens then diffuse through the embryonic tissues, eventually defining the formation of body parts.

Particularly important in the fly are four “gap” genes, which are expressed separately in broad, overlapping domains along the axis. The proteins they make in turn help regulate the expression of “pair-rule” genes, which create an extremely precise, periodic striped pattern along the embryo. The stripes establish the groundwork for the later division of the body into segments.
...

READ MORE: Quanta Magazine

A estrutura de uma ATP sintase bacteriana: mero acaso, fortuita necessidade ou design inteligente?

quarta-feira, março 13, 2019

Structure of a bacterial ATP synthase

Hui Guo, Toshiharu Suzuki, John L Rubinstein The Hospital for Sick Children Research Institute, Canada; The University of Toronto, Canada; Tokyo Institute of Technology, Japan; Kyoto-Sangyo University, Japan

RESEARCH ARTICLE Feb 6, 2019


Abstract

ATP synthases produce ATP from ADP and inorganic phosphate with energy from a transmembrane proton motive force. Bacterial ATP synthases have been studied extensively because they are the simplest form of the enzyme and because of the relative ease of genetic manipulation of these complexes. We expressed the Bacillus PS3 ATP synthase in Eschericia coli, purified it, and imaged it by cryo-EM, allowing us to build atomic models of the complex in three rotational states. The position of subunit ε shows how it is able to inhibit ATP hydrolysis while allowing ATP synthesis. The architecture of the membrane region shows how the simple bacterial ATP synthase is able to perform the same core functions as the equivalent, but more complicated, mitochondrial complex. The structures reveal the path of transmembrane proton translocation and provide a model for understanding decades of biochemical analysis interrogating the roles of specific residues in the enzyme.

https://doi.org/10.7554/eLife.43128.001

FREE PDF GRATIS: eLIFE

Como "conversas secretas" dentro das células estão transformando a biologia

NEWS FEATURE  11 MARCH 2019

How secret conversations inside cells are transforming biology

Organelles — the cell’s workhorses — mingle far more than scientists ever appreciated.

Illustration by Serge Bloch

Elie Dolgin

Nobody paid much attention to Jean Vance 30 years ago, when she discovered something fundamental about the building blocks inside cells. She even doubted herself, at first.

The revelation came after a series of roadblocks. The cell biologist had just set up her laboratory at the University of Alberta in Edmonton, Canada, and was working alone. She thought she had isolated a pure batch of structures called mitochondria — the power plants of cells — from rat livers. But tests revealed that her sample contained something that wasn’t supposed to be there. “I thought I’d made a big mistake,” Vance recalls.

After additional purification steps, she found extra bits of the cells’ innards clinging to mitochondria like wads of chewing gum stuck to a shoe. The interlopers were part of the endoplasmic reticulum (ER) — an assembly line for proteins and fatty molecules. Other biologists had seen this, too, and dismissed it as an artefact of the preparation. But Vance realized that the pieces were glued together for a reason, and that this could solve one of cell biology’s big mysteries.

In a 1990 paper, Vance showed that the meeting points between the ER and mitochondria were crucibles for the synthesis of lipids1. By bringing the two organelles together, these junctions could serve as portals for the transfer of newly made fats. This would answer the long-standing question of how mitochondria receive certain lipids — they are directly passed from the ER.

Yet most of her contemporaries, schooled in the idea that the gummy bits of ER were nothing more than contamination, doubted that such unions were important to cells. “I gave several presentations,” says Vance, “and people were sceptical.”

Not any more. Close to three decades later, Vance’s paper is seen as a landmark — one that has come to transform scientists’ understanding of how cells maintain order and function in their crowded interiors, which buzz with various types of organelles, including mitochondria, nuclei and the ER. Researchers now recognize that interactions between organelles are ubiquitous, with almost every type coming into close conversation with every other type. Probing those connections is also leading biologists to discover proteins that are responsible for holding the organelles together and maintaining a healthy cell.
...

FREE PDF GRATIS: Nature
FREE PDF GRATIS: Nature

https://www.nature.com/magazine-assets/d41586-019-00792-9/d41586-019-00792-9.pdf

Fora do tópico deste blog: transplante de úteros em mulheres que são geneticamente XY

sexta-feira, março 08, 2019

Uterus transplantation in women who are genetically XY

Amani Sampson1, Laura L. Kimberly2,3, Kara N. Goldman1, David L. Keefe1, Gwendolyn P. Quinn1,3

Author affiliations

Department of Obstetrics and Gynecology, New York University School of Medicine, New York City, New York, USA

Hansjörg Wyss Department of Plastic Surgery, New York University School of Medicine, New York City, New York, USA

Division of Medical Ethics, Department of Population Health, New York University School of Medicine, New York City, New York, USA

Correspondence to

Dr Gwendolyn P. Quinn, Obstetrics and Gynecology, NYU School of Medicine, New York NY 10016, USA; gwendolyn.quinn@nyumc.org


Abstract

Uterus transplantation is an emerging technology adding to the arsenal of treatments for infertility; specifically the only available treatment for uterine factor infertility. Ethical investigations concerning risks to uteri donors and transplant recipients have been discussed in the literature. However, missing from the discourse is the potential of uterus transplantation in other groups of genetically XY women who experience uterine factor infertility. There have been philosophical inquiries concerning uterus transplantation in genetically XY women, which includes transgender women and women with complete androgen insufficiency syndrome. We discuss the potential medical steps necessary and associated risks for uterus transplantation in genetically XY women. Presently, the medical technology does not exist to make uterus transplantation a safe and effective option for genetically XY women, however this group should not be summarily excluded from participation in trials. Laboratory research is needed to better understand and reduce medical risk and widen the field to all women who face uterine factor infertility.

+++++

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Contra Jerry Coyne et al: porque a ciência precisa da filosofia

Opinion: Why science needs philosophy

Lucie Laplane, Paolo Mantovani, Ralph Adolphs, Hasok Chang, Alberto Mantovani, Margaret McFall-Ngai, Carlo Rovelli, Elliott Sober, and Thomas Pradeu

PNAS March 5, 2019 116 (10) 3948-3952; 



Article

A knowledge of the historic and philosophical background gives that kind of independence from prejudices of his generation from which most scientists are suffering. This independence created by philosophical insight is—in my opinion—the mark of distinction between a mere artisan or specialist and a real seeker after truth.

Albert Einstein, Letter to Robert Thornton, 1944

Despite the tight historical links between science and philosophy, present-day scientists often perceive philosophy as completely different from, and even antagonistic to, science. We argue here that, to the contrary, philosophy can have an important and productive impact on science.



Despite the tight historical links between science and philosophy, hearkening back to Plato, Aristotle, and others (here evoked with Raphael’s famous School of Athens), present-day scientists often perceive philosophy as completely different from, and even antagonistic to, science. To the contrary, we believe philosophy can have an important and productive impact on science. Image credit: Shutterstock.com/Isogood_patrick.

We illustrate our point with three examples taken from various fields of the contemporary life sciences. Each bears on cutting-edge scientific research, and each has been explicitly acknowledged by practicing researchers as a useful contribution to science. These and other examples show that philosophy’s contribution can take at least four forms: the clarification of scientific concepts, the critical assessment of scientific assumptions or methods, the formulation of new concepts and theories, and the fostering of dialogue between different sciences, as well as between science and society.

FREE PDF GRATIS: PNAS

Eficiência da primeira lei da termodinâmica das proteínas de membrana: mero acaso, fortuita necessidade ou design inteligente?

quarta-feira, março 06, 2019

Thermodynamic first law efficiency of membrane proteins

Mert Gur, Mert Golcuk, Sema Zeynep Yilmaz & Elhan Taka

Received 15 Oct 2018, Accepted 29 Jan 2019, Accepted author version posted online: 06 Feb 2019, Published online: 04 Mar 2019

Source/Fonte: Nature


Abstract

Proteins are nature’s biomolecular machines. Proteins, such as transporters, pumps and motors, have complex function/operating-machinery/mechanisms, comparable to the macro-scaled machines that we encounter in our daily life. These proteins, as it is for their macro-scaled counterparts, convert (part of) other/various forms of energy into work. In this study, we are performing the first law analysis on a set of proteins, including the dopamine transporter, glycine transporters I and II, glutamate transporter, sodium–potassium pump and Ca2+ ATPase. Each of these proteins operates on a thermodynamic/mechanic cycle to perform their function. In each of these cycles, they receive energy from a source, convert part of this energy into work and reject the remaining part of the energy to the environment. Conservation of energy principle was applied to the thermodynamic/mechanic cycle of each protein, and thermodynamic first law efficiency was evaluated for each cycle, which shows how much of the energy input per cycle was converted into useful work. Interestingly, calculations based on experimental data indicate that proteins can operate under a range of efficiencies, which vary based on the extracellular and intracellular ion and substrate concentrations. The lowest observed first law efficiency was 50%, which is a very high value if compared to the efficiency of the macro-scaled heat engines we encounter in our daily lives.

Communicated by Ramaswamy H. Sarma

Keywords: Thermodynamics, first law analysis, first law efficiency, biomolecular machines, proteins, neurotransmitter transporters, ATP-powered pumps

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Origem da vida: um cenário geoquímico universal para condensação de formamida e a química prebiótica

Chemistry – A European Journal Volume 25, Issue 13
 
Review

Open Access

A Universal Geochemical Scenario for Formamide Condensation and Prebiotic Chemistry

Prof. Raffaele Saladino, Prof. Ernesto Di Mauro, Prof. Juan Manuel García‐Ruiz
 
First published: 19 September 2018


Abstract

The condensation of formamide has been shown to be a robust chemical pathway affording molecules necessary for the origin of life. It has been experimentally demonstrated that condensation reactions of formamide are catalyzed by a number of minerals, including silicates, phosphates, sulfides, zirconia, and borates, and by cosmic dusts and meteorites. However, a critical discussion of the catalytic power of the tested minerals, and the geochemical conditions under which the condensation would occur, is still missing. We show here that mineral self‐assembled structures forming under alkaline silica‐rich solutions are excellent catalysts for the condensation of formamide with respect to other minerals. We also propose that these structures were likely forming as early as 4.4 billion years ago when the whole earth surface was a reactor, a global scale factory, releasing large amounts of organic compounds. Our experimental results suggest that the conditions required for the synthesis of the molecular bricks from which life self‐assembles, rather than being local and bizarre, appears to be universal and geologically rather conventional
.
 
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Células usam açúcares para se comunicar em nível molecular

terça-feira, março 05, 2019

Encoding biological recognition in a bicomponent cell-membrane mimic

Cesar Rodriguez-Emmenegger, Qi Xiao, Nina Yu. Kostina, Samuel E. Sherman, Khosrow Rahimi, Benjamin E. Partridge, Shangda Li, Dipankar Sahoo, Aracelee M. Reveron Perez, Irene Buzzacchera, Hong Han, Meir Kerzner, Ishita Malhotra, Martin Möller, Christopher J. Wilson, Matthew C. Good, Mark Goulian, Tobias Baumgart, Michael L. Klein, and Virgil Percec

PNAS published ahead of print February 28, 2019 

Contributed by Michael L. Klein, January 22, 2019 (sent for review December 27, 2018; reviewed by Stephen Z. D. Cheng and Timothy J. Deming)

Models of nanosegregated bilayer structures

Significance

The seminal fluid mosaic model of the cell membranes suggests a lipid bilayer sea, in which cholesterol, proteins, glycoconjugates, and other components are swimming. Complementing this view, a microsegregated rafts model predicts clusters of components that function as relay stations for intracellular signaling and trafficking. However, elucidating the arrangement of glycoconjugates responsible for communication and recognition between cells, and cells with proteins remains a challenge. Herein, designed dendritic macromolecules are shown to self-assemble into vesicles that function as biological-membrane mimics with controlled density of sugar moieties on their periphery. Surprisingly, lowering sugar density elicits higher bioactivity to sugar-binding proteins. This finding informs a design principle for active complex soft matter with potential for applications in cellular biology and nanomedicine.

Abstract

Self-assembling dendrimers have facilitated the discovery of periodic and quasiperiodic arrays of supramolecular architectures and the diverse functions derived from them. Examples are liquid quasicrystals and their approximants plus helical columns and spheres, including some that disregard chirality. The same periodic and quasiperiodic arrays were subsequently found in block copolymers, surfactants, lipids, glycolipids, and other complex molecules. Here we report the discovery of lamellar and hexagonal periodic arrays on the surface of vesicles generated from sequence-defined bicomponent monodisperse oligomers containing lipid and glycolipid mimics. These vesicles, known as glycodendrimersomes, act as cell-membrane mimics with hierarchical morphologies resembling bicomponent rafts. These nanosegregated morphologies diminish sugar–sugar interactions enabling stronger binding to sugar-binding proteins than densely packed arrangements of sugars. Importantly, this provides a mechanism to encode the reactivity of sugars via their interaction with sugar-binding proteins. The observed sugar phase-separated hierarchical arrays with lamellar and hexagonal morphologies that encode biological recognition are among the most complex architectures yet discovered in soft matter. The enhanced reactivity of the sugar displays likely has applications in material science and nanomedicine, with potential to evolve into related technologies.

Janus glycodendrimers lipid rafts nanosegregation atomic force microscopy galectin

FREE PDF GRATIS: PNAS Sup. Info.

Colin Patterson perguntou: Vocês podem me dizer algo sobre a evolução, qualquer coisa, que seja verdade?" 2/2

quinta-feira, fevereiro 28, 2019





No dia 5 de novembro de 1981, Patterson deu uma palestra para o Grupo de Discussão de Sistemática no Museu Americano de História Natural, Nova York: 

"It's true that for the last eighteen months or so, I've been kicking around non-evolutionary or even anti-evolutionary ideas. I think always before in my life, when I've got up to speak on a subject, I've been confident of one thing – that I know more about it than anybody in the room, because I've worked on it.

Well, this time that isn't true. I'm speaking on two subjects, evolutionism and creationism, and I believe it's true to say that I know nothing whatever about either of them. One or the reasons I started taking this anti-evolutionary view, or let's call it non-evolutionary, was last year I had a sudden realization that for over twenty years I had thought that I was working on evolution in some way. Then one morning I woke up, and something had happened in the night, and it struck me that I had been working on this stuff for twenty years, and there was not one thing I knew about it. That's quite a shock, to learn that one can be so misled for so long.

So either there was something wrong with me, or there was something wrong with evolutionary theory. Naturally, I know there is nothing wrong with me, so for the last few weeks, I've tried putting a simple question to various people and groups of people.

The question is: Can you tell me anything you know about evolution, any one thing, any one thing that is true? I tried that question on the geology staff in the Field Museum of Natural History, and the only answer I got was silence. I tried it on the members of the Evolutionary Morphology Seminar at the University of Chicago, a very prestigious body of evolutionists, and all I got there was silence for a long time, and then eventually one person said, "Yes, I do know one thing. It ought not to be taught in high school.” [laughter]"

Colin Patterson perguntou: Vocês podem me dizer algo sobre a evolução, qualquer coisa, que seja verdade?" 1/2



No dia 5 de novembro de 1981, Patterson deu uma palestra para o Grupo de Discussão de Sistemática no Museu Americano de História Natural, Nova York: 

"It's true that for the last eighteen months or so, I've been kicking around non-evolutionary or even anti-evolutionary ideas. I think always before in my life, when I've got up to speak on a subject, I've been confident of one thing – that I know more about it than anybody in the room, because I've worked on it.

Well, this time that isn't true. I'm speaking on two subjects, evolutionism and creationism, and I believe it's true to say that I know nothing whatever about either of them. One or the reasons I started taking this anti-evolutionary view, or let's call it non-evolutionary, was last year I had a sudden realization that for over twenty years I had thought that I was working on evolution in some way. Then one morning I woke up, and something had happened in the night, and it struck me that I had been working on this stuff for twenty years, and there was not one thing I knew about it. That's quite a shock, to learn that one can be so misled for so long.

So either there was something wrong with me, or there was something wrong with evolutionary theory. Naturally, I know there is nothing wrong with me, so for the last few weeks, I've tried putting a simple question to various people and groups of people.

The question is: Can you tell me anything you know about evolution, any one thing, any one thing that is true? I tried that question on the geology staff in the Field Museum of Natural History, and the only answer I got was silence. I tried it on the members of the Evolutionary Morphology Seminar at the University of Chicago, a very prestigious body of evolutionists, and all I got there was silence for a long time, and then eventually one person said, "Yes, I do know one thing. It ought not to be taught in high school.” [laughter]"

Cresce o número de cientistas com Ph. D. céticos da teoria da evolução de Darwin

quarta-feira, fevereiro 27, 2019

Darwin, mais complexidade: arquiteturas supramoleculares de camadas molecularmente finas independentes, mas robustas

sexta-feira, fevereiro 22, 2019

Supramolecular architectures of molecularly thin yet robust free-standing layers

Mina Moradi1,2, Nadia L. Opara2,3, Ludovico G. Tulli1, Christian Wäckerlin4, Scott J. Dalgarno5, Simon J. Teat6, Milos Baljozovic2, Olha Popova7, Eric van Genderen2,*, Armin Kleibert8, Henning Stahlberg3, Jan Pieter Abrahams9,10, Celestino Padeste2, Philippe F.-X. Corvini1, Thomas A. Jung2,† and Patrick Shahgaldian1,†

1Institute of Chemistry and Bioanalytics, School of Life Sciences, University of Applied Sciences and Arts Northwestern Switzerland, Hofackerstrasse 35, CH-4132 Muttenz, Switzerland.

2Laboratory for Micro- and Nano-technology, Paul Scherrer Institute, Villigen CH-5232, Switzerland.

3Center for Cellular Imaging and NanoAnalytics (C-CINA), Biozentrum, University of Basel, Mattenstrasse 26, CH-4058 Basel, Switzerland.

4Empa–Swiss Federal Laboratories for Materials Science and Technology, CH-8600 Dübendorf, Switzerland.

5Institute of Chemical Sciences, Heriot-Watt University, Riccarton, Edinburgh, Scotland EH14 4AS, UK.

6Advanced Light Source, Lawrence Berkeley National Laboratory, 1 Cyclotron Road, MS6R2100, Berkeley, CA 94720, USA.

7Department of Physics, University of Basel, Klingelbergstrasse 82, 4056 Basel, Switzerland.

8Swiss Light Source, Paul Scherrer Institute, CH-5232 Villigen, Switzerland.

9Biozentrum, University of Basel, Switzerland and Laboratory of Biomolecular Research, Paul Scherrer Institute, Villigen, Switzerland.

10Institute of Biology Leiden, Leiden University, Sylviusweg 72, 2333 BE Leiden, Netherlands.

↵†Corresponding author. Email: patrick.shahgaldian@fhnw.ch (P.S.); thomas.jung@psi.ch (T.A.J.)

↵* Present address: Center for Cellular Imaging and NanoAnalytics (C-CINA), Biozentrum, University of Basel, Mattenstrasse 26, CH-4058 Basel, Switzerland.

Science Advances 22 Feb 2019: Vol. 5, no. 2, eaav4489



Fig. 3
Molecular resolution AFM imaging of the monolayer of 1.
(A) AFM images of the monolayer of 1 transferred onto HOPG via the LS method. (B) The high-resolution image of the crystalline network of the monolayer shows a highly ordered network formed from the single molecules of 1. [C (top view) and D (side view)] Molecular model of the building blocks of 1 interacting via the proposed dipole-dipole interaction in the well-ordered monolayer.

Abstract

Stable, single-nanometer thin, and free-standing two-dimensional layers with controlled molecular architectures are desired for several applications ranging from (opto-)electronic devices to nanoparticle and single-biomolecule characterization. It is, however, challenging to construct these stable single molecular layers via self-assembly, as the cohesion of those systems is ensured only by in-plane bonds. We herein demonstrate that relatively weak noncovalent bonds of limited directionality such as dipole-dipole (–CN⋅⋅⋅NC–) interactions act in a synergistic fashion to stabilize crystalline monomolecular layers of tetrafunctional calixarenes. The monolayers produced, demonstrated to be free-standing, display a well-defined atomic structure on the single-nanometer scale and are robust under a wide range of conditions including photon and electron radiation. This work opens up new avenues for the fabrication of robust, single-component, and free-standing layers via bottom-up self-assembly.

FREE PDF GRATIS: Science Advances Sup. Info.