Orientando a formação de proteínas: mero acaso, fortuita necessidade ou design inteligente?

quarta-feira, janeiro 06, 2021

Structural and mechanistic basis of the EMC-dependent biogenesis of distinct transmembrane clients


Lakshmi E Miller-Vedam, Bastian Bräuning, Katerina D Popova, Nicole T Schirle Oakdale, Jessica L Bonnar, Jesuraj R Prabu, Elizabeth A Boydston, Natalia Sevillano, Matthew J Shurtleff, Robert M Stroud, Charles S Craik, Brenda A Schulman Is a corresponding author, Adam Frost Is a corresponding author, Jonathan S Weissman Is a corresponding author s

Molecular, Cellular, and Computational Biophysics Graduate Program, University of California, San Francisco, United States; Department of Biochemistry and Biophysics, University of California, San Francisco, United States; Department of Biology, Whitehead Institute, MIT, United States; Department of Cellular and Molecular Pharmacology, University of California, San Francisco, United States; Department of Molecular Machines and Signaling, Max Planck Institute of Biochemistry, Germany; Biomedical Sciences Graduate Program, University of California, San Francisco, United States; Department of Pharmaceutical Chemistry, University of California, San Francisco, United States; Howard Hughes Medical Institute, United States


Three identical snapshots of the structure of human EMC:
Image credit: Lakshmi E Miller-Vedam, Bastian Bräuning and Katerina D Popova, created using UCSF ChimeraX (CC BY 4.0)

Abstract

Membrane protein biogenesis in the endoplasmic reticulum (ER) is complex and failure-prone. The ER membrane protein complex (EMC), comprising eight conserved subunits, has emerged as a central player in this process. Yet, we have limited understanding of how EMC enables insertion and integrity of diverse clients, from tail-anchored to polytopic transmembrane proteins. Here, yeast and human EMC cryo-EM structures reveal conserved intricate assemblies and human-specific features associated with pathologies. Structure-based functional studies distinguish between two separable EMC activities, as an insertase regulating tail-anchored protein levels and a broader role in polytopic membrane protein biogenesis. These depend on mechanistically coupled yet spatially distinct regions including two lipid-accessible membrane cavities which confer client-specific regulation, and a non-insertase EMC function mediated by the EMC lumenal domain. Our studies illuminate the structural and mechanistic basis of EMC’s multifunctionality and point to its role in differentially regulating the biogenesis of distinct client protein classes.

eLife digest

Cells are surrounded and contained by a plasma membrane consisting of a double layer of fats and proteins. These proteins monitor and facilitate the movement of food, oxygen and messages in and out of the cell, and help neighboring cells communicate. Membrane proteins are manufactured in a cell compartment called the endoplasmic reticulum. Cellular machines called ribosomes visit this compartment’s membrane to manufacture proteins that need to be secreted or embedded into the cell’s membranes. As these proteins are made, they are pulled into the endoplasmic reticulum so they can be folded correctly and inserted in the membrane. A cellular machine in this compartment’s membrane that aids this process is the endoplasmic reticulum membrane protein complex (EMC). Many steps can go wrong during protein assembly, so to control protein quality, the EMC has to accommodate the variety of complex physical features that proteins can have.

To explore the activity of the EMC, Miller-Vedam, Bräuning, Popova et al. studied the normal structure of the EMC in both yeast and human cells grown in the lab. These snapshots of the complex in different species had a lot in common, including how the complex was arranged within and around the membrane.

Next, Miller-Vedam, Bräuning, Popova et al. generated 50 mutant versions of the EMC in human cells to determine how changing different parts of the complex affected the production of three proteins that rely on the EMC to fold correctly. These proteins were an enzyme called squalene synthase, a signaling protein called the beta adrenergic receptor and sigma intracellular receptor 2, a protein involved in the regulation of cholesterol levels.

Mutations in the section of the EMC outside of the endoplasmic reticulum, within the main cellular compartment, negatively impacted the stability of squalene synthase. This section of the EMC provides a platform where proteins can associate before entering the membrane.

The part of EMC that spans the membrane contains both a fat-filled cavity and a cavity with a ‘door’ that is either open or closed. Mutations in this section disrupted the insertion of both squalene synthase and the beta adrenergic receptor into the membrane, a role performed by the cavity with the door. The specific role of the fat-filled cavity is still not fully understood, but a mutation affecting this cavity disrupts the correct production of all three proteins studied.

The largest section of the complex, which sits inside the endoplasmic reticulum, protected proteins as they folded, ensuring they were not destroyed for being folded incorrectly before they were fully formed. Mutations in this part of the EMC negatively impacted the stability of sigma intracellular receptor 2 without negatively affecting the other proteins.

This molecular dissection of the activity of the EMC provides insights into how membrane proteins are manufactured, stabilized, coordinated, and monitored for quality. These findings could contribute towards the development of new treatments for certain congenital diseases. For example, cystic fibrosis, retinitis pigmentosa, and Charcot-Marie-Tooth disease are all thought to be caused by mutations within membrane proteins that require the EMC during their production.

FREE PDF GRATIS: eLIFE

Gilbert 'falou e disse': a teoria da seleção natural de Darwin não funciona e precisa da teoria da recompensa natural!

terça-feira, janeiro 05, 2021

Natural reward drives the advancement of life

Owen M. Gilbert


Comparison of theories of natural selection and natural reward. A The theory of natural selection includes A only. B The theory of natural reward includes A and B, and the connection between them.

Abstract

Throughout the history of life on earth, rare and complex innovations have periodically increased the efficiency with which abiotic free energy and biotic resources are converted to biomass and organismal diversity. Such macroevolutionary expansions have increased the total amount of abiotic free energy utilized by life and shaped the earth’s ecosystems. Meanwhile, Darwin’s theory of natural selection assumes a historical, worldwide state of effective resource limitation, which could not possibly be true if life evolved from one or a few original ancestors. In this paper, I analyze the self-contradiction in Darwin’s theory that comes from viewing the world and universe as effectively resource limited. I then extend evolutionary theory to include a second deterministic evolutionary force, natural reward. Natural reward operates on complex inventions produced by natural selection and is analogous to the reward for innovation in human economic systems. I hypothesize that natural reward, when combined with climate change and extinction, leads to the increased innovativeness, or what I call the advancement, of life with time. I then discuss applications of the theory of natural reward to the evolution of evolvability, the apparent sudden appearance of new forms in the fossil record, and human economic evolution. I conclude that the theory of natural reward holds promise as an explanation for the historical advancement of life on earth.

Keywords

invention, entrepreneurship, innovation, success, progress, advancement

FREE PDF GRATIS: Rethinking Ecology

Nem todos os dinossauros morreram no impacto do grande asteroide Chicxulub há 66 milhões de anos!

domingo, janeiro 03, 2021

Over 13,000 elements from a single bonebed help elucidate disarticulation and transport of an Edmontosaurus thanatocoenosis

Keith Snyder, Matthew McLain, Jared Wood, Arthur Chadwick




Abstract

Over twenty years of work on the Hanson Ranch (HR) Bonebed in the Lance Formation of eastern Wyoming has yielded over 13,000 individual elements primarily of the hadrosaurid dinosaur Edmontosaurus annectens. The fossil bones are found normally-graded within a fine-grained (claystone to siltstone) bed that varies from one to two meters in thickness. Almost all specimens exhibit exquisite preservation (i.e., little to no abrasion, weathering, and breakage), but they are disarticulated which, combined with our sedimentological observations, suggests that the bones were remobilized and buried after a period of initial decay and disarticulation of Edmontosaurus carcasses. Because of the large number of recovered fossil elements, we have been able to gain deeper insight into Edmontosaurus biostratigraphy including disarticulation and transport of skeletal elements. The most common postcranial elements in the bonebed are pubes, ischia, scapulae, ribs, and limb bones. By contrast, vertebrae, ilia, and chevrons are rare. The most common craniomandibular bones include dentaries, nasals, quadrates, and jugals, whereas the premaxillae, predentaries, and braincase bones are underrepresented. Thus, overall, chondrocranial and axial elements, as well as distal elements of the limbs, are distinctly underrepresented. We hypothesize that following decay and disarticulation, hydraulic winnowing removed the articulated sections (e.g., vertebral columns) and the small, distal-most elements before, or at the same time, the remaining bones were swept up in a subaqueous debris flow that generated the deposit. Comparison of the HR Bonebed with other widely dispersed Upper Cretaceous hadrosaurid-dominated bonebeds reveals many shared attributes, which suggests similar processes at work in the formation of these bonebeds across space and time. This in turn reflects similar behavior by populations of these species around the world resulting in similar modes of death, becoming interred in similar depositional settings.

FREE PDF GRATIS: PLoS One

+++++

NOTA DESTE BLOGGER: O Dr. Arthur Chadwick é amigo pessoal deste blogger.

Mero acaso, fortuita necessidade ou design inteligente???

terça-feira, dezembro 29, 2020



Click here/Clique aqui: (157) Do You Love Me? - YouTube

Um megatsunami atingiu a costa israelense há 10.000 anos atrás.

segunda-feira, dezembro 28, 2020

A Neolithic mega-tsunami event in the eastern Mediterranean: Prehistoric settlement vulnerability along the Carmel coast, Israel

Gilad Shtienberg ,Assaf Yasur-Landau,Richard D. Norris,Michael Lazar,Tammy M. Rittenour,Anthony Tamberino,Omri Gadol,Katrina Cantu,Ehud Arkin-Shalev,Steven N. Ward,Thomas E. Levy

Published: December 23, 2020https://doi.org/10.1371/journal.pone.0243619




Abstract

Tsunami events in antiquity had a profound influence on coastal societies. Six thousand years of historical records and geological data show that tsunamis are a common phenomenon affecting the eastern Mediterranean coastline. However, the possible impact of older tsunamis on prehistoric societies has not been investigated. Here we report, based on optically stimulated luminescence chronology, the earliest documented Holocene tsunami event, between 9.91 to 9.29 ka (kilo-annum), from the eastern Mediterranean at Dor, Israel. Tsunami debris from the early Neolithic is composed of marine sand embedded within fresh-brackish wetland deposits. Global and local sea-level curves for the period, 9.91–9.29 ka, as well as surface elevation reconstructions, show that the tsunami had a run-up of at least ~16 m and traveled between 3.5 to 1.5 km inland from the palaeo-coastline. Submerged slump scars on the continental slope, 16 km west of Dor, point to the nearby “Dor-complex” as a likely cause. The near absence of Pre-Pottery Neolithic A-B archaeological sites (11.70–9.80 cal. ka) suggest these sites were removed by the tsunami, whereas younger, late Pre-Pottery Neolithic B-C (9.25–8.35 cal. ka) and later Pottery-Neolithic sites (8.25–7.80 cal. ka) indicate resettlement following the event. The large run-up of this event highlights the disruptive impact of tsunamis on past societies along the Levantine coast.

FREE PDF GRATIS: PLoS One

Nanomáquinas propulsoras: evolução convergente de arquelas, flagelos e cílios ou design inteligente?

terça-feira, dezembro 08, 2020

Propulsive nanomachines: the convergent evolution of archaella, flagella and cilia 

Morgan Beeby, Josie L Ferreira, Patrick Tripp, Sonja-Verena Albers, David R Mitchell 

FEMS Microbiology Reviews, Volume 44, Issue 3, May 2020, Pages 253–304, https://doi.org/10.1093/femsre/fuaa006 

Published: 09 March 2020

Flagellar motor structure - FEMS


ABSTRACT

Echoing the repeated convergent evolution of flight and vision in large eukaryotes, propulsive swimming motility has evolved independently in microbes in each of the three domains of life. Filamentous appendages – archaella in Archaea, flagella in Bacteria and cilia in Eukaryotes – wave, whip or rotate to propel microbes, overcoming diffusion and enabling colonization of new environments. The implementations of the three propulsive nanomachines are distinct, however: archaella and flagella rotate, while cilia beat or wave; flagella and cilia assemble at their tips, while archaella assemble at their base; archaella and cilia use ATP for motility, while flagella use ion-motive force. These underlying differences reflect the tinkering required to evolve a molecular machine, in which pre-existing machines in the appropriate contexts were iteratively co-opted for new functions and whose origins are reflected in their resultant mechanisms. Contemporary homologies suggest that archaella evolved from a non-rotary pilus, flagella from a non-rotary appendage or secretion system, and cilia from a passive sensory structure. Here, we review the structure, assembly, mechanism and homologies of the three distinct solutions as a foundation to better understand how propulsive nanomachines evolved three times independently and to highlight principles of molecular evolution.

flagella, cilia, archaella, molecular evolution, microbial motility, convergent evolution

FREE PDF GRATIS: FEMS Microbiology Reviews

Será que o cérebro humano se parece com o universo? Mero acaso, fortuita necessidade ou design inteligente?

terça-feira, novembro 17, 2020

Front. Phys., 16 November 2020 | https://doi.org/10.3389/fphy.2020.525731

The Quantitative Comparison Between the Neuronal Network and the Cosmic Web

www.frontiersin.orgF. Vazza1,2,3* and www.frontiersin.orgA. Feletti4,5

1Dipartimento di Fisica e Astronomia, Universitá di Bologna, , Bologna, Italy

2Hamburger Sternwarte, Hamburg, Germany

3Istituto di Radio Astronomia, INAF, Bologna, Italy

4Institute of Neurosurgery, Department of Neurosciences, Biomedicine, and Movement Sciences, University of Verona, Verona, Italy

5Azienda Ospedaliera‐Universitaria di Modena, Modena, Italy


1Left: section of cerebellum, with magnification factor 40x, obtained with electron microscopy (Dr. E. Zunarelli, University Hospital of Modena); right: section of a cosmological simulation, with an extension of 300 million light-years on each side (Vazza et al. 2019 A&A). Credit: University of Bologna

We investigate the similarities between two of the most challenging and complex systems in Nature: the network of neuronal cells in the human brain, and the cosmic network of galaxies. We explore the structural, morphological, network properties and the memory capacity of these two fascinating systems, with a quantitative approach. In order to have an homogeneous analysis of both systems, our procedure does not consider the true neural connectivity but an approximation of it, based on simple proximity. The tantalizing degree of similarity that our analysis exposes seems to suggest that the self-organization of both complex systems is likely being shaped by similar principles of network dynamics, despite the radically different scales and processes at play.

FREE PDF GRATIS: Frontiers in Physics

Mais uma hipótese sobre a origem da vida: modelos de precursores potenciais de células resistem às condições simuladas da Terra primitiva

quinta-feira, outubro 29, 2020

Impact of wet-dry cycling on the phase behavior and compartmentalization properties of complex coacervates

Hadi M. Fares, Alexander E. Marras, Jeffrey M. Ting, Matthew V. Tirrell & Christine D. Keating 

Nature Communications volume 11, Article number: 5423 (2020)



Abstract

Wet-dry cycling on the early Earth is thought to have facilitated production of molecular building blocks of life, but its impact on self-assembly and compartmentalization remains largely unexplored. Here, we investigate dehydration/rehydration of complex coacervates, which are membraneless compartments formed by phase separation of polyelectrolyte solutions. Solution compositions are identified for which tenfold water loss results in maintenance, disappearance, or appearance of coacervate droplets. Systems maintaining coacervates throughout the dehydration process are further evaluated to understand how their compartmentalization properties change with drying. Although added total RNA concentrations increase tenfold, RNA concentration within coacervates remains steady. Exterior RNA concentrations rise, and exchange rates for encapsulated versus free RNAs increase with dehydration. We explain these results in light of the phase diagram, with dehydration-driven ionic strength increase being particularly important in determining coacervate properties. This work shows that wet-dry cycling can alter the phase behavior and protocell-relevant functions of complex coacervates.

Editores de revistas científicas não devem contribuir para politizar a ciência!

segunda-feira, outubro 26, 2020

 Science journal editors shouldn’t contribute to politicizing science

By GENEVIEVE P. KANTER OCTOBER 23, 2020

Source/Fonte: Samuel Corum - Getty Images

When the editors of some of the world’s leading science journals agree on something, it is generally safe to assume that they are correct. So when prominent journals like ScienceNature, and the New England Journal of Medicine recently published editorials excoriating President Trump’s deadly bungling of the pandemic response and suppression of scientific activity, the editors accurately spotlighted the troubling deficiencies of the current administration.























































































But in advocating against or endorsing a presidential candidate, these editors made a grave error. In taking this extraordinary step, they made themselves vulnerable to charges of bias, overstepped their roles as science editors, and succumbed to the politicization of science that they and many other scientists find so alarming.

At first glance, these appear to be similar to run-of-the-mill newspaper endorsements. This analogy, however, is not quite right. At a newspaper, there is a wall between the news operation and the editorial office. It exists to prevent biases of the editorial staff from influencing news reporting. No such wall exists for science journals. The editors who write the editorials are the same ones who evaluate manuscripts and make the final decisions on whether to publish them.

There’s another problem: This political advocacy unnecessarily invites allusions to cronyism, echoing a less savory time when wealthy newspaper owners used their editorial pages to extol the merits of their political chums. Indeed, because of fears surrounding the appearance of undue influence and bias, many newspapers in recent years have abandoned political endorsements.

Read more here: STAT News

Transporte de membranas - elevadores condutores para o interior e exterior das células: mero acaso, fortuita necessidade ou design inteligente?

quinta-feira, outubro 15, 2020

Structural basis for the reaction cycle of DASS dicarboxylate transporters

David B Sauer, Noah Trebesch, Jennifer J Marden, Nicolette Cocco, Jinmei Song, Akiko Koide, Shohei Koide, Emad Tajkhorshid Is a corresponding author, Da-Neng Wang Is a corresponding author

Skirball Institute of Biomolecular Medicine, New York University School of Medicine, United States; Department of Cell Biology, New York University School of Medicine, United States; NIH Center for Macromolecular Modeling and Bioinformatics, Beckman Institute for Advanced Science and Technology, Department of Biochemistry, and Center for Biophysics and Quantitative Biology, University of Illinois at Urbana-Champaign, United States; Perlmutter Cancer Center, New York University School of Medicine, United States; Department of Medicine, New York University School of Medicine, United States; Department of Biochemistry and Molecular Pharmacology, New York University School of Medicine, United States

Research Article Sep 1, 2020



Abstract

Citrate, α-ketoglutarate and succinate are TCA cycle intermediates that also play essential roles in metabolic signaling and cellular regulation. These di- and tricarboxylates are imported into the cell by the divalent anion sodium symporter (DASS) family of plasma membrane transporters, which contains both cotransporters and exchangers. While DASS proteins transport substrates via an elevator mechanism, to date structures are only available for a single DASS cotransporter protein in a substrate-bound, inward-facing state. We report multiple cryo-EM and X-ray structures in four different states, including three hitherto unseen states, along with molecular dynamics simulations, of both a cotransporter and an exchanger. Comparison of these outward- and inward-facing structures reveal how the transport domain translates and rotates within the framework of the scaffold domain through the transport cycle. Additionally, we propose that DASS transporters ensure substrate coupling by a charge-compensation mechanism, and by structural changes upon substrate release.

FREE PDF GRATIS: eLIFE

Se o Big Bang não foi o começo, foi o que?

terça-feira, setembro 22, 2020

FORBES

Sep 17, 2020,02:00am EDT

If The Big Bang Wasn’t The Beginning, What Was It?

Ethan Siegel Senior Contributor

Starts With A Bang Contributor Group

Science

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


Our entire cosmic history is theoretically well-understood, but only because we understand the theory of gravitation that underlies it, and because we know the Universe's present expansion rate and energy composition. Light will always continue to propagate through this expanding Universe, and we will continue to receive that light arbitrarily far into the future, but it will be limited in time as far as what reaches us. We still have unanswered questions about our cosmic origins, but the age of the Universe is known. NICOLE RAGER FULLER / NATIONAL SCIENCE FOUNDATION

For more than 50 years, we’ve had definitive scientific evidence that our Universe, as we know it, began with the hot Big Bang. The Universe is expanding, cooling, and full of clumps (like planets, stars, and galaxies) today because it was smaller, hotter, denser, and more uniform in the past. If you extrapolate all the way back to the earliest moments possible, you can imagine that everything we see today was once concentrated into a single point: a singularity, which marks the birth of space and time itself.

At least, we thought that was the story: the Universe was born a finite amount of time ago, and started off with the Big Bang. Today, however, we know a whole lot more than we did back then, and the picture isn’t quite so clear. The Big Bang can no longer be described as the very beginning of the Universe that we know, and the hot Big Bang almost certainly doesn’t equate to the birth of space and time. So, if the Big Bang wasn’t truly the beginning, what was it? Here’s what the science tells us.

Our Universe, as we observe it today, almost certainly emerged from a hot, dense, almost-perfectly uniform state early on. In particular, there are four pieces of evidence that all point to this scenario:

- the Hubble expansion of the Universe, which shows that the amount that light from a distant object is redshifted is proportional to the distance to that object,

- the existence of a leftover glow — the Cosmic Microwave Background (CMB) — in all directions, with the same temperature everywhere just a few degrees above absolute zero,

- light elements — hydrogen, deuterium, helium-3, helium-4, and lithium-7 — that exist in a particular ratio of abundances back before any stars were formed,

- and a cosmic web of structure that gets denser and clumpier, with more space between larger and larger clumps, as time goes on.

FULL TEXT/TEXTO COMPLETO: FORBES

Megalodon, um antigo tubarão extinto de grande dimensão corporal.

segunda-feira, setembro 07, 2020

Body dimensions of the extinct giant shark Otodus megalodon: a 2D reconstruction

Jack A. Cooper, Catalina Pimiento, Humberto G. Ferrón & Michael J. Benton 

Scientific Reports volume 10, Article number: 14596 (2020) 




Abstract

Inferring the size of extinct animals is fraught with danger, especially when they were much larger than their modern relatives. Such extrapolations are particularly risky when allometry is present. The extinct giant shark †Otodus megalodon is known almost exclusively from fossilised teeth. Estimates of †O. megalodon body size have been made from its teeth, using the great white shark (Carcharodon carcharias) as the only modern analogue. This can be problematic as the two species likely belong to different families, and the position of the †Otodus lineage within Lamniformes is unclear. Here, we infer †O. megalodon body dimensions based on anatomical measurements of five ecologically and physiologically similar extant lamniforms: Carcharodon carcharias, Isurus oxyrinchus, Isurus paucus, Lamna ditropis and Lamna nasus. We first assessed for allometry in all analogues using linear regressions and geometric morphometric analyses. Finding no evidence of allometry, we made morphological extrapolations to infer body dimensions of †O. megalodon at different sizes. Our results suggest that a 16 m †O. megalodon likely had a head ~ 4.65 m long, a dorsal fin ~ 1.62 m tall and a tail ~ 3.85 m high. Morphometric analyses further suggest that its dorsal and caudal fins were adapted for swift predatory locomotion and long-swimming periods.

FREE PDF GRATIS: Scientific Reports

A estátua de Darwin vai ser demolida por causa do seu livro racista The Descent of Man???

Natural History Museum to review potentially 'offensive' Charles Darwin collection

An internal review in the wake of the Black Lives Matter protests has led to an audit into some rooms and items


By Craig Simpson

5 September 2020 • 7:00pm

Museum bosses are now desperately seeking to address what some staff believe are “legacies of colonies, slavery and empire” by potentially renaming, relabelling, or removing these traces in the institution.

The executive board told staff in documents seen by The Sunday Telegraph that “in light of Black Lives Matter and the recent anti-racist demonstrations around the world” the museum would undertake a review of existing room names and “whether any statues (or collections) or could potentially cause offence”.One of the institution’s directors said in internal documents that new action taken to address these issues would alter “the use and display of our collections and public spaces”.

Craig Simpson, “Natural History Museum to review potentially ‘offensive’ Charles Darwin collection” at Telegraph

+++++

Nota deste blogger: Eu considero deplorável a derrubada/demolição de estátuas pelo seu valor histórico. Que Darwin era racista, e racista sutil, sempre expus aqui neste blog, apesar de seus outros escritos e defensores contemporâneos dizerem o contrário. A fúria da cultura do cancelamento vai demolir a estátua de Darwin no Museu de História Natural em Londres? É melhor proteger sua estátua ali.

Ajuste fino de máquinas e sistemas moleculares: mero acaso, fortuita necessidade ou design inteligente?

sexta-feira, setembro 04, 2020

Journal of Theoretical Biology

Volume 501, 21 September 2020, 110352

Using statistical methods to model the fine-tuning of molecular machines and systems 

Steinar Thorvaldsen a Ola Hössjer b

https://doi.org/10.1016/j.jtbi.2020.110352

Under a Creative Commons license Open Access



Highlights

• Statistical methods are appropriate for modelling fine-tuning.

• Fine-tuning is detected in functional proteins, cellular networks etc.

• Constants and initial conditions of nature are deliberately tuned.

• Statistical analysis of fine-tuning model some of the categories of design.

• Fine-tuning and design deserve attention in the scientific community.

Abstract

Fine-tuning has received much attention in physics, and it states that the fundamental constants of physics are finely tuned to precise values for a rich chemistry and life permittance. It has not yet been applied in a broad manner to molecular biology. However, in this paper we argue that biological systems present fine-tuning at different levels, e.g. functional proteins, complex biochemical machines in living cells, and cellular networks. This paper describes molecular fine-tuning, how it can be used in biology, and how it challenges conventional Darwinian thinking. We also discuss the statistical methods underpinning fine-tuning and present a framework for such analysis.

Se não há ancestral comum e nem seleção natural, por que ainda chamamos de evolução?

quinta-feira, setembro 03, 2020

Annals of the New York Academy of Sciences


Patterns and impacts of nonvertical evolution in eukaryotes: a paradigm shift

Toni Gabaldón

First published: 28 August 2020 https://doi.org/10.1111/nyas.14471



Abstract

Evolution of eukaryotic species and their genomes has been traditionally understood as a vertical process in which genetic material is transmitted from parents to offspring along a lineage, and in which genetic exchange is restricted within species boundaries. However, mounting evidence from comparative genomics indicates that this paradigm is often violated. Horizontal gene transfer and mating between diverged lineages blur species boundaries and challenge the reconstruction of evolutionary histories of species and their genomes. Nonvertical evolution might be more restricted in eukaryotes than in prokaryotes, yet it is not negligible and can be common in certain groups. Recognition of such processes brings about the need to incorporate this complexity into our models, as well as to conceptually reframe eukaryotic diversity and evolution. Here, I review the recent work from genomics studies that supports the effects of nonvertical modes of evolution including introgression, hybridization, and horizontal gene transfer in different eukaryotic groups. I then discuss emerging patterns and effects, illustrated by specific examples, that support the conclusion that nonvertical processes are often at the root of important evolutionary transitions and adaptations. I will argue that a paradigm shift is needed to naturally accommodate nonvertical processes in eukaryotic evolution.

Site sobre bioluminescência

quarta-feira, setembro 02, 2020

 Pyrosomes, colonial salps, continue to be one of the most mysterious of bioluminescent organisms. Their glow can last 15 seconds or more, and it can be triggered by light, even cascading from one end of the colony to the other. The chemical origin remains unknown. It was thought to be bacterial, in part because of similar kinetics, but now appears to be intrinsic chemistry that lets this animal emit its impressive glow.

https://biolum.eemb.ucsb.edu 

A ontogenia da nadadeira sarcopterígea elucida a origem das mãos com dedos

quarta-feira, agosto 26, 2020

Sarcopterygian fin ontogeny elucidates the origin of hands with digits

Joost M. Woltering1,*, Iker Irisarri1,†, Rolf Ericsson2,‡, Jean M. P. Joss2, Paolo Sordino3 and Axel Meyer1

Science Advances 19 Aug 2020:

Vol. 6, no. 34, eabc3510



Abstract

How the hand and digits originated from fish fins during the Devonian fin-to-limb transition remains unsolved. Controversy in this conundrum stems from the scarcity of ontogenetic data from extant lobe-finned fishes. We report the patterning of an autopod-like domain by hoxa13 during fin development of the Australian lungfish, the most closely related extant fish relative of tetrapods. Differences from tetrapod limbs include the absence of digit-specific expansion of hoxd13 and hand2 and distal limitation of alx4 and pax9, which potentially evolved through an enhanced response to shh signaling in limbs. These developmental patterns indicate that the digit program originated in postaxial fin radials and later expanded anteriorly inside of a preexisting autopod-like domain during the evolution of limbs. Our findings provide a genetic framework for the transition of fins into limbs that supports the significance of classical models proposing a bending of the tetrapod metapterygial axis.

FREE PDF GRATIS: Science Advances

Introduction to Phylogenetic Networks - David A. Morrison

quinta-feira, agosto 20, 2020

 

Recent advances in rooted phylogenetic networks: the long road to ...

FREE DOWNLOAD GRATIS

Darwin, o problema da forma biológica permanece sem solução, mano!

segunda-feira, agosto 17, 2020

 On the problem of biological form

Marta Linde-Medina 

Theory in Biosciences volume 139, pages299–308(2020)

Ver a imagem de origem

Source/Fonte

Abstract

Embryonic development, which inspired the first theories of biological form, was eventually excluded from the conceptual framework of the Modern Synthesis as irrelevant. A major question during the last decades has centred on understanding whether new advances in developmental biology are compatible with the standard view or whether they compel a new theory. Here, I argue that the answer to this question depends on which concept of morphogenesis is held. Morphogenesis can be conceived as (1) a chemically driven or (2) a mechanically driven process. According to the first option, genetic regulatory networks drive morphogenesis. According to the second, morphogenesis results from an invariant tendency of embryonic tissues to restore changes in mechanical stress. While chemically driven morphogenesis allows an extension of the standard view, mechanically driven morphogenesis would deeply transform it. Which of these hypotheses has wider explanatory power is unknown. At present, the problem of biological form remains unsolved.

Subscription or payment needed/Requer assinatura ou pagamento: Theory in Biosciences

Darwin, modelar a biologia evolutiva na física não funciona, mano!

Historicity at the heart of biology

Maël Montévil 

Theory in Biosciences (2020)


Abstract

Most mathematical modeling in biology relies either implicitly or explicitly on the epistemology of physics. The underlying conception is that the historicity of biological objects would not matter to understand a situation here and now, or, at least, historicity would not impact the method of modeling. We analyze that it is not the case with concrete examples. Historicity forces a conceptual reconfiguration where equations no longer play a central role. We argue that all observations depend on objects defined by their historical origin instead of their relations as in physics. Therefore, we propose that biological variations and historicity come first, and regularities are constraints with limited validity in biology. Their proper theoretical and empirical use requires specific rationales.

Subscription or payment needed/Requer assinatura ou pagamento: Theory in Biosciences

Artigo de 2017 esperava sanar as fissuras/encobrir as rachaduras na biologia evolutiva

Evolutionary Biology volume 45, pages 127–139 (2018)

Hierarchy Theory of Evolution and the Extended Evolutionary Synthesis: Some Epistemic Bridges, Some Conceptual Rifts

Alejandro Fábregas-Tejeda & Francisco Vergara-Silva

Ver a imagem de origem

Abstract: 

Contemporary evolutionary biology comprises a plural landscape of multiple co-existent conceptual frameworks and strenuous voices that disagree on the nature and scope of evolutionary theory. Since the mid-eighties, some of these conceptual frameworks have denounced the ontologies of the Modern Synthesis and of the updated Standard Theory of Evolution as unfinished or even flawed. In this paper, we analyze and compare two of those conceptual frameworks, namely Niles Eldredge’s Hierarchy Theory of Evolution (with its extended ontology of evolutionary entities) and the Extended Evolutionary Synthesis (with its proposal of an extended ontology of evolutionary processes), in an attempt to map some epistemic bridges (e.g. compatible views of causation; niche construction) and some conceptual rifts (e.g. extra-genetic inheritance; different perspectives on macroevolution; contrasting standpoints held in the “externalism–internalism” debate) that exist between them. This paper seeks to encourage theoretical, philosophical and historiographical discussions about pluralism or the possible unification of contemporary evolutionary biology.

Subscription or payment needed/Requer assinatura ou pagamento: Evolutionary Biology

Microscopia revisitada

Revealing architectural order with quantitative label-free imaging and deep learning

Syuan-Ming Guo, Li-Hao Yeh, Jenny Folkesson, Ivan E Ivanov, Anitha P Krishnan, Matthew G Keefe, Ezzat Hashemi, David Shin, Bryant B Chhun, Nathan H Cho, Manuel D Leonetti, May H Han, Tomasz J Nowakowski, Shalin B Mehta 

Chan Zuckerberg Biohub, United States; Department of Anatomy, University of California, San Francisco, United States; Department of Neurology, Stanford University, United States



Abstract

We report quantitative label-free imaging with phase and polarization (QLIPP) for simultaneous measurement of density, anisotropy, and orientation of structures in unlabeled live cells and tissue slices. We combine QLIPP with deep neural networks to predict fluorescence images of diverse cell and tissue structures. QLIPP images reveal anatomical regions and axon tract orientation in prenatal human brain tissue sections that are not visible using brightfield imaging. We report a variant of U-Net architecture, multi-channel 2.5D U-Net, for computationally efficient prediction of fluorescence images in three dimensions and over large fields of view. Further, we develop data normalization methods for accurate prediction of myelin distribution over large brain regions. We show that experimental defects in labeling the human tissue can be rescued with quantitative label-free imaging and neural network model. We anticipate that the proposed method will enable new studies of architectural order at spatial scales ranging from organelles to tissue.

eLife digest

Microscopy is central to biological research and has enabled scientist to study the structure and dynamics of cells and their components within. Often, fluorescent dyes or trackers are used that can be detected under the microscope. However, this procedure can sometimes interfere with the biological processes being studied.

Now, Guo, Yeh, Folkesson et al. have developed a new approach to examine structures within tissues and cells without the need for a fluorescent label. The technique, called QLIPP, uses the phase and polarization of the light passing through the sample to get information about its makeup.

A computational model was used to decode the characteristics of the light and to provide information about the density and orientation of molecules in live cells and brain tissue samples of mice and human. This way, Guo et al. were able to reveal details that conventional microscopy would have missed. Then, a type of machine learning, known as ‘deep learning’, was used to translate the density and orientation images into fluorescence images, which enabled the researchers to predict specific structures in human brain tissue sections.

QLIPP can be added as a module to a microscope and its software is available open source. Guo et al. hope that this approach can be used across many fields of biology, for example, to map the connectivity of nerve cells in the human brain or to identify how cells respond to infection. However, further work in automating other aspects, such as sample preparation and analysis, will be needed to realize the full benefits.

FREE PDF GRATIS: eLife

Mais uma hipótese sobre a origem da vida: surgimento de atividade catalítica em um autorreplicador

terça-feira, agosto 04, 2020

Chance emergence of catalytic activity and promiscuity in a self-replicator

Jim Ottelé, Andreas S. Hussain, Clemens Mayer & Sijbren Otto

Nature Catalysis volume 3, pages547–553(2020)



Abstract

How life can emerge from inanimate matter is one of the grand questions in science. Self-replicating molecules are necessary for the transition from chemistry to biology, but they need to acquire additional functions for life to emerge. Catalysis is one of the most essential of such functionalities, but mechanisms through which self-replicators can acquire catalytic and, in extension, metabolic properties have remained elusive. Here we show how catalytic activity and promiscuity in a self-replicator emerges through co-option: features that are selected to benefit replication inadvertently result in an arrangement of chemical functionalities that is conducive to catalysis. Specifically, we report self-assembly driven self-replicators that promote both a model retro-aldol reaction and the cleavage of fluorenylmethoxycarbonyl groups, with the latter transformation exerting a positive feedback on replication (protometabolism). Such chance invention of new function at the molecular level marks a pivotal step toward the de novo synthesis of life.

SUBSCRIPTION OR PAYMENT NEEDED/REQUER ASSINATURA OU PAGAMENTO:

O impacto de Darwin na sociedade em menos de 3 minutos

sexta-feira, julho 31, 2020

<iframe width="560" height="315" src="https://www.youtube.com/embed/HzLkvoj5TTc" frameborder="0" allow="accelerometer; autoplay; encrypted-media; gyroscope; picture-in-picture" allowfullscreen></iframe>

Origem da Vida: o dilema da mão de Deus???

quinta-feira, julho 30, 2020

Prebiotic chemistry and human intervention

Clemens Richert 

Nature Communications

Source/Fonte:

Abstract

Experimentalists in the field of prebiotic chemistry strive to re-enact what may have happened when life arose from inanimate material. How often human intervention was needed to obtain a specific result in their studies is worth reporting.

FREE PDF GRATIS: Nature Communications

+++++

EXCERPT/EXCERTO

Plausibility is important. So, perhaps it is time to think about ways out of the “Hand of God” dilemma.
...
...one may want to state more explicitly what prebiotic scenario a specific experiment is believed to address. This will not solve the “Hand of God dilemma”, but it may allow the reader to gauge what geochemical conditions were assumed when the experiment was planned.