Os efeitos da nicotina são transmitidos através das gerações de ratos: Lamarck redivivus???

Nicotine exposure of male mice produces behavioral impairment in multiple generations of descendants

Deirdre M. McCarthy, Thomas J. Morgan Jr., Sarah E. Lowe, Matthew J. Williamson, Thomas J. Spencer, Joseph Biederman, Pradeep G. Bhide 

Published: October 16, 2018 https://doi.org/10.1371/journal.pbio.2006497

Source/Fonte: The Scientist

Abstract

Use of tobacco products is injurious to health in men and women. However, tobacco use by pregnant women receives greater scrutiny because it can also compromise the health of future generations. More men smoke cigarettes than women. Yet the impact of nicotine use by men upon their descendants has not been as widely scrutinized. We exposed male C57BL/6 mice to nicotine (200 μg/mL in drinking water) for 12 wk and bred the mice with drug-naïve females to produce the F1 generation. Male and female F1 mice were bred with drug-naïve partners to produce the F2 generation. We analyzed spontaneous locomotor activity, working memory, attention, and reversal learning in male and female F1 and F2 mice. Both male and female F1 mice derived from the nicotine-exposed males showed significant increases in spontaneous locomotor activity and significant deficits in reversal learning. The male F1 mice also showed significant deficits in attention, brain monoamine content, and dopamine receptor mRNA expression. Examination of the F2 generation showed that male F2 mice derived from paternally nicotine-exposed female F1 mice had significant deficits in reversal learning. Analysis of epigenetic changes in the spermatozoa of the nicotine-exposed male founders (F0) showed significant changes in global DNA methylation and DNA methylation at promoter regions of the dopamine D2 receptor gene. Our findings show that nicotine exposure of male mice produces behavioral changes in multiple generations of descendants. Nicotine-induced changes in spermatozoal DNA methylation are a plausible mechanism for the transgenerational transmission of the phenotypes. These findings underscore the need to enlarge the current focus of research and public policy targeting nicotine exposure of pregnant mothers by a more equitable focus on nicotine exposure of the mother and the father.

Author summary

Use of tobacco products is a major public health concern throughout the world. Cigarette smoking by pregnant women receives significant attention by scientific, public health, and public policy experts because it poses health risks for the mother and her children. Although more men smoke cigarettes than women, the health consequences of paternal smoking for their descendants are much less explored. Using a mouse model, we show that the offspring of nicotine-exposed males have hyperactivity, attention deficit, and cognitive inflexibility. These behavioral phenotypes are associated with attention deficit hyperactivity disorder (ADHD) and autism spectrum disorder in humans. Cognitive inflexibility persists into the third (F2) generation. The neurotransmitters dopamine and noradrenaline and their receptors, critically implicated in neurodevelopmental disorders, are also altered in the offspring’s brains. The nicotine-exposed males show significant alterations in spermatozoal DNA methylation patterns, especially at dopamine receptor gene promoter regions, implicating epigenetic modification of germ cell DNA as a mechanism for the transgenerational transmission of the behavioral and neurotransmitter phenotypes. The impact of nicotine on germ cells and the neurobehavioral impairments in multiple subsequent generations call for renewed focus of research and public policy on tobacco use by men and its consequences for their descendants.

Citation: McCarthy DM, Morgan TJ Jr, Lowe SE, Williamson MJ, Spencer TJ, Biederman J, et al. (2018) Nicotine exposure of male mice produces behavioral impairment in multiple generations of descendants. PLoS Biol 16(10): e2006497. https://doi.org/10.1371/journal.pbio.2006497

Academic Editor: Eric Nestler, Icahn School of Medicine at Mount Sinai, United States of America

Received: April 27, 2018; Accepted: September 13, 2018; Published: October 16, 2018

Copyright: © 2018 McCarthy 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: All relevant data are within the paper and its Supporting Information files.

Funding: Jim and Betty Anne Rodgers Chair Fund at Florida State University (grant number F00662). The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Escher Fund for Autism http://www.germlineexposures.org (grant number). The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. National Institute on Drug Abuse https://www.drugabuse.gov/ (grant number R15 DA043848). The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Competing interests: I have read the journal's policy and the authors of this manuscript have the following potential competing interests. Pradeep Bhide: Dr. Bhide is a co-founder and consultant to Avekshan LLC, Tallahassee, FL, a pharmaceutical enterprise engaged in the development of novel therapies for attention deficit hyperactivity disorder (ADHD). Dr. Bhide is an inventor in following patents or patent applications relevant to ADHD therapy: US Patent, “Class of non-stimulant treatment and ADHD and related disorders” (#US9623023 B2), and US patent application, “Methods and compositions to prevent addiction (#US20130289061 A1). Deirdre McCarthy: Ms. McCarthy is a co-founder and consultant to Avekshan LLC, Tallahassee, FL, a pharmaceutical enterprise engaged in the development of novel therapies for attention deficit hyperactivity disorder (ADHD). Thomas Spencer: Dr. Spencer received research support or was a consultant from the following sources: Alcobra, Avekshan, Ironshore, Lundbeck, Shire Laboratories Inc, Sunovion, the FDA, and the Department of Defense. Consultant fees are paid to the Clinical Trials Network at the Massachusetts General Hospital (MGH) and not directly to Dr. Spencer. Dr. Spencer has been on an advisory board for the following pharmaceutical companies: Alcobra. Dr. Spencer received research support from Royalties and Licensing fees on copyrighted ADHD scales through MGH Corporate Sponsored Research and Licensing. Through MGH corporate licensing, Dr. Spencer is an inventor on a US Patent, “Class of non-stimulant treatment and ADHD and related disorders” (#US9623023 B2), and US patent application, “Methods and compositions to prevent addiction" (#US20130289061 A1). Joseph Biederman: Dr. Biederman is currently receiving research support from the following sources: AACAP, The Department of Defense, Food & Drug Administration, Headspace, Lundbeck, Neurocentria Inc., NIDA, PamLab, Pfizer, Shire Pharmaceuticals Inc., Sunovion, and NIH. Dr. Biederman has a financial interest in Avekshan LLC, a company that develops treatments for attention deficit hyperactivity disorder (ADHD). His interests were reviewed and are managed by Massachusetts General Hospital and Partners HealthCare in accordance with their conflict of interest policies. Dr. Biederman’s program has received departmental royalties from a copyrighted rating scale used for ADHD diagnoses, paid by Ingenix, Prophase, Shire, Bracket Global, Sunovion, and Theravance; these royalties were paid to the Department of Psychiatry at MGH. In 2017, Dr. Biederman is a consultant for Aevi Genomics, Akili, Guidepoint, Ironshore, Medgenics, and Piper Jaffray. He is on the scientific advisory board for Alcobra and Shire. He received honoraria from the MGH Psychiatry Academy for tuition-funded CME courses. Through MGH corporate licensing, he is an inventor on US Patent, “Class of non-stimulant treatment and ADHD and related disorders” (#US9623023 B2), and US patent application, “Methods and compositions to prevent addiction (#US20130289061 A1). In 2016, Dr. Biederman received honoraria from the MGH Psychiatry Academy for tuition-funded CME courses, and from Alcobra and APSARD. He was on the scientific advisory board for Arbor Pharmaceuticals. He was a consultant for Akili and Medgenics. He received research support from Merck and SPRITES. Thomas Morgan, Sara Lowe, and Matthew Williamson have no competing interests to declare.

Abbreviations: 3-MT, 3-methoxytyramine; ADHD, attention deficit hyperactivity disorder; DOPAC, 3,4-dihydroxyphenylacetic acid; HVA, homovanillic acid; MeDIP, methylated DNA immunoprecipitation; miRNA, microRNA; NE, norepinephrine; P0, postnatal day 0; qPCR, quantitative PCR

FREE PDF GRATIS: PLoS Biology

Princípios da geometria química subjacente à seletividade quiral na aminoacilação da mini hélice do RNA: mero acaso, fortuita necessidade ou design inteligente?

Principles of chemical geometry underlying chiral selectivity in RNA minihelix aminoacylation 

Tadashi Ando Shunichi Takahashi Koji Tamura

Nucleic Acids Research, Volume 46, Issue 21, 30 November 2018, Pages 11144–11152, https://doi.org/10.1093/nar/gky909

Published: 15 October 2018 

Article history

Received: 08 August 2018 Revision Received: 10 September 2018

Accepted: 02 October 2018

 

Source/Fonte: Courses Lumen Learning

Abstract

The origin of homochirality in L-amino acid in proteins is one of the mysteries of the evolution of life. Experimental studies show that a non-enzymatic aminoacylation reaction of an RNA minihelix has a preference for L-amino acid over D-amino acid. The reaction initiates by approaching of a 3′-oxygen of the RNA minihelix to the carbonyl carbon of an aminoacyl phosphate oligonucleotide. Here, employing molecular dynamics simulations, we examined the possible mechanisms that determine this chiral selectivity. The simulation system adopted a geometry required for the chemical reaction to occur more frequently with L-alanine than that with D-alanine. For L-alanine, the structure with this geometry was formed by a combination of stable dihedral angles along alanyl phosphate backbone with a canonical RNA structure, where the methyl group of alanine was placed on the opposite side of the approaching 3′-hydroxyl group with respect to the carbonyl plane. For D-alanine, the methyl group and the 3′-hydroxyl group were placed on the same side with respect to the carbonyl plane, which significantly decreased its ability to approach 3′-oxygen close to the carbonyl carbon compared to L-alanine. The mechanism suggested herein can explain experimentally observed chiral preferences.

Issue Section: Chemical Biology and Nucleic Acid Chemistry

FREE PDF GRATIS: Nucleic Acids Research Sup. Info.

Darwin, durma com um barulho desses: as celebridades foram convocadas para alavancar maior aceitação da teoria da evolução na sociedade!

Celebrity Opinion Influences Public Acceptance of Human Evolution

Steven Arnocky, Emma Bozek, Caroline Dufort, Samantha Rybka, Robyn Hebert

First Published September 19, 2018 Research Article 

https://doi.org/10.1177/1474704918800656

Article information 

Article has an altmetric score of 118 Open Access Creative Commons Attribution, Non Commercial 4.0 License

Article Information

Volume: 16 issue: 3,

Article first published online: September 19, 2018; Issue published: July 1, 2018 

Received: July 06, 2017; Accepted: August 21, 2018

Steven Arnocky1, Emma Bozek1, Caroline Dufort1, Samantha Rybka1, Robyn Hebert1

1 Nipissing University, North Bay, Ontario, Canada

Corresponding Author: Steven Arnocky, Department of Psychology, Nipissing University, 100 College Drive, North Bay, Ontario, Canada P1B 8L7. Email: stevena@nipissingu.ca

This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License (http://www.creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages (https://us.sagepub.com/en-us/nam/open-access-at-sage).

Source/Fonte: Justin Bieber, by Lou Stejskal [CC BY 2.0], via Wikimedia Commons.

Abstract

The present research examined the influence of celebrity opinion upon individuals’ acceptance of the theory of evolution. Priming stimuli were developed purveying pro-evolution, anti-evolution, or neutral opinion (Study 1). When paired with a male celebrity or expert source (Study 2), the male celebrity, but not the male expert, influenced undergraduates’ acceptance of evolution. The influence of the male celebrity on acceptance of evolution was replicated in a community sample (Study 3). When paired with a female celebrity source, undergraduates’ acceptance of evolution was similarly influenced (Study 4). Together, these findings extend our understanding of the reach of credible celebrity endorsers beyond consumer behavior to core individual beliefs, such as those surrounding the acceptance of human evolution.

Keywords celebrity, interpersonal influences, social influences, theory of evolution, religiosity, attitudes

FREE PDF GRATIS: Evolutionary Psychology

O oxigênio poderia estar disponível para a vida tão cedo quanto 3.5 bilhões de anos atrás

Early Archean origin of Photosystem II

Tanai Cardona, Patricia Sánchez‐Baracaldo, A. William Rutherford, Anthony W. Larkum

First published: 09 November 2018
https://doi.org/10.1111/gbi.12322

Abstract

Photosystem II is a photochemical reaction center that catalyzes the light‐driven oxidation of water to molecular oxygen. Water oxidation is the distinctive photochemical reaction that permitted the evolution of oxygenic photosynthesis and the eventual rise of eukaryotes. At what point during the history of life an ancestral photosystem evolved the capacity to oxidize water still remains unknown. Here, we study the evolution of the core reaction center proteins of Photosystem II using sequence and structural comparisons in combination with Bayesian relaxed molecular clocks. Our results indicate that a homodimeric photosystem with sufficient oxidizing power to split water had already appeared in the early Archean about a billion years before the most recent common ancestor of all described Cyanobacteria capable of oxygenic photosynthesis, and well before the diversification of some of the known groups of anoxygenic photosynthetic bacteria. Based on a structural and functional rationale, we hypothesize that this early Archean photosystem was capable of water oxidation to oxygen and had already evolved protection mechanisms against the formation of reactive oxygen species. This would place primordial forms of oxygenic photosynthesis at a very early stage in the evolutionary history of life.

Keywords
Archean Chloroflexi Cyanobacteria evolution photosystem Proteobacteria 

reaction center water oxidation

Funding Information
Imperial College London
Leverhulme Trust. Grant Number: RPG‐2017‐223
Royal Society
Biotechnology and Biological Sciences Research Council. Grant Numbers: BB/K002627/1, BB/L011206/1

Publication History
Version of Record online: 09 November 2018
Manuscript accepted: 11 October 2018 Manuscript revised: 03 October 2018
Manuscript received: 13 September 2018

FREE PDF GRATIS: Geobiology

Novo código genético descoberto!!!

Mitogenomics reveals a novel genetic code in Hemichordata

Yuanning Li Kevin M Kocot Michael G Tassia Johanna T Cannon Matthias Bernt Kenneth M Halanych

Genome Biology and Evolution, evy254, https://doi.org/10.1093/gbe/evy254

Published: 23 November 2018

Article history

Received: 02 July 2018 Revision Received: 20 September 2018

Accepted: 13 November 2018 

 

Source/Fonte: Graptolite.net

Abstract

The diverse array of codon reassignments has demonstrated that the genetic code is not universal in nature. Exploring mechanisms underlying codon reassignment is critical for understanding the evolution of the genetic code during translation. Hemichordata, comprising worm-like Enteropneusta and colonial filter-feeding Pterobranchia, is the sister taxon of echinoderms and is more distantly related to chordates. However, only a few hemichordate mitochondrial genomes have been sequenced hindering our understanding of mitochondrial genome evolution within Deuterostomia. In this study, we sequenced four mitochondrial genomes and two transcriptomes, including representatives of both major hemichordate lineages and analysed together with public available data. Contrary to the current understanding of the mitochondrial genetic code in hemichordates, our comparative analyses suggest that UAA encodes Tyr instead of a “Stop” codon in the pterobranch lineage Cephalodiscidae. We also predict that AAA encodes Lys in pterobranch and enteropneust mitochondrial genomes, contradicting the previous assumption that hemichordates share the same genetic code with echinoderms for which AAA encodes Asn. Thus, we propose a new mitochondrial genetic code for Cephalodiscus and a revised code for enteropneusts. Moreover, our phylogenetic analyses are largely consistent with previous phylogenomic studies. The only exception isthe phylogenetic position of the enteropneust Stereobalanus, whose placement has been unstable in previous studies, as sister to all other described enteropneusts. With broader taxonomic sampling, we provide evidence that evolution of mitochondrial gene order and genetic codes in Hemichordata are more dynamic than previously thought and these finding provide insights into mitochondrial genome evolution within this clade. 

genetic codon reassignment, Hemichordata, Deuterostomia, mitogenomics

Issue Section: Research article

© The Author(s) 2018. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com 

FREE PDF GRATIS: Genome Biology and Evolution
 
Supplementary Data - docx file

Cientistas chocados: descobertas de pesquisa radical revelam que o mtDNA pode ser herdado dos pais!

Biparental Inheritance of Mitochondrial DNA in Humans 

 

Shiyu Luo, C. Alexander Valencia, Jinglan Zhang, Ni-Chung Lee, Jesse Slone, Baoheng Gui, Xinjian Wang, Zhuo Li, Sarah Dell, Jenice Brown, Stella Maris Chen, Yin-Hsiu Chien, Wuh-Liang Hwu, Pi-Chuan Fan, Lee-Jun Wong, Paldeep S. Atwal, and Taosheng Huang
PNAS published ahead of print November 26, 2018  

https://doi.org/10.1073/pnas.1810946115

Add to Cart ($10)

Edited by Douglas C. Wallace, Children’s Hospital of Philadelphia and University of Philadelphia, Philadelphia, PA, and approved October 29, 2018 (received for review June 26, 2018)

 

Source/Fonte

Wikimedia

Significance

The energy-producing organelle mitochondrion contains its own compact genome, which is separate from the nuclear genome. In nearly all mammals, this mitochondrial genome is inherited exclusively from the mother, and transmission of paternal mitochondria or mitochondrial DNA (mtDNA) has not been convincingly demonstrated in humans. In this paper, we have uncovered multiple instances of biparental inheritance of mtDNA spanning three unrelated multiple generation families, a result confirmed by independent sequencing across multiple unrelated laboratories with different methodologies. Surprisingly, this pattern of inheritance appears to be determined in an autosomal dominantlike manner. This paper profoundly alters a widespread belief about mitochondrial inheritance and potentially opens a novel field in mitochondrial medicine.

Abstract

Although there has been considerable debate about whether paternal mitochondrial DNA (mtDNA) transmission may coexist with maternal transmission of mtDNA, it is generally believed that mitochondria and mtDNA are exclusively maternally inherited in humans. Here, we identified three unrelated multigeneration families with a high level of mtDNA heteroplasmy (ranging from 24 to 76%) in a total of 17 individuals. Heteroplasmy of mtDNA was independently examined by high-depth whole mtDNA sequencing analysis in our research laboratory and in two Clinical Laboratory Improvement Amendments and College of American Pathologists-accredited laboratories using multiple approaches. A comprehensive exploration of mtDNA segregation in these families shows biparental mtDNA transmission with an autosomal dominantlike inheritance mode. Our results suggest that, although the central dogma of maternal inheritance of mtDNA remains valid, there are some exceptional cases where paternal mtDNA could be passed to the offspring. Elucidating the molecular mechanism for this unusual mode of inheritance will provide new insights into how mtDNA is passed on from parent to offspring and may even lead to the development of new avenues for the therapeutic treatment for pathogenic mtDNA transmission.

human genetics
mitochondria
biparental inheritance
paternal transmission
mtDNA

Footnotes

↵1Present address: Section of Molecular Genetics, PerkinElmer Genomics, Branford, CT 06405.

↵2Present address: Center for Medical Genetics, School of Life Sciences, Central South University, 410008 Changsha, Hunan, China.

↵3P.S.A. and T.H. contributed equally to this work.
↵4To whom correspondence should be addressed. Email: taosheng.huang@cchmc.org.

Author contributions: P.S.A. and T.H. designed research; S.L., J.Z., N.-C.L., J.S., B.G., Z.L., S.D., J.B., S.M.C., Y.-H.C., W.-L.H., and P.-C.F. performed research; S.L., C.A.V., J.Z., J.S., X.W., L.-J.W., and T.H. analyzed data; S.L., C.A.V., J.S., and T.H. wrote the paper; and N.-C.L., Y.-H.C., W.-L.H., P.-C.F., P.S.A., and T.H. evaluated patients and their families.

The authors declare no conflict of interest.

This article is a PNAS Direct Submission.

This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1810946115/-/DCSupplemental.

 

+++++

 

Subscription or payment needed/Requer assinatura ou pagamento: PNAS

+++++

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

+++++

NOTA DESTE BLOGGER:

Parem as impressoras, mais um dogma caí por terra e os livros textos de Biologia precisam ser atualizados! Alô MEC, estamos de olho!!!

 

Os tentilhões de Darwin escolhem parceiros para acasalar parecidos com os pais.

Darwin’s finches choose parent lookalikes as mates

A preference for mating with similar individuals can have a key role in speciation. Research on Darwin’s finches suggests that individuals might use the likeness of their parents as a guide for choosing mates. 

Lewis G. Spurgin & Tracey Chapman

New species form when groups of individuals in a population become reproductively isolated and can no longer mate with each other to produce living, healthy offspring. For decades, evolutionary biologists have sought to understand the links between an individual’s choice of mate and reproductive isolation between populations and species¹. Writing in Proceedings of the National Academy of Sciences, Grant and Grant² provide evidence suggesting that two species of Darwin’s finch learn features of their parents early in life and use this knowledge to inform their choice of mate in adulthood, a process known as sexual imprinting. Their study raises fascinating questions about the roles of learning and genetics in mate choice, and how matings between similar individuals (assortative mating) drive the evolution of new species.

Darwin’s finches live in the Galapagos archipelago. They are an iconic group of approximately 15 bird species that have contributed hugely to our understanding of natural selection and speciation^3–5. Previous work has shown that the cultural inheritance of song can promote reproductive isolation between different species of Darwin’s finch⁶. However, it was not known whether sexual imprinting based on morphological features such as body size and beak characteristics could similarly promote reproductive isolation, or play a part in the rare cases of mating between species that produce hybrid individuals. 

If sexual imprinting is key in directing mate choice, then individuals should choose mates that resemble their parents, and also themselves. In addition, if sexual imprinting contributes to matings between species, then the parents of the hybrid individuals that result from such matings should more closely resemble the other species than their own. To test these hypotheses, Grant and Grant analysed 22 years of data on body size, beak size and beak shape in two finch species — Geospiza fortis and Geospiza scandens — living on the same island.

...

FREE PDF GRATIS: Nature

A mecânica dos olhos embrionários: mero acaso, fortuita necessidade ou design inteligente?

Strain-triggered mechanical feedback in self-organizing optic-cup morphogenesis

S. Okuda1,2,3,*, N. Takata1,†, Y. Hasegawa1,‡, M. Kawada1, Y. Inoue3, T. Adachi3, Y. Sasai3,§ and M. Eiraku1,3,*

1RIKEN Center for Developmental Biology, Kobe 650-0047, Japan.
2PRESTO, Japan Science and Technology Agency, Kawaguchi 332-0012, Japan.
3Institute for Frontier Life and Medical Sciences, Kyoto University, Kyoto 606-8507, Japan.

↵*Corresponding author. Email: eiraku@infront.kyoto-u.ac.jp (M.E.); satoru.okuda@riken.jp (S.O.)

↵† Present address: Center for Vascular and Developmental Biology, Feinberg Cardiovascular Research Institute, Northwestern University Chicago, IL 60611, USA.

↵‡ Present address: Department of Neurology, Children’s Hospital of Philadelphia Research Institute, Philadelphia, PA 19104, USA.

↵§ Deceased.

Science Advances 21 Nov 2018:
Vol. 4, no. 11, eaau1354
DOI: 10.1126/sciadv.aau1354 

 

 

Abstract

Organogenesis is a self-organizing process of multiple cells in three-dimensional (3D) space, where macroscopic tissue deformations are robustly regulated by multicellular autonomy. It is clear that this robust regulation requires cells to sense and modulate 3D tissue formation across different scales, but its underlying mechanisms are still unclear. To address this question, we developed a versatile computational model of 3D multicellular dynamics at single-cell resolution and combined it with the 3D culture system of pluripotent stem cell–derived optic-cup organoid. The complementary approach enabled quantitative prediction of morphogenesis and its corresponding verification and elucidated that the macroscopic 3D tissue deformation is fed back to individual cellular force generations via mechanosensing. We hereby conclude that mechanical force plays a key role as a feedback regulator to establish the robustness of organogenesis.

INTRODUCTION

During organogenesis, morphogens dynamically organize spatial patterns of cell differentiation in three-dimensional (3D) tissues (1, 2). According to the pattern, individual cells generate characteristic mechanical forces to form the entire organ structure in 3D space (3–5). Many molecules have been identified as key signaling factors that regulate each step of patterning and force generation. However, these molecular signals are not enough to explain the entire regulatory mechanism of morphogenesis. In particular, it is still unclear how individual cells sense and modulate the entire 3D tissue formation across different scales. Previous studies have revealed cellular mechanosensing mechanisms (6–8), which may also be involved in the cross-scale regulatory mechanism of 3D tissue formation. Therefore, in this study, we focus on the mechanical aspect of morphogenesis and reveal the role of mechanical force in regulating 3D tissue formation across different scales.

Recent progress in the stem cell field has enabled us to form various 3D tissues in vitro (9, 10). For instance, we have reported a culture system of pluripotent stem cell–derived optic-cup organoids, which well recapitulates a typical process seen in vivo (11, 12); on the basis of the Wnt antagonism, the distal part of optic vesicle (OV) differentiates into neural retina (NR), whereas the adjacent part becomes retinal pigment epithelium (RPE). According to the differentiation pattern, the NR invaginates into the surrounding RPE in the apically convex direction. Subsequently, a hinge structure is formed along the boundary between the inner NR and outer RPE to generate a cup-like tissue shape. From a mechanical point of view, this stepwise process proceeds autonomously without external forces from the surroundings such as lens placode and periocular mesenchyme.

To explain this self-organizing process, we have previously found several key candidates of driving force and suggested a relaxation-expansion model (11) that explains the mechanism of optic-cup formation through four sequential phases (fig. S1A). In phase 1, semispherical OV autonomously generates the differentiation pattern composed of distal NR and the surrounding RPE. In phase 2, the distal NR decreases its stiffness according to the reduction of apical myosin accumulation. In phase 3, the boundary between NR and RPE causes apical constriction, by which the NR is passively invaginated. In phase 4, the NR causes rapid proliferation and facilitates the NR invagination by itself. Although this model is consistent with previous experimental findings, our further mechanical analyses have prompted the investigation of more elaborate mechanisms.

In the present study, we elucidate a mechanical force that is fed back from macroscopic 3D tissue deformation to individual cellular force generation during optic-cup morphogenesis. On the basis of previous mathematical models (13–19), we developed a versatile 3D vertex model that adequately describes general 3D multicellular dynamics at single-cell resolution. The in vitro culture of optic-cup formation enables us to observe and perturb specific cell behaviors in 3D living tissues, whereas the in silico recapitulation enables us to predict its mechanisms comprehensively (15, 16, 20, 21). By combining the in vitro and in silico approaches, we found key cell behaviors required for the NR invagination and the subsequent hinge formation along the NR-RPE boundary and elucidate the key role of mechanical force in the self-organizing optic-cup formation.
 

RESULTS
 

Quantitative simulations predict key mechanisms in optic-cup morphogenesis

To elucidate mechanisms of 3D tissue morphogenesis, we attempted to combine in vitro and in silico systems. The optic-cup formation is a complex 3D deformation process to form several characteristic structures such as the apically convex, thicker NR, the adjacent, thinner RPE, and the sharply wedged hinge structure at the NR-RPE boundary (Fig. 1, A to D). The optic-cup formation follows various single-cell behaviors in 3D space, such as cellular contraction, extension, stiffening, softening, adhesion, growth, rearrangement, division, and apoptosis (11). In particular, cells at the NR-RPE boundary form an anisotropic hinge shape (Fig. 1E and movie S1). These cell behaviors dynamically change according to the differentiation state of individual cells from OV to NR and RPE in a dorsoventrally asymmetric manner (2, 12, 22).

FREE PDF GRATIS: Science Advances Sup. Info.

A opinião de celebridades influencia na aceitação da evolução humana pelo público?

Celebrity Opinion Influences Public Acceptance of Human Evolution

Steven Arnocky, Emma Bozek, Caroline Dufort, Samantha Rybka, Robyn Hebert

First Published September 19, 2018 Research Article 

https://doi.org/10.1177/1474704918800656

Article Information

Volume: 16 issue: 3

Article first published online: September 19, 2018; Issue published: July 1, 2018 

Received: July 06, 2017; Accepted: August 21, 2018

Steven Arnocky1, Emma Bozek1, Caroline Dufort1, Samantha Rybka1, Robyn Hebert1

1Nipissing University, North Bay, Ontario, Canada

Corresponding Author: Steven Arnocky, Department of Psychology, Nipissing University, 100 College Drive, North Bay, Ontario, Canada P1B 8L7. Email: stevena@nipissingu.ca

This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License (http://www.creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages (https://us.sagepub.com/en-us/nam/open-access-at-sage).

Abstract

The present research examined the influence of celebrity opinion upon individuals’ acceptance of the theory of evolution. Priming stimuli were developed purveying pro-evolution, anti-evolution, or neutral opinion (Study 1). When paired with a male celebrity or expert source (Study 2), the male celebrity, but not the male expert, influenced undergraduates’ acceptance of evolution. The influence of the male celebrity on acceptance of evolution was replicated in a community sample (Study 3). When paired with a female celebrity source, undergraduates’ acceptance of evolution was similarly influenced (Study 4). Together, these findings extend our understanding of the reach of credible celebrity endorsers beyond consumer behavior to core individual beliefs, such as those surrounding the acceptance of human evolution.

Keywords celebrity, interpersonal influences, social influences, theory of evolution, religiosity, attitudes

FREE PDF GRATIS: Evolutionary Psychology

Como a proteína pode se enovelar: usando ribossomos

Protein Knotting by Active Threading of Nascent Polypeptide Chain Exiting from the Ribosome Exit Channel

Pawel Dabrowski-Tumanski†‡∥, Maciej Piejko†‡∥, Szymon Niewieczerzal‡, Andrzej Stasiak*¶§, and Joanna I. Sulkowska*‡†

† Faculty of Chemistry, University of Warsaw, Pasteura 1, 02-093, Warsaw, Poland

‡ Centre of New Technologies, University of Warsaw, Banacha 2c, 02-097, Warsaw, Poland

¶ Center for Integrative Genomics, University of Lausanne, 1015 Lausanne, Switzerland

§ Swiss Institute of Bioinformatics, 1015 Lausanne, Switzerland

J. Phys. Chem. B, Article ASAP

DOI: 10.1021/acs.jpcb.8b07634

Publication Date (Web): September 10, 2018

Copyright © 2018 American Chemical Society

*(A.S.) E-mail: Andrzej.Stasiak@unil.ch

 

*(J.I.S.) E-mail: j.sulkowska@cent.uw.edu.pl

This article is part of the William A. Eaton Festschrift special issue.

Abstract

The mechanism of folding of deeply knotted proteins into their native structure is still not understood. Current thinking about protein folding is dominated by the Anfinsen dogma, stating that the structure of the folded proteins is uniquely dictated by the amino acid sequence of a given protein and that the folding is driven uniquely by the energy gained from interactions between amino acids that contact each other in the native structure of the protein. The role of ribosomes in protein folding was only seen as permitting the folding to progress from the N-terminal part of nascent protein chains. We propose here that ribosomes can participate actively in the folding of knotted proteins by actively threading nascent chains emerging from the ribosome exit channels through loops formed by a synthesized earlier portion of the same protein. Our simulations of folding of deeply knotted protein Tp0624 positively verify the proposed ribosome-driven active threading mechanism leading to the formation of deeply knotted proteins.

Subscription/payment needed/Requer assinatura-pagamento: J Phys Chem B

Desviando a resistência aos antibióticos pela redução da evolução bacteriana

Inhibiting the Evolution of Antibiotic Resistance

Mark N. Ragheb 1 2 Maureen K. Thomason 1 Chris Hsu 1 Patrick Nugent 1 John Gage 1 Ariana N. Samadpour 1 Ankunda Kariisa 1Christopher N. Merrikh 1 Samuel I. Miller 1 3 David R. Sherman 4 5 Houra Merrikh 1 3 6

1 Department of Microbiology, University of Washington, Seattle, WA, USA

2 Molecular and Cellular Biology Graduate Program and Medical Scientist Training Program, University of Washington, Seattle, WA, USA

3 Department of Genome Sciences, University of Washington, Seattle, WA, USA

4 Center for Infectious Disease Research, Seattle, WA, USA

5 Interdiscipinary Program of Pathobiology, Department of Global Health, University of Washington, Seattle, WA, USA

Received 15 June 2018, Revised 17 August 2018, Accepted 9 October 2018, Available online 15 November 2018.

Published: November 15, 2018

https://doi.org/10.1016/j.molcel.2018.10.015 Get rights and content

Under a Creative Commons license open access

Highlights

• The bacterial transcription-coupled repair (TCR) factor Mfd promotes mutagenesis

• Mfd-driven mutagenesis accelerates the evolution of antimicrobial resistance (AMR)

• The rapid evolution of AMR requires Mfd’s interaction with RpoB and UvrA

• Mfd may be an ideal target for “anti-evolution” drugs that inhibit AMR development

Summary

Efforts to battle antimicrobial resistance (AMR) are generally focused on developing novel antibiotics. However, history shows that resistance arises regardless of the nature or potency of new drugs. Here, we propose and provide evidence for an alternate strategy to resolve this problem: inhibiting evolution. We determined that the DNA translocase Mfd is an “evolvability factor” that promotes mutagenesis and is required for rapid resistance development to all antibiotics tested across highly divergent bacterial species. Importantly, hypermutator alleles that accelerate AMR development did not arise without Mfd, at least during evolution of trimethoprim resistance. We also show that Mfd’s role in AMR development depends on its interactions with the RNA polymerase subunit RpoB and the nucleotide excision repair protein UvrA. Our findings suggest that AMR development can be inhibited through inactivation of evolvability factors (potentially with “anti-evolution” drugs)—in particular, Mfd—providing an unexplored route toward battling the AMR crisis.

FREE PDF GRATIS: Molecular Cell

Pássaros extintos do Cretáceo voavam!!!

The most complete enantiornithine from North America and a phylogenetic analysis of the Avisauridae

Jessie Atterholt​1,2,3, J. Howard Hutchison1, Jingmai K. O’Connor4,5

November 13, 2018

Author and article information

1Department of Integrative Biology, University of California, Berkeley, CA, USA
2Raymond M. Alf Museum of Paleontology, Claremont, CA, USA
3Graduate College of Biomedical Sciences, Western University of Health Sciences, Pomona, CA, USA
4Key Laboratory of Vertebrate Evolution, Institute of Vertebrate Paleontology and Paleoanthropology, Chinese Academy of Sciences, Beijing, People’s Republic of China
5CAS Center for Excellence in Life and Paleoenvironment, Beijing, People’s Republic of China 

DOI 10.7717/peerj.5910 

Published2018-11-13Accepted2018-10-08Received2018-03-28 Academic EditorFabien Knoll Subject Areas Evolutionary Studies, Paleontology Keywords Enantiornithes, Evolution, Late Cretaceous, Fossil bird Copyright© 2018 Atterholt et al. Licence This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, reproduction and adaptation in any medium and for any purpose provided that it is properly attributed. For attribution, the original author(s), title, publication source (PeerJ) and either DOI or URL of the article must be cited. Cite this article Atterholt J, Hutchison JH, O’Connor JK. (2018) The most complete enantiornithine from North America and a phylogenetic analysis of the Avisauridae. PeerJ 6:e5910 https://doi.org/10.7717/peerj.5910

The authors have chosen to make the review history of this article public. 

A skeletal reconstruction of Mirarce eatoni showing preserved skeletal elements (white).

Illustration: Scott Hartman.

Abstract

The most complete known North American enantiornithine was collected in 1992 but never formally described. The so-called “Kaiparowits avisaurid” remains one of the most exceptional Late Cretaceous enantiornithine fossils. We recognize this specimen as a new taxon, Mirarce eatoni (gen. et sp. nov.), and provide a complete anatomical description. We maintain that the specimen is referable to the Avisauridae, a clade previously only known in North America from isolated tarsometatarsi. Information from this specimen helps to clarify evolutionary trends within the Enantiornithes. Its large body size supports previously observed trends toward larger body mass in the Late Cretaceous. However, trends toward increased fusion of compound elements across the clade as a whole are weak compared to the Ornithuromorpha. The new specimen reveals for the first time the presence of remige papillae in the enantiornithines, indicating this feature was evolved in parallel to dromaeosaurids and derived ornithuromorphs. Although morphology of the pygostyle and (to a lesser degree) the coracoid and manus appear to remain fairly static during the 65 million years plus of enantiornithine evolution, by the end of the Mesozoic at least some enantiornithine birds had evolved several features convergent with the Neornithes including a deeply keeled sternum, a narrow furcula with a short hypocleidium, and ulnar quill knobs—all features that indicate refinement of the flight apparatus and increased aerial abilities. We conduct the first cladistic analysis to include all purported avisuarid enantiornithines, recovering an Avisauridae consisting of a dichotomy between North and South American taxa. Based on morphological observations and supported by cladistic analysis, we demonstrate Avisaurus to be paraphyletic and erect a new genus for “A. gloriae,” Gettyia gen. nov.

Cite this as Atterholt J, Hutchison JH, O’Connor JK. (2018) The most complete enantiornithine from North America and a phylogenetic analysis of the Avisauridae. PeerJ 6:e5910 https://doi.org/10.7717/peerj.5910  

FREE PEDF GRATIS: PeerJ

Nova teoria sobre a origem da água na Terra

Origin of Earth's Water: Chondritic Inheritance Plus Nebular Ingassing and Storage of Hydrogen in the Core

Jun Wu, Steven J. Desch, Laura Schaefer, Linda T. Elkins‐Tanton, Kaveh Pahlevan

Peter R. Buseck

First published: 09 October 2018 

https://doi.org/10.1029/2018JE005698

Source/Fonte: NASA

Abstract

Recent developments in planet formation theory and measurements of low D/H in deep mantle material support a solar nebula source for some of Earth's hydrogen. Here we present a new model for the origin of Earth's water that considers both chondritic water and nebular ingassing of hydrogen. The largest embryo that formed Earth likely had a magma ocean while the solar nebula persisted and could have ingassed nebular gases. The model considers iron hydrogenation reactions during Earth's core formation as a mechanism for both sequestering hydrogen in the core and simultaneously fractionating hydrogen isotopes. By parameterizing the isotopic fractionation factor and initial bulk D/H ratio of Earth's chondritic material, we explore the combined effects of elemental dissolution and isotopic fractionation of hydrogen in iron. By fitting to the two key constraints (three oceans' worth of water in Earth's mantle and on its surface; and D/H in the bulk silicate Earth close to 150 × 10⁻⁶), the model searches for best solutions among ~10,000 different combinations of chondritic and nebular contributions. We find that ingassing of a small amount, typically >0–0.5 oceans of nebular hydrogen, is generally demanded, supplementing seven to eight oceans from chondritic contributions. About 60% of the total hydrogen enters the core, and attendant isotopic fractionation plausibly lowers the core's D/H to ~130 × 10⁻⁶. Crystallized magma ocean material may have D/H ≈ 110 × 10⁻⁶. These modeling results readily explain the low D/H in core‐mantle boundary material and account for Earth's inventory of solar neon and helium.

Plain Language Summary

People have long had curiosity in the origin of Earth's water (equivalently hydrogen). Solar nebula has been given the least attention among existing theories, although it was the predominating reservoir of hydrogen in our early solar system. Here we present a first model for Earth's water origin that quantifies contribution from the solar nebula in addition to that from chondrites, the primary building blocks of Earth. The model considers dissolution of nebular hydrogen into the early Earth's magma oceans and reaction between hydrogen and iron droplets within the magma ocean. Such processes not only delivered countless hydrogen atoms from the mantle to the core but also generated an appreciable difference in hydrogen isotopic composition (2H/1H ratio) between the mantle and core. Fitting the model to current knowledge about Earth's hydrogen produces best combinations of nebular and chondritic contributions to Earth's water. We find that nearly one out of every 100 water molecules on Earth came from the solar nebula. Our planet hides majority of its water inside, with roughly two oceans in the mantle and four to five oceans in the core. These results suggest inevitable formation of water on sufficiently large rocky planets in extrasolar systems.             

FREE PDF GRATIS: J of Geophysical Research Planets