Lentes bifocais de um olho complexo de larvas

quinta-feira, setembro 28, 2017

A Complex Lens for a Complex Eye

Aaron L. Stahl Regina S. Baucom Tiffany A. Cook Elke K. Buschbeck

Integrative and Comparative Biology, icx116, https://doi.org/10.1093/icb/icx116

Published: 02 September 2017

Source/Fonte: Current Biology


A key innovation for high resolution eyes is a sophisticated lens that precisely focuses light onto photoreceptors. The eyes of holometabolous larvae range from very simple eyes that merely detect light to eyes that are capable of high spatial resolution. Particularly interesting are the bifocal lenses of Thermonectus marmoratus larvae, which differentially focus light on spectrally-distinct retinas. While functional aspects of insect lenses have been relatively well studied, little work has explored their molecular makeup, especially in regard to more complex eye types. To investigate this question, we took a transcriptomic and proteomic approach to identify the major proteins contributing to the principal bifocal lenses of T. marmoratus larvae. Mass spectrometry revealed 10 major lens proteins. Six of these share sequence homology with cuticular proteins, a large class of proteins that are also major components of corneal lenses from adult compound eyes of Drosophila melanogaster and Anopheles gambiae. Two proteins were identified as house-keeping genes and the final two lack any sequence homologies to known genes. Overall the composition seems to follow a pattern of co-opting transparent and optically dense proteins, similar to what has been described for other animal lenses. To identify cells responsible for the secretion of specific lens proteins, we performed in situ hybridization studies and found some expression differences between distal and proximal corneagenous cells. Since the distal cells likely give rise to the periphery and the proximal cells to the center of the lens, our findings highlight a possible mechanism for establishing structural differences that are in line with the bifocal nature of these lenses. A better understanding of lens composition provides insights into the evolution of proper focusing, which is an important step in the transition between low-resolution and high-resolution eyes.

Issue Section: Low Spatial Resolution Vision

© The Author 2017. Published by Oxford University Press on behalf of the Society for Integrative and Comparative Biology. All rights reserved. For permissions please email: journals.permissions@oup.com.


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Uma hélice molecular que gira a 100 graus Celsius: outro caso de complexidade irredutível?

segunda-feira, setembro 25, 2017

Structure and in situ organisation of the Pyrococcus furiosus archaellum machinery

Bertram Daum  Is a corresponding author Janet Vonck Annett Bellack Paushali Chaudhury Robert Reichelt Sonja-Verena Albers Reinhard Rachel Werner Kühlbrandt

Max Planck Institute of Biophysics, Germany University of Exeter, United Kingdom University of Regensburg, Germany University of Freiburg, Germany


Left: 3-D view of a Pyrococcus furiosus cell obtained by electron cryo-tomograpy. Right: Composite CryoEM structure of the archaellum machinery.


The archaellum is the macromolecular machinery that Archaea use for propulsion or surface adhesion, enabling them to proliferate and invade new territories. The molecular composition of the archaellum and of the motor that drives it appears to be entirely distinct from that of the functionally equivalent bacterial flagellum and flagellar motor. Yet, the structure of the archaellum machinery is scarcely known. Using combined modes of electron cryo-microscopy (cryoEM), we have solved the structure of the Pyrococcus furiosus archaellum filament at 4.2 Å resolution and visualise the architecture and organisation of its motor complex in situ. This allows us to build a structural model combining the archaellum and its motor complex, paving the way to a molecular understanding of archaeal swimming motion.

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Uma visão fenomenológica e dinâmica de homologia

Biological Theory

September 2017, Volume 12, Issue 3, pp 169–180 | Cite as

A Phenomenological and Dynamic View of Homology: Homologs as Persistently Reproducible Modules


Authors and affiliations

Daichi G. Suzuki, Senji Tanaka

Open AccessOriginal Article

First Online: 22 May 2017


Homology is a fundamental concept in biology. However, the metaphysical status of homology, especially whether a homolog is a part of an individual or a member of a natural kind, is still a matter of intense debate. The proponents of the individuality view of homology criticize the natural kind view of homology by pointing out that homologs are subject to evolutionary transformation, and natural kinds do not change in the evolutionary process. Conversely, some proponents of the natural kind view of homology argue that a homolog can be construed both as a part of an individual and a member of a natural kind. They adopt the Homeostatic Property Cluster (HPC) theory of natural kinds, and the theory seems to strongly support their construal. Note that this construal implies the acceptance of essentialism. However, looking back on the history of the concept of homology, we should not overlook the fact that the individuality view was proposed to reject the essentialist interpretation of homology. Moreover, the essentialist notions of natural kinds can, in our view, mislead biologists about the phenomena of homology. Consequently, we need a non-essentialist view of homology, which we name the “persistently reproducible module” (PRM) view. This view highlights both the individual-like and kind-like aspects of homologs while stripping down both essentialist and anti-essentialist interpretations of homology. In this article, we articulate the PRM view of homology and explain why it is recommended over the other two views.


Essentialism Homology Individuals Natural kinds Persistently reproducible modules PRM view


Trilobitas tinham estômago, contrariando prévias pressuposições sobre sua evolução e o sistema digestivo

sexta-feira, setembro 22, 2017

The oldest known digestive system consisting of both paired digestive glands and a crop from exceptionally preserved trilobites of the Guanshan Biota (Early Cambrian, China)

Melanie J. Hopkins , Feiyang Chen, Shixue Hu, Zhifei Zhang 

Published: September 21, 2017 https://doi.org/10.1371/journal.pone.0184982


The early Cambrian Guanshan biota of eastern Yunnan, China, contains exceptionally preserved animals and algae. Most diverse and abundant are the arthropods, of which there are at least 11 species of trilobites represented by numerous specimens. Many trilobite specimens show soft-body preservation via iron oxide pseudomorphs of pyrite replacement. Here we describe digestive structures from two species of trilobite, Palaeolenus lantenoisi and Redlichia mansuyi. Multiple specimens of both species contain the preserved remains of an expanded stomach region (a “crop”) under the glabella, a structure which has not been observed in trilobites this old, despite numerous examples of trilobite gut traces from other Cambrian Lagerstätten. In addition, at least one specimen of Palaeolenus lantenoisi shows the preservation of an unusual combination of digestive structures: a crop and paired digestive glands along the alimentary tract. This combination of digestive structures has also never been observed in trilobites this old, and is rare in general, with prior evidence of it from one juvenile trilobite specimen from the late Cambrian Orsten fauna of Sweden and possibly one adult trilobite specimen from the Early Ordovician Fezouata Lagerstätte. The variation in the fidelity of preservation of digestive structures within and across different Lagerstätten may be due to variation in the type, quality, and point of digestion of food among specimens in addition to differences in mode of preservation. The presence and combination of these digestive features in the Guanshan trilobites contradicts current models of how the trilobite digestive system was structured and evolved over time. Most notably, the crop is not a derived structure as previously proposed, although it is possible that the relative size of the crop increased over the evolutionary history of the clade.

Citation: Hopkins MJ, Chen F, Hu S, Zhang Z (2017) The oldest known digestive system consisting of both paired digestive glands and a crop from exceptionally preserved trilobites of the Guanshan Biota (Early Cambrian, China). PLoS ONE 12(9): e0184982. https://doi.org/10.1371/journal.pone.0184982

Editor: Steffen Kiel, Naturhistoriska riksmuseet, SWEDEN
Received: April 17, 2017; Accepted: September 4, 2017; Published: September 21, 2017

Copyright: © 2017 Hopkins 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: Fossil collection was partly financed by the National 973 Program (2013CB835002) and 111 Project of China (P201102007). This work represents a contribution to the research programmes from the National Natural Science Foundation of China (NSFC 41425008 and 41621003 to ZZ). The funders had no role in the study design, data collections and analysis, decision to publish, or preparation of the manuscript.

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


Design em 4D - Projeto Nucleoma - mais problemas para a teoria da evolução de Darwin???

The 4D nucleome project

Job Dekker, Andrew S. Belmont, Mitchell Guttman, Victor O. Leshyk, John T. Lis, Stavros Lomvardas, Leonid A. Mirny, Clodagh C. O’Shea, Peter J. Park, Bing Ren, Joan C. Ritland Politz, Jay Shendure, Sheng Zhong & the 4D Nucleome Network

Affiliations Contributions Corresponding author

Nature 549, 219–226 (14 September 2017) doi:10.1038/nature23884 

Received 27 January 2017 Accepted 27 July 2017 Published online 13 September 2017

The 4D Nucleome project.


The 4D Nucleome Network aims to develop and apply approaches to map the structure and dynamics of the human and mouse genomes in space and time with the goal of gaining deeper mechanistic insights into how the nucleus is organized and functions. The project will develop and benchmark experimental and computational approaches for measuring genome conformation and nuclear organization, and investigate how these contribute to gene regulation and other genome functions. Validated experimental technologies will be combined with biophysical approaches to generate quantitative models of spatial genome organization in different biological states, both in cell populations and in single cells.

Subject terms: Epigenomics Gene regulation


Colégio de Médicos dos Estados Unidos contra o suicídio auxiliado por médicos

Ethics and the Legalization of Physician-Assisted Suicide: An American College of Physicians Position Paper

Lois Snyder Sulmasy, JD; Paul S. Mueller, MD, MPH (*); for the Ethics, Professionalism and Human Rights Committee of the American College of Physician


Calls to legalize physician-assisted suicide have increased and public interest in the subject has grown in recent years despite ethical prohibitions. Many people have concerns about how they will die and the emphasis by medicine and society on intervention and cure has sometimes come at the expense of good end-of-life care. Some have advocated strongly, on the basis of autonomy, that physician-assisted suicide should be a legal option at the end of life. As a proponent of patient-centered care, the American College of Physicians (ACP) is attentive to all voices, including those who speak of the desire to control when and how life will end. However, the ACP believes that the ethical arguments against legalizing physician-assisted suicide remain the most compelling. On the basis of substantive ethics, clinical practice, policy, and other concerns articulated in this position paper, the ACP does not support legalization of physician-assisted suicide. It is problematic given the nature of the patient–physician relationship, affects trust in the relationship and in the profession, and fundamentally alters the medical profession's role in society. Furthermore, the principles at stake in this debate also underlie medicine's responsibilities regarding other issues and the physician's duties to provide care based on clinical judgment, evidence, and ethics. Society's focus at the end of life should be on efforts to address suffering and the needs of patients and families, including improving access to effective hospice and palliative care. The ACP remains committed to improving care for patients throughout and at the end of life.


FREE PDF GRATIS: Annals of Internal Medicine

Há quase 40 anos os cientistas sabem que o Big Bang não é a origem do universo!

The Big Bang Wasn't The Beginning, After All

Ethan Siegel , Contributor

A Universe that expands and cools today, like ours does, must have been hotter and denser in the past. Initially, the Big Bang was regarded as the singularity from which this ultimate, hot, dense state emerged. But we know better today. NASA/GSFC

A Universe that expands and cools today, like ours does, must have been hotter and denser in the past. Initially, the Big Bang was regarded as the singularity from which this ultimate, hot, dense state emerged. But we know better today.

The Universe began not with a whimper, but with a bang! At least, that's what you're commonly told: the Universe and everything in it came into existence at the moment of the Big Bang. Space, time, and all the matter and energy within began from a singular point, and then expanded and cooled, giving rise over billions of years to the atoms, stars, galaxies, and clusters of galaxies spread out across the billions of light years that make up our observable Universe. It's a compelling, beautiful picture that explains so much of what we see, from the present large-scale structure of the Universe's two trillion galaxies to the leftover glow of radiation permeating all of existence. Unfortunately, it's also wrong, and scientists have known this for almost 40 years.

The idea of the Big Bang first came about back in the 1920s and 1930s. When we looked out at distant galaxies, we discovered something peculiar: the farther away from us they were, the faster they appeared to be receding from us. According to the predictions of Einstein's General Relativity, a static Universe would be gravitationally unstable; everything needed to either be moving away from one another or collapsing towards one another if the fabric of space obeyed his laws. The observation of this apparent recession taught us that the Universe was expanding today, and if things are getting farther apart as time goes on, it means they were closer together in the distant past.

Read more/Leia mais: FORBES

Filotaxia: mero acaso, fortuita necessidade ou design inteligente?


Cris Kuhlemeier
Institute of Plant Sciences, University of Bern Altenbergrain, 21 CH-3013, Bern, Switzerland


Leaves and flowers are arranged in regular patterns around the stem of a plant, a phenomenon known as phyllotaxis. Different arrangements occur, such as distichous, decussate or spiral (Figure 1). Most prevalent in nature are spirals in which the average divergence angles between successive organs are close to 137.5°, the so-called ‘golden angle’. It is this exact number that has given phyllotaxis its special flavor as a quantitative developmental problem, and over the centuries, it has enjoyed the attention of scientists far beyond botany. In the 1830s mathematicians described the spirals as they related to the Fibonacci numbers, and in the 1860s improved microscopes made it possible for botanists to observe the initiation of leaf and flower primordia in a diversity of plants. This descriptive work led to the conclusion that new organ primordia form in the first available space between existing primordia, a conclusion still valid today. But how does it work? Ideas from the early 20th century suggested that an inhibitor produced by existing primordia diffuses towards the shoot apical meristem: where the concentration of the inhibitor falls below a threshold value, an organ is initiated. Other models dating back to the 1870s have tried to explain phyllotactic patterning by applying the laws of mechanics. Such models went through a long period of marginal interest, but have experienced a remarkable renaissance over the past 20 years. In this Primer I will give a broad overview of phyllotaxis, its emergence from the shoot apical meristem, how auxin and its transporter function as a ‘pattern generator’, and the role of tissue mechanics and computational modeling.

FREE PDF GRATIS: Current Biology

Hoje J. Robert Oppenheimer seria perseguido e expulso pela Nomenklatura científica

"O cientista... deve ser livre para fazer qualquer pergunta, duvidar de qualquer afirmação, buscar qualquer evidência, corrigir quaisquer erros." J. Robert Oppenheimer, físico.

"The scientist... must be free to ask any question, to doubt any assertion, to seek for any evidence, to correct any errors." J. Robert Oppenheimer, physicist.

The Virtual Human Embryo Project: morfologia embrionária digitalmente reproduzida

quarta-feira, setembro 20, 2017

The Virtual Human Embryo

Welcome to The Virtual Human Embryo (VHE), a 14,250-page, illustrated atlas of human embryology, which presents all 23 Carnegie Stages of development during the 8-week embryonic period.

This $3.2 million, 11-year initiative engaged a team led by Dr. Raymond F. Gasser—one of the leading embryologists of the last half century. His team created thousands of restored, digitized, and labeled serial sections from the world's largest collection of preserved human embryos. They used these serial sections to create animations, fly-throughs, and 3-D reconstructions.

The VHE is now available to researchers, educators, and students everywhere. Read More...

Abordando as questões éticas levantadas pelas entidades sintéticas humanas com características tipo embrião

Addressing the ethical issues raised by synthetic human entities with embryo-like features

John Aach, Jeantine Lunshof Eswar Iyer George M Church

Harvard Medical School, United States University of Groningen, The Netherlands



The "14-day rule" for embryo research stipulates that experiments with intact human embryos must not allow them to develop beyond 14 days or the appearance of the primitive streak. However, recent experiments showing that suitably cultured human pluripotent stem cells can self-organize and recapitulate embryonic features have highlighted difficulties with the 14-day rule and led to calls for its reassessment. Here we argue that these and related experiments raise more foundational issues that cannot be fixed by adjusting the 14-day rule, because the framework underlying the rule cannot adequately describe the ways by which synthetic human entities with embryo-like features (SHEEFs) might develop morally concerning features through altered forms of development. We propose that limits on research with SHEEFs be based as directly as possible on the generation of such features, and recommend that the research and bioethics communities lead a wide-ranging inquiry aimed at mapping out solutions to the ethical problems raised by them.


FREE PDF GRATIS: eLIFE Correction/Correção

A história inicial dos Neandertais e Denisovans

Early history of Neanderthals and Denisovans

Alan R. Rogers a,1, Ryan J. Bohlender b, and Chad D. Huff b ReadCube 

Author Affiliations

a Department of Anthropology, University of Utah, Salt Lake City, UT 84112;

b Department of Epidemiology, MD Anderson Cancer Center, Houston, TX 77030

Edited by Richard G. Klein, Stanford University, Stanford, CA, and approved July 7, 2017 (received for review April 18, 2017)

Source/Fonte: New Scientist


Neanderthals and Denisovans were human populations that separated from the modern lineage early in the Middle Pleistocene. Many modern humans carry DNA derived from these archaic populations by interbreeding during the Late Pleistocene. We develop a statistical method to study the early history of these archaic populations. We show that the archaic lineage was very small during the 10,000 y that followed its separation from the modern lineage. It then split into two regional populations, the Neanderthals and the Denisovans. The Neanderthal population grew large and separated into largely isolated local groups.


Extensive DNA sequence data have made it possible to reconstruct human evolutionary history in unprecedented detail. We introduce a method to study the past several hundred thousand years. Our results show that (i) the Neanderthal–Denisovan lineage declined to a small size just after separating from the modern lineage, (ii) Neanderthals and Denisovans separated soon thereafter, and (iii) the subsequent Neanderthal population was large and deeply subdivided. They also (iv) support previous estimates of gene flow from Neanderthals into modern Eurasians. These results suggest an archaic human diaspora early in the Middle Pleistocene.

human evolution archaic admixture introgression Neanderthals Denisovans


1To whom correspondence should be addressed. Email: rogers@anthro.utah.edu.

Author contributions: A.R.R. and C.D.H. designed research; A.R.R. and R.J.B. performed research; A.R.R. and R.J.B. analyzed data; and A.R.R. wrote the paper.

The authors declare no conflict of interest.

This article is a PNAS Direct Submission.

See Commentary on page 9761.

This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1706426114/-/DCSupplemental.

Freely available online through the PNAS open access option.


60 anos do dogma central da biologia

terça-feira, setembro 19, 2017

60 years ago, Francis Crick changed the logic of biology

Matthew Cobb 

Published: September 18, 2017 https://doi.org/10.1371/journal.pbio.2003243


In September 1957, Francis Crick gave a lecture in which he outlined key ideas about gene function, in particular what he called the central dogma. These ideas still frame how we understand life. This essay explores the concepts he developed in this influential lecture, including his prediction that we would study evolution by comparing sequences.

Citation: Cobb M (2017) 60 years ago, Francis Crick changed the logic of biology. PLoS Biol 15(9): e2003243.

Published: September 18, 2017

Copyright: © 2017 Matthew Cobb. 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.

Funding: Cold Spring Harbor Laboratory Sydney Brenner Research Scholarship. The funder 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.

Provenance: Not commissioned; externally peer reviewed.


O status epistêmico da teoria evolucionária

The Epistemic Status of Evolutionary Theory

Gijsbert van den Brink, Jeroen de Ridder & René van Woudenberg

Pages 1-19 | Published online: 18 Sep 2017

Source/Fonte: Internet image


The theory of evolution continues to be a bone of contention among certain groups of theistic believers. This paper aims to bring some light to the debate about it, by introducing a framework for epistemic appraisal which can provide a realistic and sober assessment of the epistemic credentials of the various parts of evolutionary theory. The upshot is a more nuanced epistemic appraisal of the theory of evolution, which shows that there are significant differences in epistemic standing between its various parts. Any serious conversation about the theory of evolution ought to reflect these facts.

KEYWORDS: Evolution, epistemic status, creationism, scientific theory, ancient earth, common ancestry

FREE PDF GRATIS: Theology and Science

John Stuart Mill 'falou e disse': conhecer todo o assunto requer ouvir o que outros têm a dizer

segunda-feira, setembro 18, 2017

“A única maneira pela qual um ser humano pode fazer alguma abordagem em conhecer todo o assunto, é ouvir o que pode ser dito por pessoas de toda a variedade de opinião e estudar todos os modos nos quais pode ser observado por cada caráter de mente. Nenhum homem sábio jamais adquiriu sua sabedoria de qualquer modo, a não ser isso; nem está na natureza do intelecto humano se tornar sábio de qualquer outra maneira.”

the only way in which a human being can make some approach to knowing the whole of a subject, is by hearing what can be said about it by persons of every variety of opinion, and studying all modes in which it can be looked at by every character of mind. No wise man ever acquired his wisdom in any mode but this; nor is it in the nature of human intellect to become wise in any other manner.”

― John Stuart Mill, On Liberty Source/Fonte 

MORE Mecanismo Online para Referências

Prezado usuário!

Informamos que o MORE é totalmente baseado na NBR 6023/2002, norma da ABNT atualmente em vigor.

O MORE conta com um e-mail (morerexlab@gmail.com) onde é possível enviar dúvidas e/ou sugestões para Equipe MORE. As dúvidas relacionadas as normas da ABNT são respondidas pela Bibliotecária da UFSC.

Atualmente é possível armazenar suas referências por coleções criadas segundo suas necessidades e/ou preferências. Também é possível pesquisar e importar uma referência para o seu rol de referências.

Encontra-se disponível a possibilidade de geração de referências a documentos jurídicos (legislação e jurisprudência), patentes, partituras, normas técnicas, slides, filmes e vídeos, além da manutenção das funcionalidades anteriores.

Para adicionar a referência do MORE ao seu trabalho acadêmico basta inserir: MORE: Mecanismo online para referências, versão 2.0. Florianópolis: UFSC Rexlab, 2013. Disponível em: ‹ http://www.more.ufsc.br/ . Acesso em: XX XXX XXXX.

Desta forma você estará contribuindo para a difusão do Sistema MORE.

De onde vêm as células do coração?

sábado, setembro 16, 2017

Id genes are essential for early heart formation

Thomas J. Cunningham1,10, Michael S. Yu1,2,10, Wesley L. McKeithan1,3,4,10, Sean Spiering1, Florent Carrette1, Chun-Teng Huang1, Paul J. Bushway2, Matthew Tierney1, Sonia Albini1, Mauro Giacca5, Miguel Mano6, Pier Lorenzo Puri1,7, Alessandra Sacco1, Pilar Ruiz-Lozano1,8, Jean-Francois Riou9, Muriel Umbhauer9, Gregg Duester1, Mark Mercola1,4,11 and Alexandre R. Colas1,11

- Author Affiliations

1Sanford Burnham Prebys Medical Discovery Institute, La Jolla, California, 92037, USA;

2Department of Bioengineering, University of California at San Diego, La Jolla, California 92037, USA;

3Graduate School of Biomedical Sciences, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, California 92037, USA;

4Department of Medicine and Cardiovascular Institute, Stanford University, Palo Alto, California 94305, USA;

5International Centre for Genetic Engineering and Biotechnology, 34149 Trieste, Italy;

6Center for Neuroscience and Cell Biology (CNC), University of Coimbra, 3004-504 Coimbra, Portugal;

7Istituti di Ricovero e Cura a Carattere Scientifico, Fondazione Santa Lucia, 00179 Rome, Italy;

8Regencor, Inc., Los Altos, California 94022, USA;

9UMR 7622 Developmental Biology, Sorbonne Universités, University Pierre and Marie Curie, F- 75005 Paris, France

Corresponding author: acolas@sbpdiscovery.org

↵10 These authors contributed equally to this work.

↵11 These authors contributed equally to this work.


Deciphering the fundamental mechanisms controlling cardiac specification is critical for our understanding of how heart formation is initiated during embryonic development and for applying stem cell biology to regenerative medicine and disease modeling. Using systematic and unbiased functional screening approaches, we discovered that the Id family of helix–loop–helix proteins is both necessary and sufficient to direct cardiac mesoderm formation in frog embryos and human embryonic stem cells. Mechanistically, Id proteins specify cardiac cell fate by repressing two inhibitors of cardiogenic mesoderm formation—Tcf3 and Foxa2—and activating inducers Evx1, Grrp1, and Mesp1. Most importantly, CRISPR/Cas9-mediated ablation of the entire Id (Id1–4) family in mouse embryos leads to failure of anterior cardiac progenitor specification and the development of heartless embryos. Thus, Id proteins play a central and evolutionarily conserved role during heart formation and provide a novel means to efficiently produce cardiovascular progenitors for regenerative medicine and drug discovery applications.


cardiac progenitors cardiac mesoderm specification heartless Id proteins CRISPR/Cas9-mediated quadruple knockout platform for cardiac disease modeling and drug discovery


Supplemental material is available for this article.

Article published online ahead of print. Article and publication date are online at http://www.genesdev.org/cgi/doi/10.1101/gad.300400.117.

Freely available online through the Genes & Development Open Access option.

Received April 12, 2017. Accepted July 17, 2017.

© 2017 Cunningham et al.; Published by Cold Spring Harbor Laboratory Press

This article, published in Genes & Development, is available under a Creative Commons License (Attribution 4.0 International), as described at http://creativecommons.org/licenses/by/4.0/.

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Modelo do sistema imunológico humano de cobaia humanizada inadequado para pesquisas de células-tronco

Alloimmune Responses of Humanized Mice to Human Pluripotent Stem Cell Therapeutics

Nigel G. Kooreman9, Patricia E. de Almeida9, Jonathan P. Stack9, Raman V. Nelakanti, Sebastian Diecke, Ning-Yi Shao, Rutger-Jan Swijnenburg, Veronica Sanchez-Freire, Elena Matsa, Chun Liu, Andrew J. Connolly, Jaap F. Hamming, Paul H.A. Quax, Michael A. Brehm, Dale L. Greiner, Dale L. Greiner, Leonard D. Shultz, Joseph C. Wu10. 

9These authors contributed equally

10Lead Contact

Open access funded by Bloodwise

Article Info

Publication History

Published: August 22, 2017 Accepted: July 26, 2017

Received in revised form: April 23, 2017 Received: July 9, 2015

User License

Creative Commons Attribution (CC BY 4.0)


• Innate immunity is crucial in rejection of minor HA mismatched grafts

• Stem cell alloimmune responses modeled with an “allogenized mouse”

• Humanized mice are unable to fully model immune responses to stem cell allografts

Splenocytes and graft-infiltrating lymphocytes display an exhausted phenotype


There is growing interest in using embryonic stem cell (ESC) and induced pluripotent stem cell (iPSC) derivatives for tissue regeneration. However, an increased understanding of human immune responses to stem cell-derived allografts is necessary for maintaining long-term graft persistence. To model this alloimmunity, humanized mice engrafted with human hematopoietic and immune cells could prove to be useful. In this study, an in-depth analysis of graft-infiltrating human lymphocytes and splenocytes revealed that humanized mice incompletely model human immune responses toward allogeneic stem cells and their derivatives. Furthermore, using an “allogenized” mouse model, we show the feasibility of reconstituting immunodeficient mice with a functional mouse immune system and describe a key role of innate immune cells in the rejection of mouse stem cell allografts.


Diretrizes éticas COPE para revisores paritários

COPE Ethical Guidelines for Peer Reviewers

Peer review in all its forms plays an important role in ensuring the integrity of the scholarly record. The process depends to a large extent on trust, and requires that everyone involved behaves responsibly and ethically. Peer reviewers play a central and critical part in the peer-review process, but too often come to the role without any guidance and unaware of their ethical obligations. COPE has produced some guidelines which set out the basic principles and standards to which all peer reviewers should adhere during the peer-review process in research publication. The aim has been to make them generic so that they can be applied across disciplines.

Origem dos animais: o relógio molecular e o registro fóssil podem ser reconciliados?

quinta-feira, setembro 14, 2017

The origin of animals: Can molecular clocks and the fossil record be reconciled?

John A. Cunningham, Alexander G. Liu, Stefan Bengtson, Philip C. J. Donoghue

First published: 5 December 2016 Full publication history


The evolutionary emergence of animals is one of the most significant episodes in the history of life, but its timing remains poorly constrained. Molecular clocks estimate that animals originated and began diversifying over 100 million years before the first definitive metazoan fossil evidence in the Cambrian. However, closer inspection reveals that clock estimates and the fossil record are less divergent than is often claimed. Modern clock analyses do not predict the presence of the crown-representatives of most animal phyla in the Neoproterozoic. Furthermore, despite challenges provided by incomplete preservation, a paucity of phylogenetically informative characters, and uncertain expectations of the anatomy of early animals, a number of Neoproterozoic fossils can reasonably be interpreted as metazoans. A considerable discrepancy remains, but much of this can be explained by the limited preservation potential of early metazoans and the difficulties associated with their identification in the fossil record. Critical assessment of both records may permit better resolution of the tempo and mode of early animal evolution.


Contra a maré - livro crítico sobre como a Física e a Astronomia são feitas

Against the tide - A Critical Review by Scientists of How Physics and Astronomy Get Done

Martín López Corredoira & Carlos Castro Perelman (Eds.) 


Nobody should have a monopoly of the truth in this universe. The censorship and suppression of challenging ideas against the tide of mainstream research, the blacklisting of scientists, for instance, is neither the best way to do and filter science, nor to promote progress in the human knowledge. The removal of good and novel ideas from the scientific stage is very detrimental to the pursuit of the truth. There are instances in which a mere unqualified belief can occasionally be converted into a generally accepted scientific theory through the screening action of refereed literature and meetings planned by the scientific organizing committees and through the distribution of funds controlled by "club opinions". It leads to unitary paradigms and unitary thinking not necessarily associated to the unique truth. This is the topic of this book: to critically analyze the problems of the official (and sometimes illicit) mechanisms under which current science (physics and astronomy in particular) is being administered and filtered today, along with the onerous consequences these mechanisms have on all of us.

Apart from the editors, Juan Miguel Campanario, Brian Martin, Wolfgang Kundt, J. Marvin Herndon, Marian Apostol, Halton C. Arp, Tom Van Flandern, Andrei P. Kirilyuk, Dmitri Rabounski and Henry H. Bauer, all of them professional researchers, reveal a pessimistic view of the miseries of the actual system, while a glimmer of hope remains in the "leitmotiv" claim towards the freedom in doing research and attaining an acceptable level of ethics in science.

About The Author


Martín López Corredoira is a researcher at the Instituto de Astrofísica de Canarias (Tenerife, Spain). He holds a Ph.D. in Physics from the University of La Laguna at Tenerife and a Ph.D. in Philosophy from the University of Seville (Spain). He has authored articles in peer reviewed journals of astrophysics, and two books on philosophy in Spanish: Diálogos entre Razón y Sentimiento and Somos Fragmentos de Naturaleza Arrastrados por Sus Leyes.

Carlos Castro Perelman is a researcher affiliated with the Center for Theoretical Studies of Physical Systems at Clark Atlanta University (USA). He has a Ph.D. in Physics from the University of Texas at Austin and a B.S. from the Massachusetts Institute of Technology. He is the author of over 115 articles on such topics as: the extended relativity theory in Clifford spaces, gravity, supersymmetry, strings, p-branes, fractals, quantum field theory, mathematical physics, number theory


by Martín López Corredoira and Carlos Castro Perelman

It is always necessary to take a critical look at the way in which scientific research actually gets done. While Philosophy and Sociology have long established themselves as full-blown academic disciplines with an ever-increasing literature, there is a dearth of such literature written by practising scientists. The aim of this book is to gather the views of some working physicists and astronomers on the influence of the social structures of science within which scientists are obliged to carry out their research, and examine the ways in which they are sometimes used in negative ways to destroy careers and hinder innovative research. At the present time there are no widely known academic outlets where scientists can express their opinions about the scientific establishment. Not so long ago there were astronomical journals where one could raise these issues but these journals have either ceased to exist or have been revamped into pure research journals. Physicists have no outlet for expressing their views—especially unorthodox views—on the nature of the scientific method and/or social structures affecting their research because journals for physicists are solely dedicated to research. This book aims to fill this current gap in the literature with a sample of critical papers.

The essay “Challenging dominant physics paradigms” by Campanario and Martin is a general analysis of the difficulties found by well-qualified scientists to challenge scientific orthodoxy. Particular cases of dissidence are reflected in the autobiographical odysseys narrated by Kundt, Arp or Castro Perelman. Castro Perelman tells us about the illicit, shameful censorship and blacklisting of scientists taking place in the electronic e-archives web-site <http://arXiv.org> and which is the most important internet site for preprints in Physics, Astronomy and Mathematics. Scientific and political elites in Western democracies control the system, according to Arp. Anonymity in the peer-review system is susceptible of corruption—says Marvin Herndon—and interferes with the objective examination of extraordinary ideas on their merits—says Van Flandern. These problems of science are worldwide and present in rich countries like the United States, as pointed out by Marvin Herndon, as well as in developing countries. Apostol talks about the corruption, decadence and mafias in Romania hidden behind the use of politically correct terms: “technological transfer”, “international cooperation”, “scientometrics”, etc. Like the example of Romania, many other countries have similar problems. The same problems in Physics and Astronomy are widespread in all fields of science and in all areas of research performed by humans. One representative of the text outside the fields of Physics and Astronomy is the essay by Bauer, where a critical study of analytical chemistry and the conflict of interests in science is presented. We considered it interesting because the context of his essay is applicable to all the sciences in general. The situation in Astrophysics is widely described in López Corredoira’s essay on the oldest profession. Kundt tackles some aspects of astrophysics too, Arp focuses in the research of cosmology, and Van Flandern’s article focuses on the solar system. 

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A aptidão darwinista desmoronando diante das evidências - não é mensurável

segunda-feira, setembro 11, 2017

Variability in Fitness Effects Can Preclude Selection of the Fittest

Annual Review of Ecology, Evolution, and Systematics

Vol. 48:- (Volume publication date December 2017) 

Review in Advance first posted online on August 28, 2017. (Changes may still occur before final publication.) 

Christopher J. Graves1,2 and Daniel M. Weinreich1,2

1Department of Ecology and Evolutionary Biology, Brown University, Providence, Rhode Island, 02912; email: Christopher_graves@alumni.brown.edu, daniel_weinreich@brown.edu

2Center for Computational and Molecular Biology, Brown University, Providence, Rhode Island, 02912

The fitness of a genetic trait (an allele) may vary over time, rather than remain constant. In this simple model, populations with two different alleles (black or yellow) see-saw between advantage and disadvantage as their relative fitness changes over time (blue line below). Credit: Weinreich et. al. - PhysOrg


Evolutionary biologists often predict the outcome of natural selection on an allele by measuring its effects on lifetime survival and reproduction of individual carriers. However, alleles affecting traits like sex, evolvability, and cooperation can cause fitness effects that depend heavily on differences in the environmental, social, and genetic context of individuals carrying the allele. This variability makes it difficult to summarize the evolutionary fate of an allele solely on the basis of its effects on any one individual. Attempts to average over this variability can sometimes salvage the concept of fitness. In other cases, evolutionary outcomes can be predicted only by considering the entire genealogy of an allele, thus limiting the utility of individual fitness altogether. We describe a number of intriguing new evolutionary phenomena that have emerged in studies that explicitly model long-term lineage dynamics and discuss implications for the evolution of infectious diseases.

Expected final online publication date for the Annual Review of Ecology, Evolution, and Systematics Volume 48 is November 2, 2017. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.





The phrase "survival of the fittest" makes the principle of evolution by natural selection easy to understand—individuals with a trait that adapts them well to their circumstances are more likely to pass that trait along. But as a new study explains, multiple factors make predicting the fate of a trait fiendishly difficult.

Fundamentally, the problem is that a trait conveyed by a gene variant, or allele, may be advantageous for one or a few generations, but provide no advantage or become a liability when circumstances change, said senior author Daniel Weinreich, a professor of ecology and evolutionary biology at Brown University. But most theoretical models of population genetics assume that fitness remains constant.

Perhaps the most obvious way that the fitness of a trait can vary is that the environment can change, not only over time but also over space.

Another dimension that can vary is the "social" life of alleles. Alleles that result in "cheating" are abundant in nature, but they are most effective when they are rare. Once everyone is cheating, it might no longer be an advantage, so the trait over time can become a victim of its own success.

That any of these circumstances can change over time adds yet another layer of complexity, Weinreich said, because the rate at which circumstances change matters.

Indeed, Weinreich said, many models for predicting the fate of alleles have overlooked the possibility that traits can go completely extinct.

Meanwhile, the rate of environmental change is very similar to the rate at which natural selection acts, the math becomes especially tricky.

Weinreich said he plans to delve deeper into the complexities of changes in fitness deriving from varying rates of change in social (e.g. cheaters), genetic (e.g. competing alleles) or environmental (e.g., weather) parameters.

“The overlap between ecological and evolutionary processes—that those two things speak to each other very intimately in a way that’s been overlooked in many models—is the way forward,” Weinreich said. “That’s what’s needed to make critical improvements to models.“