Evolução rápida do espectro de mutação humana

segunda-feira, dezembro 18, 2017

Rapid evolution of the human mutation spectrum

Kelley Harris, Jonathan K Pritchard 

Stanford University, United States Howard Hughes Medical Institute, Stanford University, United States



DNA is a remarkably precise medium for copying and storing biological information. This high fidelity results from the action of hundreds of genes involved in replication, proofreading, and damage repair. Evolutionary theory suggests that in such a system, selection has limited ability to remove genetic variants that change mutation rates by small amounts or in specific sequence contexts. Consistent with this, using SNV variation as a proxy for mutational input, we report here that mutational spectra differ substantially among species, human continental groups and even some closely related populations. Close examination of one signal, an increased TCC

→TTC mutation rate in Europeans, indicates a burst of mutations from about 15,000 to 2000 years ago, perhaps due to the appearance, drift, and ultimate elimination of a genetic modifier of mutation rate. Our results suggest that mutation rates can evolve markedly over short evolutionary timescales and suggest the possibility of mapping mutational modifiers.

eLife digest

DNA is a molecule that contains the information needed to build an organism. This information is stored as a code made up of four chemicals: adenine (A), guanine (G), cytosine (C), and thymine (T). Every time a cell divides and copies its DNA, it accidentally introduces ‘typos’ into the code, known as mutations. Most mutations are harmless, but some can cause damage. All cells have ways to proofread DNA, and the more resources are devoted to proofreading, the less mutations occur. Simple organisms such as bacteria use less energy to reduce mutations, because their genomes may tolerate more damage. More complex organisms, from yeast to humans, instead need to proofread their genomes more thoroughly.

Recent research has shown that humans have a lower mutation rate than chimpanzees and gorillas, their closest living relatives. Humans and other apes copy and proofread their DNA with basically the same biological machinery as yeast, which is about a billion years old. Yet, humans and apes have only existed for a small fraction of this time, a few million years. Why then do humans need to replicate and proofread their DNA differently from apes, and could it be that the way mutations arise is still evolving?

Previous research revealed that European people experience more mutations within certain DNA motifs (specifically, the DNA sequences ‘TCC’, ‘TCT’, ‘CCC’ and ‘ACC’) than Africans or East Asians do.

Now, Harris (who conducted the previous research) and Pritchard have compared how various human ethnic groups accumulate mutations and how these processes differ in different groups.

Statistical analysis of the genomes of thousands of people from all over the world did indeed show that the mutation rates of many different three-letter DNA motifs have changed during the past 20,000 years of human evolution. Harris and Pritchard report that when groups of humans left Africa and settled in isolated populations across different continents, each population quickly became better at avoiding mutations in some genomic contexts, but worse in others. This suggests that the risk of passing on harmful mutations to future generations is changing and evolving at an even faster rate than was originally suspected.

The results suggest that every human ethnic group carries specific variants of the genes which ensure that DNA replication and repair are accurate. These differences appear to influence which types of mutations are frequently passed down to future generations. An important next step will be to identify the genetic variants that could be controlling mutational patterns and how they affect human health.


Torque humano não está presente no cérebro do chimpanzé

sexta-feira, dezembro 15, 2017

NeuroImage Volume 165, 15 January 2018, Pages 285-293

Human torque is not present in chimpanzee brain

XiangLi a, Timothy J.Crow, b, William D.Hopkins, c, d, Qiyong Gong, e, Neil Roberts, a

a School of Clinical Sciences, University of Edinburgh, EH16 4TJ, United Kingdom

b POWIC, University Department of Psychiatry, Warneford Hospital, Oxford, OX3 7JX, United Kingdom

c Yerkes National Primate Research Center, Atlanta, GA 30029, USA

d Neuroscience Institute, Georgia State University, Atlanta, GA 30302, USA

e Huaxi MR Research Center (HMRRC), Department of Radiology, West China Hospital of Sichuan University, Chengdu, Sichuan 610041, China

Received 28 June 2017, Revised 3 October 2017, Accepted 8 October 2017, Available online 12 October 2017.

 Species difference in left-right positional brain asymmetry (AsymLR).


We searched for positional brain surface asymmetries measured as displacements between corresponding vertex pairs in relation to a mid-sagittal plane in Magnetic Resonance (MR) images of the brains of 223 humans and 70 chimpanzees. In humans deviations from symmetry were observed: 1) a Torque pattern comprising right-frontal and left-occipital “petalia” together with downward and rightward “bending” of the occipital extremity, 2) leftward displacement of the anterior temporal lobe and the anterior and central segments of superior temporal sulcus (STS), and 3) posteriorly in the position of left occipito-temporal surface accompanied by a clockwise rotation of the left Sylvian Fissure around the left-right axis. None of these asymmetries was detected in the chimpanzee, nor was associated with a sex difference. However, 4) an area of cortex with its long axis parallel to the olfactory tract in the orbital surface of the frontal lobe was found in humans to be located higher on the left in females and higher on the right in males. In addition whereas the two hemispheres of the chimpanzee brain are equal in extent in each of the three dimensions of space, in the human brain the left hemisphere is longer (p = 3.6e-12), and of less height (p = 1.9e-3), but equal in width compared to the right. Thus the asymmetries in the human brain are potential correlates of the evolution of the faculty of language.


Torque Petalia Occipital bending Asymmetry Chimpanzee Superior temporal sulcus

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Decodificado o sistema de navegação das células do cérebro: mero acaso, fortuita necessidade ou design inteligente???

quinta-feira, dezembro 14, 2017

Ephrin-A/EphA specific co-adaptation as a novel mechanism in topographic axon guidance

Felix Fiederling, Markus Weschenfelder, Martin Fritz, Anne von Philipsborn, Martin Bastmeyer, Franco Weth


The retinotectal projection.
The topographic projection in the chicken visual system connects RGCs from the retina to the midbrain's optic tectum.


Genetic hardwiring during brain development provides computational architectures for innate neuronal processing. Thus, the paradigmatic chick retinotectal projection, due to its neighborhood preserving, topographic organization, establishes millions of parallel channels for incremental visual field analysis. Retinal axons receive targeting information from quantitative guidance cue gradients. Surprisingly, novel adaptation assays demonstrate that retinal growth cones robustly adapt towards ephrin-A/EphA forward and reverse signals, which provide the major mapping cues. Computational modeling suggests that topographic accuracy and adaptability, though seemingly incompatible, could be reconciled by a novel mechanism of coupled adaptation of signaling channels. Experimentally, we find such ‘co-adaptation’ in retinal growth cones specifically for ephrin-A/EphA signaling. Co-adaptation involves trafficking of unliganded sensors between the surface membrane and recycling endosomes, and is presumably triggered by changes in the lipid composition of membrane microdomains. We propose that co-adaptative desensitization eventually relies on guidance sensor translocation into cis-signaling endosomes to outbalance repulsive trans-signaling.

eLife digest

The human brain contains roughly 100 billion neurons, which are organized into complex networks. But how does the brain establish these networks in the first place? Neurons have long projections known as axons and, in the developing brain, these axons form structures called growth cones at their tips. The growth cones possess finger-like appendages that probe their surroundings in search of signals displayed on the surface of other cells. These signals guide the growth cones to their targets and move the axon tip into a position where it can form connections with other neurons within a particular network.

The signals that growth cones follow are often distributed in concentration gradients so that the levels of a signal may be low at one end of a brain structure and gradually increase to a maximum level at the other end. In the developing visual system, for example, about one million axons from the retina reach their proper targets in visual regions of the brain by reading gradients of signals called ephrins and Ephs. However, when Fiederling et al. studied retinal neurons in a petri dish, they found that the axons became much less sensitive to both signals upon prolonged exposure to them. This unexpected finding raised a new question. If neurons rely upon these gradients for navigation, how do they continue to find their way if they also become less sensitive to those signals over time?

Fiederling et al. used a computer to simulate the events occurring in the developing brain. The simulations were based on the idea that navigating growth cones sense the ratio of ephrins to Ephs, instead of sensing the individual concentrations of these signals. Thus, by keeping the amounts of all involved sensors in strict proportion to each other while continuously re-adjusting them, the axons could still be accurately guided to their targets even though the neurons would become less sensitive to the signals. Experiments in neurons grown in petri dishes confirmed that retinal growth cones do exactly this and regulate the amounts of ephrin and Eph sensors on their outer membranes in a highly coordinated manner using a previously unknown mechanism.

Given that signaling requires energy, the brain may have evolved this system to reduce the costs associated with wiring itself up. The system also offers greater flexibility than guidance based on the absolute concentrations of the signals. If other regions of the brain use a similar mechanism to establish their own wiring patterns, then understanding such basic mechanisms might eventually provide insights into diseases of miswiring such as schizophrenia and autism.


Jerry Fodor, o crítico persistente do neodarwinismo


Jerry Fodor’s Enduring Critique of Neo-Darwinism

By Stephen Metcalf December 12, 2017

The philosopher Jerry Fodor was important for the same reason you’ve probably never heard of him: he was unimpressed, to put it politely, by the intellectual trends of the day. His focus was the philosophy of the mind, and he regarded much of what went on in brain labs as make-work. “If the mind happens in space at all, it happens somewhere north of the neck,” he wrote in The London Review of Books, in 1999. “What exactly turns on knowing how far north?” Fodor was indifferent to recent developments in European thought—everything since Kant, more or less. But he was that rare thing, a man who could lift your spirits while derogating your world view. When he died, last month, philosophy Twitter filled with variations of the same sentiment: I loved Jerry, even though he was wrong about everything.

Fodor first made his name at M.I.T., in the sixties and seventies, by pioneering a theory of the mind. He offered an updated version of what is sometimes called, in philosophy survey courses, rationalism. He didn’t think it was possible that we started our lives as blank slates and acquired, through experience alone, our mental repertoires; combining aspects of Chomsky’s theory of linguistic innateness with Turing’s insights into mathematical computation, he argued that there had to be a prior, unacquired “language of thought”—the title of his career-making book—out of which everyday cognition emerges. In offering a naturalistic account of mental representations, he staked out a middle ground where nobody thought one was possible: between our ordinary (or “folk”) notions about our own psychology—the fact that people “account for their voluntary behavior by citing beliefs and desires they entertain”—and the neurophysiology of the brain.

As his career progressed, Fodor became a skeptic—but that doesn’t quite capture it. What do you get when you cross a unicorn with a gadfly? He became skeptical of his own earlier, more strictly modular thesis of the brain. Our reasoning is too holistic in its inferences for it to proceed solely from mechanical rule-following, he decided. “The moon looks bigger when it’s on the horizon; but I know perfectly well it’s not. My visual perception module gets fooled, but I don’t. The question is: who is this I?” (There is, as of yet, no A.I. for this I.) But nothing inspired his skepticism more than the current vogue for Charles Darwin—specifically, the fusion of evolutionary biology, Mendelian genetics, and cognitive neuroscience known as neo-Darwinism.

“Neo-Darwinism is taken as axiomatic,” he wrote in “What Darwin Got Wrong,” co-written with Massimo Piattelli-Palmarini, a cognitive scientist, and published in 2010. “It goes literally unquestioned. A view that looks to contradict it, either directly or by implication, is ipso facto rejected, however plausible it may otherwise seem.” Fodor thought that the neo-Darwinists had confused the loyalty oath of modernity—nature is without conscious design, species evolve over time, the emergence of Homo sapiens was without meaning or telos—with blind adherence to the fallacy known as “natural selection.” That species are a product of evolutionary descent was uncontroversial to Fodor, an avowed atheist; that the mechanism guiding the process was adaptation via a competition for survival—this, Fodor believed, had to be wrong.

Fodor attacked neo-Darwinism on a purely conceptual and scientific basis—its own turf, in other words. He thought that it suffered from a “free rider” problem: too many of our phenotypic traits have no discernible survival value, and therefore could not plausibly be interpreted as products of adaptation. “Selection theory cannot distinguish the trait upon which fitness is contingent from the trait that has no effect on fitness (and is merely a free rider),” he wrote. “Advertising to the contrary notwithstanding, natural selection can’t be a general mechanism that connects phenotypic variation with variation in fitness. So natural selection can’t be the mechanism of evolution.”

“What Darwin Got Wrong” was greeted with dismissive howls—and it is possible Fodor got the biology wrong. But he got the ideology exactly right. Fodor was interested in how the distinction between an adaptation and a free rider might apply to our own behavior. It seems obvious to us that the heart is for circulating blood and not for making thump-thump noises. (Fodor did not believe this for was defensible, either, but that is for another day.) Pumping is therefore an “adaptation,” the noise is a “free rider.” Is there really a bright sociobiological line dividing, say, the desire to mate for life from the urge to stray? The problem isn’t that drawing a line is hard; it’s that it’s too easy: you simply call the behavior you like an adaptation, the one you don’t like a free rider. Free to concoct a just-so story, you may now encode your own personal biases into something called “human nature.”

Read more here/Leia mais aqui: The New York Times 


Este blogger não viu este artigo do New York Times traduzido na Folha de São Paulo. Alguém viu? Por que será, hein??? Compreensível o silêncio da Folha de São Paulo - quando a questão é Darwin, a Grande Mídia adota o moto: Darwin locuta causa finita! Pobre jornalismo científico!!!

Freud foi uma fraude: um triunfo de uma pseudociência. Falta Darwin cair!

Freud Was a Fraud: A Triumph of Pseudoscience

Frederick Crews has written a reassessment of Freud based on newly available correspondence and re-evaluation of previously available materials. He shows that Freud was a fraud who deceived himself and succumbed to pseudoscience.

Harriet Hall on December 12, 2017

Psychiatry is arguably the least science-based of all the medical specialties, and Freudian psychoanalysis is arguably the least science-based psychotherapy. Freud’s theories have been widely criticized as unscientific, and treatment of mental disorders has increasingly turned to psychotropic medications and effective therapies like cognitive behavioral therapy (CBT). Freud’s impact on 20th century thought is undeniable, but he got almost everything wrong. He was not only not scientific; he was a liar and a fraud. A new book, Freud: The Making of an Illusion, by Frederick Crews, may put the final nail in his coffin.
Crews had access to material not available to previous biographers. The extensive early correspondence between Freud and his fiancée, Martha Bernays, has only recently been released, and it is very revealing of Freud’s character flaws, his sexist attitudes, and his regular use of cocaine.
Freud was trained as a scientist, but he went astray, following wild hunches, willfully descending into pseudoscience, covering up his mistakes, and establishing a cult of personality that long outlived him.
His early work in science was scattershot and lacked follow-through. He “deftly criticized premature conclusions reached by others but never crucially tested any of his own hypotheses.” He was lazy, reluctant to collect enough evidence to make sure a finding was not an anomaly; he generalized from single cases, even using himself as the single case. In an early article “On Coca” he demonstrated poor scholarship, omitting crucial references, citing references from another bibliography without reading them, and making careless errors (misstating names, dates, titles, and places of publication).

His advocacy of cocaine

His advocacy of cocaine was irrational. He wanted to justify his own use of the drug, which he took for migraines, indigestion, depression, fatigue, and many other complaints; and he presented it as a panacea. He claimed it was harmless, refusing to see clear evidence that it was addictive. When nasal applications resulted in tissue necrosis, he treated it by applying more cocaine! He used it to treat a friend’s morphine addiction and only succeeded in leaving the patient addicted to both morphine and cocaine. Then he claimed the treatment had been successful! And in his reports, he referred to other successful cases that never existed. There were many instances where it appeared that his own drug use affected his judgment.
He published a scientific study on the physiological effects of cocaine on reaction time and muscle strength. His only experimental subject was himself! In his write-up, he first tried to explain away his failure to test other subjects, and then claimed he had confirmed his results by testing colleagues, which was a lie. The study was riddled with other methodological flaws, and Crews comments that it “may rank among the most careless research studies ever to see print.”

Charcot and hysteria

Freud spent several months at Charcot’s Salpêtrière hospital in Paris. Another observer, Delboeuf, spent only a week there and quickly realized patients were being sadistically abused and coerced into stereotyped hysterical performances through hypnosis, strong suggestion, peer pressure, and other influences. Freud saw the same evidence Delboeuf saw, but his hero worship of Charcot and his need to ingratiate himself with his mentor made him blind to what was really going on. He believed Charcot had understood and mastered hysteria. Crews comments, “Every stage magician hopes that his audience will consist of precisely such eyewitnesses as Freud.”
Before specializing in the treatment of hysteria and neuroses, he practiced general medicine and neurology. He practiced useless electrotherapy for at least two years and may have continued using it even after he realized it was bogus. But later he claimed to have “soon” realized it was placebo and to have promptly stopped using it. He sent patients to spas for immobility and fattening regimens. He prescribed hydrotherapy. He steered patients to a gynecologist who treated hysterical women with surgical procedures like hysterectomy and excision of the clitoris. He put patients in needless jeopardy, acting on impulsive, sometimes fatal misjudgments. He became so enthusiastic about cocaine that he tried it on everything, even on a case of diphtheria that he misdiagnosed as “throat croup;” he interpreted transient symptomatic improvements as cures and failed to do any follow-up. At one point, he admitted privately that he had yet to help any patients.
In the first years of his practice, he was preoccupied with the rank and status of his patients. He came to specialize in a “disease of the rich,” hysteria, which could never be cured and which generated a continuing stream of income. When some of his “hysteric” patients were subsequently shown to have organic diseases, he still maintained that hysteria was part of the clinical picture. He never admitted being wrong, in one case saying his diagnosis had not been incorrect but had not been correct either. Crews says, “He chose to remain deceived even after having been proven wrong.”

Evidence of dishonesty

He treated pampered, rich socialites. His attitude towards them was cynical; they provided a steady source of income by not being cured, and in one case he rushed back to see a patient in the fear that he might get well in his absence. He had little sympathy for his patients; he actively despised most people, especially those of the lower social orders. He was a misogynist who believed women were biologically inferior. He treated his wife abominably.
Few of his ideas were original. He plagiarized. He borrowed ideas from rivals but then backdated them and treated them as his own. His debts to others were originally acknowledged but “eventually suppressed in favor of the specious appeal to clinical experience. ”He was “actively evasive, malicious, and dishonest” in covering up his mistakes. Crews relates many instances where he re-wrote history, changing the story to put himself in a better light.
He made things up as he went along, constantly changing his theories and methods but not making any actual progress towards a successful treatment.
If a patient disagreed with his interpretation, (“No, I’m not in love with my brother-in-law.”) that only strengthened his conviction that he was right. He violated patient confidentiality. If a former patient improved after leaving his treatment, he took the credit. He was oblivious to the dangers of confirmation bias.
The editors of Freud’s letters and other papers were members of his cult and were dishonest. Comparison to the original documents shows that they changed words and omitted passages that they thought would have made him look bad. They “put the most damning evidence under the rug.” For example, “Out of 284 letters Freud wrote to Fliess, only 168 were represented, and all but 29 of them underwent diplomatic and often silent alteration.”
One of the foundational cases of psychoanalysis, the prototype of a cathartic cure, was the “Anna O” case reported in a book by Breuer and Freud. They said she had recovered after Breuer’s treatment, but that wasn’t true. In fact, she got worse and was hospitalized. After leaving psychoanalytic treatment, she improved on her own and eventually led a successful life as an activist opposing the sex trade. (This was interpreted in psychoanalytic terms as a means of unconsciously wishing to prevent her mother from having sex with her father!) She probably didn’t even have a psychiatric illness, but rather a physical, neurologic one, and many of her most troubling symptoms were caused by the morphine addiction Breuer had inflicted on her. Freud’s interpretation of the case contradicted the facts: he was either lying or venting a delusion of his own.
He found his true métier as a storyteller, using anecdotes from his own case history to illustrate how his mind was “cured” of bafflement over the origin of mysterious symptoms. He described adventures of the intellect. His orientation was more literary than scientific.
Crews says, “Freud was something of a specialist in gleaning precious admissions from people who couldn’t be reached for checking.” His “standard practice was to smear his former associates as soon as they posed an obstacle to his goals.”
Read more here/Leia mais aqui: ScienceBasedMedicine

Marx já era, Freud idem, e Darwin não está se sentindo muito bem - prevalece na Academia, não pelo rigor do contexto de justificação teórica, mas pela força da aceitação a priori de uma teoria científica.

A motilidade da cinesina é impulsionada pela dinâmica de subdomínio: mero acaso, fortuita necessidade ou design inteligente???

terça-feira, dezembro 12, 2017

Kinesin motility is driven by subdomain dynamics

Wonmuk Hwang Is a corresponding author Matthew J Lang Is a corresponding author Martin Karplus Is a corresponding author

Texas A&M University, United States Korea Institute for Advanced Study, Korea Vanderbilt University, United States Vanderbilt University School of Medicine, United States Harvard University, United States ISIS, Université de Strasbourg, France


Overview of kinesin structure and motility cycle.


The microtubule (MT)-associated motor protein kinesin utilizes its conserved ATPase head to achieve diverse motility characteristics. Despite considerable knowledge about how its ATPase activity and MT binding are coupled to the motility cycle, the atomic mechanism of the core events remain to be found. To obtain insights into the mechanism, we performed 38.5 microseconds of all-atom molecular dynamics simulations of kinesin-MT complexes in different nucleotide states. Local subdomain dynamics were found to be essential for nucleotide processing. Catalytic water molecules are dynamically organized by the switch domains of the nucleotide binding pocket while ATP is torsionally strained. Hydrolysis products are 'pulled' by switch-I, and a new ATP is 'captured' by a concerted motion of the α0/L5/switch-I trio. The dynamic and wet kinesin-MT interface is tuned for rapid interactions while maintaining specificity. The proposed mechanism provides the flexibility necessary for walking in the crowded cellular environment.

eLife digest

Motor proteins called kinesins perform a number of different roles inside cells, including transporting cargo and organizing filaments called microtubules to generate the force needed for a cell to divide. Kinesins move along the microtubules, with different kinesins moving in different ways: some ‘walk’, some jump, and some destroy the microtubule as they travel along it. All kinesins power their movements using the same molecule as fuel – adenosine triphosphate, known as ATP for short.

Energy stored in ATP is released by a chemical reaction known as hydrolysis, which uses water to break off specific parts of the ATP molecule. The site to which ATP binds in a kinesin has a similar structure to the ATP binding site of many other proteins that use ATP. However, little was known about the way in which kinesin uses ATP as a fuel, including how ATP binds to kinesin and is hydrolyzed, and how the products of hydrolysis are released. These events are used to power the motor protein.

Hwang et al. have used powerful computer simulation methods to examine in detail how ATP interacts with kinesin whilst moving across a microtubule. The simulations suggest that regions (or 'domains') of kinesin near the ATP binding site move around to help in processing ATP. These kinesin domains trap a nearby ATP molecule from the environment and help to deliver water molecules to ATP for hydrolysis. Hwang et al. also found that the domain motion subsequently helps in the release of the hydrolysis products by kinesin.

The domains around the ATP pocket vary among the kinesins and these differences may enable kinesins to fine-tune how they use ATP to move. Further investigations will help us understand why different kinesin families behave differently. They will also contribute to exploring how kinesin inhibitors might be used as anti-cancer drugs.


Escultura de órgãos por rigidez da matriz extracelular padronizada: mero acaso, fortuita necessidade ou design inteligente???

Organ sculpting by patterned extracellular matrix stiffness

Justin Crest Alba Diz-Muñoz Dong-Yuan Chen Daniel A Fletcher David Bilder Is a corresponding author

University of California-Berkeley, United States


A mechanical stiffness gradient in the follicle basement membrane.


How organ-shaping mechanical imbalances are generated is a central question of morphogenesis, with existing paradigms focusing on asymmetric force generation within cells. We show here that organs can be sculpted instead by patterning anisotropic resistance within their extracellular matrix (ECM). Using direct biophysical measurements of elongating Drosophila egg chambers, we document robust mechanical anisotropy in the ECM-based basement membrane (BM) but not in the underlying epithelium. Atomic force microscopy (AFM) on wild-type BM in vivo reveals an anterior–posterior (A–P) symmetric stiffness gradient, which fails to develop in elongation-defective mutants. Genetic manipulation shows that the BM is instructive for tissue elongation and the determinant is relative rather than absolute stiffness, creating differential resistance to isotropic tissue expansion. The stiffness gradient requires morphogen-like signaling to regulate BM incorporation, as well as planar-polarized organization to homogenize it circumferentially. Our results demonstrate how fine mechanical patterning in the ECM can guide cells to shape an organ.

eLife digest

All organs have specific shapes and architectures that are necessary for them to work properly. Many different factors are responsible for arranging the right cells into the correct positions to make an organ. These include physical forces that act within and around cells to pull them into the right shape and location.

A structure called the extracellular matrix surrounds cells and provides them with support; it can also guide cell movements. It is not clear whether the extracellular matrix plays only a passive role or a more active, instructive role in shaping organs, in part, because it is difficult to measure the physical forces within densely packed cells.

The ovaries of the fruit fly Drosophila melanogaster provide a simple system in which to study how organs take their shape. Crest et al. developed a method to measure forces in the fly ovary as it changes from being an initially spherical group of cells to its final elongated tube shape. The results revealed that, during this process, the extracellular matrix becomes gradually stiffer from one end of the ovary to the other. This change is the main factor responsible for the cell rearrangements that shape the developing organ.

This work reveals that, along with providing structural support to cells, the mechanical properties of the matrix also actively guide how organs form. In the future, these findings may aid efforts to grow organs in a laboratory and to regenerate organs in human patients.


Co-expressão de xenopsina e opsina rabdomérica em fotorreceptores com microvília e cílios: mero acaso, fortuita necessidade ou design inteligente???

Co-expression of xenopsin and rhabdomeric opsin in photoreceptors bearing microvilli and cilia

Oliver Vöcking Ioannis Kourtesis Sharat Chandra Tumu Harald Hausen Is a corresponding author

University of Bergen, Norway University of Pittsburgh, United States


Scenarios for eye PRC evolution.
C-opsin, xenopsin and r-opsin are present in the bilaterian ancestor.


Ciliary and rhabdomeric opsins are employed by different kinds of photoreceptor cells, such as ciliary vertebrate rods and cones or protostome microvillar eye photoreceptors, that have specialized structures and molecular physiologies. We report unprecedented cellular co-expression of rhabdomeric opsin and a visual pigment of the recently described xenopsins in larval eyes of a mollusk. The photoreceptors bear both microvilli and cilia and express proteins that are orthologous to transporters in microvillar and ciliary opsin trafficking. Highly conserved but distinct gene structures suggest that xenopsins and ciliary opsins are of independent origin, irrespective of their mutually exclusive distribution in animals. Furthermore, we propose that frequent opsin gene loss had a large influence on the evolution, organization and function of brain and eye photoreceptor cells in bilaterian animals. The presence of xenopsin in eyes of even different design might be due to a common origin and initial employment of this protein in a highly plastic photoreceptor cell type of mixed microvillar/ciliary organization.

eLife digest

Animal eyes have photoreceptor cells that contain light-sensitive molecules called opsins. Although all animal photoreceptor cells of this kind share a common origin, the cells found in different organisms can differ considerably. The photoreceptor cells in flies, squids and other invertebrates store a type of opsin called r-opsin in thin projections on the surface known as microvilli. On the other hand, the visual photoreceptor cells in human and other vertebrate eyes transport another type of opsin (known as c-opsin) into more prominent extensions called cilia.

It has been suggested that the fly and vertebrate photoreceptor cells represent clearly distinct evolutionary lineages of cells, which diverged early in animal evolution. However, several organisms that are more closely related to flies than to vertebrates have eye photoreceptor cells with cilia. Do all eye photoreceptors with cilia have a common origin in evolution or did they emerge independently in vertebrates and certain invertebrates?

The photoreceptor cells of a marine mollusc called Leptochiton asellus, are unusual because they bear both microvilli and cilia, suggesting they have intermediate characteristics between the two well-known types of photoreceptor cells. Previous studies have shown that these photoreceptor cells use r-opsin, but Vöcking et al. have now detected the presence of an additional opsin in the cells. This opsin is a member of the recently discovered xenopsin family of molecules. Further analyses support the findings of previous studies that suggested this type of opsin emerged early on in animal evolution, independently from c-opsin. Other invertebrates that have cilia on their eye photoreceptors also use xenopsin and not c-opsin.

The findings of Vöcking et al. suggest that, in addition to c-opsin and r-opsin, xenopsin has also driven the evolution of photoreceptor cells in animals. Eye photoreceptor cells in invertebrates with cilia probably share a common origin with the microvilli photoreceptor cells that is distinct from that of vertebrate visual cells. The observation that two very different types of opsin can be produced within a single cell suggests that the molecular processes that respond to light in photoreceptor cells may be much more complex than previously anticipated. Further work on these processes may help us to understand how animal eyes work and how they are affected by disease.


Origem da vida - um problema para a Física, uma revisão de questões fundamentais: mero acaso, fortuita necessidade ou design inteligente???

Reports on Progress in Physics


Origins of life: a problem for physics, a key issues review

Sara Imari Walker

Published 14 August 2017 • © 2017 IOP Publishing Ltd 

Reports on Progress in Physics, Volume 80, Number 9

Author e-mails


Author affiliations

School of Earth and Space Exploration and Beyond Center for Fundamental Concepts in Science, Arizona State University, Tempe, AZ, United States of America

Blue Marble Space Institute of Science, Seattle, WA, United States of America

ORCID iDs Sara Imari Walker https://orcid.org/0000-0001-5779-2772


Received 25 March 2014 Accepted 8 June 2017 

Accepted Manuscript online 8 June 2017 Published 14 August 2017 

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Sara Imari Walker 2017 Rep. Prog. Phys. 80 092601

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Corresponding Editor Bob Austin


The origins of life stands among the great open scientific questions of our time. While a number of proposals exist for possible starting points in the pathway from non-living to living matter, these have so far not achieved states of complexity that are anywhere near that of even the simplest living systems. A key challenge is identifying the properties of living matter that might distinguish living and non-living physical systems such that we might build new life in the lab. This review is geared towards covering major viewpoints on the origin of life for those new to the origin of life field, with a forward look towards considering what it might take for a physical theory that universally explains the phenomenon of life to arise from the seemingly disconnected array of ideas proposed thus far. The hope is that a theory akin to our other theories in fundamental physics might one day emerge to explain the phenomenon of life, and in turn finally permit solving its origins.


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As enigmáticas xenopsinas: mero acaso, fortuita necessidade ou design inteligente?

Evolution: The enigmatic xenopsins

Detlev Arendt Is a corresponding author

European Molecular Biology Laboratory, Germany University of Heidelberg, Germany

INSIGHT Oct 19, 2017

The evolution of opsins and photoreceptor cells.


A new member of the family of light-sensitive proteins called opsins has stirred up our view of photoreceptors.


Regulação gênica: um interruptor transcricional controla a meiose - mero acaso, fortuita necessidade ou design inteligente?

Gene Regulation: A transcriptional switch controls meiosis

A Elizabeth Hildreth Karen M Arndt Is a corresponding author

University of Pittsburgh, United States

INSIGHT Oct 24, 2017

Transcriptional switching between two mRNA transcripts regulates the assembly of the kinetochore during meiosis.


A key protein involved in the segregation of meiotic chromosomes is produced 'just in time' by the regulated expression of two mRNA isoforms.




Two papers in eLife, Elçin Ünal, Folkert van Werven and colleagues at the University of California at Berkeley and the Francis Crick Institute report a transcriptional switch that controls the timing of a critical event in the development of the yeast Saccharomyces cerevisiae (Chen et al., 2017; Chia et al., 2017).

Os microtúbulos tripleto de centríolos são necessários na formação de centríolo estável e herança em células humanas

Centriole triplet microtubules are required for stable centriole formation and inheritance in human cells

Jennifer T Wang Dong Kong Christian R Hoerner Jadranka Loncarek Tim Stearns Is a corresponding author

Stanford University, United States Center for Cancer Research, United States National Cancer Institute, National Institutes of Health, United States Stanford School of Medicine, United States



Centrioles are composed of long-lived microtubules arranged in nine triplets. However, the contribution of triplet microtubules to mammalian centriole formation and stability is unknown. Little is known of the mechanism of triplet microtubule formation, but experiments in unicellular eukaryotes indicate that delta-tubulin and epsilon-tubulin, two less-studied tubulin family members, are required. Here, we report that centrioles in delta-tubulin and epsilon-tubulin null mutant human cells lack triplet microtubules and fail to undergo centriole maturation. These aberrant centrioles are formed de novo each cell cycle, but are unstable and do not persist to the next cell cycle, leading to a futile cycle of centriole formation and disintegration. Disintegration can be suppressed by paclitaxel treatment. Delta-tubulin and epsilon-tubulin physically interact, indicating that these tubulins act together to maintain triplet microtubules and that these are necessary for inheritance of centrioles from one cell cycle to the next.

eLife digest

Most structures inside a cell have a short lifespan and are continually replaced. Centrioles – specialized structures that help cells divide, and send and receive signals – are among the few exceptions and can persist through many cell generations. Centrioles are cylindrical structures that are made up of protein tubes called microtubules. Specifically, nine groups of three microtubules, known as triplet microtubules, are linked together to make the walls of the cylinder. The triplets of microtubules are only found in centrioles, and until now it was not known what role this specific formation plays.

Now, Wang et al. studied two lesser known members of the protein family that build the microtubules, called delta-tubulin and epsilon-tubulin. When either of these proteins was removed from human cells grown in the laboratory, the centrioles only had single microtubules rather than the usual triplets. The centrioles still formed at the correct time, but disappeared soon after the cell had divided.

When the cells were then treated with a drug that stabilizes the microtubules, the centrioles no longer disappeared once the cell had divided. This suggests that the triplet microtubule formation is needed to stabilize and maintain the centrioles through the cell divisions. Moreover, the results were similar for delta- and epsilon-tubulin, and it appears that the proteins work together to help stabilize the triplet microtubules.

Defects in centrioles are associated with many diseases, including some types of cancer and many genetic conditions that can lead to heart or kidney disease, obesity, diabetes and many others. Deeper knowledge of centriole structure and its role may help us to better understand these diseases.