A Strange Tale Of Fish Eye Evolution

By William Feeney

Evolution allows animals to develop superb adaptations to survive and flourish in environmental niches. The evolution of fish eyes is one such intriguing example. However, tracing how different kinds of fish eyes evolved is not always easy. New research is finally throwing some light on this evolutionary feat and it is helping us understand how new species are born.

The diversity of life on Earth is a result of evolutionary processes acting over millions of years. Small changes to the genetic make-up of an organism, such as those that sometimes occur during sexual reproduction, can confer an advantage over competitors and are passed onto the next generation. Changes that result in a disadvantage, by contrast, are filtered out of the population.

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Switching off anxiety with light

Receptors for the messenger molecule serotonin can be modified in such a way that they can be activated by light. Together with colleagues, neuroscientists from the Ruhr-Universität Bochum (RUB) report on this finding in the journal “Neuron”. An imbalance in serotonin levels seems to cause anxiety and depression. The researchers have provided a new model system for investigating the mechanism underlying these dysfunctions in cell cultures as well as living organisms.

G protein coupled receptors play an important role in medicine and health

One receptor, which is important for the regulation of serotonin levels in the brain, is the 5-HT1A receptor. It belongs to a protein family called G protein coupled receptors (GPCRs). These receptors can activate different signalling pathways in cells to support or suppress various signalling events. “About 30 per cent of the current drugs target specifically GPCRs”, says Prof Dr Stefan Herlitze from the Department of General Zoology and Neurobiology at the RUB. Due to the lack of tools to control intracellular signalling pathways with high temporal and spatial accuracy, it was so far difficult to analyse these pathways precisely.

Coupling of visual pigments to serotonin receptors

Applying optogenetic methods the scientists in Bochum used cone opsins from the mouse and human eye to control specifically serotonin signalling pathways either with blue or red light. Prof Dr Stefan Herlitze has been working with optogenetic techniques since 2005 and is one of the pioneers in the field. The light-activated serotonin receptors can be switched on within milliseconds, are extremely light sensitive in comparison to other optogenetic tools and can be repetitively activated. “We hope that with the help of these optogenetic tools, we will be able to gain a better understanding about how anxiety and depression originate”, states RUB neuroscientist Dr Olivia Masseck.

Successful behavioural tests

The scientists also demonstrated that they were able to modulate mouse emotional behaviour using the light-activated receptors. When they switched on the serotonergic signals by light in a certain brain area, the mice became less anxious.

Light Work

Understanding more about the human brain’s estimated 100 billion interconnected nerve cells, or neurons, could help us develop new treatments for disorders such as Parkinson’s disease, autism, schizophrenia and epilepsy. One method of investigating brain activity is to genetically engineer an animal, such as a mouse, so that its neurons produce a light-sensitive protein, opsin. Neuron activity can then be triggered by shining light on the brain, once it’s exposed in the anaesthetised animal. The computer simulation here illustrates a light beam hitting clusters of opsin on a neuron surface. The resulting nerve signals can be detected in connected neurons by inserting tiny probes to measure the electrical and genetic activity inside them. Scientists have recently developed a computer-guided robotic arm to insert the probes with greater accuracy than previously possible.

Written by Mick Warwicker

  • Ed Boyden
  • MIT McGovern Institute and Sputnik Animation

Switching off anxiety with light

Receptors for the messenger molecule serotonin can be modified in such a way that they can be activated by light. Together with colleagues, neuroscientists from the Ruhr-Universität Bochum (RUB) report on this finding in the journal “Neuron.” An imbalance in serotonin levels seems to cause anxiety and depression. The researchers have provided a new model system for investigating the mechanism underlying these dysfunctions in cell cultures as well as living organisms.

Olivia A. Masseck, Katharina Spoida, Deniz Dalkara, Takashi Maejima, Johanna M. Rubelowski, Lutz Wallhorn, Evan S. Deneris, Stefan Herlitze. Vertebrate Cone Opsins Enable Sustained and Highly Sensitive Rapid Control of Gi/o Signaling in Anxiety Circuitry. Neuron, 2014; 81 (6): 1263 DOI: 10.1016/j.neuron.2014.01.041

Nerve cells containing the light-activated 5-HT1A receptor (green) and the naturally occuring 5-HT1A receptor (red).  Credit: © RUB, image: Masseck

Noninvasive brain control

Optogenetics, a technology that allows scientists to control brain activity by shining light on neurons, relies on light-sensitive proteins that can suppress or stimulate electrical signals within cells. This technique requires a light source to be implanted in the brain, where it can reach the cells to be controlled.

MIT engineers have now developed the first light-sensitive molecule that enables neurons to be silenced noninvasively, using a light source outside the skull. This makes it possible to do long-term studies without an implanted light source. The protein, known as Jaws, also allows a larger volume of tissue to be influenced at once.

This noninvasive approach could pave the way to using optogenetics in human patients to treat epilepsy and other neurological disorders, the researchers say, although much more testing and development is needed. Led by Ed Boyden, an associate professor of biological engineering and brain and cognitive sciences at MIT, the researchers described the protein in the June 29 issue of Nature Neuroscience.

Optogenetics, a technique developed over the past 15 years, has become a common laboratory tool for shutting off or stimulating specific types of neurons in the brain, allowing neuroscientists to learn much more about their functions.

The neurons to be studied must be genetically engineered to produce light-sensitive proteins known as opsins, which are channels or pumps that influence electrical activity by controlling the flow of ions in or out of cells. Researchers then insert a light source, such as an optical fiber, into the brain to control the selected neurons.

Such implants can be difficult to insert, however, and can be incompatible with many kinds of experiments, such as studies of development, during which the brain changes size, or of neurodegenerative disorders, during which the implant can interact with brain physiology. In addition, it is difficult to perform long-term studies of chronic diseases with these implants.

Mining nature’s diversity

To find a better alternative, Boyden, graduate student Amy Chuong, and colleagues turned to the natural world. Many microbes and other organisms use opsins to detect light and react to their environment. Most of the natural opsins now used for optogenetics respond best to blue or green light.

Boyden’s team had previously identified two light-sensitive chloride ion pumps that respond to red light, which can penetrate deeper into living tissue. However, these molecules, found in the bacteria Haloarcula marismortui and Haloarcula vallismortis, did not induce a strong enough photocurrent — an electric current in response to light — to be useful in controlling neuron activity.

Chuong set out to improve the photocurrent by looking for relatives of these proteins and testing their electrical activity. She then engineered one of these relatives by making many different mutants. The result of this screen, Jaws, retained its red-light sensitivity but had a much stronger photocurrent — enough to shut down neural activity.

“This exemplifies how the genomic diversity of the natural world can yield powerful reagents that can be of use in biology and neuroscience,” says Boyden, who is a member of MIT’s Media Lab and the McGovern Institute for Brain Research.

Using this opsin, the researchers were able to shut down neuronal activity in the mouse brain with a light source outside the animal’s head. The suppression occurred as deep as 3 millimeters in the brain, and was just as effective as that of existing silencers that rely on other colors of light delivered via conventional invasive illumination.

A key advantage to this opsin is that it could enable optogenetic studies of animals with larger brains, says Garret Stuber, an assistant professor of psychiatry and cell biology and physiology at the University of North Carolina at Chapel Hill.

“In animals with larger brains, people have had difficulty getting behavior effects with optogenetics, and one possible reason is that not enough of the tissue is being inhibited,” he says. “This could potentially alleviate that.”

Restoring vision

Working with researchers at the Friedrich Miescher Institute for Biomedical Research in Switzerland, the MIT team also tested Jaws’s ability to restore the light sensitivity of retinal cells called cones. In people with a disease called retinitis pigmentosa, cones slowly atrophy, eventually causing blindness.

Friedrich Miescher Institute scientists Botond Roska and Volker Busskamp have previously shown that some vision can be restored in mice by engineering those cone cells to express light-sensitive proteins. In the new paper, Roska and Busskamp tested the Jaws protein in the mouse retina and found that it more closely resembled the eye’s natural opsins and offered a greater range of light sensitivity, making it potentially more useful for treating retinitis pigmentosa.

This type of noninvasive approach to optogenetics could also represent a step toward developing optogenetic treatments for diseases such as epilepsy, which could be controlled by shutting off misfiring neurons that cause seizures, Boyden says. “Since these molecules come from species other than humans, many studies must be done to evaluate their safety and efficacy in the context of treatment,” he says.

Boyden’s lab is working with many other research groups to further test the Jaws opsin for other applications. The team is also seeking new light-sensitive proteins and is working on high-throughput screening approaches that could speed up the development of such proteins.

Let's Go, Rick Steves, and Walking in London: A Review Comparing different travel guides for London

A good guide can be a total vacation save when you’re exploring an unfamiliar place with a time. First time visitors to London have not finished packing up that led to one or two good travel guides in their backpacks. But with so many choices, taking the right book can actually become one of the most frustrating travel planning: rails are some redundant, some compliment one another, some are complete, others are superficial.Let ‘s Go London City guidebooks, Rick Steves’ Great Britain, and Andrew Duncan Walking London are three very different books that have distinct purposes. And while certainly not the only London guides worth checking out, there is a 99% chance that at least one of them suits your individual needs. Let’s Go is probably the hottest business travel literature in the world at this time. They have put out guides that are stylish, economical, and-with a new version published every year, timely and accurate. Their London City Guide is no exception. Within the 350 + pages of the book, you will find heaps of detailed advice on eating, drinking, nightlife, museums and galleries, shopping, transport and accommodation (including hostels, bed & breakfasts, and even living rooms. ) All this information is conveniently organized by district. Within the pages of the guide Let’s Go find one for maps, charts, maps and more maps. lines the streets of London sprawling, casual, old-meets-new can make navigation difficult, but you’ll be fine if you’re carrying the guide Let’s Go: the first 8 and last 31 pages are devoted entirely to the maps. Bottom, Let’s Go has some ‘advertising on its pages, some of which can be intrusive at times. And even more significantly, Let’s Go lacks personality. It ‘full of practical information such as addresses, prices and hours, but it lacks that human touch that can be so comforting for a traveler in an unfamiliar place. This is where the game Rick Steves travel stories personal opinions frankly and historical curiosities to Rick Steves’ Great Britain a perfect companion to (or replacement) Let’s Go guide with a section entitled “Delusions of London, you know this guy is pulling no punches. But what really makes it stand out from Steves travel writer and his drawings. He insists that his readers get a visual representation of everything he writes. His guide is filled with easy to follow, hand-drawn maps of everything from entire regions, cities and districts, right down to floorplans of galleries, museums and castles. -And as you probably guessed from the title-Rick Steves’ Britain does not deal exclusively in London. The book covers all the best that England, Wales and Scotland have to offer. This makes it perfect for travelers who plan to spend time outside of London for part of their journey. Steves also publishes a guide of the city of London-specific, but with 80 + pages of the book in Britain devoted exclusively to London, why bother? My only problem with writing Steves’ is that while he certainly does not bear to throw away money, may not be enough for some budget-oriented travelers (like those on a student budget.) For example, his recommendations to address accommodation almost exclusively with hotels, hostels, giving only a hint. And while people in Let’s Go understand that you’re willing to walk eight miles for a cheap drink, Steves’ readers have to resign themselves to the idea that they are going to pay $ 10 for a beer. Last but by no means least, we strongly recommend checking out Walking London by Andrew Duncan. It ‘s a very special book, not an all-encompassing guide to the city, but a manual step-by-step tour to 30 do-it-yourself walking through the most famous districts of the city. Even if you’re not one of the turns in its entirety, holding a copy of Walking in London stock exchange days is guaranteed not to miss important points of reference, good food, or photo opportunities as you are walking from place to place. Although I do not recommend using London as a tourist guide Walking alone makes it a striking partner for any of the most complete guides or country. If you decide to take it, I support the “Westminster and St. James ‘and’ Bankside and Southwark” missed like two walks. Whatever you decide to go with books, there is an important secret to using them correctly: to study before you go. What better way to ruin a vacation than spending all the time with his face buried in a guidebook.

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Ivan Villafuerte

Sin Are Acids In The Eyes

This guy was standing on a corner in Greenpoint, Brooklyn preaching about “the DNA of sin.” He told me, “Sin are acids in the eyes called OpSin…which form free radicals causing aging, disease, and death.” I think he also said his church sell anti-aging products. It was a lot to take in…

More photos of Preachers and Super Religious Folk and from the Random Strangers Series.

Octopus-Inspired Camouflage Flashes to Life in Smart Material! (TECHNOLOGY)

     Octopuses and their cephalopod cousins are the undisputed masters of disguise. An octopus can change its color, texture and luminosity faster than you can say “camouflage.”

     So far our lowly human attempts at imitation have been quite crude. But a flashy new smart material might just be our closest step yet.

     The main tool the octopus uses for its visual display is a cell called a chromatophore. These small, pigment-filled sacs expand and contract to create an array of colors and patterns. How does the octopus decide what colors and patterns to make? Recent research suggests that octopuses can also sense light—and possibly even color—through photo-sensitive cells (called opsins) in their skin.

     The idea of a material that can both sense and create visual change is quite appealing to science (and the military). Renowned cephalopod researcher Roger Hanlon, a senior scientist at Woods Hole Marine Biological Laboratory, and John Rogers, a professor of materials science and engineering at the University of Illinois at Urbana-Champaign (whose previous work includes flexible temporary tattoo-like circuits), teamed up with a crew of international researchers to create a changing heat- and light-sensitive sheet of pixels, described earlier this week in Proceedings of the National Academy of Sciences.

Photo sensible nanomaterial, based in octopus skin

More facts and Science in: www.newhorizonshept.tumblr.com



How plankton gets jet lagged

A hormone that governs sleep and jet lag in humans may also drive the mass migration of plankton in the ocean, scientists at the European Molecular Biology Laboratory (EMBL) in Heidelberg, Germany, have found. The molecule in question, melatonin, is essential to maintain our daily rhythm, and the European scientists have now discovered that it governs the nightly migration of a plankton species from the surface to deeper waters. The findings, published online today in Cell, indicate that melatonin’s role in controlling daily rhythms probably evolved early in the history of animals, and hold hints to how our sleep patterns may have evolved.

In vertebrates, melatonin is known to play a key role in controlling daily activity patterns – patterns which get thrown out of synch when we fly across time zones, leading to jet lag. But virtually all animals have melatonin. What is its role in other species, and how did it evolve the task of promoting sleep? To find out, Detlev Arendt’s lab at EMBL turned to the marine ragworm Platynereis dumerilii. This worm’s larvae take part in what has been described as the planet’s biggest migration, in terms of biomass: the daily vertical movement of plankton in the ocean. By beating a set of microscopic ‘flippers’ – cilia – arranged in a belt around its midline, the worm larvae are able to migrate toward the sea’s surface every day. They reach the surface at dusk, and then throughout the night they settle back down to deeper waters, where they are sheltered from damaging UV rays at the height of day. 

“We found that a group of multitasking cells in the brains of these larvae that sense light also run an internal clock and make melatonin at night.” says Detlev Arendt, who led the research. “So we think that melatonin is the message these cells produce at night to regulate the activity of other neurons that ultimately drive day-night rhythmic behaviour.”

Maria Antonietta Tosches, a postdoc in Arendt’s lab, discovered a group of specialised motor neurons that respond to melatonin. Using modern molecular sensors, she was able to visualise the activity of these neurons in the larva’s brain, and found that it changes radically from day to night. The night-time production of melatonin drives changes in these neurons’ activity, which in turn cause the larva’s cilia to take long pauses from beating. Thanks to these extended pauses, the larva slowly sinks down. During the day, no melatonin is produced, the cilia pause less, and the larva swims upwards.

“When we exposed the larvae to melatonin during the day, they switched towards night-time behaviour,” says Tosches, “it’s as if they were jet lagged.”

The work strongly suggests that the light-sensing, melatonin-producing cells at the heart of this larva’s nightly migration have evolutionary relatives in the human brain. This implies that the cells that control our rhythms of sleep and wakefulness may have first evolved in the ocean, hundreds of millions of years ago, in response to pressure to move away from the sun.

“Step by step we can elucidate the evolutionary origin of key functions of our brain. The fascinating picture emerges that human biology finds its roots in some deeply conserved, fundamental aspects of ocean ecology that dominated life on Earth since ancient evolutionary times,” Arendt concludes.

Shedding a light on pain: A technique developed by Stanford bioengineers could lead to new treatments

The mice in Scott Delp’s lab, unlike their human counterparts, can get pain relief from the glow of a yellow light.

Right now these mice are helping scientists to study pain – how and why it occurs and why some people feel it so intensely without any obvious injury. But Delp, a professor of bioengineering and mechanical engineering, hopes one day the work he does with these mice can also help people who are in chronic, debilitating pain.

"This is an entirely new approach to study a huge public health issue," Delp said. "It’s a completely new tool that is now available to neuroscientists everywhere." He is the senior author of a research paper published Feb. 16 in Nature Biotechnology.

A switch for pain

The mice are modified with gene therapy to have pain-sensing nerves that can be controlled by light. One color of light makes the mice more sensitive to pain. Another reduces pain. The scientists shone a light on the paws of mice through the Plexiglas bottom of the cage.

Graduate students Shrivats Iyer and Kate Montgomery, who led the study, say it opens the door to future experiments to understand the nature of pain and also touch and other sensations that are part of our daily lives but little understood.

"The fact that we can give a mouse an injection and two weeks later shine a light on its paw to change the way it senses pain is very powerful," Iyer said.

For example, increasing or decreasing the sensation of pain in these mice could help scientists understand why pain seems to continue in people after an injury has healed. Does persistent pain change those nerves in some way? If so, how can they be changed back to a state where, in the absence of an injury, they stop sending searing messages of pain to the brain?

Leaders at the National Institutes of Health agree that the work could have important implications for treating pain. “This powerful approach shows great potential for helping the millions who suffer pain from nerve damage,” said Linda Porter, the pain policy adviser at the National Institute of Neurological Disorders and Stroke and a leader of the NIH’s Pain Consortium.

"Now, with a flick of a switch, scientists may be able to rapidly test new pain-relieving medications and, one day, doctors may be able to use light to relieve pain," she said.

Accidental discovery

The researchers took advantage of a technique called optogenetics, which involves light-sensitive proteins called opsins that are inserted into the nerves. Optogenetics was developed by Delp’s colleague Karl Deisseroth, a co-author of the journal article. He has used the technique as a way of activating precise regions of the brain to better understand how the brain functions. Deisseroth is a professor of bioengineering, psychiatry and behavioral sciences.

Delp, who has an interest in muscles and movement, saw the potential for using optogenetics not just for studying the brain – interesting though those studies may be – but also for studying the many nerves outside the brain. These are the nerves that control movement, pain, touch and other sensations throughout our body, and that are involved in diseases such as amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig’s Disease.

A few years ago Stanford Bio-X, which encourages interdisciplinary projects such as this one, supported Delp and Deisseroth in their efforts to use optogenetics to control the nerves that excite muscles. In the process of doing that work, Delp said, his student at the time, Michael Llewellyn, occasionally found that he had placed the opsins into nerves that signal pain rather than those that control muscle.

That accident sparked a new line of research. Delp said, “We thought, ‘Wow, we’re getting pain neurons; that could be really important.’” He suggested that Montgomery and Iyer focus on those pain nerves that had been a byproduct of the muscle work.

A faster approach

A key component of the work was a new approach to quickly incorporate opsins into the nerves of mice. The researchers started with a virus that had been engineered to contain the DNA that produces the opsin. Then they injected those modified viruses directly into mouse nerves. Weeks later, only the nerves that control pain had incorporated the opsin proteins and would fire, or be less likely to fire, in response to different colors of light.

The speed of the viral approach makes it very flexible, both for this pain work and for future studies. Researchers are developing newer forms of opsins with different properties, such as responding to different colors of light. “Because we used a viral approach we could, in the future, quickly turn around and use newer opsins,” said Montgomery, who is a Stanford Bio-X fellow.

This entire project, which spans bioengineering, neuroscience and psychiatry, is one Delp says could never have happened without the environment at Stanford that supports collaboration across departments. The pain portion of the research came out of support from NeuroVentures, which was a project incubated within Bio-X to support the intersection of neuroscience and engineering or other disciplines. That project was so successful it has spun off into the Stanford Neurosciences Institute, of which Delp is now a deputy director.

Delp said that many challenges must be met before results of these experiments – either new drugs based on what they learn, or optogenetics directly – could become available to people but that he always has that as a goal.

"Developing a new therapy from the ground up would be incredibly rewarding," he said. "Most people don’t get to do that in their careers."

Delp and Deisseroth have started a company called Circuit Therapeutics to develop therapies based on optogenetics.

Optogenetic toolkit goes multicolor

Optogenetics is a technique that allows scientists to control neurons’ electrical activity with light by engineering them to express light-sensitive proteins. Within the past decade, it has become a very powerful tool for discovering the functions of different types of cells in the brain.

Most of these light-sensitive proteins, known as opsins, respond to light in the blue-green range. Now, a team led by MIT has discovered an opsin that is sensitive to red light, which allows researchers to independently control the activity of two populations of neurons at once, enabling much more complex studies of brain function.

“If you want to see how two different sets of cells interact, or how two populations of the same cell compete against each other, you need to be able to activate those populations independently,” says Ed Boyden, an associate professor of biological engineering and brain and cognitive sciences at MIT and a senior author of the new study.

The new opsin is one of about 60 light-sensitive proteins found in a screen of 120 species of algae. The study, which appears in the Feb. 9 online edition of Nature Methods, also yielded the fastest opsin, enabling researchers to study neuron activity patterns with millisecond timescale precision.

Boyden and Gane Ka-Shu Wong, a professor of medicine and biological sciences at the University of Alberta, are the paper’s senior authors, and the lead author is MIT postdoc Nathan Klapoetke. Researchers from the Howard Hughes Medical Institute’s Janelia Farm Research Campus, the University of Pennsylvania, the University of Cologne, and the Beijing Genomics Institute also contributed to the study.

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CIRpy - A Python interface for the Chemical Identifier Resolver (CIR)

In the past I have used the ChemSpider API (through ChemSpiPy) to resolve chemical names to structures. Unfortunately this doesn’t work that well for IUPAC names and I found myself wondering whether it was worth setting up a system that would try a number of different resolvers. More specifically, I wanted a system that would first try using OPSIN to match IUPAC names, and if that failed, try a ChemSpider lookup. Just as I was about to start doing this myself, I came across the Chemical Identifier Resolver (CIR) that does exactly that (and much more).

CIR is a web service created by by the CADD Group at the NCI that performs various chemical name to structure conversions. In short, it will (attempt to) resolve the structure of any chemical identifier that you throw at it. Under the hood it uses a combination of OPSIN, ChemSpider and CIR’s own database.

To simplify interacting with CIR through Python, I wrote a simple wrapper called CIRpy that handles constructing url requests and parsing XML responses. It’s available on github here.

Using it is a simple case of copying cirpy.py into a directory on your python path. Here’s an example using the resolve function:

import cirpy

smiles_string = cirpy.resolve('Aspirin','smiles')

There are full details of all available options in the readme.