X-ray laser reveals how bacterial protein morphs in response to light

Human biology is a massive collection of chemical reactions, from the intricate signaling network that powers our brain activity to the body's immune response to viruses and the way our eyes adjust to sunlight. All involve proteins, known as the molecules of life; and scientists have been steadily moving toward their ultimate goal of following these life-essential reactions step by step in real time, at the scale of atoms and electrons.

Now, researchers have captured the highest-resolution snapshots ever taken with an X-ray laser that show changes in a protein's structure over time, revealing how a key protein in a photosynthetic bacterium changes shape when hit by light. They achieved a resolution of 1.6 angstroms, equivalent to the radius of a single tin atom.

"These results establish that we can use this same method with all kinds of biological molecules, including medically and pharmaceutically important proteins," said Marius Schmidt, a biophysicist at the University of Wisconsin-Milwaukee who led the experiment at the Department of Energy's SLAC National Accelerator Laboratory. There is particular interest in exploring the fastest steps of chemical reactions driven by enzymes -- proteins that act as the body's natural catalysts, he said: "We are on the verge of opening up a whole new unexplored territory in biology, where we can study small but important reactions at ultrafast timescales."

The results, detailed in a report published online Dec. 4 in Science, have exciting implications for research on some of the most pressing challenges in life sciences, which include understanding biology at its smallest scale and making movies that show biological molecules in motion.

A New Way to Study Shape-shifting Proteins

The experiment took place at SLAC's Linac Coherent Light Source (LCLS), a DOE Office of Science User Facility. LCLS's X-ray laser pulses, which are about a billion times brighter than X-rays from synchrotrons, allowed researchers to see atomic-scale details of how the bacterial protein changes within millionths of a second after it's exposed to light.

"This experiment marks the first time LCLS has been used to directly observe a protein's structural change as it happens. It opens the door to reaching even faster time scales," said Sébastien Boutet, a SLAC staff scientist who oversees the experimental station used in the study. LCLS's pulses, measured in quadrillionths of a second, work like a super-speed camera to record ultrafast changes, and snapshots taken at different points in time can be compiled into detailed movies.

The protein the researchers studied, found in purple bacteria and known as PYP for "photoactive yellow protein," functions much like a bacterial eye in sensing blue light. The mechanism is very similar to that of other receptors in biology, including receptors in the human eye. "Though the chemicals are different, it's the same kind of reaction," said Schmidt, who has studied PYP since 2001. Proving the technique works with a well-studied protein like PYP sets the stage to study more complex and biologically important molecules at LCLS, he said.

Chemistry on the Fly

In the LCLS experiment, researchers prepared crystallized samples of the protein, and exposed the crystals, each about 2 millionths of a meter long, to blue laser light before jetting them into the LCLS X-ray beam.

The X-rays produced patterns as they struck the crystals, which were used to reconstruct the 3-D structures of the proteins. Researchers compared the structures of the proteins that had been exposed to light to those that had not to identify light-induced structural changes.

"In the future we plan to study all sorts of enzymes and other proteins using this same technique," Schmidt said. "This study shows that the molecular details of life's chemistry can be followed using X-ray laser crystallography, which puts some of biology's most sought-after goals within reach."

Researchers from the University of Wisconsin-Milwaukee and SLAC were joined by researchers from Arizona State University; Lawrence Livermore National Laboratory; University of Hamburg and DESY in Hamburg, Germany; State University of New York, Buffalo; University of Chicago; and Imperial College in London. The work was supported by the National Science Foundation, National Institutes of Health and Lawrence Livermore National Laboratory.

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The above story is based on materials provided by SLAC National Accelerator Laboratory . Note: Materials may be edited for content and length.

Response to viral infections depends on entry route of virus

Insects can transmit viral diseases to humans. Therefore, understanding how insects cope with viral infection, and what immune mechanisms are triggered, can be important to stop diseases transmission. In a study published in this week's issue of the scientific journal PLOS Pathogens, researchers from the Instituto Gulbenkian de Ciencia (IGC; Portugal) now show that the entry route of the virus changes how the insect host responds to it. Using the fruit flies as a model of study, they discovered an immune mechanism that is specifically effective when flies are infected through feeding.

Dengue, yellow fever and chikungunya are diseases caused by viruses that are transmitted to humans via mosquitoes. However, for the transmission to occur it is necessary that the virus completes an infection cycle so that the insect becomes infected. This may take up to several days after the entry of the virus into the host, which is why it becomes so important to study viral infection in insects.

Until now two main antiviral defense mechanisms of fruit flies were known. One of these mechanisms acts by interfering with the reading of the viral genes or its genome, blocking its replication within the host; the other, is a protective mechanism conferred by bacteria living inside cells of the host. However, the studies leading to the identification of these mechanisms were conducted in a set up that did not explore different entry routes in the host. The fruit fly (Drosophila melanogaster), used as a model organism to study immunity in insects, is normally infected by injection, which might mimic the bites of mites that occur in nature. However, this mode of infection might not recapitulate well natural oral infections that occur when insects eat contaminated food, as when mosquitoes feed on blood of infected humans. Luis Teixeira's team, at the IGC, set up to investigate if there could be differences when viruses used different entry routes to infect flies.

Álvaro Gil Ferreira, investigator in Teixeira's laboratory and first author of this study, discovered that when flies were fed with food containing virus they would require an immune mechanism that had been described only to be activated for infections caused by bacteria or fungi, the so called Toll pathway. He reached this conclusion by studying mutants of flies that lacked proteins involved in this mechanism. Álvaro Gil Ferreira observed that these mutant flies survived less to viral infection than the normal flies, which indicated that those proteins of the Toll pathway were playing a role in the defense against viral infection.

Then, the research team went on to investigate if this same mechanism was also required when flies were infected through an injection in the thorax. They observed no differences between the survival of mutant flies and the normal flies after viral infection, indicating that the proteins of the Toll pathway were not playing a significant defensive role in this setup. The researchers observed that the same tissues of the fly were being infected independently of the entry route of the virus, but the infection spread faster when flies were injected with virus. The reason for this might be the fact that the injection in the thorax leads to a widespread systemic infection, since the viral particles can reach faster many tissues of the fly, through the fluid in the fly body cavity (the hemolymph, a fluid similar to the blood). When the virus enters the host through feeding, the researchers observed that in the first days of the infection the viral particles are confined to a specific tissue.

Luis Teixeira says: "This work shows how dramatically the response to viral infection changes with the way the viruses enter the organism. It also demonstrates how the mechanisms involved in the response to natural routes of infection may be more complex than the infection response with the protocol normally used in the laboratory."

Álvaro Gil Ferreira adds: "We showed that this mechanism is blocking several viruses that infect the fruit flies. By comprehending the details of the mechanisms of insects involved in the defense against viruses we may find targets to block human diseases transmitted by insects."

Knowing better the host's responses upon viral infection by different routes might also help to explain some biological phenomena observed in nature. For example, the survival of honeybees contaminated with virus seems to depend on the entry route of the virus. If contaminated through bites of mites, the honeybees die, whereas if they receive the virus from their progenitors, they can live.

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The above story is based on materials provided by Instituto Gulbenkian de Ciencia . Note: Materials may be edited for content and length.

VR Films Are Going to Be All Over Sundance in 2015

In the months since the last festival in Park City, Utah, Oculus experiences have become the ultimate crowd-pleaser at all kinds of industry events. HBO brought a Game of Thrones experience to South By Southwest in March. Then, after Oculus’ $2 billion acquisition by Facebook, Legendary Pictures one-upped HBO with a Jaeger-piloting simulation at Comic-Con International this summer. And, of course, VR made a huge splash at E3 (again) this year. Basically, anywhere there’s been a gathering of people interested in any form of media in the last 12 months, there’s been a VR experience in the offing. And now that virtual reality is also coming in the form of Google Cardboard and Samsung’s Gear VR the demonstrations are just beginning. (Some of Sundance’s New Frontier offerings are being presented in Cardboard and on Samsung’s device.)

A still from Chris Milk's Evolution of Verse VR experience.

A still from Chris Milk’s Evolution of Verse VR experience.

courtesy Evolution of Verse

Part of the appeal of these VR installations, of course, is that the Oculus Rift is still in developer-only mode—there’s not a consumer version yet. For the time being, it’s a cool novelty to tell your colleagues about as you hang up another conference badge and get back to work. But Sundance is a unique case: a lot of the New Frontier projects are made by filmmakers—people who see virtual reality as a new way to experience movies, not just promote them. Creation is the prime mover here, not ancillary marketing.

So, what’s in the offing? For starters, Chris Milk is back with a collaboration he did with VFX firm Digital Domain and production house VRSE.works called Evolution of Verse, a CGI “journey from beginning to new beginning” using Cardboard. Then there’s Kaiju Fury!, which puts you in a city as monsters are about to lay it to waste. Peña’s Project Syria will explore VR’s potential as a documentary tool—putting viewers on the ground in the war-torn country to show the effects of the conflict there on children. Artists Félix Lajeunesse and Paul Raphaël will also be showing a series of live-action experiences, including one that lets users sit in the room while a pianist works on music. [Ed.—They brought this to SXSW last year, and it remains one of the most surprisingly intimate experiences we’ve seen on the Rift.]

A still from Perspective; Chapter 1: The Party.

A still from Perspective; Chapter 1: The Party.

courtesy Perspective; Chapter 1: The Party

And, in what might be the most thought-provoking piece at New Frontier, the program also will get a VR experience from a Sundance vet Rose Troche, who Frilot says “wanted to make a piece about date rape and do it in a way where there was a lot of gray zones.” The director, who first came to the film festival 21 years ago with the black-and-white lesbian dramedy Go Fish, teamed up with CG whiz Morris May for Perspective; Chapter I: The Party. It’s a VR experience that takes a fairly conventional premise—awkward college students hanging out at a party—and turns it into a first-hand experience where a girl and guy “meet, drink, and misinterpreted signals turn into things that cannot be undone.”

On paper, Troche and May’s piece sounds like the kind of VR effort that could be as emotionally affecting as any film. And the rest of the slate beyond Perspective reads like any independent film festival line-up. Remove the words “virtual reality,” and the subject matter has the kind of resonance any indie fest programmer would be proud of: documentaries, a story about a father’s time in the military in Chile, a look into the lives of Mongolian yak herders. Sounds like a main competition line-up at Sundance, not specifically the New Frontier one. That’s the point. Filmmaking is just filmmaking, VR just gives it a new theater—one that Sundance’s trendy-scarf-clad film nerds might finally be starting to see themselves in.

“Last year people were putting on the DK1 and the first thing filmmakers are looking for is image quality, and that’s where filmmakers wondered This is really cool, but what about what it looks like?” Frilot says. “But now the technology has ramped up to a stage where it’ll be wholly embraced by filmmakers.”

Check out the full line up for New Frontier, which runs Jan. 22 to Feb. 1 during the Sundance Film Festival, below.

1979 Revolution Game

Artists: Navid Khonsari, Vassiliki Khonsari

1979 Revolution Game presents an innovative approach to non-fiction storytelling. Designed to engage players with an immersive “on the ground” experience of the Iranian Revolution, the game integrates an emotionally impactful narrative with interactive moral choices and intuitive touchscreen gameplay while remaining true to history.


Artist: Oscar Raby

This immersive documentary uses virtual reality technology to put the user in the footsteps of director Oscar Raby’s father, who in 1973 was a 22-year-old army officer stationed in the north of Chile, on the day when the Caravan of Death came to his regiment.


Artist: Max Rheiner

Flying is one of the oldest dreams of humankind. Birdly is an experiment to capture this dream, to simulate the experience of being a bird from a first-person perspective. This embodiment is conducted through a full-body virtual reality setup.


Artist: François Quévillon

This interactive installation uses the audience’s body motions and positions to explore 3-D reconstructions of urban and natural spaces that are transformed according to live environmental data, including meteorological and astronomical phenomena.

Evolution of Verse

Artist: Chris Milk

Chris Milk, working with visual effects powerhouse Digital Domain and virtual reality production company VRSE.works, has created this photo-realistic CGI-rendered 3-D virtual reality film that takes the viewer on a journey from beginning to new beginning.

Kaiju Fury!

Artist: Ian Hunter

A dark energy experiment leads to a devastating attack by monstrous Kaiju, and you are standing at ground zero—all in 360-degree, stereoscopic 3-D cinematic virtual reality. You will “be there” as the beasts lay waste to a crumbling city and humanity makes its last stand.


Artist: Pleix

Paradise is certainly not paradisiacal if you look at it through our eyes. But neither is it totally devoid of humor, melancholy, and absurdity. Perhaps it is first and foremost life as it is, and then a touch exaggerated in the digital overdrive.

Perspective; Chapter I: The Party

Artists: Rose Troche, Morris May

A young college woman attends a party with the intention of shedding her “shy girl” persona. At the same party, a young man is after a similar reinvention. They meet, drink, and misinterpreted signals turn into things that cannot be undone. Virutal reality simulators let viewers experience both characters.


Artists: Daniel Kwan, Daniel Scheinert

Possibilia is a multi-layered narrative experience from acclaimed directing duo the Daniels. The story of two quarreling lovers splits exponentially into more and more possible worlds as their relationship unravels.

Project Syria

Artists: Nonny de la Peña

More than one million children have fled Syria and news reports indicate children are being specifically targeted in the violence. By combining pioneering virtual reality technologies with audio and video captured during a real event, audiences feel transported to the powerful scene, becoming witnesses as the intense tragedy unfolds.

The VR works of Felix & Paul

Artists: Félix Lajeunesse, Paul Raphaël

Felix & Paul’s groundbreaking live-action virtual reality experiences range from independent documentary to fictional work with major Hollywood studios and stars. These experiences let viewers sit in the room with musicians making music, roam the Mongolian plains with yak herders, and experience an encounter with the afterlife.

Way to Go

Artists: Vincent Morisset

It is a walk in the woods. It is an astonishing online and virtual reality interactive experience, a restless panorama, a mixture of hand-made animation, 360-degree video capture, music, dreaming, and code; but mostly it is a walk in the woods, c’mon!

Zero Point

Artist: Danfung Dennis

Zero Point, a 3-D and 360-degree documentary for the Oculus Rift headset, creates an entirely new digital dimension. From combat training simulations at the Department of Defense to research labs at Stanford to indie game developers and hackers, this immersive experience highlights the future of virtual reality.

Case for Chimpanzee Rights Rejected by Appeals Court

Tommy, the chimpanzee plaintiff of a Nonhuman Rights Project lawsuit, in his cage in Gloversville, New York.

Tommy, the chimpanzee plaintiff of a Nonhuman Rights Project lawsuit, in his cage in Gloversville, New York. Pennebaker Hegedus Films

The plaintiff in a landmark lawsuit seeking legal rights for a chimpanzee has lost his case—for now.

A New York appeals court this morning rejected the lawsuit, filed by the Nonhuman Rights Project, on behalf of Tommy, a 26-year-old chimp kept alone by his owners in an upstate warehouse.

The Nonhuman Rights Project argued that Tommy should be considered a person—in legal terms, an entity capable of having rights, and in his case one specific right: not to be wrongfully imprisoned.

“Petitioner requests that this Court enlarge the common-law definition of ‘person’ in order to afford legal rights to an animal,” wrote the judges in their decision. “We decline to do so.”

Attorney Steven Wise, founder of the Nonhuman Rights Project, said they will appeal the decision to New York’s highest court. “We think the court was wrong in some very fundamental ways,” he said.

The lawsuit was originally filed last December, along with similar suits on behalf of three other privately-owned chimpanzees in New York. The suits sought so-called writs of habeas corpus; had they been granted, the chimpanzees’ owners would have been forced to justify the chimps’ captivity.

That would have likely resulted in the chimps’ transfer to sanctuaries designed for their care, and would have explicitly acknowledged that chimpanzees, and potentially other animals, can have legal rights. Such a decision would be unprecedented.

Each of the cases was rejected by lower courts, then appealed. Today’s decision is the first appeals court ruling.

The judges did not challenge the claim, supported with affidavits filed by nine leading primatologists, that chimps are extraordinary beings: social, emotional and highly intelligent, sharing much in common with their human cousins.

Instead they rejected Wise’s argument that legal rights arise from an abiding respect for individual liberty and self-determination. Rather, said the court, rights are contingent upon responsibility. If a chimp can’t be expected to fulfill his social duties, neither can he have rights.

“Unlike human beings, chimpanzees cannot bear any legal duties, submit to societal responsibilities or be held legally accountable for their actions,” wrote the judges.

“In our view, it is this incapability to bear any legal responsibilities and societal duties that renders it inappropriate to confer upon chimpanzees the legal rights—such as the fundamental right to liberty protected by the writ of habeas corpus—that have been afforded to human beings,” they concluded.

'It really gets to the heart of the issue: Who is a person?'

The Nonhuman Rights Project had addressed that argument in their brief, countering that young children and adults with severe mental disabilities are not expected to fulfill the social obligations of mature adults, but are still granted legal rights.

While that is true, wrote the judges, “it is undeniable that, collectively, human beings possess the unique ability to bear legal responsibility.”

The decision came as no surprise to legal experts and observers. Even those who support the case acknowledge that it’s controversial. Still, there was dismay at the court’s reasoning.

“It is unfortunate,” said primatologist Mary Lee Jensvold, who works with chimpanzees trained to use sign language and filed an affidavit describing their cognitive similarities to humans.

Chimps might not be able to acknowledge our society’s expectations, said Jensvold, but it’s worth remembering that in their own societies, they are capable—and indeed expected—to perform duties of child-rearing and hunting.

“I’m sure cultural anthropologists could think of many examples of human individuals being transplanted from one culture to another. They don’t function very well, and maybe they don’t fulfill their rights and duties,” said Jensvold. “But we’re not going to take their personhood away from them.”

David Cassuto, an animal law scholar at Pace University, criticized the Court’s rationale that the rights of children or mentally disabled adults is rooted in the collective capacities of humans.

“A habeas corpus petition is about an individual, not a species,” said Cassuto. “It has nothing to do with the potential of that individual’s species.”

There are reasons to be wary of extending legal personhood to chimps—one might feel it’s a matter best left to legislatures, rather than courts—but those reasons “are not the ones articulated here,” Cassuto said.

To Cassuto, the decision touched on a deeper discomfort with extending a traditionally human concept to a non-human. Indeed, many critics of the Nonhuman Rights Project’s arguments say that treating a chimpanzee as a person threatens to diminish the personhood of humans.

“We could see over time some of our most vulnerable humans losing out in a rights struggle if they’re in direct competition with some particularly intelligent non-human animals,” said Richard Cupp, a Pepperdine University law professor, in an Associated Press interview in October.

Animal law professor David Favre of Michigan University took a longer view of the decision. “I was impressed that the judges clearly understood the full depth of what was being argued, and met it head-on,” said Favre. “It really gets to the heart of the issue: Who is a person? Now counterarguments can be crafted.”

The idea of rights as being contingent upon responsibilities “is not a principle carved in stone somewhere,” said Favre. “I think there’s still room for Steve to discuss this and counter that argument. The legal system has a long-standing interest in helping those who can’t help themselves.”

In a statement issued by the Nonhuman Rights Project, the group said it will soon file an appeal challenging the court’s decision.

Wise cited as an important precedent Byrn v. New York City Health & Hospitals Commission Corporations, an abortion rights case in which it was established that personhood, at least in New York state, is not simply a function of meeting social obligations.

“This is not the end of the road,” Wise said. “These are the early moments.”

11 Things You Won’t Want to Miss at Art Basel This Week


If Thanksgiving is behind us and Chrismakwanzukkah is ahead of us, that must mean it’s time for Art Basel Miami Beach. Starting today, over 50,000 people will descend on Miami to browse and buy wares from a global contingency of more than 1,000 galleries and thousands of individual artists who gather for the main event—as well as a dozen other art fairs with names like Design Miami, Scope, and Untitled. Which all adds up to this: You’re going to need some help in determining which people, places, and things are must-sees. That’s where we come in. If you’re among those 50,000 art fans and/or scenesters, here are the best of the best exhibitions and installations you’ll want to make sure you check out.

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