Mysteries of 'molecular machines' revealed: Phenix software uses X-ray diffraction spots to produce 3-D image

Scientists are making it easier for pharmaceutical companies and researchers to see the detailed inner workings of molecular machines.

'Inside each cell in our bodies and inside every bacterium and virus are tiny but complex protein molecules that synthesize chemicals, replicate genetic material, turn each other on and off, and transport chemicals across cell membranes,' said Tom Terwilliger, a Los Alamos National Laboratory scientist.

'Understanding how all these machines work is the key to developing new therapeutics, for treating genetic disorders, and for developing new ways to make useful materials.'

To understand how a machine works you have to be able to see how it is put together and how all its parts fit together. This is where the Los Alamos scientists come in. These molecular machines are very small: a million of them placed side by side would take up less than an inch of space. Researchers can see them however, using x-rays, crystals and computers. Researchers produce billions of copies of a protein machine, dissolve them in water, and grow crystals of the protein, like growing sugar crystals except that the machines are larger than a sugar molecule.

Then they shine a beam of X-rays at a crystal and measure the brightness of each of the thousands of diffracted X-ray spots that are produced. Then researchers use the powerful Phenix software, developed by scientists at Los Alamos, Lawrence Berkeley National Laboratory, Duke and Cambridge universities, to analyze the diffraction spots and produce a three-dimensional picture of a single protein machine. This picture tells the researchers exactly how the protein machine is put together.

The 3-D Advance

Recently Los Alamos scientists worked with their colleagues at LBNL and Cambridge University to make it even easier to visualize a molecular machine. In a report in the journal Nature Methods this month, Los Alamos scientists and their team show that they can obtain three-dimensional pictures of molecular machines using X-ray diffraction spots that could not previously be analyzed.

Some molecular machines contain a few metal atoms or other atoms that diffract X-rays differently than the carbon, oxygen, nitrogen, and hydrogen atoms that make up most of the atoms in a protein. The Phenix software finds those metal atoms first, and then uses their locations to find all the other atoms. For most molecular machines, however, metal atoms have to be incorporated into the machine artificially to make this all work.

The major new development to which Los Alamos scientists have contributed was showing that powerful statistical methods could be applied to find metal atoms even if they do not scatter X-rays very differently than all the other atoms. Even metal atoms such as sulfur that are naturally part of almost all proteins can be found and used to generate a three-dimensional picture of a protein. Now that it will often be possible to see a three-dimensional picture of a protein without artificially incorporating metal atoms into them, many more molecular machines can be studied.

Cracking the Cascade

Molecular machines that have recently been seen in three-dimensional detail include a 'huge' molecular machine called Cascade that was reported in the journal Science this summer. The Cascade machine is present in bacteria and can recognize DNA that comes from viruses that infect the bacteria. The Cascade machine is made up of 11 proteins and an RNA molecule and looks like a seahorse, with the RNA molecule winding through the whole 'body' of the seahorse. If a foreign piece of DNA in the bacterial cell is complementary to part of the RNA molecule then another specialized machine can come by and chop up the foreign DNA, saving the bacterium from infection.

Los Alamos and Cambridge University scientists who were developing the Phenix software were part of the team that visualized this protein machine for the first time. The Phenix software has been used to determine the three-dimensional shapes of over 15,000 different protein machines and has been cited by over 5000 scientific publications.

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The above story is based on materials provided by DOE/Los Alamos National Laboratory . Note: Materials may be edited for content and length.

Discovery in fight against antibiotic-resistant bacteria

For four years, researchers at UCL have been trying to find out how bacteria can withstand antibiotics, so as to be able to attack them more effectively. These researchers now understand how one defence mechanism works and the results of their research have been published in the scientific journal Cell.

There are two main families of bacteria : those that are surrounded by a single membrane (or one outer wall) and those that are surrounded by two membranes (or two outer walls). The team of Jean-François Collet, professor at the de Duve Institute at UCL, looked at this second type of bacteria.

For a bacterium to survive, it has to keep its two outer walls intact. If one of these walls is damaged, the bacterium dies. So it was vital for the UCL researchers to analyse the protection mechanisms of these bacterial "walls' (to find their weak spot), so as to be able to fight these defence systems more effectively by developing new antibiotics.

The researchers examined a protein that is found between these two protective walls, known as RcsF. When all is well, this protein is continually sent to the second outer wall. However, if the bacterium is attacked (by an antibiotic, for instance) the machinery that sends RcsF to the outer wall no longer works: instead of being on the second outer wall, RcsF is stuck between the two fortifications (membranes), from where it sends out an alarm signal. This signal prompts the bacterium to trigger defence systems (by sending other back-up proteins) so as to resist the attacking antibiotic.

In this process, the UCL researchers succeeded in discovering how the protein RcsF manages to sound the alarm. In practical terms, when it is stressed, stuck between the two walls, RcsF contacts another protein, IgaA. The interaction between these two proteins raises the alarm.

What was the point of discovering this alarm mechanism?

In terms of basic research, the researchers wanted to understand how the alarm system worked. They made a twofold, unexpected discovery: the fact that the protein RcsF positions itself on the second outer wall (on the surface of the bacterium) and the fact that it interacts with a second protein, IgaA. This discovery gives rise to other interesting questions, since it suggests that other proteins may take the same path.

In terms of applied research, given that this alarm helps defend bacteria against antibiotics, the UCL researchers aimed to gain a better understanding of how these proteins work so as to be able to develop new antibiotics, which would bypass this alarm system and hence, ultimately, fight more effectively against bacterial infections (such as urinary infections linked to the bacterium Escherichia-coli, for example). To be specific, the researchers believe that it will be possible to use the proteins in this system as a target to break through the bacteria's defence system and create new antibiotics.

The resistance of certain bacteria to antibiotics is currently a major health problem. More and more bacteria are becoming resistant to the antibiotics available at the moment, because they are acquiring new defence mechanisms. The UCL discovery could therefore provide a response to this growing problem.

Story Source:

The above story is based on materials provided by Université catholique de Louvain - UCL . Note: Materials may be edited for content and length.

An Orangutan Has (Some) Human Rights, Argentine Court Rules

Sandra, a 28-year-old orangutan now living at the Buenos Aires Zoo. Roger Schultz/Flickr

An orangutan named Sandra has become the first non-human animal recognized as a person in a court of law.

The Association of Officials and Lawyers for Animal Rights, an animal advocacy group, had asked Argentine courts recognize the 28-year-old great ape’s right to freedom from unjust imprisonment.

On Friday, an appeals court declared that Sandra, who is owned by the Buenos Aires Zoo, is a “non-human person” who has been wrongfully deprived of her freedom.

Sandra, who was born in German zoo and sent to Argentina two decades ago, at an age when wild orangutans are still living at their mother’s side, won’t be given complete freedom.

Having lived her entire life in captivity, Sandra likely could not survive in the wild. Instead, if the zoo does not challenge the decision within 10 working days, Sandra will be sent to a sanctuary in Brazil.

“This opens the way not only for other Great Apes, but also for other sentient beings which are unfairly and arbitrarily deprived of their liberty in zoos, circuses, water parks and scientific laboratories,” said lawyer Paul Buompadre, one of the activists who filed the suit, to the La Nacion newspaper.

The decision may have ramifications for other great apes. In the United States, a group called the Nonhuman Rights Project is currently seeking similar rights for four privately-owned chimpanzees in New York state.

According to the Nonhuman Rights Project, chimpanzees deserve rights—not full human rights, but at least a few basic ones—because they are so similar to humans.

They’ve so far been unsuccessful. Their latest court defeat came in early December, when a New York appeals court argued that, regardless of their intelligence or feelings, chimpanzees can’t fulfill the social obligations expected of anyone with rights.

The Argentine court, however, made no mention of social duties. Sandra is simply enough like a human person to be considered a person, they ruled.

“We intend to bring the Argentine case to the attention of the New York appellate courts immediately,” said Nonhuman Rights Project founder Steven Wise in a statement. “We believe it will assist the courts in reaching a similar conclusion for our chimpanzee plaintiffs.”

The Business of Security Is Business

infocux/Flickr

Today’s security landscape feels more like a James Bond movie than normal life. International intrigue is now a standard equation for any large-scale cyber-attack, as we’ve seen recently with the Sony breach and the potential for North Korea being behind it all. Events like this are great fodder for politicos and make for glib and gossipy water cooler talk about the latest celebrity leaks, but they obscure the real dangers just beneath the surface. What if skilled, persistent attackers targeted critical infrastructure like the water supply or electric grid, rather than a Hollywood studio pushing a silly movie? What if they targeted your business?

With many calling 2014 the year of the data breach, corporate security teams are on notice. They face a wide range of threat actors, from nation-state cyber espionage to highly skilled patient attackers for hire, down to home gamers and nuisance attackers.

Corporate IT and security teams are feeling the pressure of this dynamic threat landscape. They know they’re being targeted and that they are vulnerable. A CISOs challenge today is incredibly difficult. Two monumental structural changes, mobility and cloud computing, have transformed their networks from well-defined and protected “walled gardens” to distributed collections of third party partners, with varying degrees of security capabilities. Today, essentially, the Internet is the corporate network.

According to recent research by PwC, the number of reported security incidents around the globe has risen 48 per cent in the last year. However, what is more worrying is that less than 17 per cent of businesses globally are fully prepared for an online security incident according to research by the Economist Intelligence Unit (EIU) sponsored by Arbor Networks.

This comes at a time when executive and board-level awareness of these threats is already pronounced. If the CISO is unable to communicate in terms the executive team and board understand then they don’t get the appropriate level of support that is needed. This executive and board-level awareness of the threat landscape means CISOs have an opportunity to champion their own role as risk managers and defenders of the business. If CISOs are to deliver an understandable call to action and gain the credibility to push their strategic plans, they need to deploy a range of tactics to make their voices heard including:

Make security relevant for management: The CISO must communicate threats in a way that the leadership team understands. This is a tremendous opportunity for the CISO to position his/her role as beyond technology, but to the broader role of corporate risk management.

Know your audience: If you get time with the CFO and talk botnets, you’re likely to see their eyes glaze over faster than you can say Distributed Denial of Service (DDoS). The primary message a CISO needs to convey is the threat that attacks of any kind pose in terms of lost revenue, reduced productivity and damage to the brand. A Chief Legal Officer will be interested in the regulatory and compliance aspects of a breach. Know your audience and tailor the message accordingly.

Specific examples: As the kids say these days, keep it real. Make the key points relevant to your specific organization. Senior executives have little interest in theories or hypothesis. They are very interested in case studies, examinations of their business, and understanding the potential impact that these attacks can have on their business plans, financial goals or standing with regulators.

Without the proper level of understanding and buy in from the executives and Board, this is a recipe for disaster for the CISO, and the organization. Today’s effective CISO is a business-person first, a communicator second and technologist third. This is a fundamental transformation that is taking place in organizations around the world. Those that succeed will be able to work with the executives and Board in a way that is meaningful and that ensures support and funding required to protect the business.

Dan Holden is the Director of ASERT, Arbor Networks’ Security Engineering and Response Team.

The Internet of Anything: An Accelerator That’ll Churn Out Startups for VR’s Bright Future

Josh Valcarcel/WIRED

Mike Rothenberg envisions a world where psychiatrists help people conquer their fear of heights using virtual reality, where students learn new skills in immersive virtual worlds, where paraplegics can roam digital streets without leaving their beds.

That world isn’t here yet, despite recent advances in VR technology, but Rothenberg thinks it’s close. To get there, however, we’re going to need more companies building new hardware and software. And that’s going to take capital. “The innovators have been stepping up for decades,” he says. “It’s time for the financiers to step-up.”

That includes Rothenberg himself. Last week, his venture capital firm Rothenberg Ventures announced a new startup incubator, dubbed River, that will provide $100,000 in seed funding to 10 different companies, plus provide office space in San Francisco and mentoring from tech industry veterans. The firm is now recruiting its first cohort, and it will be taking applications until January 11.

Of course, virtual reality was supposed to be just around the corner back in the early 1990s. But now the dream is back, and it looks like it may be more than just hype this time around. Many developers have already gotten their hands on Oculus rift headsets, and the general public will likely be able to buy them early next year. Meanwhile, Samsung has already shipped its Gear VR headset, and Sony is expected to follow suit next year with its Project Morpheus device.

What’s different this time around, Rothenberg says, is that the technology is better—we can finally explore virtual worlds without getting nauseous—but also that it’s cheaper. It’s now a matter of perfecting the hardware, and finding applications for virtual reality. “We believe that VR will touch every industry eventually,” he says. “Just like the internet is now ubiquitous, and touches everyone’s life.”

These new companies will need more than just money. Business incubators have long played a big role in helping new businesses get off the ground by providing work space, mentorship, and sometimes funding. But Rothenberg—who has already invested in virtual reality companies Altspace VR, which aims to make social media into a 3-D, immersive experience, and 3-D camera company Matterport —realized that there were no incubators focusing specifically on virtual reality companies. So he decided he’d have to start one himself.

With River, Rothenberg hopes to accelerate this process by building a community for early-stage virtual reality startups to collaborate and network, and providing a physical location to demo their technology to investors, mentors, and the press. “These aren’t things where you send a business plan over and it makes sense,” he says. “You’ve got to actually experience it.”

Argentine Court Rules that an Orangutan Has (Some) Human Rights

Sandra, a 28-year-old orangutan now living at the Buenos Aires Zoo. Roger Schultz/Flickr

An orangutan named Sandra has become the first non-human animal recognized as a person in a court of law.

The Association of Officials and Lawyers for Animal Rights, an animal advocacy group, had asked Argentine courts recognize the 28-year-old great ape’s right to freedom from unjust imprisonment.

On Friday, an appeals court declared that Sandra, who is owned by the Buenos Aires Zoo, is a “non-human person” who has been wrongfully deprived of her freedom.

Sandra, who was born in German zoo and sent to Argentina two decades ago, at an age when wild orangutans are still living at their mother’s side, won’t be given complete freedom.

Having lived her entire life in captivity, Sandra likely could not survive in the wild. Instead, if the zoo does not challenge the decision within 10 working days, Sandra will be sent to a sanctuary in Brazil.

“This opens the way not only for other Great Apes, but also for other sentient beings which are unfairly and arbitrarily deprived of their liberty in zoos, circuses, water parks and scientific laboratories,” said lawyer Paul Buompadre, one of the activists who filed the suit, to the La Nacion newspaper.

The decision may have ramifications for other great apes. In the United States, a group called the Nonhuman Rights Project is currently seeking similar rights for four privately-owned chimpanzees in New York state.

According to the Nonhuman Rights Project, chimpanzees deserve rights—not full human rights, but at least a few basic ones—because they are so similar to humans.

They’ve so far been unsuccessful. Their latest court defeat came in early December, when a New York appeals court argued that, regardless of their intelligence or feelings, chimpanzees can’t fulfill the social obligations expected of anyone with rights.

The Argentine court, however, made no mention of social duties. Sandra is simply enough like a human person to be considered a person, they ruled.

“We intend to bring the Argentine case to the attention of the New York appellate courts immediately,” said Nonhuman Rights Project founder Steven Wise in a statement. “We believe it will assist the courts in reaching a similar conclusion for our chimpanzee plaintiffs.”

The Business of Security Is Business

infocux/Flickr

Today’s security landscape feels more like a James Bond movie than normal life. International intrigue is now a standard equation for any large-scale cyber-attack, as we’ve seen recently with the Sony breach and the potential for North Korea being behind it all. Events like this are great fodder for politicos and make for glib and gossipy water cooler talk about the latest celebrity leaks, but they obscure the real dangers just beneath the surface. What if skilled, persistent attackers targeted critical infrastructure like the water supply or electric grid, rather than a Hollywood studio pushing a silly movie? What if they targeted your business?

With many calling 2014 the year of the data breach, corporate security teams are on notice. They face a wide range of threat actors, from nation-state cyber espionage to highly skilled patient attackers for hire, down to home gamers and nuisance attackers.

Corporate IT and security teams are feeling the pressure of this dynamic threat landscape. They know they’re being targeted and that they are vulnerable. A CISOs challenge today is incredibly difficult. Two monumental structural changes, mobility and cloud computing, have transformed their networks from well-defined and protected “walled gardens” to distributed collections of third party partners, with varying degrees of security capabilities. Today, essentially, the Internet is the corporate network.

According to recent research by PwC, the number of reported security incidents around the globe has risen 48 per cent in the last year. However, what is more worrying is that less than 17 per cent of businesses globally are fully prepared for an online security incident according to research by the Economist Intelligence Unit (EIU) sponsored by Arbor Networks.

This comes at a time when executive and board-level awareness of these threats is already pronounced. If the CISO is unable to communicate in terms the executive team and board understand then they don’t get the appropriate level of support that is needed. This executive and board-level awareness of the threat landscape means CISOs have an opportunity to champion their own role as risk managers and defenders of the business. If CISOs are to deliver an understandable call to action and gain the credibility to push their strategic plans, they need to deploy a range of tactics to make their voices heard including:

Make security relevant for management: The CISO must communicate threats in a way that the leadership team understands. This is a tremendous opportunity for the CISO to position his/her role as beyond technology, but to the broader role of corporate risk management.

Know your audience: If you get time with the CFO and talk botnets, you’re likely to see their eyes glaze over faster than you can say Distributed Denial of Service (DDoS). The primary message a CISO needs to convey is the threat that attacks of any kind pose in terms of lost revenue, reduced productivity and damage to the brand. A Chief Legal Officer will be interested in the regulatory and compliance aspects of a breach. Know your audience and tailor the message accordingly.

Specific examples: As the kids say these days, keep it real. Make the key points relevant to your specific organization. Senior executives have little interest in theories or hypothesis. They are very interested in case studies, examinations of their business, and understanding the potential impact that these attacks can have on their business plans, financial goals or standing with regulators.

Without the proper level of understanding and buy in from the executives and Board, this is a recipe for disaster for the CISO, and the organization. Today’s effective CISO is a business-person first, a communicator second and technologist third. This is a fundamental transformation that is taking place in organizations around the world. Those that succeed will be able to work with the executives and Board in a way that is meaningful and that ensures support and funding required to protect the business.

Dan Holden is the Director of ASERT, Arbor Networks’ Security Engineering and Response Team.

The Internet of Anything: An Accelerator That’ll Churn Out Startups for VR’s Bright Future

Josh Valcarcel/WIRED

Mike Rothenberg envisions a world where psychiatrists help people conquer their fear of heights using virtual reality, where students learn new skills in immersive virtual worlds, where paraplegics can roam digital streets without leaving their beds.

That world isn’t here yet, despite recent advances in VR technology, but Rothenberg thinks it’s close. To get there, however, we’re going to need more companies building new hardware and software. And that’s going to take capital. “The innovators have been stepping up for decades,” he says. “It’s time for the financiers to step-up.”

That includes Rothenberg himself. Last week, his venture capital firm Rothenberg Ventures announced a new startup incubator, dubbed River, that will provide $100,000 in seed funding to 10 different companies, plus provide office space in San Francisco and mentoring from tech industry veterans. The firm is now recruiting its first cohort, and it will be taking applications until January 11.

Of course, virtual reality was supposed to be just around the corner back in the early 1990s. But now the dream is back, and it looks like it may be more than just hype this time around. Many developers have already gotten their hands on Oculus rift headsets, and the general public will likely be able to buy them early next year. Meanwhile, Samsung has already shipped its Gear VR headset, and Sony is expected to follow suit next year with its Project Morpheus device.

What’s different this time around, Rothenberg says, is that the technology is better—we can finally explore virtual worlds without getting nauseous—but also that it’s cheaper. It’s now a matter of perfecting the hardware, and finding applications for virtual reality. “We believe that VR will touch every industry eventually,” he says. “Just like the internet is now ubiquitous, and touches everyone’s life.”

These new companies will need more than just money. Business incubators have long played a big role in helping new businesses get off the ground by providing work space, mentorship, and sometimes funding. But Rothenberg—who has already invested in virtual reality companies Altspace VR, which aims to make social media into a 3-D, immersive experience, and 3-D camera company Matterport —realized that there were no incubators focusing specifically on virtual reality companies. So he decided he’d have to start one himself.

With River, Rothenberg hopes to accelerate this process by building a community for early-stage virtual reality startups to collaborate and network, and providing a physical location to demo their technology to investors, mentors, and the press. “These aren’t things where you send a business plan over and it makes sense,” he says. “You’ve got to actually experience it.”

Photos: See the Progress on NYC’s Long-Awaited 2nd Avenue Subway

The first phase of NYC's Second Avenue Subway line is scheduled to open in 2016. Metropolitan Transportation Authority/Flickr

The first phase of NYC's Second Avenue Subway line is scheduled to open in 2016.

Metropolitan Transportation Authority/Flickr

It's the biggest expansion of the city's subway system in generations. Metropolitan Transportation Authority/Flickr

It's the biggest expansion of the city's subway system in generations.

Metropolitan Transportation Authority/Flickr

Last month, workers finished blasting work for Phase 1, which will run from 57th Street to 96th Street. Metropolitan Transportation Authority/Flickr

Last month, workers finished blasting work for Phase 1, which will run from 57th Street to 96th Street.

Metropolitan Transportation Authority/Flickr

This is the site of a new station at 86th Street and Second Ave. Metropolitan Transportation Authority/Flickr

This is the site of a new station at 86th Street and Second Ave.

Metropolitan Transportation Authority/Flickr

The new stations will be climate controlled, which is a big deal—temperatures on NYC subway platforms have been clocked at over 100 degrees Fahrenheit. Metropolitan Transportation Authority/Flickr

The new stations will be climate controlled, which is a big deal—temperatures on NYC subway platforms have been clocked at over 100 degrees Fahrenheit.

Metropolitan Transportation Authority/Flickr

When the new line does open, it should ease crowding on the 4, 5, and 6 lines that now serve Manhattan's East Side. Metropolitan Transportation Authority/Flickr

When the new line does open, it should ease crowding on the 4, 5, and 6 lines that now serve Manhattan's East Side.

Metropolitan Transportation Authority/Flickr

And it will be easier to get around on the East Side in general. Metropolitan Transportation Authority/Flickr

And it will be easier to get around on the East Side in general.

Metropolitan Transportation Authority/Flickr

The MTA expects the line to serve 200,000 daily riders when it opens. Metropolitan Transportation Authority/Flickr

The MTA expects the line to serve 200,000 daily riders when it opens.

Metropolitan Transportation Authority/Flickr

But there's plenty of work left to do, including laying tracks. Metropolitan Transportation Authority/Flickr

But there's plenty of work left to do, including laying tracks.

Metropolitan Transportation Authority/Flickr

And turning newly created caverns into something people will recognize at tunnels and stations. Metropolitan Transportation Authority/Flickr

And turning newly created caverns into something people will recognize at tunnels and stations.

Metropolitan Transportation Authority/Flickr

For New Yorkers, the Second Avenue Subway is something of a punchline, an accepted local synonym for “when pigs fly.” It’s easy to see why: City officials have been talking about a second line on Manhattan’s East Side since the 1920s, and the construction has been delayed so many times that former man-in-charge Michael Bloomberg says he’s got a 50-50 shot at living to see it open (he’s 72).

The line eventually will run 8.5 miles under Second Avenue from Harlem to the Financial District. New York’s Metropolitan Transportation Authority says the first phase, from 57th Street to 96th Street, will open in 2016, after nine years and some $4.45 billion. Still, it’s easy to be skeptical of either one of those numbers, even if you aren’t a jaded and cynical New Yorker.

But for the workers who spend their days digging, blasting, and building, the project is real. And progress is being made. To prove it, the MTA has published a fresh set of photos showing off what’s happening under the island’s mica schist bedrock. So take a look at a project that’s literally decades in the making.