When good gut bacteria get sick

Being sick due to an infection can make us feel lousy. But what must the ecosystem of bacteria, or microbiota, colonizing our guts be going through when hit with infection? A study from Brigham and Women's Hospital (BWH) has utilized unique computational models to show how infection can affect bacteria that naturally live in our intestines. The findings may ultimately help clinicians to better treat and prevent gastrointestinal infection and inflammation through a better understanding of the major alterations that occur when foreign bacteria disrupt the gut microbiota.

"Our gut contains ten-times more bacterial cells than there are human cells in our body," said Lynn Bry, MD, PhD, director of the BWH Center for Clinical and Translational Metagenomics, senior study author. "The behavior of these complex bacterial ecosystems when under attack by infection can have a big impact on our health."

The study is published July 11, 2014 in PLOS ONE.

Georg Gerber, MD, PhD, MPH, co-director of the BWH Center for Clinical and Translational Metagenomics, co-first study author, developed novel computer algorithms to analyze the different stages of infection when a pathogen known as Citrobacter rodentium, which causes disease in mice similar to food-poisoning in humans, was introduced into the guts of mice. Bry and her team generated a two-month time-series of the population levels of bacteria throughout multiple sites in the intestine. The computational framework, known as Microbial Counts Trajectories Infinite Mixture Model Engine, developed by Gerber, was used to identify dynamic changes within the complex communities of bacteria in the gut associated with infection and inflammation.

The researchers observed many disruptions in the normal bacteria at different locations in the gut during the infection. For instance, they discovered a microbial signature in the colon involving species belonging to the genus Mucispirillum that showed decreases early in infection before the onset of symptoms. Other signatures included increases in populations of bacteria from the Clostridiales and Lactobacillales families occurring after the pathogen had disappeared. Interestingly, some of these signatures occurred in locations in the gut where the pathogen was not directly damaging host cells.

"From a clinical perspective, these new microbial signatures we identified could help clinicians detect early stages of inflammation or subtle persistent disease in patients with gastrointestinal disorders, such as inflammatory bowel disease," said Bry. "Moreover, several time-dependent microbial signatures we identified may be leveraged to conduct further research of other infectious and inflammatory conditions."

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The above story is based on materials provided by Brigham and Women's Hospital . The original article was written by Marjorie Montemayor-Quellenberg. Note: Materials may be edited for content and length.

Beloved crape myrtle in nurseries now susceptible to bacterial leaf spot

It's enough to send gardeners into conniptions.

Crape myrtle, a tree adored for its bright flowers that scream summer, care-free maintenance and even its colorful bark, now has a disease problem -- although so far, only in the commercial nursery setting.

University of Florida researchers had been getting sporadic reports from nursery owners over the last five years of a leaf spot problem, and those reports have only increased in frequency. Through genetic testing, scientists identified the disorder as being caused by the bacterium Xanthomonas axonopodis. The disease is most likely spread by wind-driven rain or overhead irrigation, and some crape myrtle varieties are more susceptible than others.

"I've been working with crape myrtles for a long time, and they've been such a disease-resistant plant for such a long time, so it's pretty significant when their susceptibility to disease is increased," said Gary Knox, an environmental horticulture professor with UF's Institute of Food and Agricultural Sciences.

The U.S. crape myrtle crop had a value of nearly $43 million in 2010, and Florida is its second-biggest producer, behind Texas. Florida has more companies producing crape myrtle, however, with 130 compared with 72 in Texas.

In the June issue of the journal Plant Disease, the UF/IFAS team outlined the first report of the disease and the work they did to identify it. They believe it is the first report of the bacterium causing leaf spot in crape myrtle.

Bacterial leaf spot doesn't kill the ornamental tree, but creates spots on its leaves that eventually turn yellow and drop.

The researchers say, for now, the disease affects only crape myrtle commercial producers and is spread by factors such as overhead irrigation systems and large numbers of plants kept in close quarters.

The bad news is that the bacterium is widespread.

"I think you can safely say that nearly every crape myrtle producer would have the disease at this point," Knox said.

While the disease appears contained in the commercial sector, that could change.

"Most bacterial diseases can be spread in wind-driven rain, and in Florida, we know there's no shortage of that," said Mathews Paret, an assistant professor of plant pathology who led the study.

Paret and Knox are based at the North Florida Research and Education Center in Quincy.

Scientists suggest an integrated management approach to the problem, rather than a silver bullet that only stops the problem temporarily.

Choosing resistant varieties, moving from overhead irrigation to drip irrigation and the limited use of bactericides would be part of such an integrated strategy, the researchers said.

The varieties Natchez, Osage, Fantasy, Basham's Party Pink and Miami have proven highly resistant to bacterial leaf spot while Carolina Beauty, Arapaho, Tuscarora, White Chocolate, Red Rocket and Rhapsody in Pink were more susceptible in field trials funded by the Florida Nursery Growers and Landscape Association.

Steve Bender, a senior writer at Southern Living magazine, "The Grumpy Gardener" blogger and well-known gardening author, says it would be a huge disappointment if the disease ever makes the leap from nurseries to home gardens.

Crape myrtle is so close to Southern gardeners' hearts that they endlessly debate such topics as how to spell its name (variants include crepe myrtle, crape myrtle and even crapemyrtle), and the annual rite Bender calls "crape murder" -- an unceremonious lopping of its limbs.

It's an iconic tree, he said, mostly because it's little work for a big payoff.

"It's ideally suited to the southern climate, it blooms for a long time, it comes in lots of different colors and you even get nice color in the fall," Bender said. "It's kind of hard to kill, and pretty much any idiot can grow one. And up until now, it's had very few problems."

Technology developed to redirect proteins towards specific areas of genome

The Spanish National Cancer Research Centre (CNIO) Macromolecular Crystallography Group has managed to reprogramme the binding of a protein called BuD to DNA in order to redirect it towards specific DNA regions. Guillermo Montoya, the researcher who led the study, says the discovery: "will allow us to modify and edit the instructions contained in the genome to treat genetic diseases or to develop genetically-modified organisms." The study is published in the journal Acta Crystallographica, Section D: Biological Crystallography.

The possibility of making à la carte modifications to the genome of living organisms could have a wide variety of applications, not only in the field of synthetic biology -- the science that seeks to create new living beings or improve existing ones for their biotechnological use -- but also for the treatment of human illnesses.

To achieve this, several researchers from around the world have focused on the proteins that bind to the DNA in very specific ways: their manipulation to direct them towards specific places in the genome, linked to their binding to genetic effectors (DNA repair or activator proteins, among others), could serve to modify DNA messages or to redesign genetic circuits as needed.

The CNIO team has deciphered the DNA binding code of BurrH, a new protein that was identified in Burkholderia rhizoxinica bacteria whose BuD domain specifically binds to the genome. To get there, the researchers have resolved the complete three-dimensional structure of the protein using the biophysical technique known as X-ray crystallography.

The main advantage of BuDs lies in their high specificity: they are able to distinguish DNA sequences that differ only in two nucleotides (the letters that make up the DNA). "This high specificity acts as a GPS that allows them to find their destinations within the intricate genome map," says Montoya, adding that: "They are very versatile and easy to reprogram in comparison with other proteins used to the same end."

Montoya's group has redesigned BuDs that are capable of recognizing the areas of the genome close to mutations responsible for sickle-cell disease, a pathology caused by modifications in the beta globin gene that produce alterations in red blood cells. "The linking of DNA repair proteins to these redesigned BuDs could serve to correct genetic alterations in patients with this disease," say the researchers.

Montoya says that several companies are already interested in this new technology: "Our tool, as well as being used to treat genetic disease, could be used to genetically modify micro-organisms targeting metabolite synthesis needed to produce biofuels, for example."

Story Source:

The above story is based on materials provided by Centro Nacional de Investigaciones Oncologicas (CNIO) . Note: Materials may be edited for content and length.

Why This Sci-Fi Author Doesn’t Want to Write Like George R. R. Martin

Ty Franck. Hachette Book Group

Ty Franck and Daniel Abraham write the popular Expanse series of space adventure novels under the pen name James S. A. Corey. Franck originally dreamed up the setting as part of a failed videogame project, and later adapted it for use in a pen and paper role-playing game. Abraham was one of his players, as was superstar author George R. R. Martin. Franck went on to work for several years as Martin’s personal assistant, helping him manage his finances. People often assume that Martin had a major influence on Franck’s work, but in fact Franck never even tried to emulate Martin’s writing method, which involves a great deal of improvisation, false starts, and rewrites.

“I could not do that. I have to know where I’m going. I have to know what the next chapters are about,” Franck says in Episode 113 of the Geek’s Guide to the Galaxy podcast. “We just have very different brains for doing this work.”

Franck and Abraham recently released the fourth book in their Expanse series, Cibola Burn, which involves several factions fighting to control a deadly alien planet rich in natural resources. The series is also being adapted for television by Syfy, with Iron Man scribes Mark Fergus and Hawk Ostby attached to the project. And while Martin played a limited role in shaping Franck as a writer, his advice was critical when it came to publishing contracts and film deals.

“The ways in which George was a really great mentor was on the business side,” says Franck. “He has enormous stores of experience on that stuff, so on that side he really was a good mentor.”

Listen to our complete interview with Franck in Episode 113 of Geek’s Guide to the Galaxy (above). Then stick around after the interview as guest geeks John Joseph Adams, Doug Cohen, and Theresa DeLucci join host David Barr Kirtley to review Season 4 of Game of Thrones and discuss the prospect of the show spoiling future books in the series.

Ty Franck on book titles:

“Daniel says our titles are designed to let our readers know that we’re pretentious, and there is an element of that in there. They’re all sort of mythological ideas that loosely tie in to what we’re doing. So with the first one, waking up the great monster that’s been sleeping, is Leviathan Wakes. For the second one, Caliban is the half-human, half-monster that lives on the same island as Prospero in The Tempest who resists being controlled, who Prospero attempts to control, and Caliban fights back against being controlled by the wizard. In Hebrew mythology, Abaddon is the angel who guards the gates to hell. And the Cibola is one of the cities of gold, the great treasure that you are willing to commit murder to find that doesn’t actually exist. … The tentative title for [the next book] is Nemesis Games. … [Our publisher] really likes ‘a mythological thing has or does something.’ … Nemesis is a Greek mythological character, so they should like that.”

Ty Franck on alien worlds:

“The thing that always drove both of us crazy is you get to the alien world and you catch an alien disease, like the Martians catching our diseases in The War of the Worlds . And of course H.G. Wells had a much more limited understanding than we do today, but even the idea that aliens would have DNA is totally unfounded. I mean, yeah, our version of life stumbled across RNA and DNA as a way to create stable replicators, but those are by no means the only possible version of that. … A scientist recently did an experiment where instead of potassium you can use—I believe it was cyanide as the basis for some of the protein building blocks. So you could have a lifeform where one of its primary building blocks is a deadly poison to us. And that should go the other way too. The things that are essential proteins to our biology could easily be deadly poisons to another biosphere, so you have things like the stinging insects that land on you, sting you, drink your blood, and then fall over dead.”

Game of Thrones Season 4 Panel

Doug Cohen on avoiding spoilers:

“Starting next year, when there’s a new episode each week, I’m not going to watch the episode. I’ll wait until the episode is over, at which point I’ll ask on my Facebook account, ‘Hey guys. Can I watch this episode?’ At which point people will tell me yea or nay. If it’s safe, great, I’m all in. If not, then I’m out, and then we start taking some precautions going forward for however many years necessary to avoid spoilers. … The first thing I’m going to do is Sunday night until Monday night, that’s social media blackout time, because that’s when people are going to be tweeting, Facebooking, linking about Game of Thrones more than any other time. … The second I can’t follow the show anymore, that means I immediately stop following Game of Thrones on Facebook and Twitter. You just pull back, you hold the line, and it’s just basically those ten weeks each season. My radar will have to be up every time I’m online, every time I’m at a convention. And thankfully my friends all know how fanatical I am about not getting spoiled about Game of Thrones.”

Theresa DeLucci on handsome men:

“As a heteronormative female, I feel like they keep killing off all the really hot men. Every year the cast of hot men on the show gets smaller and smaller. It started with Khal Drogo, and then Robb. I liked the original Daario. He was fine. He looked appropriately smug and douchey enough, like how I pictured him in the book. He didn’t need the blue beard and all that. The guy they have now just looks like—I see guys who look like that in Bushwick all the time. That is not Daario. That is just some lame, generic hipster knight. He looks like he comes from Westeros. He doesn’t look like a Second Son. He doesn’t have any swagger, he doesn’t have the costume right, so Oberyn was it for me. Unless they cast Viggo Mortensen as Damphair or something, there is nothing left for me. I was so sad to see Oberyn go, because he was absolutely perfect. I watched the season premiere at the Barclay Center—4,000 seats—to watch the premiere early on a big screen for a charity event. When Pedro Pascal came on screen, you just heard 2,500 women gasp all at the same time, because he was just so perfect, and just knowing what was going to happen to him, man, that made Season 4 really hard.”

Gadget Lab Podcast: We’ve Got Android Watches Coming Out of Our Ears

Ariel Zambelich/WIRED

What’s that thing on Mat’s wrist? It’s a Samsung Gear Live, one of two Android Wear smart watches that became available to consumers this week (The other one, LG’s G Watch, was reviewed by Christina Bonnington). On this week’s show, Mat and Mike talk about both of these watches, discussing what they do, and how much of a difference they’re poised to make in our lives. Also on the agenda is a discussion about Satya Nadella’s memo to Microsoft employees. Color us flummoxed! Finally, we talk about the latest additions to our respective families: our beautiful new televisions.

Download this week’s episode directly from iTunes or subscribe in iTunes. Note: There was a weird glitch that caused the wrong file to upload this week. If you start listening to episode 216 and you hear a show from June, refresh your feed. You should hear Mat and Mike start talking about Android Wear watches right at the top of the show.

Send the hosts feedback on their personal Twitter feeds (Mat Honan is @mat, Michael Calore is @snackfight) or to the main hotline at @GadgetLab.

World Cup Piracy Crackdown Hits Sites That Weren’t Even Streaming

Buda Mendes/Getty

An Indian company is trying take down about 500 web pages in the name of the World Cup, set to reach its climax on Sunday in Brazil. The idea is to cut off pirate sites that offer illegal streaming of World Cup events by having Google remove them from its search engine, but this sweeping crackdown is hitting all sorts of other legitimate sites as well.

The June 13 takedown notice covers several sites that simply talk about watching the World Cup online, including the Bleacher Report, the BBC, and a number of interesting books hosted by Google itself. And it appears to be the result of some sloppy work by Markscan, a company that India’s Sony Entertainment Network hired to enforce its World Cup Streaming rights.

So far, Google has ignored many of the requests, and that’s a good idea, says Nate Glass, the owner of Takedown Piracy, a U.S. company that does similar copyright takedowns. “It sounds like this one company is kind of a rogue agent who’s maybe taking a scattershot approach and not really being very precise with their notices,” he says.

This Sunday’s World Cup final between Germany and Argentina will, no doubt, be one of the most-watched sporting events of all time. The group that puts on the World Cup, FIFA, says that close to 1 billion people watched the 2010 finale, and this year’s game—a trans-continental match-up pitting a European Team against one from South America—seems likely to draw in even more viewers.

Here in the U.S., the final game will be broadcast on ABC, so it will be available even to cable-cutters. But that hasn’t been the case with all of the World Cup games. ABC and ESPN, for example, made early World Cup games available to non-subscribers via broadcast television and internet streaming, but then pulled the plug on this giveaway during key elimination matches. And Sunday’s final won’t be available for free in some countries, particularly in Asia, according to the Hollywood Reporter.

That means that sites such as Firstrow and Rojadirecta will probably be busy Sunday. It’s “likely be the most pirated sporting event in history,” says Glass. “You’re talking about, potentially, millions of people.”

FIFA itself has taken steps to cut down on copyright infringement. It’s sent warning letters to streaming sites, and DMCA notices to Twitter. News of the Markscan takedown was first reported by TorrentFreak. Google, Markscan, and Sony Entertainment Network could not immediately be reached for comment.

Three Reasons Why Amazon’s New Storage Service Won’t Kill Dropbox

Amazon

Today Amazon introduced a new file storage and collaboration service called Zocalo that—on first blush, at least, looks like it might be a Dropbox killer. Much like Dropbox and other cloud storage services, Zocalo lets you sync files between the Amazon cloud and your phone or PC. It has a business twist too, helping IT staffers control who gets access to which files.

The product must be making some Dropbox executives uneasy, because unlike its other big competitors—Google and Microsoft— Dropbox itself is a pretty big Amazon customer. The startup uses Amazon’s S3 storage service to store the more than 500 million files that get uploaded to Dropbox each day.

That’s going to make it pretty much impossible for Dropbox to undercut Amazon’s pricing. Zocalo starts at $5 per user per month for 200GB of storage. Dropbox charges twice that for half as much storage.

But price isn’t everything, and Dropbox still has a several advantages that Amazon will be hard-pressed to overcome.

1. Sync is incredibly hard to get right

Dropbox’s greatest strength is that it makes syncing files with the cloud and sharing them with other users seem so easy. But it’s not. Behind the scenes, Dropbox has a vast system of software keeping track of which files have been edited when, and who has access to what. Sync is a particularly difficult problem, and one small bug can lay waste to years of important user data. Err the other way, and you’re constantly resurrecting long-deleted files.

Amazon has the technical chops to build a reliable storage and synchronization system, but making it as invisible to the end-user as Dropbox is no easy task. Dropbox has a seven-year head start here. And customers have shown, again and again, that they’re actually happy to pay more money for a tool with fewer features as long as it’s easy to use.

2. Dropbox’s “users first” strategy

Dropbox’s strategy has always been to win end-users over first, then sell to the business side. Amazon is taking the opposite approach, by appealing directly to businesses. The problem with this approach is that even if Amazon is successful in selling its service to a business, the managers of that business still have to convince their employees to use it. Employees who are already Dropbox might not want to make the switch — especially if Zocalo ends up being even slightly harder to use than Dropbox.

Could Amazon appeal directly to end users in this space? It already tried that with Amazon Cloud Drive, which is still around, but has been largely forgotten since its 2011 launch.

3. Branding

Amazon already has a dizzying number of services and features under the Amazon Web Services umbrella, and it can be hard to keep track of them all. And the company is always adding more. That means it could be easy for the product to be overlooked, much as Cloud Drive has.

That’s made all the worse by the name Zocalo. In Spanish, Zócalo means “plinth,” which is a platform for pillars or statues. It can also refer to the Plaza de la Constitución, the public square in the center of Mexico City. Unfortunately, it’s not a word that means much to non-Spanish speakers, and it’s particularly hard to remember. Bu now, just about everybody knows about Dropbox.

Independence Ahead?

Of course it’s not all smooth sailing for Dropbox and other competitors. This move will put pricing pressure on Dropbox, and it may need to spend some of $1.1 billion it’s raised on gaining more independence from Amazon. Startups are always in danger of being squashed by larger companies and bigger marketing budgets and the ability to undercut them on cost. But that problem is magnified when you’re running your service on infrastructure owned and operated by the same big companies you have to compete with. We’ve already seen this with Amazon Prime, which competes with Netflix, another major Amazon Web Services customer.

But Amazon is still a long way from killing Netflix, and that’s good news for Dropbox.