Bacteria hijack plentiful iron supply source to flourish

In an era of increasing concern about the prevalence of antibiotic-resistant illness, Case Western Reserve researchers have identified a promising new pathway to disabling disease: blocking bacteria's access to iron in the body.

The scientists showed how bacterial siderophore, a small molecule, captures iron from two abundant supply sources to fan bacterial growth -- as well as how the body launches a chemical counterassault against this infection process. Their findings appear in a recent edition of The Journal of Experimental Medicine.

"Bacterial siderophore will be an important target for therapeutics one day because it can be modified to prevent bacteria from acquiring iron, but at the same time, it's possible to preserve host access to iron," said senior author Laxminarayana Devireddy, DVM, PhD, assistant professor of pathology, Case Comprehensive Cancer Center.

Investigators knew from the outset that bacterial siderophore captures iron from the host mammal and transforms it so that bacteria can absorb and metabolize the mineral. In this investigation, Devireddy and his colleagues discovered that human mitochondria, which very closely resemble bacteria, possess their own iron-acquisition machinery -- mitochondrial siderophore. Mammalian mitochondria are membrane-encased subunits within cells that generate most of the cell's energy, and like their bacteria counterparts, mammalian mitochondria have their own siderophore mechanism that seeks out, captures and delivers iron for utilization.

At the test tube level, investigators found that bacteria can feed on iron supplied by bacterial siderophore and mitochondrial siderophore. From this glut of iron, bacteria proliferate and make the host mammal very ill with an infection.

"It's like bacteria can use their own iron-capture machinery or the host's. It just doesn't matter," Devireddy said. "They are very good at utilizing siderophore from both bacterial and mammalian siderophore sources. That means that bacteria get the most iron."

Case Western Reserve researchers also demonstrated that the absence of mitochondrial siderophore in a mammal can enhance its ability to resist infection. When investigators exposed mice deficient for mitochondrial siderophore to systemic infection by E. coli, the animals resisted infection. The reason? E. coli bacteria had less iron to access from mitochondrial siderophore-deficient mice.

Additionally, mammals are not entirely defenseless from a bacteria raid on mitochondrial siderophore iron supplies. In another phase of their investigation, scientists found that normal mice secrete the protein lipocalin 24p3, which isolates bacterial siderophore and suppresses synthesis of mammalian siderophore.

"The action of lipocalin significantly reduced the mortality of the mice from the E. coli infection, and some mice actually recovered," Devireddy said. "That kind of delay in bacterial proliferation gave the immune system time to identify and then neutralize the microbe."

These findings highlight the potential of developing effective therapeutics to reverse bacterial infection.

"Any approach that would suppress either bacterial or mitochondrial siderophore and activate lipocalin-2 would likely slow infection, allowing the host's immune system to respond," Devireddy said. "Such novel approaches would also provide a much-needed alternative to treat those infections that have become antibiotics resistant."

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The above story is based on materials provided by Case Western Reserve University . The original article was written by Jeannette Spalding. Note: Materials may be edited for content and length.

Tiny DNA pyramids enter bacteria easily -- and deliver a deadly payload

Bacterial infections usually announce themselves with pain and fever but often can be defeated with antibiotics -- and then there are those that are sneaky and hard to beat. Now, scientists have built a new weapon against such pathogens in the form of tiny DNA pyramids. Published in the journal ACS Applied Materials & Interfaces, their study found the nanopyramids can flag bacteria and kill more of them than medicine alone.

David Leong, Jianping Xie and colleagues note that some infectious pathogens can lie in wait, undetectable in the human body or in places that antibiotics have a hard time accessing. Engineered nanomedicine offers a new way to deliver drugs directly into bacterial cells, but the carriers developed so far pose problems such as toxicity. So Leong's team decided to use DNA to build a better, safer drug-delivery tool.

They made little pyramids out of DNA that were so small that thousands could fit in the period at the end of this sentence. Then, they attached gold nanomaterials as fluorescent tags and also packaged the drug actinomycin D (AMD) into the struts of the DNA pyramids. In tests on the common bacteria Escherichia coli and Staphylococcus aureus, the scientists tracked the nanopyramids as they entered the cells and released the drug payload. This killed 65 percent of the S. aureus and 48 percent of the E. coli, compared to 42 percent and 14 percent with AMD alone.

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The above story is based on materials provided by American Chemical Society . Note: Materials may be edited for content and length.

Immune system component found that resists sepsis in mice

Molecular microbiologists from the Keck School of Medicine of USC have discovered that mice lacking a specific component of the immune system are completely resistant to sepsis, a potentially fatal complication of infection. The discovery suggests that blocking this immune system component may help reduce inflammation in human autoimmune and hyper-inflammatory diseases such as rheumatoid arthritis and Type 2 diabetes.

The study was published online on June 23 in The Journal of Experimental Medicine, a leading peer-reviewed scientific journal in research medicine and immunology.

The immune system is the body's first line of defense against infection. The system, however, can also injure the body if it is not turned off after the infection is destroyed, or if it is turned on when there is no infection at all. Scientists do not yet fully understand how the immune response is turned on and off and continue to study it in hopes of harnessing its power to cure disease.

In this study, scientists have found that a component of the system, HOIL-1L, is necessary for formation of the NLRP3-ASC inflammasome signaling complex.

"This regulatory mechanism is critical in vivo, where we find that mice lacking HOIL-1L are completely resistant to sepsis, which is a lethal inflammation model of human sepsis," said Mary Rodgers, PhD, USC postdoctoral fellow and the study's first author. "Our results suggest that blocking the activity of HOIL-1L could be a new therapeutic strategy for reducing inflammation in disease."

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The above story is based on materials provided by University of Southern California - Health Sciences . The original article was written by Alison Trinidad. Note: Materials may be edited for content and length.

Sugar protects cells from bacterial invasion

No admission for bacteria: Scientists from the University of Freiburg have succeeded in preventing Pseudomonas bacteria from entering host cells with the help of a sugar complex. Dr. Thorsten Eierhoff and junior professor Dr. Winfried Römer from the Institute of Biologie II, both members of the Cluster of Excellence BIOSS Centre for Biological Signalling Studies of the University of Freiburg, have identified a sugar complex that binds the bacterial protein LecA in close cooperation with research groups led by Prof. Dr. Nicolas Winssinger from the University of Geneva, Switzerland, and Dr. Anne Imberty from the University of Grenoble, France. This protein enables the bacterium Pseudomonas aeruginosa to invade human lung cells. The researchers published their findings in the journal Angewandte Chemie.

Among other things, the hospital germ Pseudomonas aeruginosa can cause inflammation of the skin and lungs in patients with a weak immune system or a chronic illness. Moreover, these bacteria are often resistant to antibiotics. In tests conducted in cell culture, the researchers demonstrated that the germs penetrate into human lung cells 90 percent less often when treated with the agent.

The bacterial protein LecA binds the sugar galactose, which is exposed by receptors at the host cell surface. Via LecA, the bacterium attaches itself to the host cell and forces its way in. This allows the bacterium to spread through the body. The researchers developed a molecule that prevents LecA from docking onto the host cell receptors by binding to the bacterial protein with great precision. The research group led by Imberty succeeded in illustrating how the interaction between the sugar and the LecA protein looks like at the molecular level. "The agent is tailored precisely to bind to LecA: A framework of organic molecules places two galactose sugars at the right distance from one another for them to fit snugly into two of LecA's binding sites on the bacterial cell," explains Eierhoff. The agent resembles a plug made of galactose sugars that fits perfectly into the socket of LecA. Once bound to LecA, the agent works like a protective cap, preventing the Pseudomonas bacteria from invading the host cell.

The precisely fitting molecular framework was found by the research group led by the chemist Winssinger. The team arranged molecules that were potential candidates for binding partners on a chip. This allowed the scientists to test many samples at once. They determined which plug fit best with the protein LecA. The group led by Römer then tested the best-fitting molecule in cell culture to measure how many bacteria still managed to invade cells under the influence of the plug.

Binding to host cells via LecA is a significant path of invasion for Pseudomonas aeruginosa in human lung cells. The bacterium is responsible for roughly 80 percent of pneumonia-induced deaths in patients with cystic fibrosis, a genetic disorder of the mucous membranes. The researchers hope their findings will lead to the development of a novel agent capable of substantially weakening the germ.

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The above story is based on materials provided by Albert-Ludwigs-Universität Freiburg . Note: Materials may be edited for content and length.

IBM Bets $3B That the Silicon Microchip Is Becoming Obsolete

IBM’s Silicon Nanophotonics chip technology. IBM

IBM is worried that the age of silicon may be drawing to a close. So it’s going to spend $3 billion over the next half-decade to try and find new ways to power the future generations of microprocessors.

“We really do see the clock ticking on silicon,” says Tom Rosamilia, Senior Vice President of IBM Systems & Technology Group.

Today’s state-of-the-art IBM chips use silicon components that are already tiny — just 22 nanometers in width. But looking about five years into the future, parts become so small that it becomes extremely difficult to maintain a reliable on or off state. “As we get into the 7 nanometer timeframe, things really begin to taper off,” Rosamilia says.

So the first step of IBM’s $3 billion quest will fund research into ways of making these smaller chip components work — even if they don’t use silicon. IBM has high hopes for a silicon alternative, called carbon nanotubes, but the concept still needs work if it’s going to become as easy to crank out carbon nanotube chips as their silicon alternatives. Another promising area is silicon nanophotonics: a way of using light instead of electrical signals to send data around the chip.

The microprocessor industry has had an amazing ride, but already you can some fraying at the edges of Moore’s Law

Beyond that, IBM is also investing in brand new ways of number-crunching—quantum computing, or Neurosynaptic chips — that use computing models that go beyond the digital computing paradigm that has dominated the tech industry for fifty years.

The microprocessor industry has had an amazing ride, but already you can some fraying at the edges of Moore’s Law—the observation that chip performance doubles ever two years or so.

Microsoft is starting to use custom-designed chips for its Bing search engine — they say that it may be better to get performance boosts this way, rather than relying on general-purpose server chips to speed up. And scientists who maintain a list of the world’s top supercomputers worry that today’s supercomputers aren’t becoming powerful at quite the same clip.

If you ask the world’s largest chipmaker, Intel, the company will tell you that Moore’s Law is alive and well, and that it expects to crank out faster and faster chips for the foreseeable future.

So why the disconnect? Most likely, it comes down to the different business models of Intel and IBM. Although both companies make their own microprocessors, Intel rules the high-volume desktop market. It sells server chips too, but at higher volumes than IBM. Big Blue, on the other hand, is looking to carve out profitable niches for its systems, taking advantages of its expertise in software and system design to build unique systems. It’s looking for competitive differentiation—not necessarily high-volume sales.

And if quantum computers, carbon nanotubes, and computers modeled on the human brain are what it takes to get there, then IBM may be buying itself a $3 billion head start.

White Castle Honors Alice Cooper for His Dedication to Cheeseburgers

Boris Spremo/Getty

When Alice Cooper looks back on the legendary timeline of his life, there will surely be many years with special significance: 1969, when his Alice Cooper band was signed to Frank Zappa’s label; 1976, when he married his partner Sheryl Goddard; 1991, when his presence brought Wayne Campbell and Garth Algar to their knees in Wayne’s World; and 2011, when Cooper was inducted into the Rock and Roll Hall of Fame.

But now, if music’s original shock rocker ever decides to pen a follow-up to his memoir Golf Monster : A Rock ‘n’ Roller’s 12 Steps to Becoming a Golf Addict, he’ll have to include a chapter about one more very special occasion: July 7, 2014—the day Cooper entered the White Castle Cravers Hall of Fame.

The WCCHoF is located at White Castle headquarters in Columbus, Ohio, just 200 miles from Cooper’s birthplace of Detroit. Since its creation in 2001, 7,645 people have tried to get their names in the hallowed Hall, but only two percent have made the cut, putting the successful multi-hyphenate in a truly elite class.

As the pristine, post-war hero glow of the 1950s faded, America spent the late 60s entering its self-aware stage, mirroring the journey of a young Cooper, who was emerging from the unchecked optimism of teenage dreaming into the critical phase of early-20-something self-exploration. But fortunately for Cooper, he didn’t have just rock ‘n’ roll music to aid him on this journey. He also had White Castle’s iconic sliders, too.

No one can say for sure when he first fed his Frankenstein with White Castle’s unique culinary offerings, but we can deduce with reasonable certainty that it, like many events in the improbable star’s trailblazing career, was destiny—a beginning point that would run a traceable line through the life and career of Cooper, leading him back home to the Midwest, and finally into the Cravers Hall of Fame as if he was meant to be there all along.

Cooper was inducted into the Hall by Bill, Marci, and Lisa Ingram, who are the fourth generation of Ingrams to run the family-owned American institution. The company’s vice president, Jamie Richardson, moderated a brief conversation with Cooper to an audience of White Castle employees. A band was in attendance to pay tribute to Cooper and perform several of his songs, with the legend even welcoming attendees to his nightmare by joining in on “No More Mr. Nice Guy”—much to everyone’s surprise and delight.

As he was being inducted, Cooper told his audience, “a lot of my fellow rockers are going to be envious of this honor.” He was then asked how the moment stacked up against entering the Rock and Roll Hall of Fame. Ever the classy gentleman, Cooper was careful not to offend the Rock Hall by belittling it to the media and simply responded, “there’s no comparison.” As an honoree, he received a tour of the White Castle Headquarters in addition to a plaque commemorating his entrance into the selective WCCHoF.

The “School’s Out” rocker shares this honor alongside 170 inductees, including the five creators of Harold & Kumar Go to White Castle; Steven Luch of Detroit, in partnership with his potbellied pig, Nips; and Greek Orthodox Priest, Father John Stavropoulos of Canton, Ohio—Craver legends all.

Get Out! Someone Made an Emoji of Our Jerry Seinfeld Cover

Screengrab: WIRED

In the 1990s it was the Puffy Shirt, but these days Jerry Seinfeld rocks Google Glass. Maybe not at his favorite diner, but definitely on the cover of WIRED—and now in emoji.

The new Seinfeld emoji come courtesy of Jason Richards—the guy behind the @Seinfeld2000 Twitter account—and Houston-based graphic designer Kevin McCauley. And the fun doesn’t stop with Glasshole Jerry. There’s also a non-”modarn” version of @Seinfeld2000 stalwarts Jerry, Elaine, “Gerge,” “Kragnor,” Junior Mints, and even—yes—a puffy shirt.

And the best part is, you might actually be able to use these to send texts (about nothing) to your friends. McCauley created the images for a new app that is reportedly awaiting approval from the App Store.

Unfortunately, even if the app is approved the new emoji might not show up in your standard emoji keyboard. What is the deal with that? The Seinfeld Emoji web site explains, in @Seinfeld2000′s familiar brand of mangled English: “We called Apple and tried to make this hapen [sic] but honestly the CEO, Tim Cook or whatever, he was like ‘how did you get my phone number, this is my confidentiel [sic] unlisted number. I am v busy, plese [sic] stop calling,.’ And then when we called back he simply declined becase [sic] it went straght [sic] to voicemail after only one ring or whatever.”

New internet rule: Write to us in Seinfeld emojis or don’t write to us at all.