Diverse gut bacteria associated with favorable ratio of estrogen metabolites

Postmenopausal women with diverse gut bacteria exhibit a more favorable ratio of estrogen metabolites, which is associated with reduced risk for breast cancer, compared to women with less microbial variation, according to a new study published in the Endocrine Society's Journal of Clinical Endocrinology & Metabolism (JCEM).

Since the 1970s, it has been known that in addition to supporting digestion, the intestinal bacteria that make up the gut microbiome influence how women's bodies process estrogen, the primary female sex hormone. The colonies of bacteria determine whether estrogen and the fragments left behind after the hormone is processed continue circulating through the body or are expelled through urine and feces. Previous studies have shown that levels of estrogen and estrogen metabolites circulating in the body are associated with risk of developing postmenopausal breast cancer.

"In women who had more diverse communities of gut bacteria, higher levels of estrogen fragments were left after the body metabolized the hormone, compared to women with less diverse intestinal bacteria," said one of the study's authors, James Goedert, MD, of the National Institutes of Health's National Cancer Institute (NCI) in Bethesda, MD. "This pattern suggests that these women may have a lower risk of developing breast cancer."

As part of the cross-sectional study, researchers analyzed fecal and urine samples from 60 postmenopausal women enrolled in Kaiser Permanente Colorado. The women were between the ages of 55 and 69, and all participants had a mammogram with normal results in the previous six to eight weeks. The samples were analyzed for bacterial diversity and the ratio of estrogen fragments to estrogen, a predictor of breast cancer risk.

"Our findings suggest a relationship between the diversity of the bacterial community in the gut, which theoretically can be altered with changes in diet or some medications, and future risk of developing breast cancer," Goedert said. "Findings from this proof-of-principle study need to be replicated in larger groups of women. But we are hopeful that because the microbiome can change the way the body processes estrogens, it may one day offer a target for breast cancer prevention."

Other authors of the study include: Barbara J. Fuhrman, Roberto Flores and Mitchell H. Gail of NCI; Heather Spencer Feigelson of Kaiser Permanente Colorado in Denver, CO; Xia Xu of the Frederick National Laboratory for Cancer Research in Frederick, MD; and Jacques Ravel of the University of Maryland in Baltimore, MD.

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

HP Acquires Open Source Cloud Pioneer Eucalyptus



Tech giant HP is acquiring Eucalyptus, makers of an open source system that helps companies build cloud computing services in their own data centers.

Following the deal, Eucalyptus CEO Marten Mickos will become senior vice president and general manager of HP’s cloud business, reporting directly to HP CEO Meg Whitman. HP’s current head of cloud, CTO Martin Fink, will shift his attention to other areas of the company, such as such as the blue skies research division HP Labs.

Marten Mickos.

Marten Mickos. Andrew Smart of AC Cooper

According to Bill Hilf, senior vice president of product, services, and strategy for HP’s cloud business, who will report to Mickos, the acquisition provides a needed leader for the company’s cloud operation and additional engineering talent needed to expand and hone the company’s cloud software and services—technology that provides a meaning of building and hosting large online software applications. But, he says, it also fills a gap in HP’s technology. It provides a way for customers to dovetail private cloud services in their own data centers with the popular public cloud service from Amazon.

“The really what Eucalyptus provides: AWS interoperability,” he says, referring to Amazon Web Services, the company’s sweeping collection of cloud offering. “It lets customers build an app in their own data center, and then they can, say, push that same application to AWS.”

HP is just one of many tech giants seeking to offer software that will let business span private and public services in this way. From VMware to Microsoft, these are companies aiming to serve companies that want to keep some technology in house—for reasons of cost, security, and privacy—but also take advantage of public cloud services, which provide a more convenient and flexible way of building and running software applications

At first blush, the move seems odd. HP’s cloud efforts have been focused on OpenStack, an open source cloud system that competes with the similar technology offered by Eucalyptus. OpenStack was originally created by NASA to overcome limitations in Eucalyptus’ technology. And Mickos has long been critical of OpenStack, calling it the “Soviet Union” of cloud technology.

But the move isn’t as unlikely as some might think. Mickos has recently changed his tune regarding the competition. “OpenStack is (in my humble opinion) the name of a phenomenon of enormous proportions,” he wrote in a blog post explaining why he was keynoting an OpenStack conference. He still expressed concern about the collective governance of OpenStack—which is what led him to compare OpenStack with the Soviet Union—but he wrote that he actually wanted Eucalyptus to become a real contributor to the OpenStack project.

The thrust of his post was that OpenStack and Eucalyptus fill two very different needs. Eucalyptus helps companies build private clouds that are compatible with Amazon’s public clouds. OpenStack, on the other hand, helps power web giants like eBay who aren’t worried about Amazon compatibility. “Eucalyptus is the name of a tightly focused piece of software that serves a unique use case,” he wrote.

Mickos’ assessment of the differences between OpenStack and Eucalyptus is debatable. Cloudscaling, for example, offers a version of OpenStack designed for Amazon compatibility. But his new found love for the project it does show how much progress OpenStack has made, and how much his own view has changed.

Additional reporting by Cade Metz

Feds Threatened to Fine Yahoo $250K Daily for Not Complying With PRISM

Government slide showing when Yahoo and other internet companies began supplying data to the PRISM program. Courtesy of The Washington Post

A secret and scrappy court battle that Yahoo launched to resist the NSA’s PRISM spy program came to an end in 2008 because the Feds threatened the internet giant with a massive $250,000 a day fine if it didn’t comply.

The detail of the threat became public today after 1,500 pages worth of documents were unsealed in the case, revealing new information about the aggressive battle the Feds fought to force the company to bow to its demands. The information was first reported by the Washington Post following a blog post published by Yahoo’s general counsel disclosing that the documents had been unsealed and revealing for the first time the government’s threat of a fine.

Yahoo fought to unseal the case documents to provide better transparency about the government’s data collection programs and the FISA Court’s controversial history in approving nearly every data request the government makes.

The company disputed the initial order in 2007 because it deemed the bulk demand for email metadata to be unconstitutionally broad, but it lost that fight both in the Foreign Intelligence Surveillance Court and during appeal to the Foreign Intelligence Court of Review. It was among the first of nine internet companies to fall to the government’s demands for customer data and was a crucial win for the Feds since they were allowed to wield the ruling as part of their demand to other companies to comply.

Each of the internet companies fell in line with the program at separate times in the wake of that ruling.

“The released documents underscore how we had to fight every step of the way to challenge the U.S. Government’s surveillance efforts,” Yahoo General Counsel Ron Bell wrote in a post published after the unsealing. “At one point, the U.S. Government threatened the imposition of $250,000 in fines per day if we refused to comply.”

The unsealing of FISA Court documents is extremely rare but, as Bell noted, it was

“an important win for transparency, and [we] hope that these records help promote informed discussion about the relationship between privacy, due process, and intelligence gathering.”

The company is in the process of making all of the 1,500 pages available to the public and says it will provide a link to them online when they are ready. Bell noted that “[d]espite the declassification and release, portions of the documents remain sealed and classified to this day, unknown even to our team.”

Yahoo’s secret battle, and the PRISM program, came to light only last year after documents released by NSA whistleblower Edward Snowden exposed the data-collection program. Yahoo, Google, Apple and other companies were harshly criticized for complying with the program and seemingly putting up no resistance to it. But shortly after the program was exposed, Yahoo’s dogged battle with the Feds to resist its inclusion in the program came to light only after another document leaked by Snowden exposed the company’s legal fight against the FISA Court order.

Yahoo fought back on Fourth Amendment grounds, insisting that such a request required a probable-cause warrant and that the surveillance request was too broad and unreasonable and, therefore, violated the Constitution.

Yahoo also felt that warrantless requests placed discretion for data collection “entirely in the hands of the Executive Branch without prior judicial involvement” thereby ceding to the government “overly broad power that invites abuse” and possible errors that would result in scooping up data of U.S. citizens as well.

The request for data initially came under the Protect America Act, legislation passed in the wake of the 9/11 terrorist attacks that allowed the Director of National Intelligence and the Attorney General to authorize “the acquisition of foreign intelligence information concerning persons reasonably believed to be outside the United States” for periods of up to one year, if the acquisition met five criteria. The Protect America Act sunset in February 2008, but was incorporated into the FISA Amendments Act in July that year.

Under the law, the government has to ensure that reasonable procedures are in place to ensure that the targeted person is reasonably believed to be located outside the U.S. and that a significant purpose of the collection is to obtain foreign intelligence. In its request to Yahoo, the government apparently proposed additional measures it planned to use to ensure that its data collection was reasonable.

But Yahoo felt the procedures and measures the government proposed to undertake were insufficient and refused to comply with the data request. The government then asked the FISA Court to compel Yahoo to comply, which it did.

Yahoo applied to appeal the decision and requested a stay in the data collection pending the appeal. But the FISA Court refused the stay, and beginning in March 2008, Yahoo was forced to comply with the request for data in the meantime “under threat of civil contempt.”

Five months later, in August 2008, the FISA Court of Review found that the data request, undertaken for national security reasons, qualified for an exception to the warrant requirement under the Fourth Amendment and upheld the original court’s order to comply.

As for Yahoo’s concern that the request was too broad and opened the possibility for potential abuse, the judges wrote that the company had “presented no evidence of any actual harm, any egregious risk of error, or any broad potential for abuse in the circumstances of the instant case” and called Yahoo’s concerns “little more than a lament about the risk that government officials will not operate in good faith.”

To support their ruling, the judges wrote that the government “assures us that it does not maintain a database of incidentally collected information from non-targeted United States persons, and there is no evidence to the contrary.”

A year’s worth of Snowden revelations, however, have now shown this to have been a misguided statement on the part of the judges.

Last known living rescue dog of 9/11 [Life Lines]

Image of from www.eonline.com

Image of Bretagne from www.eonline.com

On this anniversary of 9/11 we remember not only the victims but also the heroes of that fateful day including countless first responders as well as their rescue animals that searched tirelessly for victims. The last known living rescue dog from 9/11 is Bretagne, a 15-year old golden retriever who returned to the memorial site with her handler Denise Corliss. She was only 2 years old at the time of the 9/11 attacks.

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According to veterinarian Dr. Cindy Otto who took care of the search dogs at ground zero, these animals brought hope to an otherwise dismal place. Bretagne has remained busy helping with other search and rescue operations including Hurricanes Katrina and Ivan until her retirement at age 9.

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This Is the New Batmobile—And It’s Kind of Ugly

Director Zack Snyder posted this image of the Batmobile on Twitter last night.

Director Zack Snyder posted this image of the Batmobile on Twitter last night. Zack Snyder

Batman v Superman: Dawn of Justice director Zack Snyder took to Twitter last night to reveal Batman’s latest ride, and … well, fans of the sleek lines of the classic 1966 and 1989 Batmobiles might want to just look away now before it gets too painful.

Here’s the thing: Understandably the Batmobile isn’t just any car, and has to deal with all manner of problems and situations more complicated than “parallel parking on a busy city street” or “where to put all the groceries,” but why that means that the Batmobile has to look more like a Transformer than, you know, a car is a bit hard to grok.

It seemed unlikely that the Tumbler from The Dark Knight could ever be regarded as an understated take on Batman’s town car, but apparently that’s where we’ve reached. By the time Ben Affleck’s Caped Crusader gets his first solo movie, it wouldn’t be the least bit surprising if the next generation Batmobile turns out to be larger than Gotham City itself.

Suffice to say, the internet reaction to the new vehicle has been as positive as could be expected:

It’s too late to hope that the powers that be will suddenly get wise and replace this new Batmobile with something more sensible, but we could get lucky: Superman might destroy it in the first half hour of the movie.

Using Smartphones to Track Our Everyday Moral Judgments



Our lives are surprisingly packed with morally loaded experiences. We see others behaving badly (or well), and we behave well (or badly) ourselves. In a new study, researchers used a smartphone app to track moral and immoral acts committed or witnessed by more than 1,200 people as they went about their days. It’s one of the first attempts to quantify the moral landscape of daily life, and it contains some interesting hints about how people are influenced by the behavior or others, as well as by their own political and religious leanings.

Wilhelm Hofmann, a social psychologist at the University of Cologne in Germany, and his colleagues pinged study participants with text messages at random times and asked them to report any moral or immoral acts they’d committed, been the target of, witnessed, or simply heard about within the previous hour. Such acts turned out to be common: of the 13,240 responses collected over the course of the study study, 29 percent included a morally significant event. These were roughly evenly split between moral acts (in the judgment of the person reporting the event), such as helping a lost tourist or giving a sandwich to a homeless person, and acts deemed immoral, such as petty theft or smoking in a car full of children. Most of these acts–64 percent—occurred in public places. Another 23 percent occurred at home.

There’s much more to the study, but that finding alone is interesting because it shows how often we make moral judgments in daily life, says Jonathan Haidt, a social psychologist at New York University’s Stern School of Business, who was not involved in the work. “My view is that moral psychology is the operating system of human social life,” he said. “To the extent that we’re able to interact with strangers it’s because we create these dense webs of moral norms and then we judge each other relentlessly on them and know that we’ll be judged, and that’s what makes it all work.”

In recent years, psychologists and neuroscientists have grown increasingly interested in studying the roots of human morality. Until now, they’ve relied largely on questionnaires and fictional moral dilemmas like the infamous trolley problems (variations on the question, “Would you shove one person in front of an oncoming trolley car in order to save the lives of five other people?”).

The new study attempts to take morality research out of the lab and into the real world, in this case, into the lives of 1,252 US and Canadian adults recruited through Craigslist, Twitter, and other sources. The findings, reported today in Science , are largely consistent with what researchers previously have found with surveys and lab studies (and the rest of us have encountered in real life).


A screenshot from the smartphone app used in the study. Wilhelm Hofmann

For example, there were hints of hypocrisy, or at least selective awareness. People were about three times as likely to report committing a moral act as an immoral one, but about 2.5 times as likely to report hearing about someone else behaving badly as doing good deeds. (It’s all those other people doing bad things).

The study also supports the idea, proposed by Haidt and popularized in his book The Righteous Mind, that people with different political leanings emphasize different aspects of morality. Hoffmann and colleagues found that people who self-identified as liberal reported more events having to do with fairness or unfairness, for example, while conservatives reported more events having to do with sanctity or degradation (talking with a relative about God and meditating, for example, or, conversely, catching a teenage son watching porn).

The researchers found no evidence that religious people commit moral acts more often than nonreligious people. Religious people reported hearing about fewer immoral acts, however, which the authors suggest may be due largely to being selective about the company they keep (and perhaps not watching Game of Thrones, although the study didn’t actually examine that).

They did find evidence for a phenomenon psychologists call moral contagion: People who were the target of a moral act were more likely to commit a moral act later in the day. But there was also evidence for a countervailing influence called moral self-licensing. People who committed a moral act earlier in the day were more likely to slack off, morally speaking: They committed fewer moral and more immoral acts later in the day.

It might be possible to use of some of these findings to craft public policies that encourage good behavior, says co-author Mark Brandt of Tilburg University in the Netherlands. “It may be possible to take advantage of moral contagion by making people the targets of moral acts more often or at least reminding them of times when they were a target of moral charity,” Brandt said. Similarly, he says, warning people about the possibility of self-licensing and stressing the importance of moral consistency might be useful in recycling programs or other efforts to care for the environment.

The smartphone approach raises many possibilities for future research on moral psychology. For example, to study the factors that influence moral behavior, researchers could text people survey questions or tests of moral judgement as they pass through certain locations—as they walk by a church, for example, or a neighborhood with a lot of crime—or right after they see or commit certain types of acts.

“This kind of technology could be used to see how communities respond to sociologically relevant events like a terrorist attack, a basketball victory, or extreme weather—all things that seem to pull people together,” Haidt said. For example, he says, New Yorkers often say people were nicer to each other in the immediate aftermath of 9/11. “If you’re tracking people over time, it would be interesting to see if people do more nice things for each other, if they’re more trusting and cooperative, when the local team wins. If there’s a threat, does everyone band together, or do people band together along ethnic lines or lines of similarity?”

Ticks that vector Lyme disease move west into North Dakota

According to the U.S. Centers for Disease Control, there are more than 300,000 cases of Lyme disease in the U.S. each year. Last year, most Lyme disease cases reported to the CDC were concentrated heavily in the Northeast and upper Midwest, with 96 percent of cases in 13 states. In fact, the disease gets its name from the northeastern town of Lyme, Connecticut, where it was first discovered.

However, a new article published in the Journal of Medical Entomology reports that the ticks that vector Lyme disease -- Ixodes scapularis, also known as blacklegged ticks or deer ticks -- are moving westward, and for the first time have been found to be established in North Dakota. Even worse, deer ticks that were infected with the bacterium that causes Lyme disease (Borrelia burgdorferi) were found as well.

Researchers sampled ticks at nine locations throughout North Dakota by trapping small mammals and then removing the attached ticks. When they found I. scapularis, they screened them for Borrelia burgdorferi and for two other types of bacteria that can lead to two other tick-borne diseases called Anaplasmosis and Babesiosis.

I. scapularis ticks were collected in six of the nine counties surveyed, and two of the counties seemed to have established poulations because all life stages -- eggs, larvae, nymphs, and adults -- were present.

"This represents an expansion of the predicted range for this tick species and is of concern because of the ability of this tick species to transmit various disease-causing agents," the authors wrote. "I. scapularis and associated pathogens have become established in northeastern North Dakota."

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

Intestinal bacteria needed for strong flu vaccine responses in mice

Mice treated with antibiotics to remove most of their intestinal bacteria or raised under sterile conditions have impaired antibody responses to seasonal influenza vaccination, researchers have found.

The findings suggest that antibiotic treatment before or during vaccination may impair responses to certain vaccines in humans. The results may also help to explain why immunity induced by some vaccines varies in different parts of the world.

In a study to be published in Immunity, Bali Pulendran, PhD, and colleagues at Emory University demonstrate a dependency on gut bacteria for strong immune responses to the seasonal flu and inactivated polio vaccines.

Antibody responses to vaccines containing immune stimulating substances called adjuvants were not affected by a lack of gut bacteria. For example, bacteria were not critical for responses to the Tdap (Tetanus-Diphtheria-Pertussis) vaccine.

"Our results suggest that the gut microbiome may be exerting a powerful effect on immunity to vaccination in humans, even immunity induced by a vaccine that is given at a distant site," says Pulendran, Charles Howard Candler professor of pathology and laboratory medicine at Emory University School of Medicine and Yerkes National Primate Research Center.

The first author of the paper is postdoctoral fellow Jason Oh, PhD. Collaborators including Andrew Gewirtz, PhD, at Georgia State University and Balfour Sartor, MD, at the University of North Carolina contributed to the paper.

Pulendran says the impetus for this study was a previous study involving an analysis of the immune response to influenza vaccination in humans, using the "systems vaccinology" approach that his lab had pioneered. He and his colleagues had observed that in humans given the flu vaccine, the expression of the gene encoding TLR5, a few days after vaccination was correlated with strong antibody responses weeks later. TLR5 encodes a protein that enables immune cells to sense flagellin, the main structural protein for the whips (flagella) many bacteria use to propel themselves.

The ability of immune cells to sense flagellin appears to be the critical component affecting vaccine responses, the researchers found. Mice lacking TLR5 -- but still colonized with bacteria -- have diminished responses to flu vaccines, similar to antibiotic-treated or germ-free mice. Oral reconstitution of antibiotic treated mice with bacteria containing flagellin, but not with mutant bacteria lacking flagellin, could restore the diminished antibody response.

"These results demonstrate an important role for gut bacteria in shaping immunity to vaccination, and raise the possibility that the microbiome could be harnessed to modulate vaccine efficacy," says Pulendran. "The key question is the extent to which this impacts protective immunity in humans."

Pulendran says that his team is planning a study in humans to address this issue.

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The above story is based on materials provided by Emory Health Sciences . Note: Materials may be edited for content and length.

Impact on gut microbiota of fermented milk product containing probiotics revealed by new technology

Scientists from INRA and Danone Nutricia Research have shown the effect of a fermented milk product containing probiotics on the gut microbiota, using a novel high resolution bioinformatics tool. The product affected certain gut bacteria without changing the global composition of the microbial community. These findings, published in Scientific Reports on 11 September 2014, open new perspectives to understand the effects of probiotics on our health.

Fermented foods, and especially yoghurts, contain large amounts of live bacteria. We have been consuming them since the Neolithic Era (12,000 years ago), but our understanding of their impact on the digestive tract remains limited. Until recently, technological barriers prevented from studying in details the billions of bacteria living in our gut. The European consortium MetaHIT[1], coordinated by INRA, has made major breakthroughs in this field that expanded the scientific knowledge on the role of this microbiota and resulted in the discovery of many bacterial species hitherto unknown.

Building on these new technologies, teams from INRA and Danone Nutricia Research succeeded in analyzing for the first time with great accuracy the effects of consuming a fermented milk product containing probiotics such as Bifidobacterium lactis, on gut bacteria. "In this study, we studied the effect of the product on individuals afflicted with Irritable Bowel Syndrome (IBS), a pathology affecting 20% of the population in industrialized countries" says Dusko Ehrlich who led the research at INRA.

Researchers observed that, upon intake of this fermented milk product comprised of probiotics, the abundance of certain bacteria naturally producing butyrate increased, though the global composition of the flora remained unchanged. Butyrate is known for its beneficial effects on gut health. Previous studies have shown a decrease in butyrate producing bacteria in IBS individuals. Moreover, the scientists observed a decrease of Bilophila wadsworthia bacteria, which is thought to be involved in the development of intestinal diseases.

This pilot study on 28 individuals leads to relevant and reliable scientific hypotheses relating health and the consumption of fermented milk products containing probiotics. It also shows the potential in using new tools to analyze existing interactions between gut microbiota and probiotics. "Up until now, it was impossible to study the impact of probiotics on gut microbiota at a bacterial species level; from now on we will have a much more detailed view of the dynamics of this ecosystem" says Dusko Ehrlich.

What are probiotics?

Probiotics are "live micro-organisms which, when administered in adequate amounts, confer a health beneļ¬t on the host, beyond the common nutritional effects" (FAO/WHO, 2001). They facilitate fiber digestion, boost the immune system and prevent or treat diarrhea. Today, dozens of bifidobacteria and lactobacilli are marketed in certain foods such as yoghurts or fermented milk products.

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The above story is based on materials provided by INRA-France . Note: Materials may be edited for content and length.

Our microbes are a rich source of drugs

Bacteria that normally live in and upon us have genetic blueprints that enable them to make thousands of molecules that act like drugs, and some of these molecules might serve as the basis for new human therapeutics, according to UC San Francisco researchers who report their new discoveries in the September 11, 2014 issue of Cell.

The scientists purified and solved the structure of one of the molecules they identified, an antibiotic they named lactocillin, which is made by a common bacterial species, Lactobacillus gasseri, found in the microbial community within the vagina. The antibiotic is closely related to others already being tested clinically by pharmaceutical companies. Lactocillin kills several vaginal bacterial pathogens, but spares species known to harmlessly dwell in the vagina.

This example suggests that there may be an important role for many naturally occurring drugs -- made by our own microbes -- in maintaining human health, said the senior author of the study, Michael Fischbach, PhD, an assistant professor of bioengineering with the UCSF School of Pharmacy, who has established a career discovering interesting molecules made by microbes.

"We used to think that drugs were developed by drug companies, approved by the FDA, and prescribed by physicians, but we now think there are many drugs of equal potency and specificity being produced by the human microbiota," Fischbach said.

About a third of all medicines used in the clinic are derived from microbes and plants, Fischbach said. These include antibiotics like penicillin, numerous drugs used in cancer chemotherapy, and cholesterol-lowering drugs. Although those who prospect for drugs from microbes have been combing the depths of the oceans and probing exotic soils around the globe, only now have scientists begun to look within our own bodies.

There are hundreds of bacterial species associated with each of us, and thousands of distinct strains among them. We do not all harbor the same species, and different species are found at different body sites.

Through research funded by the National Institutes of Health's Human Microbiome Project and other studies, scientists in recent years have begun to describe the microbiomes -- ecosystems made up of many microbial species -- found in the gut, skin, nasal passages, mouth and vagina.

They have started to identify microbiomes in which species diversity and abundance differ from the normal range in ways that are associated with disease risks. However, the identification of molecules that govern interactions between microbes and their human hosts has lagged; only a handful have been identified, Fischbach said.

By developing new data-analysis software and putting it to work on an extensive genetic database developed from human-associated bacterial samples collected as part of the ongoing Human Microbiome Project, Fischbach's lab team identified clusters of bacterial genes that are switched-on in a coordinated way to guide the production of molecules that are biologically active in humans.

Like language-translation programs, the mathematical algorithm Fischbach's team developed, called ClusterFinder, uses machine-learning principals to draw conclusions from new data, based on what is already known -- in this case previously identified relationships between gene clusters in soil and marine bacterial species and the molecules they produce.

Using ClusterFinder, Fischbach's team for the first time systematically analyzed genomes from microbiome species and data on gene activity from human samples to identify 3,118 distinct clusters of bacterial genes that are found in various human body sites. The gene clusters his team identified encode enzymes that serve as molecular factories to produce specific drug-like molecules that fit into known classes of pharmaceuticals.

The new study reveals that the genus-level analysis commonly used to identify bacteria within human microbiomes is not detailed enough to predict which drug-like molecules the bacteria make, Fischbach said. Individual species, and different strains within each species, differ in the molecules they produce.

"We need to learn what these molecules are and what they are doing," Fischbach said. "This could represent a pool of molecules with many tantalizing candidates for drug therapy.

"It's been clear for several years that variations and changes in the human microbiome have interesting effects on the human host, and now we can begin to determine why this is true on a molecular level."

UCSF postdoctoral fellow Mohamed S. Donia, PhD, designed and conducted key experiments and took the lead in drafting the newly published study. Other co-authors include UCSF postdoctoral fellow Peter Cimermancic, PhD; postdoctoral fellow Christopher J. Schulze, PhD, from Stanford University; associate professor Roger G. Linington, PhD, from UC Santa Cruz; chemistry lecturer Laura C. Wieland Brown, PhD, from Indiana University; John Martin and Makedonka Mitreva, PhD, assistant professor, from Washington University, St. Louis; and Jon Clardy, PhD, professor at Harvard Medical School.

The research was funded by the National Institutes of Health, the Defense Advanced Research Projects Agency, the W.M. Keck Foundation, the David and Lucile Packard Foundation and the UCSF Program for Breakthrough Biomedical Research. Fischbach is on the scientific advisory boards of NGM Biopharmaceuticals and Warp Drive Bio.

How bacteria battle fluoride

He's not a dentist, but Christopher Miller is focused on fluoride. Two studies from his Brandeis University lab provide new insights into the mechanisms that allow bacteria to resist fluoride toxicity, information that could eventually help inform new strategies for treating harmful bacterial diseases. The studies appear in The Journal of General Physiology (JGP).

Although most animal cells are protected from direct exposure to fluoride, this toxic element is a serious threat to single-celled organisms like bacteria and yeast. As a result, their plasma membranes carry two different types of proteins to help rid the cell of unwanted fluoride: fluoride/hydrogen antiporters use energy to actively pump fluoride "uphill" out of the cell; and fluoride-specific "Fluc" ion channels mediate the passive "downhill" movement of fluoride across the cell membrane.

Fluc channels were first identified by Miller and colleagues very recently, in 2013. In the September issue of JGP, they now provide the first quantitative data demonstrating how these passive channels can help protect bacteria from fluoride. The authors found that fluoride accumulates in E. coli lacking Fluc when the external environment is acidic. In such acidic environments, fluoride enters the cell in the form of HF (hydrofluoric acid) -- which easily permeates the membrane -- and breaks down in the cell's lower acidity; Fluc provides a means of escape for the highly charged fluoride ions. They also found that bacteria proliferation was stalled by high fluoride exposure, indicating that targeting Fluc channels with antibiotics could be an effective way to slow bacterial growth.

In the August issue of JGP, Miller and colleagues unearthed new information about fluoride/hydrogen antiporters -- also recently discovered -- which are part of the CLC superfamily of proteins that are known for exporting chloride. The authors explored why this subset demonstrates higher selectivity for fluoride -- which is essential for their function because chloride is so much more abundant in the environment -- and were able to determine key structural differences that could account for the preferential selectivity of fluoride.

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The above story is based on materials provided by The Rockefeller University Press . Note: Materials may be edited for content and length.

Overstock.com Becomes First Major Retailer to Accept Bitcoin Worldwide


Ariel Zambelich/WIRED. Coin design: Gail Anderson + Joe Newton

Overstock.com was the first major online retailer to embrace bitcoin, accepting payments in the digital currency here in the U.S. beginning in early January. And now, it’s the first to accommodate bitcoin across the globe.

Early this morning, the Salt Lake City-based company started accepting bitcoin payments in all foreign countries. Anyone anywhere can now use the digital currency to purchase anything offered by Overstock, from phone accessories to lawn furniture—though there are certain countries where the company doesn’t ship purchases. “As long as you can get on the internet, you can order and pay in bitcoin,” says Overstock founder and CEO Patrick Byrne. “You can order in North Korea if you want—as long as you’re having things delivered to, say, Singapore.”

Online retailers Newegg and TigerDirect already accept bitcoin in both the U.S. and Canada, and smaller operations use bitcoin for international transactions, but Overstock, a company with $1.3 billion in annual sales, is stretching the reach of the digital currency still farther. Many questions hover over the future of bitcoin, a new type of money overseen by software running on across a vast network of machines. It’s still unclear how the governments of the world will regulate use of the currency. But it continues to evolve.

Today, even bitcoin’s biggest supporters tend to hoard their bitcoin rather than spend them, seeing the digital currency, whose price is volatile, as more of an investment than anything else. But with Overstock expanding globally—and companies such as Dell considering similar arrangements—it’s getting easier to actually pay for stuff with bitcoin. “This seems to be great news,” says Roger Ver, one of bitcoin’s biggest supporters, whose computer-parts site, Memory Dealers, has accepted the digital currency for years.

The Byrne Crusade

Overstock’s move into the world of bitcoin is driven by Byrne. A libertarian with a PhD in philosophy, Byrne, like many others, sees bitcoin as a way to free our money system from the sometimes onerous and expensive control of big banks and big government. He recently vowed to take 4 percent of all Overstock bitcoin sales and donate it to non-profits working to further the cause of the digital currency, and he’s exploring ways the technology behind bitcoin could be used to issue stock in his company—without the help of traditional stock exchanges like the NASDAQ or the NYSE.

“We swim in assumptions about how things should work, and we don’t understand the assumptions,” Byrne says, in his typically highfalutin way. “We don’t understand the functions of governments, our legal and financial institutions. We don’t need them. We can use internet.”


Patrick Byrne. Overstock.com, Inc

Bitcoin is already an international technology. Part of the attraction has always been that the open source bitcoin network lets anyone transfer money across borders without paying hefty fees to traditional operations like Western Union. But in order to achieve mainstream acceptance, it must spread to a new breed of online service—easy-to-use services run by trusted businesses, as opposed to rather amateur operations run by the likes of the bankrupt bitcoin exchange Mt. Gox. Overstock’s move into bitcoin is a step along this road, and other notable businesses are helping to legitimize the digital currency in other ways.

As Overstock began accepting international payments in bitcoin, Coinbase—the San Francisco-based startup whose technology drives these payments for Byrne and company—expanded its operation into 13 countries in Europe, and this could spark greater bitcoin adoption among merchants based there. Backed by $25 million in funding from big-name Silicon Valley venture capital firm Andressen Horowitz, Coinbase already drives bitcoin payments for eight American retailers that boast over a billion dollars a year in sales. Another notable bitcoin payments processor, BitPay, is offering its own services in Europe, and according to Moe Levin, the company’s director of European business development, about 200 new merchants are adopting the company’s service each week, compared to 200 a month as of April.

At the sane time, Coinbase is now offering Europe a consumer service that lets individuals easily send, receive, and store their bitcoin. This can help drive bitcoin purchases from the other side of the equation, and as Coinbase founder and CEO Brian Armstrong points, that’s just as important to the evolution of the currency.

The Bottom Line

Bitcoin can potentially help consumers more easily and more cheaply store and spend money, but it can also provide a shot in the arm for merchants like Overstock. As Byrne points out, accepting credit card payments—particularly from foreign countries—is rather expensive, due to steep fees from third-party processors. “International credit cards are a real mess,” Byrne says. “If you’re taking cards from a place like Russia, there is a monster surcharge tacked on because so much credit card fraud comes from there.” Overstock still pays Coinbase to handle these transactions, but according to Byrne, these fees are significantly lower.

Bitcoin payments have accounted for about one quarter of one percent of Overstock’s sales since January, or between $12,000 and $15,000 a day. Byrne calls this “a little bit more than I expected,” and he believes that with the company opening up bitcoin payments worldwide, the digital currency could drive a total of $8 million in sales by the end of the year. That’s not exactly a huge portion of the company’s revenues, but Byrne also believes bitcoin can become a way to expand the reach of his site. “We’ve never had a strong international business,” Byrne says, “and this is a good first step towards building one.”

The rub is that government regulations—or just the threat of government regulations—could stunt the growth of bitcoin. Although the open source bitcoin system operates outside the control of governments and banks, some governments are working to strictly regulate the digital currency in their jurisdictions. New York state recently proposed the creation of a bitcoin license for businesses that would require them to report enormous amounts of information if operating in the state, and many believe this will prove too onerous for companies looking to deal in the digital currency. But Byrne is among those who believe regulators will find a way to accommodate the greater bitcoin movement. “Bitcoin has already become too big to fail,” he says. “This is not a genie they can put back into the bottle.”

Uber’s Revenue Is 12 Times The Size of Lyft’s, New Study Says



The bitter battle between Uber and Lyft isn’t exactly a close fight.

According to new research that draws on credit and debit card transactions by 3.8 million Americans, Uber’s revenue was about 12 times that of its rival between May 2013 and May 2014. Across the U.S., it provided more than seven times the number of car rides, the report indicates, and it charged much higher rates for its service: $21 per ride on average, compared to Lyft’s $13.

Headquartered not far from each other in San Francisco, the two startups provide practically identical services that seek to change the way people get from place to place. Each lets you hail a car—and pay for the ride—via a smartphone app. That means the two are fighting for drivers as well as riders, and as they tussle in major American cities, they’ve clashed in sometimes spectacular ways, with Lyft accusing Uber of using underhanded tactics to snatch its drivers and news stories indicating that these were far more than just accusations.

But judging from investments in these two companies—Uber is valued at about $17 billion, Lyft at $700 million—it seemed that Uber was running the more successful business, and this new study provides a window into just how big the gap has become.

The study arrives from FutureAdvisor, a San Francisco outfit that offers software for automating the management of your stock portfolio. But in this case, the company is exploring two companies on the verge of going public, using data from an unnamed outfit that pools information from major American banks.

James McQuivey, an analyst with the Massachusetts-based research firm Forrester, is hardly surprised that the study shows Uber out in front of Lyft. After all, he points out, Uber’s ride-hailing operation had a significant head start (Uber was founded in 2009, while Lyft, in its current incarnation, launched in 2012). But he says the size of the revenue gap, as indicated by the new study, could help show why Lyft is so intent on waging a war with Uber in the media. “Lyft is trying to associate itself with Uber,” he says, “trying to punch above its weight.”

The FutureAdvisor study also indicates that Uber is acquiring new riders at a must faster clip than its rival, adding between 6,200 and 7,300 per month during 2014, compared to between 1,100 and 1,500 added by Lyft. But according to Casson Stallings, the data scientist that ran the study, both companies are growing at a significant rate relative to their size: roughly 10 percent a month. “Outside Silicon Valley,” he says, “companies would be jumping up and down over that.”

That said, as they’ve spread across various U.S. markets, Stallings says, the relative growth of both companies has slowed. In June of last year, each was growing at a rate of 25 percent per month. That could indicate why the companies are now fighting so fiercely over each other’s drivers—and why Uber is so intent on expanding overseas.

Some reports have indicated that Lyft is looking to be acquired by Uber. But just this week, Uber CEO Travis Kalanick said his company has no interest in such a move. “We’re not in acquisition mode,” he said.

Chatbots are boring. They aren’t AI. [Pharyngula]

You know I’m a bit sour on the whole artificial intelligence thing. It’s not that I think natural intelligences are anything more than natural constructions, or that I think building a machine that thinks is impossible — it’s that most of the stories from AI researchers sound like jokes. Jon Ronson takes a tour of the state of the art in chatbots, which is entertaining and revealing.

Chatbots are kind of the lowest of the low, the over-hyped fruit decaying at the base of the tree. They aren’t even particularly interesting. What you’ve got is basically a program that tries to parse spoken language, and then picks lines from a script that sort of correspond to whatever the interlocutor is talking about. There is no inner dialog in the machine, no ‘thinking’, just regurgitations of scripted output in response to the provocation of language input.

It’s most obvious when these chatbots hit the wall of something that they couldn’t interpret — all of a sudden you get a flurry of excuses. An abrupt change of subject, ‘I’m just a 15 year old boy’, ‘sorry, I missed that, I was daydreaming’, all lies, all more revealing of the literary skills of the programmer (usually pretty low), and not at all the product of the machine trying to model the world around it.

Which would be OK if the investigators recognized that they were just spawning more bastard children of Eliza, but no…some of their rationalizations are delusional.

David Hanson is a believer in the tipping-point theory of robot consciousness. Right now, he says, Zeno is "still a long way from human-level intellect, like one to two decades away, at a crude guess. He learns in ways crudely analogous to a child. He maps new facts into a dense network of associations and then treats these as theories that are strengthened or weakened by experience." Hanson’s plan, he says, is to keep piling more and more information into Zeno until, hopefully, "he may awaken—gaining autonomous, creative, self-reinventing consciousness. At this point, the intelligence will light ‘on fire.’ He may start to evolve spontaneously and unpredictably, producing surprising results, totally self-determined…. We keep tinkering in the quest for the right software formula to light that fire."

Aargh, no. Programming in associations is not how consciousness is going to arise. What you need to work on is a general mechanism for making associations and rules. The model has to be something like a baby. Have you noticed that babies do not immediately start parroting their parents’ speech and reciting grammatically correct sentences? They flail about, they’re surprised when they bump some object and it moves, they notice that suckling makes their tummy full, and they begin to construct mental models about how the world works. I’ll be impressed when an AI is given no pre-programmed knowledge of language at all, and begins with baby-talk babbling and progresses over months or years to construct its own competence in comprehending speech.

Then maybe I’ll believe this speculation about an emergent consciousness. Minds aren’t going to be produced by a sufficiently large info dump, but by developing general heuristics for interpreting complex information.

The Many Natural Wonders of the American Backyard, Captured by iPhone

Photographers often feel the need to run off to exotic locations to make pictures. But there are great photos to be made in your own backyard. Joshua White has proven that over and over again in recent years with his ongoing project, A Photographic Survey of the American Yard.

White has spent the past two years using his Apple iPhone to shoot found objects like leaves and bugs he’s picked up in his yard or neighborhood. It sounds overly simple and quite boring, but the results are beautiful.

“One day I was walking around my yard in Lancaster, Pennsylvania, where I used to live, and saw one of those tree helicopters and it caught my attention so I laid it on a purple garbage can and photographed it,” says White, 32, who now lives in West Jefferson, North Carolina and teaches photography at Appalachian State University in Boone. “That’s how it all got started.”

His process is simple. Nowadays he uses a piece of white foam core instead of a trashcan as his background, which he places in shade. He sticks whatever he’s shooting on a knitting needle to elevate it and eliminate shadows. Most photos are taken with his normal iPhone lens, but he’ll use a Photojojo Macro Lens if he needs to zoom in.

Once the image is shot, White opens it in iPhoto on his iPhone, crops as needed and makes the background pure white. Then he exports to Snapseed, where he coverts the image to black and white, then sharpens and tweaks the exposure. From there it’s back to iPhoto to double-check that the background is still pure white. The last step is uploading the pic to Instagram, where he applies the Earlybird filter.

“Sometimes I question my choice about Earlybird, but I’m 500 pictures in so it’s too late to change now,” he says.

Almost everything White shoots is dead. Although he’s willing to kill a fly for a photo, he draws the line at higher life forms like a frog, which he shot live. “I just kept picking up the frog and setting it back and taking a picture,” he says.

Besides their aesthetic appeal, White likes the photos because they’ve helped him rediscover the sense of wonder we all have as children. He says he grew up fascinated by bugs and nature and likes that he’s stopped to appreciate these things again. “I try not to be corny,” he says. “And nostalgia is a bad word, I don’t want my work to be nostalgic. But I don’t have any problem with the idea that when you were a little kid this stuff was awesome and it still is.”