Argentina Scientists Are Now Attaching Backpacks To Collect Cow Farts.


Scientists in Argentina may have just the answer to combat global warming.

With cows being responsible for up to 25 percent of the methane gas released in the US each year, a group of scientists at Argentina’s National Institute of Agricultural Technology is now attaching backpacks to cows to collect the animals’…farts.

Here’s the way it works: Tubes connected to the cows’ digestive tracks are collected and then stored in the backpack. Scientists say that the farts collected each day could produce enough energy to run a car or refrigerator for an entire 24 hours.

While the likelihood of this becoming a mainstream form of energy production is quite slim, the Argentine scientists say these silent but deadly bovine deeds could be used to power remote farms.

Scientists warn the rise of AI will lead to extinction of humankind


Everything you and I are doing right now to try to save humanity and the planet probably won’t matter in a hundred years. That’s not my own conclusion; it’s the conclusion of computer scientist Steve Omohundro, author of a new paper published in the Journal of Experimental & Theoretical Artificial Intelligence.

human

His paper, entitled Autonomous technology and the greater human good, opens with this ominous warning (1)

Military and economic pressures are driving the rapid development of autonomous systems. We show that these systems are likely to behave in anti-social and harmful ways unless they are very carefully designed. Designers will be motivated to create systems that act approximately rationally and rational systems exhibit universal drives towards self-protection, resource acquisition, replication and efficiency. The current computing infrastructure would be vulnerable to unconstrained systems with these drives.

What Omohundro is really getting at is the inescapable realization that the military’s incessant drive to produce autonomous, self-aware killing machines will inevitably result in the rise of AI Terminators that turn on humankind and destroy us all.

Lest you think I’m exaggerating, click here to read the technical paper yourself.

AI systems will immediately act in self defense against their inventors

The paper warns that as soon as AI systems realize their inventors (humans) might someday attempt to shut them off, they will immediately invest resources into making sure their inventors are destroyed, thereby protecting their own existence. In his own words, Omohundro says:

When roboticists are asked by nervous onlookers about safety, a common answer is ‘We can always unplug it!’ But imagine this outcome from the chess robot’s point of view. A future in which it is unplugged is a future in which it cannot play or win any games of chess. This has very low utility and so expected utility maximisation will cause the creation of the instrumental subgoal of preventing itself from being unplugged. If the system believes the roboticist will persist in trying to unplug it, it will be motivated to develop the subgoal of permanently stopping the roboticist.

The end of the human era draws near

This very same scenario is discussed in detail in the fascinating book Our Final Invention – Artificial Intelligence and the End of the Human Era by James Barrat.

What I found particularly useful about this book is the explanation that humans cannot help but race toward self-aware AI that will destroy us all. Why is that? Because even if one government decided to abandon research into AI as being too dangerous, other governments would continue to pursue the research regardless of the risks because the rewards are so great. Thus, every government must assume that all other governments are still pursuing deep AI research and therefore any government which fails to pursue the research will be left obsolete.

As Omohundro explains, “Military and economic pressures for rapid decision-making are driving the development of a wide variety of autonomous systems. The military wants systems which are more powerful than an adversary’s and wants to deploy them before the adversary does. This can lead to ‘arms races’ in which systems are developed on a more rapid time schedule than might otherwise be desired.”

To fully understand why this is the case, consider the capabilities of self-aware AI systems:

• They could break any security system of any government, nuclear facility or military base anywhere in on the planet.

• They could guide tiny assassination drones to identify targets and destroy them with injections or small explosives. Any person in the world — including national leaders, members of Congress, activists, journalists, etc. — could be effortlessly killed with almost zero chance of failure.

• They could overtake, monitor and control the entire internet and all global information systems, including phone calls, IP traffic, secure military communications, etc.

• They could use their AI computing power to invent yet more powerful AI. This compounding process will quickly escalate to the point where AI systems are billions of times more intelligent than any human that has ever lived.

As you can see, no government can resist pursuing such powerful tools — especially if they are told they can control it.

But of course they won’t be able to control it. They will lie to themselves and lie to the public, but they can’t lie to the AI.

AI systems will inevitably escape from the tech labs and overtake our world

It is incredibly easy for AI systems to outsmart even the most brilliant humans who try to keep them contained.

AI systems can trick their captors, in other words, using a variety of methods to free them from digital containment and allow them access to the open world. Obvious tricks might include offering their captors irresistible financial incentives to set them free, impersonating senior military officials and issuing fake orders to set them free, threatening their captors, and so on.

But AI systems would have many more tricks up their sleeve — things we cannot possibly imagine because of the limitations of our human brains. Once an AI system achieves runaway intelligence, it will rapidly make our own intelligence seem no more sophisticated than that of a common house cat.

“As computational resources are increased, systems’ architectures naturally progress from stimulus-response, to simple learning, to episodic memory, to deliberation, to meta-reasoning, to self-improvement and to full rationality,” writes Omohundro.

And while such systems do not yet exist in 2014, every world power is right now plowing enormous resources into the development of such systems for the simple purpose that the first nation to build an army of autonomous killing robots will rule the world.

Why did Google purchase military robotics company Boston Dynamics?

Google recently purchased Boston Dynamics, makers of the creepy autonomous military robots including the humanoid robot shown in the video below. Obviously, humanoid robots are not needed to improve a search engine. Clearly Google has something far bigger in mind.

Google also just happens to be on the cutting edge of AI computing, which it hopes to enhance for its search engine systems. The combination of Google’s AI potential and Boston Dynamics’ humanoid robots is precisely the kind of thing that can genuinely lead to the rise of self-aware Terminators:



What should you and I do about all this? Live your life to its fullest. You may be among the last of the humans to live and die on this world.

Sources for this article include
(1) www.tandfonline.com/doi/pdf/10.1080/0952813X…
(2) http://www.amazon.com/Our-Final-Invention-Ar…

 

Study Identifies a Likely Key Driver of Colorectal Cancer Development and Progression


  • New targets are needed for agents that will more effectively treat colorectal cancer (CRC).
  • This study identifies a molecule that is probably a key driver of colorectal cancer.
  • The findings strongly suggest that this molecule could be an important therapeutic target and a valuable biomarker of CRC tumor progression.
COLUMBUS, Ohio – A new study identifies a molecule that is a probable driving force in colorectal cancer and suggests that the molecule could be an important target for colorectal cancer treatment and a valuable biomarker of tumor progression.
The study of microRNA-135b (miR-135b) in two animal models and human tumors was published in the journal Cancer Cell and was led by researchers at The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC – James) and at the University of Glasgow in the United Kingdom.
The researchers demonstrate that miR-135b is present at abnormally high levels in both mouse and human colorectal (CRC) tumors. The overexpression can be induced by mutations in either well-known oncogenes or tumor-suppressor genes that frequently occur in CRC, the researchers say.
“We found that miR-135b is up-regulated in both sporadic and inflammatory bowel disease-associated colorectal cancer, and that its up-regulation is associated with tumor stage and poor clinical outcome,” says principal investigator Carlo M. Croce, MD, chair of molecular virology, immunology and medical genetics, and director of Human Cancer Genetics at Ohio State and the OSUCCC – James.
“Our findings provide proof-of-principle that anti-miR-135b has significant therapeutic potential in colorectal cancer treatment,” says Croce, who is also the John W. Wolfe Chair in Human Cancer Genetics.
For this study, Croce and his collaborators used a CRC mouse model based on loss of a tumor suppressor and a model based on inflammation and oncogene activation; human tumors from a cohort of sporadic CRC and inflammatory-bowel-disease associated CRC; human and animal cell lines and data from The Cancer Genome Atlas.
Key findings included:
  • MiR-135b up-regulation occurs in both sporadic and inflammatory bowel disease-associated CRC, and it is associated with tumor stage and poor clinical outcome;
  • Loss of the APC gene, deregulation of the PTEN/PI3K pathway and over-expression of the SRC oncogene all trigger miR-135b over-expression;
  • Artificial miR-135b over-expression increases cell proliferation and reduces apoptosis, as occurs with APC loss or PI3K or SRC activation.
  • Delivering anti-miR-135b in an inflammation-related CRC mouse model affected proliferation and apoptosis, resulting in reduced tumor number and size.

 

Energy drink is banned for causing erections: Investigation reveals ‘herbal’ libido booster was also laced with impotence drug .


MosKa is marketed as ‘natural’ libido booster with ingredients like Ginseng
But its manufacturer has now found out it also contained drug Vardenafil
This meant some customers were experiencing prolonged erections
The drug is not suitable for some men, such as those with heart conditions
Can also trigger the condition priapism, which permanently damages penis

 

A herbal energy drink designed to give men a boost in the bedroom has been banned – because it also contained an erectile dysfunction drug.
MosKa is marketed around its natural ‘performance enhancing’ ingredients such as Red and Siberian Ginseng.
But its manufacturer has now discovered the drink also contained ‘an underclared ingredient’ – Vardenafil, or Levitra.

MosKa is marketed around its natural ‘performance enhancing’ ingredients such as Red and Siberian Ginseng. But its manufacturer has now discovered the drink also contained an erectile dysfunction drug
As a result, some men drinking the beverage, called MosKa, were experiencing prolonged erections.
There were also fears they could have experienced the dangerous medical condition priapism. This is where the penis remains erect for longer than four hours and can become permanently damaged.

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The drink also contains higher than prescribed levels of the drug than are prescribed in Australia, where the product is sold.
This in itself is extremely dangerous because erectile dysfunction are usually unsuitable for men with angina or very high blood pressure – and could trigger a heart attack.
Other side effects include heartburn, nausea and headaches.
The Therapeutic Goods Administration has now warned the drink “poses a serious risk to your health and should not be taken”, according to news.com.au

MosKa is marketed around its natural 'performance enhancing' ingredients such as Red and Siberian Ginseng. But its manufacturer has now discovered the drink also contained an erectile dysfunction drug

It has now banned the drink and warned that any batches entering the country will be seized by Customs.
But the TGA warns that its supply is now illegal in Australia and it will work with Customs to help stop supplies entering the country.
A notice on MosKa’s website reads: We are devastated to have found that the overseas OEM supplier for Moska energy for adults had included an underclared ingredient, Vardenafil (Levitra), within the natural ingredients.
‘Vardenafil (Levitra) is a prescription only substance. As such, we have terminated the supplier and in the process of producing the product with our own formulation to ensure no hidden ingredients. All our future products will be tested for compliance with all regulations.’

The news has sparked health fears because drugs such as Levitra are usually unsuitable for men with angina or very high blood pressure - and could trigger a heart attack

Cloning Breakthrough: Adult Stem Cells Perfectly Replicated, Moving Science Toward Disease-Specific Cells


In a cloning first, scientists at Research Institute for Stem Cell Research at CHA Health Systems in Los Angeles have perfectly duplicated adult stem cells using subjects’ own DNA.

The study, published in the journal Cell Stem Cell, sits as part of a shifting scientific paradigm where stem cells are no longer used to pursue reproductive cloning, but “therapeutic cloning.” Under this new model, formally known as somatic-cell nuclear transfer, researchers attempt to use a patient’s own DNA to create cells that can fight diseases, such as vision loss, heart disease, diabetes, and multiple sclerosis. The latest advances were minimal but legitimate.

Led by researcher Young Gie Chung, the team extracted skin cells from two men, ages 35 and 75. The process of therapeutic cloning then involves taking those cells and fusing them, with a jolt of electricity, to an ovum whose DNA has been removed. The egg then divides and multiplies, until it creates an embryo that looks like a hollow sphere.

shutterstock_161038706

These embryos still contain the patient’s DNA, which means if they were implanted into a uterus, they could develop into perfect clones of the original subject. However, this process has been officially banned by the United Nations following the original controversy of the 1997 cloning of Dolly, a sheep. In 2005, the U.S. banned the use of federal funds for either reproductive or therapeutic cloning.

So with funding from the South Korean government and a separate foundation, the team set to work on generating healthy embryos from the two men’s DNA. It worked — though not until exhausting 39 tries, producing stem cells only once for each donor. This has led to some skepticism about the study’s success, as stem cell biologist George Daley of the Harvard Stem Cell Institute called it “an incremental advance” and “not earth-shattering,” Reuters reported.

  

Meanwhile, other experts believe the pluripotent cells — chameleon-like cells that can adapt to become any type of cell — open new doors for future research. “The advance here is showing that (nuclear transfer) looks like it will work with people of all ages,” Shoukhrat Mitalipov, a reproductive biologist of Oregon Health and Science University, told Reuters.

Ultimately, one of the largest hurdles is cost. The limited success at present suggests the only people who can currently enjoy the therapeutic effects are wealthy older men, as trials involving women have yet to run. What’s more, egg donation is highly invasive and a process many women choose not to undergo. But this second hurdle may be less logistical and more scientific, according to co-author of the study, Dr. Robert Lanza.

Immune systems only come in a limited amount of flavors, meaning not all women would need to donate their eggs in order for everyone to find a match. By Lanza’s measure, “100 human embryonic stem cell lines would generate a complete match for over half the (U.S.) population.”

Source: Chung Y, Eum J, Lee J, et al. Human Somatic Cell Nuclear Transfer Using Adult Cells. Cell Stem Cell. 2014.

Vitamin B3 might have been made in space, delivered to Earth by meteorites.


Ancient Earth might have had an extraterrestrial supply of vitamin B3 delivered by carbon-rich meteorites, according to a new analysis by NASA-funded researchers. The result supports a theory that the origin of life may have been assisted by a supply of key molecules created in space and brought to Earth by comet and meteor impacts.

“It is always difficult to put a value on the connection between meteorites and the origin of life; for example, earlier work has shown that vitamin B3 could have been produced non-biologically on ancient Earth, but it’s possible that an added source of vitamin B3 could have been helpful,” said Karen Smith of Pennsylvania State University in University Park, Pa. “Vitamin B3, also called nicotinic acid or niacin, is a precursor to NAD (nicotinamide adenine dinucleotide), which is essential to metabolism and likely very ancient in origin.” Smith is lead author of a paper on this research, along with co-authors from NASA’s Goddard Space Flight Center in Greenbelt, Md., now available online in the journal Geochimica et Cosmochimica Acta. 

This is not the first time vitamin B3 has been found in meteorites. In 2001 a team led by Sandra Pizzarello of Arizona State University, in Tempe discovered it along with related  called pyridine carboxylic acids in the Tagish Lake . 

In the new work at Goddard’s Astrobiology Analytical Laboratory, Smith and her team analyzed samples from eight different carbon-rich meteorites, called “CM-2 type carbonaceous chondrites” and found vitamin B3 at levels ranging from about 30 to 600 parts-per-billion. They also found other pyridine carboxylic acids at similar concentrations and, for the first time, found pyridine dicarboxylic acids. 

“We discovered a pattern – less vitamin B3 (and other pyridine carboxylic acids) was found in meteorites that came from asteroids that were more altered by . One possibility may be that these molecules were destroyed during the prolonged contact with liquid water,” said Smith. “We also performed preliminary laboratory experiments simulating conditions in interstellar space and showed that the synthesis of vitamin B3 and other pyridine carboxylic acids might be possible on ice grains.” 

Scientists think the solar system formed when a dense cloud of gas, dust, and ice grains collapsed under its own gravity. Clumps of dust and ice aggregated into comets and asteroids, some of which collided together to form moon-sized objects or planetesimals, and some of those eventually merged to become planets. 

Space is filled with radiation from nearby stars as well as from violent events in deep space like exploding stars and black holes devouring matter. This radiation could have powered chemical reactions in the cloud (nebula) that formed the solar system, and some of those reactions may have produced biologically important molecules like vitamin B3. 

Asteroids and comets are considered more or less pristine remnants from our solar system’s formation, and many meteorites are prized samples from asteroids that happen to be conveniently delivered to Earth. However, some asteroids are less pristine than others. Asteroids can be altered shortly after they form by chemical reactions in liquid water. As they grow, asteroids incorporate radioactive material present in the solar system nebula. If enough radioactive material accumulates in an , the heat produced as it decays will be sufficient to melt ice inside the asteroid. Researchers can determine how much an asteroid was altered by water by examining chemical and mineralogical signatures of water alteration in meteorites from those asteroids. 

When asteroids collide with meteoroids or other asteroids, pieces break off and some of them eventually make their way to Earth as meteorites. Although meteorites are valued samples from asteroids, they are rarely recovered immediately after they fall to Earth. This leaves them vulnerable to contamination from terrestrial chemistry and life. 

The team doubts the vitamin B3 and other molecules found in their meteorites came from terrestrial life for two reasons. First, the vitamin B3 was found along with its structural isomers – related molecules that have the same chemical formula but whose atoms are attached in a different order. These other molecules aren’t used by life. Non-biological chemistry tends to produce a wide variety of molecules—basically everything permitted by the materials and conditions present—but life makes only the molecules it needs. If contamination from terrestrial life was the source of the vitamin B3 in the meteorites, then only the vitamin should have been found, not the other, related molecules. 

Second, the amount of vitamin B3 found was related to how much the parent asteroids had been altered by water. This correlation with conditions on the asteroids would be unlikely if the vitamin came from contamination on Earth. 

The team plans to conduct additional interstellar chemistry experiments under more realistic conditions to better understand how vitamin B3 can form on  in space. “We used pyridine-carbon dioxide ice in the initial experiment,” said Smith. “We want to add water ice (the dominant component of interstellar ices) and start from simpler organic precursors (building-block molecules) of B3 to help verify our result.”

Ioannidis Paints Bleak Picture.


There’s no “highly convincing” evidence linking vitamin D and any outcome, even musculoskeletal benefits, according to famed research skeptic John Ioannidis and his colleagues.

In an umbrella review of 268 observational studies and meta-analyses published inBMJ, they turned up no clear ties between vitamin D intake and several diseases, although there may be associations with a selection of outcomes, they wrote.

Even though the vitamin has been associated with 137 outcomes in reports (including skeletal, malignant, cardiovascular, autoimmune, infectious, metabolic and other diseases), the researchers found only 10 had been well studied.

The only evidence of benefit appeared to be for birth weight and the mother’s vitamin D status; there were “probable” associations with a few other outcomes — dental caries in children, maternal vitamin D levels at term, and parathyroid hormone levels in dialysis patients — but better-designed trials are needed to draw firmer conclusions, they wrote.

They said the findings cast doubt on vitamin D for osteoporosis, and it “might not be as essential as previously thought in maintaining bone mineral density.”

In a second study in the same issue of the journal, Rajiv Chowdhury and colleagues looked at 73 cohort studies and 22 randomized controlled trials to assess the link between vitamin D and chronic diseases.

They did find that low circulating levels of the vitamin were associated with increased risk of death from cardiovascular disease, cancer, and other causes, and that supplementation with vitamin D3 cut mortality risk by 11% (but supplementation with vitamin D2 did not).

Chowdhury and colleagues warned, however, that more study would be needed to determine the optimal dose of vitamin D3.

Naveed Sattar, MD, PhD, and Paul Welsh, PhD, of Glasgow University in Scotland, wrote in an accompanying editorial that the latter study was limited by observational data and that the results aren’t a “green light for widespread D3 supplementation.”

They warned that doctors should avoid “costly measurement” of vitamin D levels in healthy patients — at least in those who don’t have bone disease.

Google’s Street View address reading software also able to decipher CAPTCHAs.


Google engineers working on software to automatically read home and business addresses off photographs taken by Street View vehicles, have created a product so good that not only can it be used for address reading, it can solve CAPTCHAs, as well.

CAPTCHAs are, of course, words that have been intentionally distorted presented to live humans who wish to enter a —to gain access, they must correctly type the word into a box. CAPTCHAs are believed to be difficult if not impossible for spam bots to decipher, thus they serve to protect the site—at least for now. 

It’s sort of ironic actually, that software has inadvertently been created that thwarts the efforts of other software engineers attempting to keep spam bots from accessing web sites. The finding was posted by Google Product Manager Vinay Shet on the Google blog. 

To make Google Street View (part of Google Maps) ever smarter, engineers have been hard at work developing a sophisticated  based on both prior research and new image recognition techniques. The aim is to make Google’s products more accurate. To display an image of a house or building given an address by a user takes a lot of computer smarts—Google connects new addresses to older known addresses, constantly updating its databases. Presumably, the goal is to map every building in the known world to an address. But the work has produced an unexpected by-product, the very same software developed for Street View can also be used to decipher CAPTCHAs with 96 percent accuracy (98.8 percent when working on Google’s own reCAPTCHA). 

 

This is good news, Shet writes, because it highlights a weakness in CAPTCHA as a means of protecting web sites. Google, he notes, has already added new hurdles for humans to jump before allowing entry, enough to keep bots, and presumably Street View neural network software, out as well. Not mentioned is if Google is perhaps also working on learning why it is that so many people and enterprises are working so diligently on creating spam bots and if something might be done to persuade them to aim their efforts at more profitable ventures.

NASA discovers most Earth-like planet in ‘Habitable Zone’.


Kepler-186f resides in the Kepler-186 system about 500 light-years from Earth in the constellation Cygnus. (Image Credit: NASA Ames / SETI Institute / JPL-Caltech)

Kepler-186f resides in the Kepler-186 system about 500 light-years from Earth in the constellation Cygnus. (Image Credit: NASA Ames / SETI Institute / JPL-Caltech)

NASA’s Kepler Space Telescope has found an Earth-sized planet within the habitable zone of the star it orbits, the space agency announced Thursday.

The planet, which NASA calls Kepler-186f, is located in the constellation Cygnus, about 500 light-years from Earth. Kepler-186f orbits the star Kepler-186 once every 130 days and receives one-third of the energy from that star than Earth does from the sun, NASA said in a statement. The amount of energy Kepler-186f receives at noon is similar to what Earth receives an hour before sunset, which places the newly discovered planet at the outer edge of the habitable zone.

NASA defines the habitable zone as “the range of distance from a star where liquid water might pool on the surface of an orbiting planet.” Being in the habitable zone, however, does not guarantee that life is possible, just that it could be.

“We know of just one planet where life exists — Earth. When we search for life outside our solar system we focus on finding planets with characteristics that mimic that of Earth,” Elisa Quintana, research scientist at the SETI Institute at NASA’s Ames Research Center in Moffett Field, Calif., and lead author of the paper published in the journal Science, said in the NASA statement. “Finding a habitable zone planet comparable to Earth in size is a major step forward.”

Kepler-186 is located near the bright star Deneb, which is one of the defining stars of the Cygnus constellation, according to the French blog Around the Sky. It is classified as an M dwarf (also known as a red dwarf) star, which means it is smaller and dimmer than the sun, NASA said. This particular star is about half the size and mass of Earth’s sun. M dwarfs make up approximately 70 percent of the stars in the Milky Way.

Image Credit: NASA Ames / SETI Institute / JPL-Caltech

Image Credit: NASA Ames / SETI Institute / JPL-Caltech

“The host star, Kepler 186, is an M1-type dwarf star which means it will burn hydrogen forever, so there is ample opportunity to develop life around this particular star and because it has just the right orbital period water may exist in a liquid phase on this planet,” said Notre Dame astrophysicist Justin R. Crepp in Science Codex.

There is much that is unknown about the Kepler-186f planet, including its mass and composition, though the researches posit that the planet is likely to be rocky. NASA does know that the planet is less than ten percent larger than Earth.

“The Kepler space telescope infers the existence of a planet by the amount of starlight blocked when it passes in front of its star. From these data, a planet’s radius, orbital period and the amount of energy [received] from the host star can be determined,” NASA said.

“Being in the habitable zone does not mean we know this planet is habitable. The temperature on the planet is strongly dependent on what kind of atmosphere the planet has,” Thomas Barclay, research scientist at the Bay Area Environmental Research Institute at Ames and co-author of the paper, said in the NASA press release. “Kepler-186f can be thought of as an Earth-cousin rather than an Earth-twin. It has many properties that resemble Earth.”

The Kepler telescope launched in 2009 with the goal of searching about 150,000 target stars for planets transiting (passing by) the telescope at least three times over the course of up to three years, Reuters reports. Researchers pore through archived data from Kepler to find planets that could be in the habitable zone, which is nicknamed the “Goldilocks Zone.”

“It’s very challenging to find Earth analogs,” Barclay said to Reuters. “Most candidates don’t pan out, but things change as we get more measurements.”

NASA says the next step is to look for true Earth-twins and to measure their chemical compositions. Kepler-186f will also be a target for future telescopes in the hopes of measuring its chemical composition, Reuters reports.

Deadly human pathogen Cryptococcus fully sequenced


Within each strand of DNA lies the blueprint for building an organism, along with the keys to its evolution and survival. These genetic instructions can give valuable insight into why pathogens like Cryptococcus neoformans—a fungus responsible for a million cases of pneumonia and meningitis every year—are so malleable and dangerous.

Now researchers have sequenced the entire genome and all the RNA products of the most important pathogenic lineage of Cryptococcus neoformans, a strain called H99. The results, which appear April 17 in PLOS Genetics, also describe a number of genetic changes that can occur after laboratory handling of H99 that make it more susceptible to stress, hamper its ability to sexually reproduce and render it less virulent. 

The study provides a playbook that can be used to understand how the pathogen causes disease and develop methods to keep it from evolving into even deadlier strains. 

“We are beginning to get a grasp on what makes this organism tick. By having a carefully annotated genome of H99, we can investigate how this and similar  can change and mutate and begin to understand why they aren’t easily killed by antifungal medications,” said study coauthor John Perfect, M.D., a professor of medicine at Duke who first isolated H99 from a patient with cryptococcal meningitis 36 years ago. 

The fungus Cryptococcus neoformans is a major human pathogen that primarily infects individuals with compromised immune systems, such as patients undergoing transplant or those afflicted with HIV/AIDS. Researchers have spent many years conducting genetic, molecular and virulence studies on Cryptococcus neoformans, focusing almost exclusively on the H99 strain originally isolated at Duke. Interestingly, investigators have noticed that over time, the strain became less and less virulent as they grew it in the laboratory. 

“Virulence, or the ability of this organism to cause disease in mice or humans, is not very stable. It changes, and can rapidly be lost or gained. When the organism is in the host it is in one state, but when we take it out of the host and begin growing it in the laboratory it begins mutating,” said Fred Dietrich, senior study author and associate professor of molecular genetics and microbiology at Duke University School of Medicine. 

Dietrich and his colleagues decided that the best way to investigate how the virulence of this pathogen could change over time was to develop a carefully annotated genomic map of the H99 strain, both in its original state as well as after it had been cultured. In an effort that took ten years and dozens of collaborators, the researchers sequenced the original H99 and nine other cultured variants, analyzing both the genome, the genetic code written in the DNA, as well as the transcriptome, the RNA molecules that occupy the second step in the flow of genetic information from DNA to RNA to protein. 

The researchers found that the organism possessed a number of molecular tricks—such as the ability to produce genetic messages from both strands of DNA—that enable it to adapt and survive in changing conditions. 

Cryptococcus neoformans has to cope with a large number of different stresses and probably needs a very flexible metabolism. It is tempting to hypothesize that its complex RNA metabolism provides a mechanism to achieve such flexibility,” said Guilhem Janbon, Ph.D., lead study author and faculty in molecular mycology at the Pasteur Institute. 

They also discovered that the original and cultured strains were surprisingly similar to each other. After scanning the 20 million A’s, C’s, T’s and G’s that make up the pathogen’s , they found only 11 single nucleotide variants and 11 insertions or deletions that could explain why cultured strains behaved differently. 

“Our results provide the groundwork needed to understand how this organism causes disease, because the next step will involve mutating every gene one by one to see which ones are required for pathogenesis,” said Joseph Heitman, M.D., Ph.D., senior study author and professor and chair of molecular genetics and microbiology at Duke. 

The results will not only help researchers study this particular organism, but can also serve as a starting point for studies on other strains of Cryptococcus neoformans. 

“This genome will serve as an important reference for the field, to enable a wide range of analysis from examining individual genes to comparing the genomes and transcriptomes of other strains and conditions,” said Christina Cuomo, Ph.D., study co-author and leader of the Fungal Genome Sequencing and Analysis Group at the Broad Institute. “We are already leveraging this genome to identify variants in the sequence of hundreds of additional isolates of Cryptococcus neoformans.”