New HIV Treatment Hope

Most T cells are not killed by the HIV virus itself, but by the body’s defense mechanism. Stopping this process could prevent a patient’s progression to AIDS.

The difference between HIV infection and full-blown AIDS is, in large part, the massive die-off of the immune system’s CD4 T-cells. But researchers have only observed the virus killing a small portion of those cells, leading to a longstanding question: What makes the other cells disappear? New research shows that the body is killing its own cells in a little-known process. What’s more, an existing, safe drug could interrupt that self-destruction, thereby offering a way to treat AIDS.

The destructive process has caught scientists by surprise. "We thought HIV infects a cell, sets up a virus production factory and then the cell dies as a consequence of being overwhelmed by virus. But there are not enough factories to explain the massive losses," says Warner Greene, director of virology and immunology at the Gladstone Institutes, whose team published two papers today in Science and Nature describing the work. (Scientific American is part of Nature Publishing Group.)

Greene suspects that researchers in the past failed to notice the process because they were looking in the wrong place. Instead of studying active CD4 T cells in the blood, his team examined spleen and tonsil tissue, where most cells are in a resting state. When HIV enters a resting cell, it transcribes its genes into DNA, but then hits a dead end: the cell's machinery isn't available to finish the replication process. This part of the story had been known for years, but Greene's team discovered that something very surprising happens next. "Instead of that being the end of the story, cells detect that DNA in their cytoplasm and launch an immune response against it, and that immune response results in the death of those cells."

The response is a self-destruct protocol called pyroptosis. In contrast to the better-known apoptosis, in which cells die quietly without triggering inflammation, pyroptosis is "not a bland, but a fiery death," Greene says. These cells spew inflammation-causing chemicals as they die, attracting more T-cells that can then become infected themselves by the newly freed HIV. "In a bacterial infection, recruiting all these cells might be a good strategy for containing the infection," Greene says, but with HIV a vicious cycle of infection results. Pyroptosis also explains why AIDS is associated with high levels of inflammation.

Experiments by Greene's team showed that blocking a key component of pyroptosis could stop the cell death entirely; they also identified the protein that senses viral DNA to kick off the process. After studying the pathway in cultured spleen and tonsil tissue, they had an opportunity to confirm the findings in a patient's freshly removed lymph node, stained for their target proteins and viewed under the microscope. It showed the traditional virus replication happening in cells at the center of the node and resting cells dying all around. To Greene, the sight was unbelievable: "We could see this pyroptotic pathway playing out like nobody's business. In this one snapshot, we could see what we had been working on for eight years."

There's good news though: Greene estimates 95 percent of the cells that die in HIV infections are killed through pyroptosis, so the findings raise hope for a new type of treatment that could prevent HIV from progressing into AIDS. "Inhibiting activation of the immune system is not a new concept, but this gives us a new pathway to target," says Robert Gallo, director of the Institute of Human Virology at the University of Maryland School of Medicine, who was not involved in the study. He warns that other pathways may be at work that are still unknown but that this one is promising if it truly accounts for the large percentage of T cell deaths.

And in fact, a drug already exists that can block pyroptosis. Known as VX-765, it was tested years ago by Vertex Pharmaceuticals as a treatment for chronic seizure disorder. A trial showed that it wasn't effective enough against seizures, but it was safe for humans. "Now it's just sitting on a shelf waiting for a disease to cure," says Greene, who is trying to arrange a phase II trial to test the drug in HIV patients."

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Uncontacted Tribes at risk

For the first time, extraordinary aerial footage of one of the world's last uncontacted tribes has been released. Survival's new film, narrated by Gillian Anderson, has launched our campaign to help protect the earth's most vulnerable peoples.

Find out more: http://www.uncontactedtribes.org

6 Terrifying Ways Crows Are Way Smarter Than You Think

#6. They Can Remember Your Face

      Next time you see a group of crows, look closely. Try to remember which one is which, and see if you can tell the difference between them the next time you pass. Odds are good that you can't; they're crows, which makes them all big black birds. On the other hand, every last one of them very likely remembers you as the weird human who kept staring at them. We know this, because researchers in Seattle performed an experiment with some crows around their college campus. They captured seven of the birds, tagged them, then let them go. And they did it all while wearing creepy skin masks, because it was funny:
      OK, so the scientists weren't just playing out horror movie fantasies -- they were testing whether the crows could recognize human faces or not. It turns out they can. To a frightening degree: Whenever the scientists walked around campus with the masks on, the crows would "scold" and dive-bomb them... because along with the ability to recognize us as individuals, the researchers also learned that crows can hold a grudge. And pretty soon, it wasn't just the first seven crows reacting. Other birds, ones that hadn't even been captured in the first place, started dive-bombing the scientists as well. In case you think they were just telling each other "get the guy with the mask," they weren't: The test was repeated with multiple people wearing multiple masks, and without fail, the crows left the masked men who hadn't messed with them alone, but went murder-crazy on the mask that had been worn while messing with them. Quick, in Point Break, which Presidential mask did Swayze wear? No idea? Don't worry, we're pretty sure Johnny Utah didn't know half the time, either. But the crows would have. "Wow. It's an honor to meet you Mr. President."
       Pretty soon, every single crow on the campus knew which masks meant trouble, and wanted the guys wearing them dead. When they didn't wear the masks, however, the crows left them alone, because even they can't see through disguises ... yet. Oh, and also none of the scientists were ever seen again. Researchers believe that the ability to recognize humans is an extension of the crows's ability to recognize each other, which helps them to warn one other about potential predators. This also means that if -- oh, let's stop kidding ourselves here -- when they rise up against us, the crows will remember who threw out those tasty bread crumbs and who thought it was funny to spray them with the hose (in all fairness, it was pretty funny, just maybe not "worth having my eyes pecked out" funny).


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Will there be a World War 3?

The First World War

A century on, there are uncomfortable parallels with the era that led to the outbreak of the First World War

“Humanity can learn from its mistakes, as shown by the response to the economic crisis, which was shaped by a determination to avoid the mistakes that led to the Depression. The memory of the horrors unleashed a century ago makes leaders less likely to stumble into war today. So does the explosive power of a modern conflagration: the threat of a nuclear holocaust is a powerful brake on the reckless escalation that dispatched a generation of young men into the trenches.

Yet the parallels remain troubling. The United States is Britain, the superpower on the wane, unable to guarantee global security. Its main trading partner, China, plays the part of Germany, a new economic power bristling with nationalist indignation and building up its armed forces rapidly. Modern Japan is France, an ally of the retreating hegemon and a declining regional power. The parallels are not exact—China lacks the Kaiser’s territorial ambitions and America’s defense budget is far more impressive than imperial Britain’s—but they are close enough for the world to be on its guard.

Which, by and large, it is not. The most troubling similarity between 1914 and now is complacency. Businesspeople today are like businesspeople then: too busy making money to notice the serpents flickering at the bottom of their trading screens. Politicians are playing with nationalism just as they did 100 years ago. China’s leaders whip up Japanophobia, using it as cover for economic reforms, while Shinzo Abe stirs Japanese nationalism for similar reasons. India may next year elect Narendra Modi, a Hindu nationalist who refuses to atone for a pogrom against Muslims in the state he runs and who would have his finger on the button of a potential nuclear conflict with his Muslim neighbours in Pakistan. Vladimir Putin has been content to watch Syria rip itself apart. And the European Union, which came together in reaction to the bloodshed of the 20th century, is looking more fractious and driven by incipient nationalism than at any point since its formation.”

Impulse Control Center: The Pre Frontal Cortex

The prefrontal cortex (PFC) is located in the very front of the brain, just behind the forehead. In charge of abstract thinking and thought analysis, it is also responsible for regulating behavior. This includes mediating conflicting thoughts, making choices between right and wrong, and predicting the probable outcomes of actions or events. This brain area also governs social control, such as suppressing emotional or sexual urges. Since the prefrontal cortex is the brain center responsible for taking in data through the body's senses and deciding on actions, it is most strongly implicated in human qualities like consciousness, general intelligence, and personality.

PFC Function

This vital region of the brain regulates thought in terms of both short-term and long-term decision making. It allows humans to plan ahead and create strategies, and also to adjust actions or reactions in changing situations. Additionally, the PFC helps to focus thoughts, which enables people to pay attention, learn, and concentrate on goals. This area is also the part of the brain that allows humans to consider several different yet related lines of thinking when learning or evaluating complex concepts or tasks. The prefrontal cortex also houses active, working memory.

Since the PFC controls intense emotions and impulses, it is sometimes referred to as the seat of good judgement. As such, a properly functioning prefrontal cortex inhibits inappropriate behaviors — including delaying gratification of needs, for things like food or sex — while encouraging wise, acceptable choices. In part, this occurs because it works to allow humans to balance immediate reward with long-term goals.

Brain Development

The prefrontal cortex has remarkably expanded in size throughout human evolution, culminating in modern Homo sapiens. This suggests a strong selection pressure in favor of its continued growth and development. The size of the PFC relative to the rest of the brain has also increased over that time; while the brain itself has only increased in size about threefold in the past five million years, the size of the PFC has increased sixfold.

Medical studies have shown that the PFC is the last section of the brain to mature. In other words, while all other brain regions are fully developed early in life, its development is not complete until around age 25. Magnetic resonance imaging (MRI) research has revealed that the prefrontal cortex changes a great deal during adolescence, as the brain's myelin matures and connects all regions of the brain together. This late growth and development is likely the reason that some otherwise intelligent and sensible teens engage in high-risk or excessive behaviors even though they understand the potential dangers.

Damage to the PFC

Unfortunately, the PFC is one of the brain regions most susceptible to injury. When the pathways between the prefrontal cortex and the rest of the brain are damaged or altered, serious personality changes can result. This is logical, since the PFC regulates so many behavior and thought-processing pathways, but can be debilitating and difficult for the injured individual as well as his family and social circle. A person who had been reserved and contemplative can become reckless and impulsive after such an injury. Likewise, a formerly outgoing person can become quiet and withdrawn.

A damaged PFC can negatively impact a person's ability to assess situations or perform tasks, particularly those of a moral or ethical nature. Since social judgements are made in this brain area, these people can also be rendered unable to discern appropriate behavior or suffer from emotional distress, such as irrational fears, anxiety, euphoria, and irritability. Some studies have found weak interconnections between the PFC and the rest of the brain among criminals, sociopaths, drug addicts, and schizophrenics, which may be further evidence of the importance of this part of the brain in individual behavior and decision-making.

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