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Humor, Media, Medicine and Society, Neuroscience, Research, Stanford News

Did extraterrestrials chew up my news release, or does artificial intelligence still have a ways to go?

Did extraterrestrials chew up my news release, or does artificial intelligence still have a ways to go?

UFO

Almost two years ago, in a Scope blog entry titled “Can Joe Six-Pack compete with Sid Cyborg?” I posed the question: “Just how long will it be before we can no longer tell our computers from ourselves?”

I think it’s safe to say we’re not there yet. Either that, or extraterrestrials have been reading my news releases and finding them puzzling.

Last week we put out a news release I’d written about a dramatic discovery by Stanford radiologists Mike Zeineh, MD, PhD, Brian Rutt, PhD, and their colleagues. In brief, they’d analyzed postmortem slabs of brain tissue from people diagnosed with Alzheimer’s, compared them with equivalent brain-tissue slabs taken from people who’d died without any Alzheimer’s-like symptoms, and noticed some striking and intriguing differences. In a key brain region essential to memory formation, Zeineh and Rutt had spotted – only in Alzheimer’s brains, not normal ones – iron deposits engulfed by mobile inflammatory cells. This observation’s potentially big implications were plenty newsworthy.

It so happened that, on the day we issued the release, a high-powered five-day-long meeting on Alzheimer’s sponsored by the eponymous Alzheimer’s Association was in session in Washington, D.C. As a result, many of the brain-oriented science writers to whom my news release was targeted were preoccupied.

I was a little anxious about that. So, the other day, I turned to my favorite search engine to see if the release had managed to get some traction in the popular press. As I’d feared, the Washington conference had sucked up a lot of the oxygen in the earthly neuroscience arena.

But apparently, the release had done better in Outer Space. I saw that it had been picked up by, for example, Red Orbit (a website that I’ve always assumed, based on its name, emanates from Mars).

My eyes were next drawn to a link to an unfamiliar outfit called AZ News, which bills itself in a tagline as an “International Online News Site.” I clicked on the link, and saw a news report with the same title as my release. I started reading the text below.

The first words were: “In autopsy mind hankie from people not diagnosed with Alzheimer’s…” I don’t know what an “autopsy mind hankie” is, but I suspect it’s a mind-blower.

I checked our release. That’s not what I’d written at all. What I’d said was, “In postmortem brain tissue from people not diagnosed with Alzheimer’s…”

It seemed pretty clear that the release had been translated into some language – I had no idea which – and then, for some reason, reverse-translated back into English. I read on.

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Global Health, HIV/AIDS, Immunology, Research, Stanford News, Women's Health

HIV study in Kenyan women: Diversity in a single immune-cell type flags likelihood of getting infected

HIV study in Kenyan women: Diversity in a single immune-cell type flags likelihood of getting infected

virally infected cellsWhen it comes to immune cells, “it takes all kinds” isn’t too bad a description of what makes for the best composition of our fighting force for warding off viruses, bacteria and incipient tumors. But in a study just published in Science Translational Medicine, Stanford infectious-disease immunologist Catherine Blish, MD, PhD, and her colleagues have found, unexpectedly, that high diversity in the overall population of one particular type of immune cells strongly correlates with an increased likelihood of subsequent infection by HIV.

The investigators had figured that diversity in so-called natural killer cells, or NK cells, would be a strength, not a detriment. “Our hypothesis was wrong,” Blish (much of whose research focuses on NK cells) told me. In this study,  it was higher, rather than lower, diversity in this immune-cell population that turned out to be associated with increased HIV susceptibility.

NK cells, fierce white blood cells that help fight viruses and tumors, harbor various combinations of receptors on their surface. Some receptors recognize signs of our other cells’ normalcy, while others recognize signs that a cell is stressed — due, say, to viral infection or cancerous mutation. On recognizing their targeted features on other cells’ surfaces, an NK cell’s “normalcy” receptors tend to inhibit it, while its stress-recognizing receptors activate it.

All told, NK cells can have many thousands of different combinations of these receptors on their surfaces, with each combination yielding a slightly different overall activation threshold. At birth, our NK cells are pretty similar to one another. But as they acquire life experience – largely from viral exposure, Blish thinks – they increasingly diverge in the specific combinations of receptors they carry on their surfaces.

From my news release on the study:

In order to assess the impact of NK-cell diversity on adult humans’ viral susceptibility, Blish and her associates turned to blood samples that had been drawn during the Mama Salama Study, a longitudinal study of just over 1,300 healthy … Kenyan women. [T]he researchers carried out a precise analysis of NK cells in the women’s blood and observed a strong positive correlation between the diversity of a woman’s NK cell population and her likelihood of becoming infected with HIV.

This correlation held up despite the women’s being statistically indistinguishable with respect to age, marital status, knowledge of sexual partners’ HIV status, history of trading sex for money or goods, sexually transmitted disease status or reported frequency of recent unprotected sex.

And the NK-diversity-dependent difference in these women’s likelihood of HIV infection was huge. From my release:

Those with the most NK-cell diversity were 10 times as likely as those with the least diversity to become infected. A 10-fold risk increase based solely on NK-cell diversity is far from negligible, said Blish. “By way of comparison, having syphilis increases the risk of contracting HIV two- to four-fold, while circumcised men’s HIV risk is reduced by a factor of 2.5 or 3,” she said.

These surprising findings  could spur the development of blood tests capable of predicting individuals’ susceptibility to viral infection.

Previously: Study: Pregnancy causes surprising changes in how the immune system responds to the flu, Revealed: Epic evolutionary struggle between reproduction and immunity to infectious disease and Our aging immune systems are still in business, but increasingly thrown out of balance
Photo by NIAID

Imaging, Immunology, Mental Health, Neuroscience, Research, Stanford News

Are iron, and the scavenger cells that eat it, critical links to Alzheimer’s?

Are iron, and the scavenger cells that eat it, critical links to Alzheimer's?

iron linkIf you’ve been riding the Alzheimer’s-research roller-coaster, brace yourself for a new twist on that wrenching disease of old age.

In a study published in Neurobiology of Aging, Stanford radiologists Mike Zeineh, MD, PhD,  and Brian Rutt, PhD, and their colleagues used a ultra-powerful magnetic-resonance-imaging (MRI) system to closely scrutinize postmortem tissue from the brains of people with and without Alzheimer’s disease. In four out of five of the Alzheimer’s brains they looked at, but in none of the five non-Alzheimer’s brains, they found what appear to be iron-containing microglia – specialized scavenger cells in the brain that can sometimes become inflammatory – in a particular part of the hippocampus, a key brain structure that’s absolutely crucial to memory formation as well as spatial orientation and navigation.

Zeineh and Rutt told me they don’t know how the iron gets into brain tissue, or why it accumulates where it does. But iron, which in certain chemical forms can be highly reactive and inflammation-inducing, is ubiquitous throughout the body. Every red blood cell that courses through our microvasculature is filled with it. So one possibility – not yet demonstrated – is that iron deposits in the hippocampus could result from micro-injury to small cerebral blood vessels there.

As surprising as the iron-laden, inflamed microglia Zeineh, Rutt and their associates saw in Alzheimer’s but not normal brains was what they didn’t see. Surprisingly, in the brain region of interest there was no consistent overlap of either iron or microglia with the notorious amyloid plaques that have been long held by many neuroscientists and pharmaceutical companies to be the main cause of the disorder. These plaques are extracellular aggregations of a small protein called beta-amyloid that are prominent in Alheimer’s patients’ brains, as well as in mouse models of the disease.

Because they weren’t able to visualize small, soluble beta-amyloid clusters (now believed to to be the truly toxic form of the protein), Rutt and Zeineh don’t rule out a major role for beta-amyloid in the early developmental stages of pathology in Alzheimer’s.

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Neuroscience, Research, Science, Stanford News

Nobelist neuroscientist Tom Südhof still spiraling in on the secrets of the synapse

Nobelist neuroscientist Tom Südhof still spiraling in on the secrets of the synapse

spiral staircase“History,” said Winston Churchill (or was it Arnold Toynbee or Edna St. Vincent Millay?), “is just one damn thing after another.” In many respects, so is good science.

And that’s just how it should be, Stanford neuroscientist and molecular physiologist Tom Südhof, MD, told me a few years ago when I interviewed him for a story I wrote in connection with the Lasker Award, a prestigious prize he’d won shortly before receiving the 2013 Nobel Prize in physiology or medicine:

Asked to recall any defining “eureka!” moments that had catapulted his hunches forward to the status of certainty, Südhof noted that in his experience, science advances step by step, not in jumps. “I believe strongly that most work is incremental,” he said. The systematic solution of highly complex problems requires a long view and plenty of patience.

Climbing a long ladder to the Nobel one small step at a time, Südhof continually raised the power of his conceptual microscope over the decades as he probed the intricate workings of synapses: the all-important junctions in the nervous system where information, in the form of chemical messengers called neurotransmitters, gets passed from one nerve cell to another.

From an explanation of Südhof’s synaptic studies:

The firing patterns of our synapses underwrite our consciousness, emotions and behavior. The simple act of taking a step forward, experiencing a fleeting twinge of regret, recalling an incident from the morning commute or tasting a doughnut requires millions of simultaneous and precise synaptic firing events throughout the brain and peripheral nervous system.

A philosopher might say that synapses collectively constitute the physiological substrate for the soul. A futurist might write (as I once did):

With nanobots monitoring every critical neural connection’s involvement in a thought or emotion or experience, you’ll be able to back up your brain – or even try on someone else’s – by plugging into a virtual-reality jack. The brain bots feed your synapses the appropriate electrical signals and you’re off and running, without necessarily moving.

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Autoimmune Disease, Immunology, Public Health, Research, Sleep, Stanford News

Cause of 2009 swine-flu-vaccine association with narcolepsy revealed?

Cause of 2009 swine-flu-vaccine association with narcolepsy revealed?

syringesBack in 2001, in the wacko cinematic tour de farce “Rat Race,” British actor Rowan Atkinson – a.k.a. the iconic “Mr. Bean” – put a humorous face on narcolepsy, a rare, chronic, incurable and lifelong sleep disorder that can strike at any time, even in the heat of a foot race.

In 2009, narcolepsy suddenly became, for a time, not quite so rare.

The swine flu pandemic sweeping the world that year was no joke. In the United States alone, the H1N1 strain of influenza virus responsible for that pandemic resulted in 274,304 hospitalizations and 12,469 deaths, as mentioned in our news release on a just-published study in Science Translational Medicine.

There probably would have been far more hospitalizations and deaths had not several vaccines tailored to that particular influenza strain been rushed to the market. Two vaccines in particular — Focetria, manufactured by Novartis, and Pandemrix, made by GlaxoSmithKline — are credited with saving a lot of lives in Europe. But there was a dark side. As our news release notes:

Populations that had been immunized with GlaxoSmithKline’s Pandemrix vaccine showed an increase in narcolepsy, but those immunized with Novartis’ Focetria did not.

That’s not news; it’s been known for some time. But the findings in the new study, whose senior author is Stanford neuroimmunologist Larry Steinman, MD, may explain why.

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Aging, Cancer, Dermatology, Genetics, Research, Stanford News

Genetic secrets of youthful skin

Genetic secrets of youthful skin

new hatEvery year, upwards of $140 billion a year gets spent on cosmetics. In the United States alone, says an authoritative report, a recent year saw upwards of 5.6 million Botox procedures, 1.1 million chemical peels, almost a half-million laser skin procedures, 196,286 eyelid surgeries and a whole bunch of face lifts.

If you’ve got the courage to compare your present-tense face with the one you were wearing 20 or even 10 years ago, you’ll see why. As I wrote in a just-published Stanford Medicine article, “Wither youth?”:

The terrain of aging skin grows all too familiar with the passing years: bags under the eyes, crow’s feet, jowls, tiny tangles of blood vessels, ever more pronounced pores and pits and pigmentation irregularities. Then there are wrinkles — long, deep “frown lines” radiating upward from the inside edges of the eyebrows and “laugh lines” that trace a furrow from our nostrils to the edges of our lips in our 40s, and finer lines that start crisscrossing our faces in our 50s. Sagging skin gets more prominent in our later years as we lose bone and fat.

“And,” I added wistfully, “it’s all right there on the very outside of us, where everyone else can see it.”

Stanford dermatologist Anne Chang, MD, who sees a whole lot of skin, got to wondering: Why does skin grow old? Armed with a sophisticated understanding of genetics, she went beyond lamenting lost youth and resolved to address the question scientifically, asking: “Can you turn back time? Can aging effects be reversed? Can you rejuvenate skin, make it young again?”

The answers she’s come up with so far – from hereditary factors to a possible underlying genetic basis for how some treatments now in common commercial cosmetic use (such as broadband light therapy) could potentially slow or even reverse the aging of skin – are described in my magazine article.

Previously: This summer’s Stanford Medicine magazine shows some skinResearchers identify genetic basis for rosacea, New study: Genes may affect skin youthfulness and Aging research comes of age
Photo by thepeachpeddler

Cancer, Imaging, Research, Stanford News, Surgery

Better tumor-imaging contrast agent: the surgical equivalent of “cut along dotted line”?

cut horseIt would be tough for most people to take a snubbed-nose scissors to an 8-1/2″ x 11″ sheet of blank paper and carve out a perfect silhouette of, say, a horse from scratch. But any kid can be an artist if it means merely cutting along a boundary separating two zones of different colors.

Tumor-excision surgery requires an artist’s touch. It can be tough to distinguish cancerous from healthy tissues, yet the surgeon needs to approach perfection in precisely removing every possible trace of the tumor while leaving as much healthy tissue intact as possible. To help surgeons out, technologists have been designing contrast agents that target only tumor cells, thus providing at least a dotted line for scalpel wielders.

Stanford pathologist and molecular-probe designer Matthew Bogyo, PhD, in a study published in ACS Chemical Biology, has now demonstrated, using mouse models of breast, lung and colon cancer, the effectiveness of a fluorescence-emitting optical contrast agent that selectively accumulates in tumors and can be used to guide surgery. In effect, the probe lights up the tumor, providing a convenient, high-resolution dotted line for its excision.

Perhaps more striking, the new study showed that this probe, designed by Bogyo’s group, is compatible with a robotic remote minimally invasive surgery system that is already enjoying widespread commercial use. Intuitive Surgical, Inc., the company that sells this system, collaborated on the study.

Previously: Stanford researchers explore new ways of identifying colon cancer, Cat guts, car crashes, and warp-speed Toxoplasma infections and Compound clogs Plasmodium’s in-house garbage disposal, hitting malaria parasite where it hurts
Photo by Merryl Zorza

Genetics, Imaging, Neuroscience, Research, Stanford News

From phrenology to neuroimaging: New finding bolsters theory about how brain operates

From phrenology to neuroimaging: New finding bolsters theory about how brain operates

phrenologyNeuroscience has come a long way since the days of phrenology, when lumps on the outside of the skull were believed to denote enhanced size and strength of the particular brain region responsible for particular individual functions. Today’s far more advanced neuroimaging technologies allow scientists to peer deep into the living brain, revealing not only its anatomical structures and the tracts connecting them but, in recent years, physiological descriptions of the brain at work.

Visualized this way, the brain appears to contain numerous “functional networks:” clusters of remote brain regions that are connected directly via white-matter tracts or indirectly through connections with mediating regions. These networks’ tightly coupled brain regions not only are wired together, but fire together. Their pulses, purrs and pauses, so to speak, are closely coordinated in phase and frequency.

Well over a dozen functional networks, responsible for brain operations such as memory, language processing, vision and emotion, have been identified via a technique called resting-state functional magnetic resonance imaging. In a resting-state fMRI scan, the individual is asked to simply lie still, eyes closed, for several minutes and relax. These scans indicate that even at rest, the brain’s functional networks continue to hum along — albeit at lower volumes — at distinguishable frequencies and phases, like so many different radio stations playing simultaneously on the same radio.

But whether the images obtained via resting-state fMRI truly reflect neuronal activity or are some kind of artifact has been controversial. Now, a new study led by neuroscientist Michael Greicius, MD, and just published in Science, has found genetic evidence that convincingly bolsters neuroimaging-based depictions of these brain-activity patterns.

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Big data, Cardiovascular Medicine, Patient Care, Public Health, Research, Stanford News

Widely prescribed heartburn drugs may heighten heart-attack risk

Widely prescribed heartburn drugs may heighten heart-attack risk

PrilosecHeartburn – that burning sensation in the chest that occurs when stomach acid rises up into your esophagus – has absolutely nothing whatsoever to do with the heart. People with heartburn (that’s a lot of us) are at no increased risk of developing heart disease. At least, not unless they’re taking the most commonly used class of drugs for treating heartburn.

That drug class would be proton-pump inhibitors, or PPIs, and it includes omeprazole (Prilosec), lansoprazole (Prevacid), esomeprazole (Nexium) and a few more. All three are available over the counter. Although the labels direct users not to take these drugs for longer than a couple of weeks without consulting their physicians, people often pop them on a daily basis for months or years on end.

But a new PLOS ONE study, led by Stanford biomedical-informatics expert Nigam Shah, PhD, MBBS, and cardiovascular surgeon Nick Leeper, MD, shows a clear association between prior use of PPIs for heartburn and elevated risk of serious cardiovascular events including heart attacks. In a news release covering that “big data” study, which combed through nearly 3 million electronic health records to ferret out the PPI/cardiovascular-risk connection, I wrote:

… PPIs are among the world’s most widely prescribed drugs, with $14 billion in annual sales… In any given year, more than 20 million Americans – about one in every 14 – use PPIs… More than 100 million prescriptions are filled every year in the United States for PPIs, a class of drugs long considered benign except for people concurrently taking the blood thinner clopidogrel (Plavix). However, the new study upends this view: It indicates that PPI use was associated with a roughly 20 percent increase in the rate of subsequent heart-attack risk among all adult PPI users, even when excluding those also taking clopidogrel.

That increased risk was seen among younger adults (under age 45), too.

The study, in other words, found that everybody’s cardiovascular risk goes up if they use PPIs. Now, a 20 percent increase in risk may not amount to much if your baseline risk is very low to begin with (say, that of a 20-year-old woman in top physical condition with no genetic predisposition to high blood pressure or elevated cholesterol). But for many of us, especially if we’re middle-aged, a little pudgy, or struggling with hypertension or hypercholesterolemia, that 20 percent looms larger.

Importantly, people who take the second-most-widely prescribed class of drugs prescribed for heartburn, so-called H2 blockers, appear to suffer no ill effects from them in the cardiovascular-risk department, according to the study’s findings. H2 blockers, which have been around longer than PPIs, are reasonably effective.

So, why do PPIs, but not H2 blockers, cause trouble? As I noted in my release:

The study’s findings lend support to an explanation for an untoward effect of PPIs on heart-disease risk proposed by Stanford scientists a few years ago. Research done then showed that PPIs impede the production of an important substance, nitric oxide, in the endothelial cells that line all of the nearly 100,000 miles of blood vessels in an averag adult’s body.

Nitric oxide relaxes blood vessels. So it figures that chronic use of a drug that shuts down that chemical’s generation could cause chronic blood-vessel constriction and follow-on cardiovascular problems.

Read those labels, people.

Previously: How efforts to mine electronic health records are beginnning to influence critical care, New research scrutinizes off-label drug use and Damage to dead-cell disposal system may increase heart disease
Photo by John

 

Evolution, Genetics, HIV/AIDS, Immunology, Infectious Disease, Research, Stanford News

Study: Chimps teach people a thing or two about HIV resistance

Study: Chimps teach people a thing or two about HIV resistance

I, personally, have never had trouble distinguishing a human being from a chimp. I look, and I know.

But I’m not a molecular biologist. Today’s sophisticated DNA-sequencing technologies show that the genetic materials of the two species, which diverged only 5 million or so years ago (an eye-blink in evolutionary time), are about 98 percent identical. Think about that next time you eat a banana.

One major exception to that parallelism: a set of three genes collectively called the major histocompatibility complex, or MHC. These genes code for proteins that sit on the surfaces of each cell in your body, where they serve as jewel cases that display bits of proteins that were once inside that cell but have since been chopped into pieces by molecular garbage disposals, transported to the cell surface and encased in one or another of the MHC proteins. That makes the protein bits highly visible to roving immune cells patrolling our tissues to see if any of the cells within are harboring any funny-looking proteins. If those roving sentry cells spot a foreign-looking protein bit, they flag the cell on whose surface it’s displayed as possibly having been infected by a virus or begun to become cancerous.

Viruses replicate frequently and furiously, so they evolve super-rapidly. If they can evade immune detection, that’s groovy from their perspective. So our MHC has to evolve rapidly, too, and as a result, different species’ MHC genes  diverge relatively quickly.  To the extent they don’t, there’s probably a good reason.

Stanford immunologist and evolutionary theorist Peter Parham, PhD, pays a lot of attention to the MHC genes. In a new study in PLOS Biology, he and his colleagues have made a discovery that may prove relevant to AIDS research, by analyzing genetic material found in chimp feces. Not zoo chimps. Wild Tanzanian chimps. As I noted in a news release about the study:

The wild chimps inhabit Gombe Stream National Park, a 13.5-square-mile preserve where they have been continuously observed from afar since famed primatologist Jane Goodall, PhD, began monitoring them more than 50 years ago.

One thing that sets the Gombe chimps apart from captive chimps, unfortunately, is a high rate of infection by the simian equivalent of HIV, the virus responsible for AIDS.

The study’s lead author, postdoc Emily Wroblewski, PhD, set up shop in a corner of Parham’s lab and extracted DNA from fecal samples legally obtained by other researchers (close contact with the animals is prohibited). Each sample could be tied to a particular Gombe-resident chimp. RNA extracted from the same sample indicated that chimp’s infection status.

Parham, Wroblewski and their colleagues found that one particular MHC gene came in 11 different varieties – astounding diversity for such a small collection of chimps (fewer than 125 of them in the entire Gombe). Surprisingly, one small part of one of those 11 gene variants was nearly identical to a piece of a protective version of its human counterpart gene, a version that seems to protect HIV- infected people slowing HIV progression to full-blown AIDS.

Why is that important? Because any piece of an MHC gene that has maintained its sequence in the face of 5 million years of intense evolutionary pressure must be worth something.

Sure enough, fecal samples from chimps with that MHC gene variant, so strikingly analogous to the protective human variant, had lower counts of virus that those from infected chimps carrying other versions of the gene.

You can believe that scientists will be closely examining the DNA sequence contained in both the human and chimp gene variant, as well as the part of the MHC protein that DNA sequence codes for. Because it must be doing something right.

Previously: Revealed: Epic evolutionary struggle between reproduction and immunity to infectious disease, Our species’ twisted family tree and Humans share history – and a fair amount of genetic material – with Neanderthals
Photo by Emily Wroblewski

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