Clusters of cancer cells get around by moving single file

In narrow blood vessels, tumor cells go marching one by one.

By unfolding into a cellular chain, clusters of cancer cells can slide through capillary tubes less than 10 micrometers wide, Sam Au of Harvard Medical School and colleagues report April 18 in the Proceedings of the National Academy of Sciences. The cells pass through the tubes in single file, each squeezing into an oblong shape and clinging to a neighbor or two. After arriving in roomier quarters, the cells regroup into round clumps, the scientists report.
Clumps of cancer cells that break off tumors and travel through the bloodstream to new sites in the body are known to spread cancer more efficiently than single cells. Many scientists believed, though, that hefty cell clusters were unable to squeeze through the body’s narrowest blood vessels.

Experiments showed that human breast and prostate cancer cells used this single-file strategy to travel through lab-made tubes, human cell‒lined tubes and the blood vessels of live zebrafish. These results could offer insights into ways to foil cancer’s spread.

Gas blasts from black holes show surprising alignment

Fountains of gas from a handful of remote galaxies all seem to be pointing in roughly the same direction, a new study reports. If the result holds up, it puts a new twist on how galaxies and black holes arise from the larger cosmic web, though some researchers worry that the alignment might just be a chance occurrence.

Out of a group of 64 galaxies that are blasting out radio waves, about a dozen are spewing jets of gas that are roughly aligned with one another, astronomers report in the June 11 Monthly Notices of the Royal Astronomical Society Letters. The galactic geysers are powered by supermassive black holes whose magnetic fields launch some infalling debris into intergalactic space. If the geysers are aligned, that means the black holes are all spinning in the same direction. And that means these galaxies, which are spread over roughly a hundred million light-years, might all have been influenced by the larger scaffolding from which they formed.
“Naively we expect that shouldn’t happen,” says Ryan Hickox, an astrophysicist at Dartmouth College who was not involved with this study. Black holes, even supermassive ones, are minuscule compared with filaments of galaxies that can span hundreds of millions of light-years. These filaments are the threads along which most matter in the universe congregates, branching through space like a cosmic spider web. Though galaxies live there, they are thought to form and develop independently of what the filaments are doing. A twisting filament should have no influence over what’s happening around one of its resident black holes.

And yet that’s the explanation favored by study lead Russ Taylor, an astrophysicist at the University of Cape Town in South Africa. “What we’re seeing is the result of a very large region in the early universe spinning coherently in the same direction,” he says. If that’s true, it adds a “new wrinkle to explain how large-scale structure formed.”

Taylor and colleagues found the apparent alignment while probing a patch of sky in the constellation Draco with the Giant Metrewave Radio Telescope in India. They don’t know the distances to the galaxies, but all seem to sit near a galactic supercluster whose light takes about 7.4 billion years to reach Earth — just over half the age of the universe.

Other researchers using different techniques have previously reported similar alignments among another set of galaxies (SN: 12/27/14, p. 6). Both studies, though, relied on a small number of galaxies, which means the alignment might not be statistically significant.

“If an alignment like this exists, it’s very interesting,” says astrophysicist Michael DiPompeo, also at Dartmouth. “But I’m not super convinced that it’s really there.” While Taylor and colleagues argue that the alignment is not a statistical fluke, DiPompeo did his own calculations that suggest otherwise. He simulated observations of 64 randomly oriented galaxy jets — the computer equivalent of repeatedly dropping a bunch of toothpicks on a table and noting where each was pointed. “I could pretty regularly get patterns that look like this,” he says.
It’s also hard to imagine how such an alignment, if it was present as the galaxies formed, could persist for billion of years, he says. “It’s not like [galaxies] form in the early universe and then just sit there blasting these jets.” Galaxies grow by colliding with other galaxies, which can change how the galaxies and their central black holes rotate.

Both DiPompeo and Hickox say it’s worth probing other galactic gatherings, though, before dismissing these alignments as a coincidence. If similar orientations appear in many galaxy clusters, then the researchers could be on to something. Hickox would also like to see distances to these galaxies. If it turns out the galaxies sit at wildly varying distances from Earth, he says, then the alignment is less likely to be real.

Taylor hopes to do just that. Colleagues are planning observations at other telescopes that will let them determine how far away these galaxies are. And Taylor is gearing up for a more thorough investigation over a much larger patch of sky with a new radio observatory in South Africa called MeerKAT, which should be ready for operation later this year.

Bear bone rewrites human history in Ireland

In a bit of Irish luck, archaeologists have found evidence of the Emerald Isle’s earliest known humans. A brown bear’s kneecap excavated in 1903, featuring stone tool incisions, pushes back the date that humans set foot in Ireland by as many as 2,500 years.

Radiocarbon dating at two independent labs places the bone’s age between about 12,800 and 12,600 years old, say Marion Dowd of the Institute of Technology, Sligo in Ireland and Ruth Carden of the National Museum of Ireland in Dublin. Melting glaciers and milder temperatures in northwestern Europe at that time made it easier for humans to reach Ireland by boat to hunt game, at least for several weeks at a time, the researchers propose in the May 1 Quaternary Science Reviews.
Until now, the oldest signs of people on Ireland came from a hunter-gatherer camp dating to about 10,290 years ago.

Carden discovered the brown bear’s kneecap while studying bones that had been packed away in boxes in the 1920s, after the bones’ 1903 discovery at Ireland’s Alice and Gwendoline Cave.

Uncertainty is stressful, but that’s not always a bad thing

Interviewing for a new job is filled with uncertainty, and that uncertainty fuels stress. There’s the uncertainty associated with preparing for the interview — what questions will they ask me? What should I put in my portfolio? And then there’s the ambiguity when you’re left to stew. Did I get the job? Or did someone else?

Scientists have recently shown that these two types of uncertainty — the kind we can prepare for, and the kind we’re just stuck with — are not created equal. The uncertainty we can’t do anything about is more stressful than the one we can. The results help show exactly what in our lives freaks us out — and why. But the findings also show a positive side to the stress we feel when not knowing what’s ahead — the closer our stress levels reflect the real ambiguity in the world, the better we perform in it.

“There is a bias in the public perception” against stress, says Claus Lamm, a cognitive neuroscientist at the University of Vienna in Austria. But stress “prepares us to deal with environmental challenges,” he notes, preparing us to fight or flee, and it keeps us paying attention to our surroundings.

For decades, scientists have been trying to figure out just what makes us stressed and why. It turns out that unpredictability is a great stressor. Studies in the 1960s and 1970s showed that rats and humans who can’t predict a negative effect (such as a small shock) end up more frazzled than those who can predict when a zap is coming. In a 2006 study, people zapped with unpredictable electric shocks to the hand rated the pain as more unpleasant than when they knew what to expect.

What is going on in the brain when judging the uncertainty of a situation and translating it to stress? Lamm and his group recently sought the answer to answer this question by combining measures of electrical activity in the brain (via electroencephalogram) with functional magnetic resonance imaging to show blood flow patterns in 25 participants getting rounds of shocks on their hands. A visual cue told the participants what to expect — sort of. Sometimes the participant knew with 100 percent certainty that either a painful shock or nothing at all was coming. Sometimes there was only 50 percent certainty. No matter what, the shock would happen (or not) in the next 15 seconds, leaving the people in the scanner with nothing to do but wait.

During that waiting period, the brain prepares for a shock in different ways, depending on whether the jolt is certain or uncertain, Lamm and his colleagues reported last February in Human Brain Mapping. During the first two seconds, the brain is processing the visual cue. “You have an initial quick evaluation,” Lamm explains, categorizing whether the stimulus is going to be aversive and whether it is certain or uncertain. If the possibility for a zap was ambiguous, there was a quick increase in blood flow to participants’ visual processing areas. This suggests the brain is getting ready to take in more information and pay more attention — to get a better read on if that shock is really coming or not.

If the zap is definitely going to happen, the last two seconds before delivery saw increased activity in the posterior insula. The insula participates in processing someone’s current state, including pain processing and emotional awareness — “basically reading out the physiological signals of your body,” Lamm says. Pain is coming, brace yourself.
When participants weren’t sure if the shock was coming, the last two seconds of waiting were accompanied by increased brain activity in areas related to sensing the environment and maintaining attention — such as the parietal lobe, orbitofrontal cortex and angular gyrus. The brain was on high alert, continuing to look for any information that could determine when and if the pain would arrive.

But this is only one kind of stress —and one kind of uncertainty. “We know a lot about what happens if you take someone and give them a stressful experience,” says Archy de Berker, a neuroscientist at University College London. “But in a way, that approach is missing out on a whole step: What is it about the experience that makes it stressful?” Is it the ambiguity? Or is it the shock to the hand? Is it both?

But there’s also more than one kind of ambiguity to prepare for. Remember the job interview scenario: You can reduce some of the uncertainty by preparing for your interview. But once the interview has passed, you’re stuck with irreducible uncertainty — that endless wait for the call that may never come.

To separate out these two forms of uncertainty, de Berker recruited 45 participants for a different hand-shock experiment. For each trial, the participant was presented with one of two rocks and asked if there was a snake under it. At first, the snake might be under rock “A” 100 percent of the time. Then it might change, and the snake might be under rock “A” only 60 percent of the time, spending the rest of the time under rock “B.” For some trials, the participant could easily learn to predict where the snake would be, while for others the rock-turner was always uncertain. But one thing remained certain: If they saw the snake, they’d get a shock, even if they predicted the outcome correctly.

As the participants played this painful game, de Berker and his colleagues monitored their skin conductance and pupil size — measures of physical stress. They also asked the participants how stressed out they felt.

The amount of ambiguity the participants had about whether the snake was under the rock was associated with their stress. If they could easily predict when the shock would come, reducing their uncertainty, they shocks were easier to take. But if the outcome remained difficult to predict — if no amount of learning was going to help — the participants were much more stressed out.

But if the participants had a good feel for just how uncertain the odds were — if their measures of stress tracked well with the amount of ambiguity — they ended up with an unexpected benefit: They performed better on the rock and snake task (though they still got shocked for their pains). The scientists published their results March 29 in Nature Communications.

The study “reveals more quantitatively how stress (both self-reported and measured with physiological arousal) is driven by… ‘irreducible uncertainty,’ uncertainty about the state of the world that we can’t control,” says Ross Otto, a neuroscientist at New York University. It’s that irreducible uncertainty — the fact that the job applicant just doesn’t know if he’s got the job until the call comes through, and there’s nothing he can do about it — that really gets to us.

But the part of the stress we can control represents the positive side of an unpleasant feeling. “We always tend to think of stress as a negative effect, you don’t want to be stressed,” Lamm says. “But in the end, if you’re not stressed you will not perform. You need a certain level of arousal to meet challenges.”

Plants might remember with prions

There’s no known mad plant disease. But prions — which show their dark side in mad cow disease — may occur in plants as a form of memory.

Prions are proteins that change shape and shift tasks, and then trigger other proteins to make the same change. Inheriting prions lets cells “remember” and replicate that shift in form and function. Now a protein called luminidependens, which is connected with flowering, shows signs of these shapeshifter and template powers, researchers report April 25 in the Proceedings of the National Academy of Sciences.

Study coauthor Susan Lindquist of the Whitehead Institute for Biomedical Research in Cambridge, Mass., and her colleagues devised a way to test plant proteins for prion power by swapping bits of them into yeast prions. Luminidependens, found in the common lab plant Arabidopsis thaliana, fit the criteria, and may be the first botanical protein shown to act like a prion. Prionlike memory might be useful in such floral tasks as keeping track of a decent winter’s chill.