Wednesday, June 5, 2019

[[I will iyH be updating this post when I find new examples.]]

Immune Cells Measure Time to Identify Foreign Proteins

Immunologists confirm an old hunch: T-cells identify what belongs in the body by timing how long they can bind to it.
The white blood cells called T-lymphocytes, such as this one shown by scanning electron microscopy, have receptors that bind to specific molecular targets. New work shows that the duration of this binding is what allows the cells to distinguish between the body’s own proteins and those of invading pathogens.

June 3, 2019
To mount a successful defense against invading organisms, the immune system must quickly and accurately identify which cells belong in the body and which do not. That might seem straightforward enough, but it’s not such an easy feat to achieve. The responsibility falls largely on the shoulders of T-cells, white blood cells with specialized receptors embedded in their surface that allow them to bind uniquely to diverse peptide fragments. Once bound, the T-cells can then initiate a focused attack against the target.
“It’s an amazing needle in a haystack that they’re trying to identify,” said Orion Weiner, a biochemist at the University of California, San Francisco. “Being able to find that incredibly rare [foreign] peptide in a sea of quite similar self-peptides is an amazing challenge. It requires a degree of both specificity and sensitivity that’s really at the limits of what’s physically possible.”
But there’s a problem: During development, millions of T-cells with distinctive receptors are produced randomly — the immune system’s way of covering all its bases, of preparing for the astronomical diversity of peptides it might encounter. Many of those peptides, however, are inevitably parts of proteins that belong in the body. While most of the T-cells that react to such “self” molecules are eliminated as development progresses, some of them continue to circulate throughout life, protecting against infected and abnormal cells without harming the body. Something keeps them in check.
How these T-cells are able to make the distinction between self and non-self, between something that should be left alone and something that shouldn’t be, has been one of the central questions driving immunology research.
Now, researchers seem prepared to hand down a definitive answer. A pair of studies, published in eLifein April, have experimentally confirmed a theory that has enjoyed growing support since the 1990s. The key lies in the timing of things: Substances that bind to T-cell receptors for less than about five seconds are deemed safe, while longer-binding molecules are slated to be destroyed. “The cell could have some way of taking very, very tiny differences in the duration of the receptor binding,” said Weiner, an author of one of the papers, “and amplifying that to a much larger cellular response.”

Paradoxical Crystal Baffles Physicists
At super-low temperatures, a crystal called samarium hexaboride behaves in an unexplained, imagination-stretching way.
Interactions between electrons inside samarium hexaboride appear to be giving rise to an exotic quantum behavior new to researchers.
Andrew Testa for Quanta Magazine
In a deceptively drab black crystal, physicists have stumbled upon a baffling behavior, one that appears to blur the line between the properties of metals, in which electrons flow freely, and those of insulators, in which electrons are effectively stuck in place. The crystal exhibits hallmarks of both simultaneously.
“This is a big shock,” said Suchitra Sebastian, a condensed matter physicist at the University of Cambridge whose findings appeared today in an advance online edition of the journal Science. Insulators and metals are essentially opposites, she said. “But somehow, it’s a material that’s both. It’s contrary to everything that we know.”
The material, a much-studied compound called samarium hexaboride or SmB6, is an insulator at very low temperatures, meaning it resists the flow of electricity. Its resistance implies that electrons (the building blocks of electric currents) cannot move through the crystal more than an atom’s width in any direction. And yet, Sebastian and her collaborators observed electrons traversing orbits millions of atoms in diameter inside the crystal in response to a magnetic field — a mobility that is only expected in materials that conduct electricity. Calling to mind the famous wave-particle duality of quantum mechanics, the new evidence suggests SmB6 might be neither a textbook metal nor an insulator, Sebastian said, but “something more complicated that we don’t know how to imagine.”

Suchitra Sebastian, an experimental condensed matter physicist at the University of Cambridge, said the discoveries she and her colleagues have made “mean that something needs to be rewritten completely.”
Courtesy of Suchitra Sebastian
“It is just a magnificent paradox,” said Jan Zaanen, a condensed matter theorist at Leiden University in the Netherlands. “On the basis of established wisdoms this cannot possibly happen, and henceforth completely new physics should be at work.”
It is too soon to tell what, if anything, this “new physics” will be good for, but physicists like Victor Galitski, of the University of Maryland, College Park, say it is well worth the effort to find out. “Oftentimes,” he said, “big discoveries are really puzzling things, like superconductivity.” That phenomenon, discovered in 1911, took nearly half a century to understand, and it now generates the world’s most powerful magnets, such as those that accelerate particles through the 17-mile tunnel of the Large Hadron Collider in Switzerland.
Theorists have already begun to venture guesses as to what might be going on inside SmB6. One promising approach models the material as a higher-dimensional black hole. But no theory yet captures the whole story. “I do not think that there is any remotely credible hypothesis proposed at this moment in time,” Zaanen said.
SmB6 has resisted classification since Soviet scientists first studied its properties in the early 1960s, followed by better-known experiments at Bell Labs.