Unknown artist, Japanese, Japan; Tokyo Isoda Koryūsai, previous attribution Japanese, active ca. 1764-1788 Flying crane (Hikaku), late 19th century Polychrome woodblock print Sheet: 25.1 x 37 cm (9 7/8 x 14 9/16 inches) Gift of Mrs. John D. Rockefeller, Jr. 34.551
Ruins of the Ludlow Colony in the aftermath of the massacre.
The Ludlow Massacre was an attack by the Colorado National Guard and Colorado Fuel & Iron Company camp guards on a tent colony of 1,200 striking coal miners and their families at Ludlow Colorado, on April 20, 1914. Some two dozen people, including miners’ wives and children, were killed. The chief owner of the mine, John D. Rockefeller Jr, was widely criticized for the incident.
The massacre, the culmination of a bloody widespread strike against Colorado coal mines, resulted in the violent deaths of between 19 and 26 people; reported death tolls vary but include two women and eleven children, asphyxiated and burned to death under a single tent. The deaths occurred after a daylong fight between militia and camp guards against striking workers. Ludlow was the deadliest single incident in the southern Colorado Coal Strike, which lasted from September 1913 through December 1914. The strike was organized by the United Mine Workers of America (UMWA) against coal mining companies in Colorado.
In retaliation for Ludlow, the miners armed themselves and attacked dozens of mines over the next ten days, destroying property and engaging in several skirmishes with the Colorado National Guard along a 40-mile front from Trinidad to Walsenburg. The entire strike would cost between 69 and 199 lives. Thomas G. Andrews described it as the “deadliest strike in the history of the United States”.
Cockerels, chicks and spiderworts (Tsuyukusa ni niwatori)
Katsushika Hokusai Japanese, 1760-1849 Unknown artist, Japanese, Japan; Tokyo Cockerels, chicks and spiderworts (Tsuyukusa ni niwatori), mid 1830’s Polychrome wood block print Image: 21.9 x 28.7 cm (8 5/8 x 11 5/16 inches) Gift of Mrs. John D. Rockefeller, Jr. 34.336
Atomic-level view provides new insight into translation of touch into nerve signals
Whether stubbing a toe or stroking a cat, the sensation of touch starts out as a mechanical force that is then transformed into an electrical signal conveying pain or other sensations. Tiny channels in neurons act as translators by helping to formulate that signal to the brain. However, scientists know little about the fine details of how these channels work.
(Image caption: Molecular roadblock: The TRAAK channel (purple and orange) dampens sensations by letting potassium ions escape from a neuron. Researchers found the channel uses a never-before-seen system for blocking that flow of ions when it closes: A lipid (yellow) from the neuron membrane (gray) protrudes into the channel.)
New work at Rockefeller University has revealed that one such channel in humans responds to mechanical force using a never-before-seen mechanism. Researchers led by Roderick MacKinnon, John D. Rockefeller Jr. Professor and head of the Laboratory of Molecular Neurobiology and Biophysics examined the TRAAK channel, which is involved in painful touch sensation, at the molecular and atomic levels, finding that it works by reducing the flow of potassium ions that create an electrical signal. The researchers’ findings were released today (December 3) in Nature.
”It is fascinating to wonder how living cells evolved molecules capable of turning small mechanical forces, such as those associated with touch, into electrical signals in the nervous system. That question served as the impetus for this work,” MacKinnon says.
The channels that act as gates in the membranes that envelop neurons, including TRAAK, allow electrically charged atoms, called ions, to move in or out. It’s this movement that is the basis for an electrical signal that carries information. TRAAK channels are one of 78 types of channels in the human body that transport potassium ions; there are other devoted to other ion types. By allowing potassium to trickle out of the neuron, TRAAK normally quiets the neurons, balancing out other channels, which would otherwise create a strong electrical signal for pain.
“TRAAK acts kind of like the brakes on a painful touch sensation, while other channels act as the gas. If you take away the brakes, innocuous touch becomes painful,” says first author Stephen Brohawn, a postdoc in the lab.
Prior work in the lab has shown TRAAK responds to membrane tension – that is stretching caused by a physical force. However, it wasn’t clear how this force caused the channel to open. In fact, scientists had previously only explained the workings of two mechanical-force sensing channels, both of which are found in bacteria.
After purifying the protein that makes up TRAAK, the team crystallized it and determined its structure using X-ray diffraction analysis. Based on the pattern produced by X-rays bounced off the crystallized protein, scientists can infer the structure of the molecule. But because it is difficult to get high-quality crystals from TRAAK, the researchers used antibodies that targeted it to create a sort of scaffold to help guide the formation of crystals.
In the structural images revealed by this work, the researchers found a unique system is responsible for holding off the flow of ions. TRAAK’s central cavity, through which the ions must pass, is flanked by two spiral-shaped chains called helices. When both of these chains are kinked upward, the channel is open so potassium can leave the cell. But when one of these two chains relaxes downward, it uncovers a sort of side door into the center of the neuron membrane.
Neuron membranes, like all cell membranes, consist of two layers of molecules called lipids that have heads facing outward and greasy chains extending inward. When TRAAK’s side door is open, one of those greasy chains, called an acyl chain, pokes into TRAAK’s central cavity, blocking it so no potassium can pass. No known channel uses a mechanism like this.
“This is the first time anyone has seen, at a molecular level, how mechanical force can open a channel in animals, including humans,” Brohawn says. “When the membrane stretches, TRAAK widens, sort of like a dot on a balloon that expands as it is inflated. That wider conformation pulls the helices upward, preventing an acyl chain from blocking the channel, and so leaving it open for potassium ions.”
“The direct involvement of lipid molecules in the gating mechanism begins to explain another well-known property of TRAAK channels – that their gating is sensitive to general anesthetics and other molecules known to enter the lipid membrane where they insert themselves between its acyl chains. By doing so, it appears these anesthetics can shut down pain sensations by locking TRAAK in an open position,” MacKinnon says.