Scientists capture first super-res X-rays of living cells

While lower-energy "soft" X-rays can already image living cells, the higher-energy "hard" ones that can view objects as small as a few nanometers haven't been able to -- until now.

 

To avoid damaging the cells, the researchers exposed them for only 0.05 seconds at a time, but still managed to image nanometer-scale structures. Britta Weinhausen/University of Göttingen

Typically, to view super small objects like molecules, the samples must first be dipped in a chemical preservative bath of death that keeps all parts entirely locked in place and thus viewable via very sophisticated tech such as X-ray devices and electron microscopes. The problem, of course, is that those molecules don't behave the same in death as they do in life, so while our current views of life at the nanoscale level are extremely detailed, they're technically speaking views of death, or at the very least, life frozen.

Now scientists at the University of Göttingen in Germany say that, using a new approach with one of the world's most sophisticated X-ray machines, the Petra III, they've been able to view -- however briefly -- actual living cells in their natural environment.

Reporting in the journal Physical Review Letters, the researchers say they grew cancer cells from the adrenal cortex on a silicon nitrate substance that is nearly transparent to X-rays. They then fed those cells nutrients and pumped away their metabolic products so that they could keep the cells alive in as close to a natural environment as possible while still being viewable by the higher-energy (aka "hard" X-ray) Petra III. While lower-energy "soft" X-rays can already image living cells, the resolution isn't as good.

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To avoid killing the cells with the powerful X-ray beams, they exposed the sample in a series of frames that each lasted a mere 0.05 seconds. They then used this same nanodiffraction approach on chemically fixed cells for comparison and found that their cellular structures were noticeably different when viewed on a scale of 30 to 50 nanometers (that is, millionths of a millimeter).

While this initial test was performed using extremely brief and powerful blasts on petri dish cancer cells, the researchers say it offers evidence that we should be able to study living cells at super high resolution without first having to change their molecular behavior -- which could dramatically improve our understanding of life, including diseases and treatments, at the nanoscale level.

ORIGINAL: CNet

by Elizabeth Armstrong Moore @ejamoore
February 28, 2014

Here’s What Happens Inside You When a Mosquito Bites

ORIGINAL: Phenomena - NatGeo
by Ed Yong

Anopheles gambiae. Credit: James D. Gathany, CDC.

The video above shows a brown needle that looks like it’s trying to bury itself among some ice-cubes. It is, in fact, the snout of a mosquito, searching for blood vessels in the flesh of a mouse.

This footage was captured by Valerie Choumet and colleagues from the Pasteur Institute in Paris, who watched through a microscope as malarial mosquitoes bit a flap of skin on an anaesthetised mouse. The resulting videos provide an unprecedented look at exactly what happens when a mosquito bites a host and drinks its blood.

For a start, look how flexible the mouthparts are! The tip can almost bend at right angles, and probes between the mouse’s cells in a truly sinister way. This allows the mosquito to search a large area without having to withdraw its mouthparts and start over.

“I was genuinely amazed to see the footage,” says James Logan from the London School of Hygiene and Tropical Medicine, who studies mosquitoes. “I had read that the mouthparts were mobile within the skin, but actually seeing it in real time was superb. What you assume to be a rigid structure, because it has to get into the skin like a needle, is actually flexible and fully controllable. The wonders of the insect body never cease to amaze me!”

From afar, a mosquito’s snout might look like a single tube, but it’s actually a complicated set of tools, encased in a sheath called the labium. You can’t see the labrum at all in the videos; it buckles when the insect bites, allowing the six mouthparts within to slide into the mouse’s skin.

Four of these—a pair of mandibles and a pair of maxillae—are thin filaments that help to pierce the skin. You can see them flaring out to the side in the video. The maxillae end in toothed blades, which grip flesh as they plunge into the host. The mosquito can then push against these to drive the other mouthparts deeper.

The large central needle in the video is actually two parallel tubes—

• the hypopharynx, which sends saliva down, and 
• the labrum, which pumps blood back up. 

When a mosquito finds a host, these mouthparts probe around for a blood vessel. They often take several attempts, and a couple of minutes, to find one. And unexpectedly, around half of the ones that Choumet tested failed to do so. While they could all bite, it seemed that many suck at sucking.
The video below shows what happens when a mosquito finally finds and pierces a blood vessel. On average, they drink for around 4 minutes and at higher magnifications, Choumet could actually see red blood cells rushing up their mouthparts. They suck so hard that the blood vessels start to collapse. Some of them rupture, spilling blood into the surrounding spaces. When that happens, the mosquito sometimes goes in for seconds, drinking directly from the blood pool that it had created.

When the mosquitoes were infected with the Plasmodium parasites that cause malaria, they spent more time probing around for blood vessels. It’s not clear why—the parasites could be controlling the insect’s nervous system or changing the activity of genes in its mouthparts. Either way, the infected mosquitoes give up much less readily in their search for blood, which presumably increases the odds that the parasites will enter a new host.

Many hours after a bite, Choumet’s team found Plasmodium in the rodents’ skin, huddled in areas that were also rife with the mosquito’s saliva. The mosquito starts salivating as soon as it probes the mouse’s skin, releasing substances that 

• prevent blood vessels from constricting, 
• stop blood from clotting, and 
• prevent inflammation. 

Sometimes, Choumet could see the saliva as small bubbles that hung around the tips of the mouthparts. And even after the mosquito stops feeding, pockets of saliva linger in the lower layers of the skin. Plasmodium parasites seem to stay in the same place—perhaps they work together with the salivary chemicals to suppress the mouse’s immune system.
The team also tested “immunised” mice, which were loaded with antibodies that recognise a mosquito’s saliva. “Some people, especially in Africa and Asia, are bitten several times every day, so we wanted to know if mosquitoes behaved differently when they bit animals that were immunised against their saliva,” says Choumet.

She found that the antibodies reacted with the insect’s saliva during a bite, forming noticeable white clumps at the tips of the probing mouthparts. This clogged up smaller blood vessels, which stopped the mosquitoes from drinking from them. But the insects got around this problem by probing around for longer, and by hitting the largest blood vessels.

Beyond the stunning videos, these discoveries are unlikely to lead to new ways of preventing or treating malaria by themselves. However, they do tell us a lot more about the event that kicks off every single malaria case—a mosquito bite. It’s a resource that other researchers will undoubtedly use. “I have submitted a grant application to investigate aspects of the interactions between mosquitoes, hosts and parasites,” says Logan. “The techniques and discoveries from this paper are very exciting to me, and will be of value to future activities of my own research group.”

Hat-tip to James Logan for alerting me to the story via Twitter, and inspiring the headline!

Reference: Choumet, Attout, Chartier, Khun, Sautereau, Robbe-Vincent, Brey, Huerre & Bain. 2012. Visualizing Non Infectious and Infectious Anopheles gambiae Blood Feedings in Naive and Saliva-Immunized Mice. PLoS ONE http://dx.doi.org/10.1371/journal.pone.0050464

Supercomputer will help researchers map climate change down to the local level

ORIGINAL: Washington Post

By Stephen P. Nash,

An advance guard of 18-wheelers is scheduled to roll into a business park in Cheyenne, Wyo., this week to unload components of a supercomputer called Yellowstone. This 1.5-quadrillion-calculations-per-second crystal ball will model future climate and forecast extreme weather.

“It’s a big deal,” said climate scientist Linda Mearns of the National Center for Atmospheric Research in Boulder, Colo. Yellowstone will help researchers calculate climate change on a regional, rather than continental, scale. With a better grasp of how warming may affect local water resources, endangered species and extreme winds, local and state governments will be able to plan more effectively.

Marika Holland, chief scientist for NCAR’s Community Earth System Modeling Project, said the new supercomputer is “close to a game-changer. We’ve had incremental improvements in our computational resources over time, but Yellowstone is a whole new scale, and there are things that we will be able to explore that just were not possible before.”

As climate models become more complex and detailed, limited computing power bottlenecks the research. Broad-brush models use less power, but they often cannot consider details that drive local climate, such as complex coastlines or the mountain ranges and valleys that affect rainfall. Researchers refer to this as a problem of “model resolution.”

“If you have an old digital camera that doesn’t have as many megapixels as a new one, you want to get that [new] camera because it takes sharper pictures, and you can store a lot more pictures on it,” said Richard Loft, a director in the computing lab at NCAR.

“It’s the same thing with Yellowstone. We’ve increased our ability to generate more-detailed pictures of the climate system, so we get a sharper, crisper view of things.”

Seven-square-mile ‘pixels’

Yellowstone will be able to generate climate projections for seven-square-mile “pixels,” instead of the 60-square-mile units typically in use now. “We’ve already had the model resolution to confirm the warming of the planet but not to talk about the winners and losers at the regional scale,” Loft said.

The new computer will cost about $30 million; it will be operated by NCAR, which is funded by the National Science Foundation. And just like your own computer, it is likely to be obsolete and ready for replacement by a faster model in about four years.

Yellowstone and its successors will allow modelers to provide a more reliable range of possible answers for local climate questions:

• How dry will it be by mid-century, say, in the watersheds that feed the Prettyboy and Loch Raven reservoirs, which supply much of Baltimore’s water? 
• How high will summer heat spike in the Shenandoah Valley? 
• Where can Florida panthers and loblolly pine, a major source of timber, survive as the climate shifts?

“Many climate scientists out there are itching to be able to do higher-resolution simulations and more experiments,” Holland said. “One of our working groups has strong links with water resource managers and water utilities. For them, models of sea-level rise, vegetation, snowpack, precipitation and stream-flow changes are all important. Those planners are living with the uncertainty of how climate changes are going to occur.”

Mathew Maltrud of the Los Alamos National Laboratory in New Mexico runs climate models that try to mimic the physics of rivers, vegetation and atmospheric moisture, sea ice and ocean currents.

“We’re moving into a realm where we have models that resemble the ocean, the atmosphere, the ice and the land to a high degree,” he said. Yellowstone will allow those components to interact more realistically.

“For example, what’s going to happen in the southwestern U.S.?” Maltrud asked. “Wetter? Drier? The models out there right now show a lot of agreement on global change, but when it comes to regional scales, there’s lots of variability. We hope to get far better representation of precipitation, which is definitely key for decision-makers. That could have a very large impact on understanding regional changes all over the world.”

The dinosaurs’ fate

Several modeling efforts intended to provide data for local and regional planners that are already underway may benefit from additional computing power.

Adam Terando, climate change research coordinator at North Carolina State University, is incorporating climatic factors into regional modeling as part of a federal effort to “make climate-change data more useful and relatable for decision-makers,” he said. His research also tries to prophesy a range of future climatic changes that could affect agriculture in the eastern United States: frost days, heat stress and the length of growing seasons.

Those decision-makers “need to know: How is climate change going to affect my wildlife refuge on the coast of North Carolina, or Virginia?” Terando said. The Southeast, for example, has high numbers of amphibian species. The amphibians are reliant on the little puddles that form in the winter and spring called vernal pools, where they hatch their young.

“If the water table changes, how will it affect them?” he asked. “We’re talking to these people already. They know they need to be doing planning now, not just for the next 10 years, but for the next 30 or 50 years, and beyond.”

Yellowstone will also allow researchers to produce climate snapshots with intervals of hours rather than days; such detail is difficult now because of limited data storage capacity. “That fine step is really what the folks that I work with — the ecologists and biologists and all the resource managers — really need,” Terando said, “because that’s much more useful for figuring out how climate change could affect different plants and animals.”

Loft has been most concerned about projections that raise the possibility of severe drought through the central and southwestern states and in Turkey and Spain — far worse conditions than the drought that has caused water rationing and the liquidation of cattle herds in Texas.

“Would you rather go to a doctor who tells you what you want to hear, or what’s really going to happen?” Loft asked. “Not everybody has the same answer to that, I guess. I’d like to know. And this machine’s going to help us know more about how bad climate is, as a threat to human civilization, and I think that’s a good thing.

“Dinosaurs didn’t have any technology to know something was coming, so they just woke up one day and found out that the planet was destroyed. But if we can know about it 30 years before it happens, and do some things to cope with it, we can still mitigate the impact on human beings,” he said.

Nash reports on climate science and teaches journalism at the University of Richmond.

Climate change around the world

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Smog and haze hover over Salt Lake City. The thick layer of smog lingering over Utah has fouled the state's mountain air so badly that health officials have warned people not to exercise outside and schools are keeping children inside for recess and sports. The smog is blamed on a weather phenomenon that pins pollution to the valley floors. Brian Nicholson / AP