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4D Printing of Life?

March 24, 2019

We’ve all heard of 3D printing, the computer-controlled buildup of a material into a three-dimensional form. So what is 4D printing? Basically, the buildup of a material that has special functional properties.

A simple example would be a material that can be induced by a signal to deform or fold itself. The signal can be heat or water. Amazingly, the heat-deformable object shown retains its structural strength and load-bearing capability, even after it’s deformed.
Still other objects can be induced to fold into a precise 3D form. The MIT Self-assembly lab is famous for such devices.

What gets more interesting is when the printed substance consists of living cells and tissues. For instance, we can now print out replacement corneas for cornea transplant. Hearts and thyroids are on the way.

So at ICFA (the fantasy conference) we wondered: What would happens if you could print out an entire human being? “Clone” is a questionable term, because it has always referred to development of an organism from a single-cell zygote; in effect, a delayed twin. A 3-D printout however would have all the structure found in the copied adult—scars, memories encoded in neural connections etc. What rights would such a printout human possess?

Clone with Joan at ICFA 2019

March 21, 2019

We couldn’t clone Gay and Joe, but we sure tried! Jeanne and Johnna, too. What a great time we had–from human CRISPR to health-improving lentiviruses, microbial invention of metazoans to 3D-printed humans. Gut bacteria fight depression, if you’re Belgian or Dutch. And the truth about the hygiene hypothesis.

Meanwhile, who could beat the diverse fauna of our setting.

See you at ICFA 2020!

Brain Stroke Zaps Gut Bacteria

March 17, 2019

The gut-brain axis means your intestinal bacteria can influence the brain. But does the brain talk back and regulate the gut?

According to West Virginia University researchers, that is what  happens.
In experimental animals, a brain stroke (brain cells die due to injury) leads to disorganization of the gut lining, for weeks afterward. And the proportion of “good” bacteria decreases, compared to the less good ones. This work has not yet been published, but we’ll look forward to the details.

Painted Butterflies–Rare Good News

March 12, 2019

Most of the news for butterflies is terrible, with monarchs and others in exponential decline. But for one species, the painted ladies swarm by the billions past LA.

Of course this species is a generalist, feeding on any sort of plant. And it’s common for environmental disruption to favor certain populations for overgrowth, while many more kinds decline, so diversity loses. Nevertheless, it’s breathtaking to see these little wings migrate up the coast.

To help the butterflies and the bees, I support the Xerces Society.

Sugar-Coated Nanomachines Cure Cancer

March 10, 2019

An idea going back to Fantastic Voyage is that physicians can shrink to microscopic size and travel through the blood vessels to treat the site of a patient’s illness. Today, we’re not shrinking human physicians, but nanomachines. This research team at University of Tokyo focuses on a particular challenge for nanomedicine, getting the therapeutic agents across the blood brain barrier. The blood brain barrier is especially challenging to fight brain tumors, such as glioblastoma, the kind that Senator McCain had. Dr. Kataoka discusses his work here.

Kataoka’s group used an ingenious trick to get their device across the blood vessel membrane. The capillaries into the brain exclude lots of things, but need nutrients—especially the sugar called glucose. The brain has one of the highest glucose uptake rates found in the body. The glucose is taken up by a protein called GLUT1 that is embedded in the membrane of the capillary cells. So the researchers built a delivery device called a “micelle” (basically a highly engineered soap bubble). The micelle contains sugar molecules attached to a carbon chaine (hydrocarbon) that dissolves into the micelle membrane. Now the whole sugar-coated object can bind to GLUT1 molecules in the capillary, and dissolve through the membrane.

How do we know it works? This micrograph shows the capillaries within the brain of a mouse. The sugar-coated micelles have a tagged molecule that fluoresces red. In the first image, we see the micelles only found within the capillary vessels. But after 60 minutes, the micelles have leaked out of the vessels into the surrounding tissue; a process known by a mouthfull of a term, “extravasation.” Extravasation is something that white blood cells normally do all the time, in most parts of the body, but not the brain.

If that’s not strange enough, at ICFA “Clone with Joan” Saturday breakfast we’ll hear more about how gut bacteria may take up residence in the brain (a controversial report) and how bacteria can treat human genetic diseases. Sounds more and more like the microbial aliens of Brain Plague.

Infrared Mice. Wait, What?

March 3, 2019

Perhaps the most curious thing about this story, of how mice were made to see infrared, is that it represents a collaboration amongst three Chinese universities plus the University of Massachusetts Medical School. Wait, what? So our leading universities are engineering our soldiers plus the Chinese to see each other glow in the dark?

The human visual spectrum spans red through violet. Red light has longer wavelength and smaller energy per photon; violet has shorter wavelength and higher energy. Recall how the protagonist of Brain Plague had one mutated gene that enabled her to see infrared, the wavelength beyond red color, shading into thermal radiation (heat). What Chrys could see might look something like this:

What animals can see infrared? Some snakes, mosquitoes and bedbugs can detect infrared. Humans can detect infrared photons—but only as bursts of many photons coming together, so pairs of them can add up. To see individual infrared photons is not possible for mammals, because we are “warm-blooded.” Because we maintain a higher temperature, our thermal energy generates “noise”; that is, random firing of the opsin proteins that absorb each photon.

But the Chinese and Massachusetts investigators made use of an optical trick with nanoparticles. The nanoparticles show a form of fluorescence called “upconversion.”

Fluorescence, the simple kind, involves a material that absorbs light at a short wavelength (lambda 1); dissipates some of its energy as heat (broken line); then emits the rest of its energy as a photon of longer wavelength (lambda 2) with lesser energy. For example, absorb blue, emit red.

Suppose however your detector absorbs infrared: Could it emit light at a shorter wavelengh, which your retina can see? Not by plain fluorescence. But upconversion means that the electron cloud absorbing the first infrared photon then absorbs a second one, and is raised to an even higher energy state. Now the electron cloud can release all its energy in one photon of shorter wavelength (lambda 2).

So the researchers injected upconversion nanoparticles into the retinas of mices. The nanoparticles coated the mouse photoreceptor cells, where they could absorb infrared and emit light in the visible range (green). When the mice were given green light (535 nanometers wavelength) they produced electrical signals. And when the nanoparticle-injected mice were exposed to near-infrared light (980 nm) them also produced electrical signals–in response to the green light emitted by upconversion of the nanoparticles.

The infrared response was imperfect, but it was good enough for the mice to distinguish patterns and shapes formed by infrared. Perhaps this kind of approach could engineer new kinds of color vision in the future. If you don’t mind your retina getting injected.

Arsenic and Old Lace–Actually, Bacteria

February 24, 2019

Ultraphyte welcomes you back!

The past two years of my break from the blog have yielded ever more reasons to thank your hardworking gut bacteria. From brain control to jet lag, bacteria on their way to poop manage to control just about everything. Microbes invented us metazoans to house them—more on that in a future post. We look more like Brain Plague all the time.

Arsenic poisoning is the stuff of plays and forensics—and all too real a hazard in ground water, particularly the western USA. Chronic exposure leads to skin problems, deterioating organs, and cancers. Yet surprisingly, individuals can vary in their sensitivity. What deterimines arsenic’s effect on our bodies?

Bacteria may play a huge role. As in Brain Plague, microbial inhabitants actually do collect arsenic and protect us from it. Michael Coryell and other in Seth Walk’s lab at Montana State conducted fascinating experiments with mice. They used mice treated with antibiotics to kill much of their normal gut bacteria. The mice (plus untreated controls) were given drinking water with arsenic. (I know, those cruel scientists.) Antibiotic-treated mice excreted more arsenic in their urine than controls (a). And the antibiotic-treated mice retained more arsenic in their organs (b). Looking at the graph, the (b) result is less convincing than the excretion result, but still intriguing, especially the dramatic difference in the lungs.

How could our bacteria protect us? The bacteria metabolize arsenic—that is, they add various chemicals to it, such as sulfurs and carbons (thiols and methyl groups). Arsenic metabolism is extremely complicated, but some chemical conversions make it more soluble and less toxic, whereas other conversions do the opposite.

Even more interesting, the researchers took germ-free mice (reared in isolation from birth, like the bubble boy) and added human gut microbiota. The so-called “humanized mice” survived arsenic much better than the germ-free mice. In fact, the researchers zeroed in on one particular species, with the mouthful name of Faecalibacterium prausnitzii.

The germ-free mice survived arsenic about five days longer if they hosted this F. prausnitzii.

I still wouldn’t drink arsenic water regularly, but it’s good to know our gut residents are looking out for us—one wonders what all else they are up to.

If you’d like to reward your helpful gut friends, remember to eat some chocolate because bacteria tell us they want it.

Hope to see you at ICFA in sunny Orlando! Remember our traditional Saturday 8:00am breakfast, Clone with Joan.