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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.

www.latimes.com/science/sciencenow/la-sci-sn-butterflies-desert-explosion-20190312-story.html

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.

 

 

From Skin to Eggs

May 18, 2017

Now that grades are turned in, I can take a moment off from the Indivisible site that’s occupied my blogging since November, to highlight a momentous event, long foreseen: Conversion of skin cells to eggs. For the first time, molecular biologists have converted mouse fibroblasts (a type of skin cell) into pluripotent stem cells (cells that have lost the skin-type specialization) which then were converted into egg cells. The eggs were then fertilized in vitro (IVF) with normal sperm, and produced viable mouse pups.

For humans they say skin-to-egg is maybe five years away. If every skin cell could be a baby, will we outlaw dandruff?

The details are more intriguing yet, as describe by Katsuhiko Hayashi in his original report.

The full process actually required two types of cells: embryonic stem cells (providing helper genes), and the skin cell-derived stem cells to become eggs. The requirement of embryonic helpers is one aspect that will prove challenging to perform in humans.

For egg production, the two types of cells are aggregated to form ovary-like tissues, “ovaries in a dish.” Within these artificial ovaries, the skin-cell derived cells differentiate (become specialized) to form functionally normal oocytes (egg cells). Remarkably, the egg cells undergo normal development including exclusion of one set of chromosomes within a tiny polar body. The successful fertilization rate is about

The study’s author describes further implications of their work here. The timing of human egg production will involve several months, and the requirement for supporting embryonic cells is a hurdle. But in the past such requirements for stem cell procedures have been superseded by chemical treatments that mimic the cells’ developmental signals.

What medical applications could this technique have, if developed in humans? Such techniques might lead to uniparental humans (the egg and sperm derived from one person); or to humans with multiple parents providing different chromosomes. One thing is clear, the role of conception in human biology would be shifted, with unknowable results for our concept of what is human.