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Window into Brain Sleep

June 8, 2014


Sleep builds learning and memory. Many studies show this–and we keep telling students that sleep will improve their grades. But how does it work? Here’s an actual window into a mouse brain, watching what might be new memories form.

At the NYU Skirball Institute (as typed, not “Screwball”) researchers Wen-Biao Gan and colleagues tested a mouse genetically modified to express Yellow Fluorescent Protein (YFP) in its brain neurons. This means that one of the mouse’s own genes in the DNA was fused to a DNA sequence encoding the fluorescent YFP; so the mouse’s own cells make the protein. Now, the researchers cut a window into the mouse’s skull, which enables them to put a microscope up to the brain and record photons coming out of YFP. Thus, one can take live pictures of individual mouse brain neurons as they grow.

How does the experiment work? First, mice are trained to learn a new task, how to climb upon a rotating bar. After learning this challenging task, the mice take a nap. That is, they are allowed to sleep as they wish for 8 hours, or else sleep-deprived for 8 hours. How the mice were sleep-deprived is described as “gentle handling” — not sure what that means. I would think 8 hours of hiphop music and fending off drunk bros would work better.

The bottom line is that:

  • After training, the microscope at the brain window detects neurons forming new “dendritic spines,” that is, branches on the nerve dendrites that may form new connections with other neurons–part of learning and stabilizing a new task or memory.
  • Mice that get to sleep form  more dendritic spines than mice that are sleep-deprived. Presumably, the well-rested mice learn their tasks better.

Much food for thought when planning your schedule next fall.


Amazon versus Hachette

May 29, 2014


Anyone living outside a box has heard by now of the megabattle between Amazon and Hachette over who gets to pocket more of the readers’ money. As the NY Times (to which I quaintly subscribe) so aptly put it, Amazon “promises a world where books are cheap, where anyone can publish anything,” whereas Hachette “is holding fast to the traditional publishing system that underpins modern culture.” So there.

Put that way, the choice could not be more stark–between good, and, well, something else good. It’s Godzilla versus MUTO–but who is which? And what about those two little people running underneath–Writer and Reader?

Ultraphyte has no real answers, but some thoughts.

  • Publishers do a lot for authors; more than most realize. Blockbusters make up for the myriad titles that never pay back their advance. Good editors help some authors reach the bar of professional communication. And good marketers promote works that would not otherwise get noticed.
  • Does the publisher’s work merit more than half the cover price? Even for ebooks? Do authors really want overpriced ebooks–or are we better off with lower price, larger volume?
  • Does the “added value” of a “traditional publisher” really merit the current backlog, approaching two years at my publisher? When anyone  could post it overnight on a website?
  • Lower price, larger volume, quicker publication all favor Amazon. But what happens when they’re the only game in town? Do we really expect them to just win and go home like Godzilla?

Personally, I’ve cheered Amazon for years as the place where all my “out of print” books could be found forever, and where I could find anything else out there. If selling kitchen and hardware stuff subsidizes books (one of the claims) so be it.

But I’d also like to see more competition. So, for the moment at least, I’ve switched my book links (at right) to Barnes and Noble.

Tell me what you think.



Microbial News at ASM

May 24, 2014

So what did we all learn at ASM, the American Society for Microbiology meeting 2014?

  • Bacteria you eat may prevent osteoporosis (bone thinning). Don’t all go out and buy probiotics, because health foods are unregulated and make outrageous claims. However, Lactobacillus reuteri makes a hormone-like molecule that does prevent bone thinning in mice. We saw slides of bones with and without. Furthermore, the bone-protective molecule inhibits development of cells that eat bone (osteoclasts). The doctors think that if post-menopausal women consume L. reuteri in some form, it may maintain bone density with fewer side effects than estrogen treatments.
  • Bacteria have a sense of touch. Before they make biofilms (multicellular communities), bacteria can “feel” the surface they touch using touch-sensitive proteins. How the touch transduction works, we still don’t understand.
  • Bacteria tell eukaryotic microbes to become multicellular bodies. Much evidence shows how bacteria and viruses activate key steps of embryonic development and immune system maturation. Now, a case has been shown in which marine bacteria tell unicelled eukaryotes called choanoflagellates to join together in rosettes.

The choanoflagellates then eat the bacteria–or do they? Do some of the bacteria take up residence?
Leading to the hypothesis that bacteria invented multicellular life to provide them a home.

  • More evidence for the bacterial home hypothesis: Human placenta contains specific bacteria. A few percent of the placental mass consist of normal bacteria, related to those of our mouths. These normal placental bacteria are actually needed for normal birth.
  • Even the deadly fungus Cryptococcus can provide a way to treat brain diseases. Cryptococcus makes an enzyme (a metal-containing protease) that can sneak its way across the blood-brain barrier. We may be able to use this enzyme to help us get therapeutic drugs into the brain.
  • Some bacteria may signal the gut via cannabinoid receptors. Getting ahead of my science fiction story, where the alien invaders take over Earth by spreading cannabinoids.

Alas, though, the “don’t floss” suggestion from previous post turned out to be a joke. Yes, keep flossing, despite the researchers who adore the dental bacteria they study.

From Brain to Biofilms in Boston: ASM 2014

May 16, 2014


Saturday we depart for Boston, five microbiologists to present our year’s work at the annual meeting of the American Society for Microbiology. To get the idea of how big it is, here’s a shot from last year’s meeting, which made the iPad program cover for this year. You can see Michael Harden and myself, viewing posters. This year Michelle, Anna, Kaitlin and Amanda brought theirs–actually, we sent the electronic files and crossed our fingers that the expensive printer service will print them out on site.

So what astounding discoveries will we hear?

  • How Cryptococcus (a fungus that commonly infects AIDS patients) uses a metalloprotease (a metal-carrying enzyme) to break through the blood-brain barrier.
  • How we might use this cryptococcal enzyme–amazingly–to deliver therapeutic drugs to the brain.
  • How global warming will impact microbial communities, such as those we need for farming.
  • How bacteria talk to each other–and us. How do we talk back?
  • Women microbiologists around the world–Egypt, South America, Asia.
  • Who are the bacteria we can’t culture? (That is, 99% of them)
  • The case against  flossing, which disrupts the (helpful?) biofilms on your teeth. (Skeptical about this one.)

Stay tuned.


Timmy the Tapeworm

May 10, 2014

Among this year’s Hugo nominees is Parasite by Mira Grant (Seanan McGuire). The novel depicts a world where everyone takes on an engineered tapeworm to maintain their own health. Some readers have questioned how such a world could be–it’s impressive that such a book even made it to the Hugo. But the author herself did her research–she herself hosted a live tapeworm named “Timmy,” as she told us at Boskone.

In fact, some physicians actually recommend hosting a tapeworm (in moderation) as a modulator of the immune system. (Don’t try on your own–there can be complications, like tapeworm in the brain.) As I posted earlier, therapy using pig parasites is now used to restore cytokine balance in the immune system. The therapeutic parasite can grow only for a limited time in the human, and cannot reproduce.

In fact, all our bodies have evolved in the presence of hosted organisms, just as we evolved in the presence of air and water. Even the bacteria that cause intestinal distress (diarrhea) have attributes that protect us from cancer. A study in PNAS 2003 showed an inverse correlation between the rates of diarrheal illness and of colon cancer.


More recently, the basis of the cancer correlation was shown to be certain toxins emitted by the bacteria, called enterotoxins. These enterotoxins mimic the body’s own regulator molecules that cause cells of the intestinal lining to differentiate for digestion. These same toxins (and regulator molecules) down-regulate cell proliferation leading to cancer. It appears that humans evolved to depend on a certain chronic level of diarrhea-causing bacteria to suppress tumor formation in the colon. But now, pharmaceutical companies are working to design versions of the enterotoxin that maximize the helpful effects without unpleasantness.

In effect, we learn something from our unwelcome visitors.

Praying Mantis 3D Glasses

May 3, 2014

In the “couldn’t invent this” department: Scientists have built 3D glasses for a praying mantis.

In their own words:

“Analysing how mantises see in three dimensions could give us clues about how 3D vision evolved and lead to novel approaches in implementing 3D recognition and depth perception in computer vision and robotics.

“A key component of the research entails presenting virtual 3D stimuli, such as moving targets within the visual field of the mantis. As a first approach, the researchers are attaching a pair of 3D glasses — the world’s tiniest – with beeswax to the mantis, and placing it in front of computer-generated images, presented on computer monitors.”

I guess this is one way to grow the audience for Avatar 2.

Acid-Adapted Genomes

April 24, 2014

Kaitlin_1Today Kaitlin Creamer ’16 of our Kenyon bacteria lab presented her sequence analysis for eight genomes of evolved E. coli strains adapted to acid. This project required next-generation sequencing, by Illumina MySeq, performed at Michigan State where our collaborators Rich Lenski and Zack Blount work. Kaitlin and Sean Bush ’17 installed Linux, Breseq and GATK among other things in order to piece together the genomes.

The Illumina method involves fragmenting your DNA into pieces of 250 base pairs. Each piece then gets sequenced by synthesizing DNA strands in both directions, with chemical terminators that get “read” by the machine. Then, all the millions of bits get overlapped in a giant megabase jigsaw puzzle. You can see just a fragment of it above. Each of the four DNA “letters” (nucleobases) gets a different color (red, blue, green, black). The other colors indicate regions that are suspect for various reasons.

The topmost sequence is the published “reference” genome of a typical laboratory E. coli  strain. If all the 250-mer pieces show a different base at one position, that suggests a mutation. Mutant varieties eventually get selected for or against. After 2000 generations (doublings) of E. coli, we found various strains that could grow faster than the ancestral strain; but only in acid. So now we’re testing the mutations in these strains to find out how certain genes help the acid-challenged bacteria.

This same sequencing method now churns out human genomes, bringing closer the day when  we all have our DNA immortalized in the cloud.


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