It is old news that exercise improves the brain–at any age, from children who walk to school, to the elderly who garden. Prolonged exercise, as in running, is what we evolved to do. Running–and the intellect involved to track down animals–led early humans into a unique form of hunting, one that required memory and calculation. But what is the physiological connection? How do the heart and skeletal muscles affect the brain?
Now, researchers are beginning to figure out the molecular basis: What specific genes and proteins do the job. It took a collection of scientists from Lebanon to NYU and Harvard to come up with this alphabet soup of a project, “Exercise promotes the expression of brain derived neurotrophic factor (BDNF) through the action of the ketone body β-hydroxybutyrate.”
The researchers set mice to running on their proverbial running wheels. After thirty days running, compared with slacker mice, the runners showed increased amounts of a brain protein called BDNF. BDNF is a protein that encourages nerves to grow; a member of the same family as nerve growth factor, the protein discovered by the famous Nobel laureate Rita Levi-Montalcini (who makes an appearance in The Highest Frontier). BDNF helps maintain synapses and grows new ones in the hippocampus, cortex and forebrain; basically everywhere needed for higher function.
So what is the molecular mechanism? The authors proposed and tested a form of “epigenetics,” a mechanism by which environmental experience alters chemical tags attached to the neurons’s DNA, or to histone proteins associated with the DNA. Epigenetic markers involve enzymes called histone deacetylases (HDAC). The HDAC removes an acetyl group from a histone, a binding protein that helps “pack” DNA and determines whether its gene gets transcribed to RNA. Here, DNA is wrapped two turns around a core of eight histones (colored).
The authors did experiments that showed that inhibitors of HDAC proteins (specifically HDAC2 and HDAC3) could prevent the histone deacetylation, leaving the DNA wrapped around histones marked with acetyl groups. Acetyl groups usually code for “go ahead” and transcribe a gene. So now the gene encoding BDNF goes ahead and gets transcribed to RNA, which then gets translated by ribosomes to make BDNF protein.
What all does this have to do with mice on their running wheels? The running mice make extra ketone bodies such as D-β-hydroxybutyrate (DBHB). Ketone bodies get made by your liver after intense exercise uses up carbohydrates. Excess ketone bodies can cause problems, but as a short-term response to exercise they supercharge the brain. In particular, DBHB blocks production of HDAC2 and HDAC3 (that is what the cross-blocked vertical lines mean, in the diagram above). Since DBHB blocks the HDACs, and the HDACs block expression of BDNF, the net result is that ketone bodies induce BDNF which enhances neurons and makes more synapses.
Atlantis of ancient ruins? Not so fast. What divers thought was an ancient Greek metropolis was actually an outgrowth of microbes. The microbes are stated to be methanogens (archaea that convert carbon dioxide and hydrogen into methane) but I think actually they are methane oxidizers. At the bottom of the ocean, methane often arises at cold seeps, places where petroleum components and minerals seep up from subsurface volcanic activity. The minerals get oxidized by bacteria, and carbonates precipitate into odd formations.
Our Gulf of Mexico is full of cold seeps, where the methane gets oxidized by sulfate bacteria, as indicated by isotope ratios. Some of the sulfate bacteria then inhabit clams that may lose their feeding ability. The reduced sulfate can then be oxidized to sulfides within symbiotic worms. Green dots show fluorescently labeled bacteria oxidizing sulfides within the worm. The size bar is 0.02 millimeters.
So indeed, there is a complex intricately cooperative civilization–of microbes. Meanwhile, carbonates precipitate with magnesium ion, forming dolomite. The dolomite formations date to several million years ago–even more ancient than the Greeks. As the authors state, “Exposure on the modern seabed in the shallow subtidal zone has caused confusion, as concretion morphology resembles archaeological stonework of the Hellenic period.”
Buried beneath reality show headlines, the NYT breathlessly informs us, “Scientists Talk Privately” about something. To wit, a group at Harvard has a secret meeting to plan to “create” an entire set of human chromosomes. Could this really be it–an Artificial Person? Without (gasp!) biological parents?
Like a rather bad Heinlein novel, there are enough contradictions to go around.
First of all, what’s so unique about making a human genome–something trillions of our own body cells do every day? The NYT informs us, the scientists will “use chemicals to manufacture all the DNA.” Mm-hm. So my own cells are made of what, if not chemicals? Cosmic ray particles, maybe?
What we call “chemicals” presumably means bulk processed petrochemical products stored in 1-kilo bottles obtained from Sigma-Aldrich or Thermo-Fisher. And “manufacture” means a concrete-slab factory, where mostly male persons “fabricate” things, as opposed to a bit of meat within a female that uses its own DNA copying enzymes.
But suppose, continues NYT, we could “use a synthetic genome to create human beings without biological parents?”
Project leader George Church (who started out as a bacterial molecular biologist) assures us we’ve got it wrong. “They’re painting a picture which I don’t think represents the project,” Church observes. The project is “not aimed at creating people, just cells.” Again, this claim represents a surprisingly parochial view of what constitutes the “natural” human reproductive process. We can argue endlessly over whether a fertilized egg or embryo constitutes a human being, but there can be no doubt that most of our bodies at some point developed from a single cell that became a few more cells.
The technology exists to replace the nucleus of an egg cell with a new nucleus. Could a “synthetic” set of human chromosomes replace the chromosomes of an egg cell? What about a skin cell transformed into an egg, something also near possibility?
Of course, no article about artificial human life is going to get away without mentioning Einstein. The crowning awful possibility: “Would it be O.K., for example, to sequence and then synthesize Einstein’s genome? If so how many Einstein genomes should be made and installed in cells, and who would get to make them?”
Please–Enough already Einstein. Myself, I’d rather recreate Mileva Marić, the physicist whom Einstein got pregnant and married, and who probably co-created his most famous works.
So why create a synthetic human genome? We don’t know, given the “secret” nature of the Harvard meeting, but let’s give them a break and assume they just want a more efficient way to “construct” a genome out of various parts and see what it does in a cell. Cell culture is a lot more efficient than running after mini-humans (mice), as some of my students can attest. Nevertheless, we approach ever nearer the day when any skin cell could become a human.
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In A Door into Ocean, the Sharers tend their entire planet, lifeshaping each apparently wild form of life to restore balance. The corals on the floating trees get helpful microbes, while the seaswallowers get lifeshaped (engineered) to resist the invaders’ poisons. Is that where we’re headed? Already our wilderness managers radio-tag every vertebrate in sight, monitoring populations like a zoo. But Hawaiian biologists are going one step farther: actively breeding corals to withstand global warming, the climate change now inevitable. Unnatural selection? Perhaps, but perhaps better than no corals left?
Ruth Gates and Madelein Van Oppen are trying just that. Gates noted some exceptionally hardy corals in Hawaii that seemed to withstand heat and acid, the two big causes of coral death. She and Van Oppen obtained grants from Paul Allen’s Ocean Challenge program. Their mission: to build Super Corals for the Future.
After a massive coral bleaching episode, Gates found regions where occasional corals bloomed surrounded by dead ones. Even the survivors’ symbiotic algae were okay. So now she propagates these survivors, and investigates their genes, trying to find out how to make corals hardier.
Does the Super Coral project represent future promise, or only vain hopes? Coral grows slowly; it’s hard to see how a few engineered polyps could propagate throughout the ocean. Rising temperatures and falling pH are happening so fast, faster than ever recorded in Earth’s history. Mitigation projects should not lull us into thinking we can ignore a rate of change that will eventually boil our planet. But perhaps on the way, we might save a few corals. Gates says, “Our project is acknowledging that a future is coming where nature is no longer fully natural.”
Surprisingly, we find corals even in regions where biologists had thought their growth impossible. Most recently the muddy mouth of the Amazon was shown to host corals, along with sea fans, fish, and sponges. Considering how much traffic the Amazon gets, we biologists might be surprised and just a bit embarrassed to have overlooked such riches. Surely it’s worth the investment to see how much life we can save, while the world’s populations make their leaders keep the world worth saving.
In the face of climate change, we commonly get caught up in the vast scale of melting Antarctica and flooding Florida. But it’s also good to step back and reflect on the everyday experience of wildlife biologists contending with saving just one form of life in one imperiled habitat. For such an example, see the Bawean Warty Pig (Sus blouchi). As its name implies, the warty pig is distinguished by the gigantic “warts” on its face. Why would a pig evolve such bulges on its ugly-enough head? For the same reason orangutans have side cheek pouches, and teens wear mohawks: To look larger and tougher than you really are. The blurred photo above suggests the photographer was anxious to get away before finding out.
The warty pig lives in only one place on Earth: Bawean, one of Indonesia’s 18,307 islands. The human population of Bawean is so poor that women outnumber men 2:1 because the husbands have to work in Vietnam or some other richer place. Not surprisingly, much of the island has been deforested. And the forest is the only place where the warty pigs remain–less than 250 adults, by camera count.
So what’s a wildlife biologist to do? A PLoS ONE study by Mark Rademaker, Eva Rode-Margono and colleagues gives us some idea. They report the First Ecological Study of the rarest pigs on Earth. Note: The virtue of PLoS ONE is that you don’t have to prove to reviewers that your subject is “important.” You only have to show that you’ve done statistics that convince someone the results are “significant” (different from chance) as meant by mathematicians. Presumably the warty pigs are important enough to Mark and Eva that they spent two months there (November-December, 2014-2015, the same time as my season in Antarctica) on an island with no airstrip.
The most important thing they did was to record the animals. 690.31 camera-trap days, to be exact. By building up the counts over time, the researchers could show that the count “stabilized” by 500 days; that is, the researchers can claim mathematical confidence that their searching has counted most but not all of the few hundred warty pigs. For most of the pigs observed, the researchers also determined sex and age. How were sex and age determined? By the patterns of warts and of golden yellowish hair. Interestingly, the male to female ratio was 1:2, similar to that of Bawean humans. This point the researchers do not explain. Presumably the male pigs are not off working in Vietnam.
The researchers do spend a great deal of energy and mathematics on describing the warty pigs’ habitat preferences. They conclude, “We interpret the negative relationship between S. blouchi density and distance to nearest border as a direct link with increasing distance to the community forests at the edge of the forest.” In other words, pigs like to live in “community forests,” that is, forests managed by the local community with a say in land use decisions, and partial protection for wildlife. To its credit, Bawean island does maintain eleven protected nature reserves and three community forests.
The authors conclude with Conservation Recommendations: to declare the warty pigs Endangered, primarily on the basis of their small total number. Remember that such a small number of a vertebrate species can lead to inbreeding and genetic bottleneck. Fortunately the current population looks pretty healthy for now. So there’s hope for the rarest pig–thanks to their catching the eye of Jake-and-Neytiri-like starry-eyed biologists, with the financial support of the Indonesian Ministry of Research and Technology and the Office of Conservation of Natural Resources. As someone waiting on NSF right now, I sure can appreciate that one.
In Orlando for ICFA 37, I had the pleasure of exploring the latest bizarre biology with Gay and Joe Haldeman, Cat Rambo, Sherry Vint, Jeanne Griggs, Sandy Lindow, among others. From tree networks to jet-lagged bacteria, it was the most fun at breakfast I’ve had in a long time. An unexpected bonus was remembering Joe’s The Forever War. Unfortunately Joe’s pic didn’t come out on my phone, but there are plenty of him out there in Google, including this one along with Gay (who, next to Cat, did come out on mine.)
Back in 1974, The Forever War was ahead of its time in presenting a partly-positive view of genderless society; and also a plausible model for evolution of a eusocial colony (such as ants or mole rats) or even a multicellular organism. The story is told by a soldier Mandella (which I always thought referred to Peter, Paul & Mary’s song) in a Vietnam-like war that goes on across the light-years for no clear reason. Over the centuries, society encourages same-sex relations in order to curb overpopulation, until finally only a few heteros remain to reproduce. In biology, analogous trajectories have led to evolution of eusocial insects, in which only a few queens and drones reproduce. And in microbes you can trace analogous evolutionary paths to multicellular life with a soma and germ line.
The notion of same-sex society to limit human population seems quaint today, with gay marriage and all kinds of tech-assisted reproduction. But a closer look gets more interesting. What our Western society does encourage today is androgeny, cross-gender, and cross-careering, with inevitable postponement of reproduction. Heteros increasingly use the non-reproductive sexual practices invented by gays. And yes, most Western countries are declining in population. In the US, our native-born population is shrinking, but the decline is offset by immigration. Are we outsourcing our breeding to war-torn countries that feed us refugees? Maybe we should treat them with a little more respect.
If you heard it on NPR it must be true. A newly discovered bacterium, Ideonella sakaiensis, can munch its way through a notoriously indestructible form of plastic, called polyethylene terephthalate, or the cute acronym PET. For recyclers, it’s the #1 plastic. From strawberry containers to Ishampoo bottles, it’s all around us. What makes it so conveniently immortal? It’s the concentration of aromatic rings; that is, usually six-carbon rings with alternating double bonds like benzene. This kind of molecule used to be called “xenobiotic,” meaning so alien to life that no living microbe could ever break it down.
But as microbiologists know, plastic is just another arrangement of carbons and hydrogens, and an occasional oxygen, so eventually with enough evolution, DNA will make a slightly twisted enzyme that can munch the polymer down to its monomer parts. Hence the Ideonella bacterial enzyme, PETase (the “ase” part means “I eats it”).
PETase hydrolyzes the ester bond that links each terephthalate link to its neighbor. You can think of ester bonds as the weak link in the chain, like the connection between two Lego bricks: If it’s going to break, there’s where it will happen. All kinds of biomolecules are connected by esters, including sugar chains (carbohydrates) and the phosphodiester bonds of DNA. What makes PET different is that the enzyme has to fit itself to the aromatic portion, to recognize where to stuff the ester into its active site. Afterward, still other enzymes such as MHETase have to break down the aromatic portion. Surprisingly, the microbial domain is full of aromatic degrading enzymes because wood and leaves are full of such compounds, called lignin.
So how did the Japanese discoverers find this bacterium? They collected hundreds of samples–from a PET bottle recycling site. Of course, in that environment, a soil bacterium that eats PET could find a competitive edge. Soil is one of the most competitive environments out there, full of predatory and cannibalistic microbes. To get ahead, either you cooperate with them (we’ve had many posts on that) or you out-eat them, eating something they can’t. The researchers had to (1) isolate the bacterium as colonies in culture–a real trick, as 99.9% of bacteria won’t; (2) prove that it actually breaks down PET and assembles the carbon into its own cell parts. A lot of work to find, but any contaminated waste site is a potential source of microbial recyclers.