Where Does Oxygen Come From?

Boring into the photosynthetic reaction center of plants, where O2 is synthesized.

Oxygen might be important to us, but it is really just a waste product. Photosynthetic bacteria found that the crucial organic molecules of life that they were making out of CO2 and storing in the form of reduced compounds (like fats and sugars) had to get those reducing units (i.e. electrons) from somewhere. And water stepped up as a likely candidate, with its abudance and simplicity. After you take four electrons away from two water molecules, you are left with four protons and one molecular oxygen molecule, i.e. O2. The protons are useful to fuel the proton-motive force system across the photosynthetic membrane, making ATP. But what to do with the oxygen? It just bubbles away, but can also be used later in metabolism to burn up those high-energy molecules again, if you have evolved aerobic metabolism.

On the early earth, reductants like reduced forms of iron and sulfur were pretty common, so they were the original sources of electrons for all metabolism. Indeed, most theories of the origin of life place it in dynamic rocky redox environments like hydrothermal vents that had such conducive chemistry. But these compounds are not quite common enough for universal photosynthesis. For example, a photosynthetic bacterium floating at the top of the ocean would like to continue basking in the sun and metabolizing, even if the water around it is relatively clear of reduced iron, perhaps because of competition from its colleagues. What to do? The cyanobacteria came up with an amazing solution- split water!

A general overview of plant and cyanobacterial photosystems, comprising the first (PSII), where the first light quantum hits and oxygen is split, an intervening electron transport chain where energy is harvested, and the second (PS1), where a second light quantum hits, more energy is harvested, and the electron ends up added to NADP. From the original water molecules, protons are used to power the membrane proton-motive force and ATP synthesis, while the electrons are used to reduce CO2 and create organic chemicals.

A schematic of the P680 center of photosystem II. Green chlorophylls are at the center, with magnesium atoms (yellow). Light induces electron movement as denoted by the red arrows, out of the chlorophyll center and onwards to other cytochrome molecules. Note that the electrons originate at the bottom out of the oxygen evolving complex, or OEC, (purple), and are transferred via an aromatic tyrosine (TyrZ) side chain, coordinating with a nearby histidine (H189) protein side chain.

This is not very easy, however, since oxygen is highly, even notoriously "electronegative". That is, it likes and keeps its electrons. It takes a super-oxidant to strip those electrons off. Cyanobacteria came up with what is now called photosystem II (that is, it was discovered after photosystem I), which collects light through a large quantum antenna of chlorophyll molecules, ending up at a special pairing of chlorophyll molecules called P680. These collect the photon, and in response bump an electron up in energy and out to an electron chain that courses through the rest of the photosynthetic system, including photosystem I. At this point, P680 is hungry for an electron, indeed has the extreme oxidation potential needed to take electrons from oxygen. And one is conducted in from the oxygen evolving center (OEC), sitting nearby.

A schematic illustrating both the evolutionary convergence that put both photosystems (types I and II) into one organism (cyanobacteria, which later become plant chloroplasts), and the energy levels acquired by the main actors in the photosynthetic process, quoted in electron volts. At the very bottom (center) is a brief downward slide as oxygen is split by the pulling force of the super-oxidation state of light-activated P680. After the electrons are light-excited, they drop down in orderly fashion through a series of electron chain transits to various cytochromes, quinones, ferredoxins, and other carriers that generate either protons or chemical reducing power as they go along. Note how the depth of the oxygen-splitting oxidation state is unique among photosynthetic systems.

A recent paper resolves the long-standing problem of how exactly oxygen is oxidized by cyanobacteria and plants at the OEC, at the very last step before oxygen release. This center is a very strained cubic metal complex of one calcium and four manganese atoms, coordinated by oxygen atoms. The overall process is that two water molecules come in, four protons and four electrons are stripped off, and the remaining oxygens combine to form O2. This is, again, part of the grand process of metabolism, whose point is to add those electrons and protons to CO2, making the organic molecules of life, generally characterized as (-CH2-), such as fats, sugars, etc. Which can be burned later back into CO2. Metals are common throughout organic chemistry as catalysts, because they have a wonderful property of de-localizing electrons and allowing multiple oxidation states, (number of extra or missing electrons), unlike the more sparse and tightly-held states of the smaller elements. So they are used in many redox cofactors and enzymes to facilitate electron movement, such as in chlorophyll itself.

The authors provide a schematic of the manganese-calcium OEC reaction center. The transferring tyrosine is at top, calcium is in fuschia/violet, the manganese atoms are in purple, and the oxygens are in red. Arrows point to the oxygens destined to bond to each other and "evolve" away as O2. Note how one of these (O6) is only singly-coordinated and is sort of awkwardly wedged into the cube. Note also how the bond lengths to calcium are all longer than those to manganese, further straining the cube. These strains help to encourage activation and expulsion of the target oxygens.

Here, in the oxygen evolving center, the manganese atoms are coordinated all around with oxygens, which presents the question- which ones are the ones? Which are destined to become O2, and how does the process happen? These researchers didn't use complicated femtosecond X-ray systems or cyclotrons, (though they draw on the structural work of those who did), but room-temperature FTIR, which is infrared spectroscopy highly sensitive to organic chemical dynamics. Spinach leaf chloroplasts were put through an hour of dark adaptation, (which sets the OEC cycle to state S1), then hit with flashes of laser light to advance the position of the oxygen evolving cycle, since each flash (5 nanoseconds) induces one electron ejection by P680, and one electron transfer out of the OEC. Thus the experimenters could control the progression of the whole cycle, one step at a time, and then take extremely close FTIR measurements of the complexes as they do their thing in response to each single electron ejection. Some of the processes they observed were very fast (20 nanoseconds), but others were pretty slow, up to 1.5 milliseconds for the S4 state to eject the final O2 and reset to the S0 state with new water molecules. They then supplement their spectroscopy with the structural work from others and with computer dynamics simulations of the core process to come up with a full mechanism.

A schematic of the steps of oxygen evolution out of the manganese core complex, from states S0 to S4. Note the highly diverse times that elapse at the various steps, noted in nano, micro, or milli seconds. This is discussed further in the text.

Other workers have provided structural perspectives on this question, showing that the cubic metal structure is bit more weird than expected. An extra oxygen (numbered as #6) wedges its way in the cube, making the already strained structure (which accommodates a calcium and a dangling extra manganese atom) highly stressed. This is a complicated story, so several figures are provided here to give various perspectives. The sequence of events is that first, (S0), two waters enter the reaction center after the prior O2 molecule has left. Water has a mix of acid (H+) and base (OH-) ionic forms, so it is easy to bring in the hydroxyl form instead of complete water, with matching protons quickly entering the proton pool for ATP production. Then another proton quickly leaves as well, so the waters have now become two oxygens, one hydrogen, and four electrons (S0). Two of the coordinated manganese atoms go from their prior +4, +4 oxidation state to +3 and +2, acting as electron buffers. 

The first two electrons are pulled out rapidly, via the nearby tyrosine ring, and off to the P680 center (ending at S2, with Mn 3+ and Mn 4+). But the next steps are much slower, extricating the last two electrons from the oxygens and inducing them to bond each other. With state S3 and one more electron removed, both manganese atoms are back to the 4+ state. In the last step, one last proton leaves and one last electron is extracted over to the tyrosine oxygen, and the oxygen 6 is so bereft as to be in a radical state, which allows it to bow over to oxygen 5 and bond with it, making O2. The metal complex has nicely buffered the oxidation states to allow these extractions to go much more easily and in a more coordinated fashion than can happen in free solution.

The authors provide a set of snapshots of their infrared spectroscopy-supported simulations (done with chemical and quantum fidelity) of the final steps, where oxygens, in the bottom panel, bond together at center. Note how the atomic positions and hydrogen attachments also change subtly as the sequence progresses. Here the manganese atoms are salmon, oxygen red, calcium yellow, hydrogen white, and a chlorine molecule is green.

This closely optimized and efficient reaction system is not just a wonder of biology and of earth history, but an object lesson in chemical technology, since photolysis of water is a very relevant dream for a sustainable energy future- to efficiently provide hydrogen as a fuel. Currently, using solar power to run water electrolyzers is not very efficient (20% for solar, and 70% for electrolysis = 14%). Work is ongoing to design direct light-to-hydrogen hydrolysis, but so far uses high heat and noxious chemicals. Life has all this worked out at the nano scale already, however, so there must be hope for better methods.

• The US carried off an amazing economic success during the pandemic, keeping everything afloat as 22 million jobs were lost. This was well worth a bit of inflation on the back end.
• Death
• Have we at long last hit peak gasoline?
• The housing crisis and local control.
• The South has always been the problem.
• The next real estate meltdown.

On the Spectrum

Autism, broader autism phenotype, temperament, and families. It turns out that everyone is on the spectrum.

The advent of genomic sequencing and the hunt for disease-causing mutations has been notably unhelpful for most mental diseases. Possible or proven disease-causing mutations pile up, but they do little to illuminate the biology of what is going on, and even less towards treatment. Autism is a prime example, with hundreds of genes now identified as carrying occasional variants with causal roles. The strongest of these variants affect synapse formation among neurons, and a second class affects long-term regulation of transcription, such as turning genes durably on or off during developmental transitions. Very well- that all makes a great deal of sense, but what have we gained?

Clinically, we have gained very little. What is affected are neural developmental processes that can't be undone, or switched off in later life with a drug. So while some degree of understanding slowly emerges from these studies, translating that to treatment remains a distant dream. One aspect of the genetics of autism, however, is highly informative, which is the sheer number of low-effect and common mutations. Autism can be thought of as coming in two types, genetically- those due to a high effect, typically spontaneous or rare mutation, and those due to a confluence of common variants. The former tends to be severe and singular- an affected child in a family that is otherwise unaffected. The latter might be thought of as familial, where traits that have appeared (mildly) elsewhere in the family have been concentrated in one child, to a degree that it is now diagnosable.

This pattern has given rise to the very interesting concept of the "Broader Autism Phenotype", or BAP. This stems from the observation that families of autistic children have higher rates where ... "the parents, grandparents, and collaterals are persons strongly preoccupied with abstractions of a scientific, literary, or artistic nature, and limited in genuine interest in people." Thus there is not just a wide spectrum of autism proper, based on the particular confluence of genetic and other factors that lead to a diagnosis and its severity, but there is also, outside of the medical spectrum, quite another spectrum of traits or temperaments which tend toward autism and comprise various eccentricities, but have not, at least to date, been medicalized.

The common nature of these variants leads to another question- why are they persistent in the population? It is hard to believe that such a variety and number of variations are exclusively deleterious, especially when the BAP seems to have, well, rather positive aspects. No, I would suggest that an alternative way to describe BAP is "an enhanced ability to focus", and develop interests in salient topics. Ever meet people who are technically useless, but warm-hearted? They are way off on the non-autistic part of the spectrum, while the more technically inclined, the fixers of the world and scholars of obscure topics, are more towards the "ability to focus" part of the spectrum. Only when such variants are unusually concentrated by the genetic lottery do children appear with frank autistic characteristics, totally unable to deal with social interactions, and given to obsessive focus and intense sensitivities.

Thus autism looks like a more general lens on human temperament and evolution, being the tip of a very interesting iceberg. As societies, we need the politicians, backslappers, networkers, and con men, but we also need, indeed increasingly as our societies and technologies developed over the centuries, people with the ability and desire to deal with reality- with technical and obscure issues- without social inflection, but with highly focused attention. Militaries are a prime example, fusing critical needs of managing and motivating people, with a modern technical base of vast scope, reliant on an army of specialists devoted to making all the machinery work. Why does there have to be this tradeoff? Why can't everyone be James Bond, both technically adept and socially debonaire? That isn't really clear, at least to me, but one might speculate that in the first place, dealing with people takes a great deal of specialized intelligence, and there may not be room for everything in one brain. Secondly, the enhanced ability to focus on technical or artistic topics may actively require, as is implicit in doing science and as was exemplified by Mr. Spock, an intentional disregard of social niceties and motivations, if one is to fully explore the logic of some other, non-human, world.

• Autistic comedy?
• What happened to the war on poverty?
• How to think about cancer treatments.
• 95 year old judges, really? 

Founders, Schmounders

Elie Mystal rakes constitutional originalism over the coals, in "A Black Guy's Guide to the Constitution".

I was raised to revere the founders and the elegant, almost scriptural document they constructed to rule our society. But suppose I was a black person, knowing that these founders were the rich white guys of their time, owners and abusers of slaves? I might think that while their aspirations were rhetorically high, their constitution was rather more utilitarian in its denial of true democracy to most people living in the colonies, its indirect and unjust approach to the democracy it did allow, and its euphemistically stated, but absolute, denial of freedom to "other persons". I would have experienced the US legal and cultural system as one of systematic oppression, dedicated to the proposition that while white, rich, men might be equal in some way and enjoy a rules-based system, the larger point of the system was to maintain power in their hands, and deny it to all others.

At least that is the sense one gets from Mystal's book, which, along with a lot of colorful language and wry jokes, assembles a trenchant rebuke of the American constitution, of conservatives, of Republicans, and especially of the originalist ideology of jurisprudence. Every hot button topic gets its due, and every amendment its contrarian interpretation. The second amendment is easy- it is about a regulated militia, after all, not about some commandment handed down from Charlton Heston to the ammosexuals of the nation to stock up on AR-15s and have a mass shooting if they are feeling a little antsy. 

Police brutality, prejudice, impunity, and immunity from accountabiliy is another easy, if painful, target. Mystal describes how he has been profiled and roughed up, for no other reason than being black. The legal system seems to have driven a semi through the fourth amendment against unreasonable searches when it comes to vehicles owned by black people, for one thing. And the fifth amendment comes into play as well- why do we allow police to play cat and mouse with suspects, trying to trip them up and get them to confess, cutting corners and playing games with their Miranda rights? Mystal makes a strong case for doing away with this whole theater of intimidation, with its slippery slope to fraud and torture, by barring police from eliciting or transmitting confessions at all, period. He notes that anyone with even a glancing acquaintance with the legal profession has learned to say nothing to police without a lawyer by her side.

Mystal's approach to abortion, however, is where this book really shines. Was Roe "wrongly decided"? Hardly. In the first place, Mystal provides an interesting discussion of "substantive" due process, (fifth amendment, and fourteenth), meaning that the rights and protections of the constitution are not to be taken merely literally or trifled with by twisting their meanings. They must be afforded by realistic means and set in a legal / civil system that supports their spirit. And that means that the right to privacy is a thing. While its poetic origin may be in the "penumbras" of the constitution, it is integral to the very idea of much of it- the concept unreasonable searches, of rights against self-incrimination, of any sort of rights of the individual vs the state. This is not to mention the ninth amendment, which asserts that just because the constitution and bill of rights mentions some rights explicitly, that others by their ommission are not covered. Privacy would, in general terms, clearly fall in this category.

But where else could a right to abortion be found? Plenty of places. One is the equal protection clause of the fourteenth amendment. Mystal, and many others, note that this should be taken as applying to women, making the whole equal rights amendment (ERA) unnecessary, given a modicum of enlightened interpretation. It could also be taken to afford men and women equal protections regarding reproduction, meaning that the penalty for a roll in the hay should not be grossly unequal, as it is when abortion is banned. Mystal goes on to suggest that the eighth amendment against cruel and unusual punishment could be invoked as well. If men were faced, as a penalty for sex, months of mental and physical torment, and then the excruciating labor of birth, one could be sure that no court would consider banning abortion for a nanosecond. And how much more cruel and vindictive is it be if that pregnancy arose from rape? There is also, after all, the thirteen amendment against involuntary servitude/labor.

Originalists brazenly throw their so-called principles out the window when it comes to abortion. Unenumerated rights? Never heard of them. Keeping the state out of the most sacred precincts of our private lives? No comment. Colonial attitudes towards abortion were very loose, nothing like the personhood-at-conception garbage we get today from the right/Catholic wing. It just goes to show that a little knowledge (here, of biology) can be a dangerous thing.

It is really originalism and conservatism, however, that is the overarching and corrosive topic Mystal takes on. The founders were people of their time, and that was a white supremacy kind of time. They wrote a constitution with hopeful ideals and judicious language which insulated it somewhat (though hardly enough!) from the prejudices of their day. To say that our current interpretation of their words should be confined to whatever psychoanalysis we can make of their meanings at the time would lock our whole political and legal system into those same prejudices that they were trying to overcome. To take the second amendment, Mystal argues (I am not sure how successfully) that its "militias" were most keenly understood to mean bands of Southern planters gathering together to prevent or put down slave revolts. Southerners did not want to be dependent on Federal sympathy and arms, and thus insisted that a right to raise their own militias for their own peculiar needs should be enshrined in the constitution. Well, if we were to restrict outselves to such an interpretation, that would have significant effects on our practice of the second amendment. Gun control would be allowed in the North, just not in the South, allowing guns to white males with certain property qualifications, perhaps, and certain mental proclivities.

Even the civil war amendments would be infected with originalism, since very few people at that time envisioned the full social equality of black citizens. It is remarkable to consider the flurry of anti-miscegenation laws passed during the Jim Crow era, after the Southern slave owners had spent a century or two conducting forced miscegenation. Whence the squeemishness? Anyhow, consistent originalism would never have struck down such laws, or abetted the civil rights movement for blacks, let alone gays. Mystal imagines the nettlesome questioning of a prospective conservative justice going like: "Do you believe that Loving v. Virgina was rightly decided?" This case was about the social system of the South, which Mystal tries to separate from the legal and political aspects, and clearly on originalist principles could not be decided as it was. And much more so on Obergefell, which draws on the fourteenth amendment's due process concept to free personal choices (of gay people) from government intrusion, again doubtless totally in contradiction to the social vision and intention of any of its authors.

Instead of fixating on the past so much, in constitutional interpretation, we might think about the future more.

So originalism, for all its rhetorical seductiveness, (after one has been properly indoctrinated in the divine virtues of the founding fathers), is an absurdity for a country with even the tiniest ambition towards social progress, or change of any kind. It amounts to extreme conservatism, pure and simple. Mystal is relentlessly dismissive of the conservative mindset, tied as it is (ever more explicitly in our polarized moment) to regressive, even violent, racial anti-minority politics. 

What is the deal with conservatives? I think there is another unenumerated right that undergirds all these tensions, which is the right to win, and win by inheriting what our forebears wrought- physically, monetarily, politically, socially. America is a highly competitive country- we compete in making money, in politics, in sports, in war. In any society there is an inherent tension between the cohesiveness required to build common structures, like a constitution, or a military, and the the competitiveness that, if channeled properly, can also build great things, but if let loose, can tear down everything. The right to succeed in business, and to bequeath those gains to one's children- that is a widely shared dream. Our founders saw that there had to be limits to this dream, however. The creaky aristocracies of Europe fed on centuries of priviledge and inheritance. America was fundamentally opposed to noble privileges, but in their slaveholding and other businesses, the founders were far from averse to hereditary privileges in general.

It was the whites who won all this- won the American continent from its native inhabitants, won the slaves from their native hearths, invented the technologies like the cotton gin, devised the capitalist system, etc., etc. Who has a right to inherit all these winnings? Conservatives subscribe to a fundamentally competitive system. That is why Trump won the hearts of a rabid base. Lying isn't a bug, it is a feature, an intrinsic part of winning in a duplicitous cultural competition- and winning is everything. To conservatives, social justice is a fundamental affront. Who said the world was fair? Not us! Constitutional originalism is way of expressing this denial of social progress and justice in concrete, and superficially palatable, terms. For as Mystal reiterates, the justices are not calling balls and strikes- constitutional interpretation runs rather freely, as we can see from second amendment jurisprudence. That is why capture of the supreme court has been such a existential project of the right for decades.

Counterpoised to the conservative conception of (lack of) justice in America is that of the left, perhaps best exemplified by the California Reparations task force. If one looks back and considers the losses of enslaved and oppressed Americans, one quickly reaches astronomical levels of reparations that would be required in a just world. How to make up for death and torture? How to make up for the bulldozing of entire communities? How to make up for centuries of economic, social, political, and legal disadvantage? There is simply no way to make up what has been lost, and to do so would open up many other claims, especially by Native Americans, all inhabitants of Vietnam, Iraq, and Afghanistan, not to mention countless other victims of historical processes going back centuries and ranging world-wide. Justice is a massive can of worms, if looking back in time. But how about something simple, like affirmative action, giving formerly oppressed people a small leg up in the current system? Conservatives can't stand that either, and cry anti-white racism. 

It frankly boggles the mind, how greedy some people can be. But I think the problem of inheritance remains a central touchstone. In each generation, does everyone share equally in the inheritances from the past, or does one race inherit more, do children of the rich inherit more, do the well-connected send their children into the halls of power? The only way to insure a fresh and fair start for each generation is to, not only demolish the idea of inherited nobility as our founders did, (and which we are edging back toward with extreme economic inequality), but go a little beyond that to end other forms of inheritance ... of money and power. The meritocratic systems of higher education did a great deal in the twentieth century to advance this ideal, allowing students from all backgrounds to aspire to, and achieve, all kinds of success. This made the US incredibly powerful and the envy of the world. Liberals should continue this tradition by attacking all forms of entrenched and inherited power, from private schools to the shameful lack of inheritance taxation. The better way to make reparations is to pay it forward, with more just future world.

• Entering blackness.
• "Private jets are on average 10 times more carbon intensive than commercial flights"
• The perils of ransomware.
• The incredible and thoughtless craven-ness of Republicans.
• Our problem with futile medicine.
• Wow- lots of papers (in bad science journals) are duplicated, plagiarized, or fake ... the paper mills.

The Development of Metamorphosis

Adulting as a fly involves a lot of re-organization.

Humans undergo a slight metamorphosis, during adolescence. Imagine undergoing pupation like insects do and coming out with a totally new body, with wings! Well, Kafka did, and it wasn't very pleasant. But insects do it all the time, and have been doing it for hundreds of millions of years, taking to the air and dominating the biosphere. What goes on during metamorphosis, how complete is its refashioning of the body, and how did it evolve? A recent paper (review) considered in detail how the brains of insects change during metamorphosis, finding a curious blend of birth, destruction, and reprogramming among their neurons.

Time is on the Y axis, and the emergence of later, more advanced types of insects is on the X axis. This shows the progressive elaboration of non-metamorphosis (ametabolous), partially metamorphosing (hemimetabolous), and fully metamorphosing (holometabolous) forms. Dragonflies are only partially metamorphosing in this scheme, though their adult forms are often highly different from their larval (nymph) form.

Insects evolved from crustaceans, and took to land as small silvertail-like creatures with exoskeletons, roughly 450 million years ago. Over 100 million years, they developed the process of metamorphosis as a way to preserve the benefits of their original lifestyle for early development, in moist locations, while conquering the air and distance as adults. Early insect types are termed ametabolous, meaning that they have no metamorphosis at all, developing straight from eggs to an adult-style form. These go through several molts to accommodate growth, but don't redesign their bodies. Next came hemimetabolous development, which is exemplified by grasshoppers and cockroaches. Also dragonflies, which significantly refashion themselves during the last molt, gaining wings. In the nymph stage, those wings were carried around as small patches of flat embryonic tissue, and then suddenly grow out at the last molt. Dragonflies are extreme, and most hemimetabolous insects don't undergo such dramatic change. Last came holometabolous development, which involves pupation and a total redesign of the body that can go from a caterpillar to a butterfly.

The benefit of having wings is pretty clear- it allows huge increases in range for feeding and mating. Dragonflies are premier flying predators. But as a larva, wallowing in fruit juice or leaf sap or underwater, as dragonflies are, wings and long legs would be a hindrance. This conundrum led to the innovation of metamorphosis, based on the already somewhat dramatic practice of molting off the exoskeleton periodically. If one can grow a whole new skeleton, why not put wings on it, or legs? And metamorphosis has been tremendously successful, used by over 98% of insect species.

The adult insect tissues do not come from nowhere- they are set up as arrested embryonic tissues called imaginal discs. These are small patches that exist in the larva at specific positions. During pupation, while much of the rest of the body refashions itself, imaginal discs rapidly develop into future tissues like wings, legs, genitalia, antennas, and new mouth parts. These discs have a fascinating internal structure that prefigures the future organ. The leg disc is concentrically arranged with the more distant future parts (toes) at its center. Transplanting a disc from one insect to another or one place to another doesn't change its trajectory- it will still become a leg wherever it is put. So it is apparent that the larval stage is an intermediate stage of organismal development, where a bunch of adult features are primed but put on hold, while a simpler and much more primitive larval body plan is executed to accommodate its role in early growth and its niche in tight, moist, hidden places.

The new paper focuses on the brain, which larva need as well as adults. So the question is- how does the one brain develop from the other? Is the larval brain thrown away? The answer is that no, the brain is not thrown away at all, but undergoes its own quite dramatic metamorphosis. The adult brain is substantially bigger, so many neurons are added. A few neurons are also killed off. But most of the larval neurons are reprogrammed, trimmed back and regrown out to new regions to do new functions.

In this figure, the neurons are named as mushroom body outgoing neuron (MBON) or dopaminergic neuron (DAN, also MBIN for incoming mushroom body neuron), mushroom body extrinsic neuron to calyx (MBE-CA), and mushroom body protocerebral posterior lateral 1 (PPL1). MBON-c1 is totally reprogrammed, MBON-d1 changes its projections substantially, as do the (teal) incoming neurons, and MBON-12 was not operational in the larval stage at all. Note how MBON-c1 is totally reprogrammed to serve new locations in the adult.

The mushroom body, which is the brain area these authors focus on, is situated below the antennas and mediates smell reception, learning, and memory. Fly biologists regard it as analogous to our cortex- the most flexible area of the brain. Larvae don't have antennas, so their smell/taste reception is a lot more primitive. The mushroom body in drosophila has about a hundred neurons at first, and continuously adds neurons over larval life, with a big push during pupation, ending up with ~2200 neurons in adults. Obviously this has to wire into the antennas as they develop, for instance.

The authors find that, for instance, no direct connections between input and output neurons of the mushroom body (MBIN and MBON, respectively) survive from larval to adult stages. Thus there can be no simple memories of this kind preserved between these life stages. While there are some signs of memory retention for a few things in flies, for the most part the slate is wiped clean. 

"These MBONs [making feedback connections] are more highly interconnected in their adult configuration compared to their larval one: their adult configuration shows 13 connections (31% of possible connections), while their larval configuration has only 7 (17%). Importantly, only three of these connections (7%) are present in both larva and adult. This percentage is similar to the 5% predicted if the two stages were wired up independently at their respective frequencies."

Interestingly, no neuron changed its type- that is, which neurotransmitter it uses to communicate. So, while pruning and rewiring was pervasive, the cells did not fundamentally change their stripes. All this is driven by the hormonal system (juvenile hormone, which blocks adult development, and ecdysone, which drives molting, and in the absence of juvenile hormone, pupation) which in turn drives a program of transcription factors that direct the genes needed for development. While a great deal is known about neuronal pathfinding and development, this paper doesn't comment on those downstream events- how it is that selected neurons are pruned, turned around, and induced to branch out in totally new directions, for instance. That will be the topic of future work.

• Corrupt business practices. Why is this lawful?
• Why such easy bankruptcy for corporations, but not for poor countries?
• Watch the world's mesmerizing shipping.
• Oh, you want that? Let me jack up the price for you.
• What transgender is like.
• "China has arguably been the biggest beneficiary of the U.S. security system in Asia, which ensured the regional stability that made possible the income-boosting flows of trade and investment that propelled the country’s economic miracle. Today, however, General Secretary of the Chinese Communist Party Xi Jinping claims that China’s model of modernization is an alternative to “Westernization,” not a prime example of its benefits."