One Pump to Rule ... a Tiny Vesicle

Synaptic vesicles are powered by a single pump that has two speeds- on and off.

While some neural circuits are connected by direct electrical contact, via membrane pores, most use a synapse, where the electrical signal stops, gets turned into secretion of a neurotransmitter molecule, which crosses to the next cell, where receptors pick it up and boot up a new electrical signal. A slow and primitive system, doubtless thanks to some locked-in features of our evolutionary history. But it works, thanks to a lot of improvements and optimization over the eons.

The neurotransmitters, of which there are many types, sit ready and waiting at the nerve terminals in synaptic vesicles, which are tiny membrane bags that are specialized to hold high concentrations of their designated transmitter, and to fuse rapidly with the (pre-) synaptic membrane of their nerve terminal, to release their contents when needed, into the synaptic cleft between the two neurons. While the vesicle surfaces are mostly composed of membranes, it is the suite of proteins on their surfaces that provide all the key functions, such as transport of neurotransmitters, sensing of the activating nerve impulse (voltage), fusing with the plasma membrane, and later retrieval of the fused membrane patches/proteins and recycling into new synaptic vesicles.

Experimental scheme- synaptic vesicles are loaded with a pH-sensitive fluorescent dye that tells how the V-ATPase (pink) is doing pumping protons in, powered by ATP from the cytoplasm. The proton gradient is then used by the other transporters in the synaptic vesicle (brown) to load it with its neurotransmitter.

The neurotransmitters of whatever type are loaded into synaptic vesicles by proton antiporter pumps. That is, one or two protons are pumped out in exchange for a molecule of the transmitter being pumped in. They are all proton-powered. And there is one source of that power, an ATP-using proton pump called a V-type ATPase. These ATPases are deeply related to the F-type ATP synthase that does the opposite job, in mitochondria, making ATP from the proton gradient that mitochondria set up from our oxygen-dependent respiration / burning of food. Both are rotors, which spin around as they carefully let protons go by, while a separate domain of the protein- attached via stator and rotor segments- makes or breaks down ATP, depending on the direction of rotation. Both enzymes can go in either direction, as needed, to pump protons either in or out, and traverse the reaction ADP <=> ATP. It is just an evolutionary matter of duplication and specialization that the V-type and F-type enzymes have taken separate paths and turn up where they do.

Intriguingly, synaptic vesicles are each served by one V-type ATPase. One is enough. That means that one molecule has to flexibly respond to variety of loads, from the initial transmitter loading, to occasional replenishment and lots of sitting around. A recent paper discussed the detailed function of the V-type ATPase, especially how it handles partial loads and resting states. For the vesicles spend most of their time full, waiting for the next nerve impulse to come along. The authors find that this ATPase has three states it switches between- pumping, resting, and leaking. 

Averaging over many molecules/vesicles, the V-type ATPase pump operates as expected. Add ATP, and it acidifies its vesicle. The Y-axis is the fluorescent signal of proton accumulation in the vesicle. Then when a poison of the ATPase is added (bafilomycin), the gradient dissipates in a few minutes.

They isolate synaptic vesicles directly from rat brains and then fuse them with smaller experimental vesicles that contain a fluorescent tracer that is sensitive to pH- just the perfect way to monitor what is going on in each vesicle, given a powerful enough microscope. The main surprise was the stochastic nature of the performance of single pumps. Comparing the average of hundreds of vesicles (above) with a trace from a single vesicle (below) shows a huge difference. The single vesicle comes up to full acidity, but then falls back for long stretches of time. These vesicles are properly loaded and maintained on average, but individually, they are a mess, falling back to pH / chemical baseline with alarming frequency.

On the other hand, at the single molecule level, the pump is startlingly stochastic. Over several hours, it pumps its vesicle full of protons, then quits, then restarts several times.

The authors checked that the protons had no other way out that would look like this stochastic unloading event, and concluded that the loss of protons was monotonic, thus due to general leakage, not some other channel that occasionally opens to let out a flood of protons. But then they added an inhibitor that blocks the V-ATPase, which showed that particularly (and peculiarly) rapid events of proton leakage come from the V-ATPase, not general membrane leakage. They have a hard time explaining this, discounting various theories such that it represents ATP synthesis (a backwards reaction, in the face of overwhelming ratios of ATP/ADP in their experiment), or that the inactive mode of the pump can switch to a leakage mode, or that the pump naturally leaks a bit while it operates in the forward direction. It appears that only while the pump is on and churning through ATP, it can occasionally fail catastrophically and leak out a flood of protons. But then it can go on as if nothing had happened and either keep pumping or take a rest break.

Regulation by ATP is relatively minor, with a flood of ATP helping keep the pump more active longer. But physiological concentrations tend to be stable, so not very influential for pumping rates. These are two separate individual pumps/vesicles shown, top and bottom. It is good to see the control- the first segment of time when no ATP was present and the pump could not run at all. But then look at the bottom middle trace- plenty of ATP, but nothing going on- very odd. Lastly, the sudden unloading seen in some of these traces (bottom right) is attributed to an extremely odd leakage state of the same V-ATPase pump. Not something you want to see, generally.

The main finding is that this pump has quite long dwell times (3 minutes or so) under optimal conditions, and switches with this time period between active pumping and an inactive resting state. And that the pumping dwell time is mostly regulated, not by the ambient ATP concentration, but by the proton gradient, which is expressed by some combination of the charge differential across the vesicle membrane and the relative proton concentration gradient (the chemical gradient). It is a bit like a furnace, which has only two speeds- on or off, though in this case the thermostat is pretty rough. They note that other researchers have noted that synaptic vesicles seem to have quite variable amounts of transmitter, which must derive from the variability of this pump seen here. But averaged over the many vesicles fused during each neuronal firing, this probably isn't a big deal.

The behavior of this pump is a bit weird, however, since most machines that we are familiar with show more gradual breakdowns under stress, straining and slowing down. But here, the pump just decides to shut down for long periods of time, generally when the vesicle is fully charged up, but sometimes when it is not. It is a reflection that we are near the quantum level here, dealing with molecules that are very large in some molecular sense, but still operating at the atomic scale, particularly at the key choke points of this kind of protein that surely involve subtle shifts of just a few atoms that impart this regulatory shift, from active to inactive. What is worse, the pump sometimes freaks out completely and, while in its on state, switches to a leaking state that lets out protons ten times faster than the passive leakage through the rest of the vesicle membrane. The authors naturally urge deeper structural studies of what might be going on!

• Our soylent future.
• India and the new world order.
• A war within.
• Greenland's ice is at risk.

America as Hegemon

The imperial track record is not good, but the hegemonic track record isn't all that bad.

I was recently visiting the USS Hornet, a WW2-era aircraft carrier now turned into a museum on San Francisco bay. Soon after, it was Fleet Week, when the US navy pays a visit to the Bay Area in force, capped by a Blue Angels air show. An appalling display of naked militarism, granted. But also an occasion to reflect on our world-wide empire, the nature of American power, the competence of our military, and the state of things internationally.

It was a little weird, seeing decades-old technology swooping up and down the bay, which has been, beneath this benevolent protection, so restlessly advancing the technological frontier in totally different directions- computers, phones, applications, streaming, social media. Which trends are more important for America's place in the world? Which technologies rule? What are we doing with all this military hardware? I tend to have pretty conservative views on all this, that the US is right to stick with the post-WW2 consensus that our military should be as strong as possible, and partner with like-minded countries around the world to advance the vision of that era, of human rights and democracy for all. 

When we have tried to do this task directly, in Vietnam, Iraq, and Afghanistan, however, it has generally turned out very badly. The Iraq war was misconceived from the start, and went downhill from there. Despite the laudible aim of sparing the Iraqi people from the continued depredations of Saddam Hussein, the lying and the incompetence at all levels made the cure far worse than the disease, with anarchy and hundreds of thousands dead. But let's write that one off as a George Bush-as-decider blunder.

The Afghanistan debacle is more painful to contemplate, in some ways, in what it says about our fundamental incompetence as an imperial power. Its rationale was straightforward, international support wide-spread, and our power there absolute in the opening acts of the takeover. Yet with all those advantages, we ended up, twenty years later, turning tail and watching our hand-built Afghan military melt away even before we left the country. The Russians had, frankly, a better record in their Imperial Afghan turn. 

It is an appalling track record, really. We evidently and thankfully do not have the advantage of ruthlessness that ancient Rome enjoyed, or modern day spoilers like Russia and Iran. But nor, apparently, do we have the advantage of friendly relations, favorable hearts & minds, and good intelligence. We were constantly led astray by "friends" with all kinds of personal vendettas and agendas. We pride ourselves in our independence from the rest of the world, and thus know little about it, which means that we go into these settings woefully unprepared, besotted by whatever ideological issue du jure is fashionable in the US. Our priorities in Afghanistan seemed to be to hold elections and educate women. But were those the right aims? And even if so, were they carried out with any kind of wisdom and sense of priorities and proper preparation?

Most concretely, our military relationship was a disaster. The US military tried to make the new Afghan military into its own image and graft onto it its own systems and capablities, creating a dependence that caused immediate failure when Afghans caught wind that we were really, actually, going to leave. This was an incredible result, especially after the US military had been responsible for "training" countless militaries all over the world for decades. 

What on earth were we doing? Similarly to the intelligence failures, the military failures came from some fundamental inability to understand the problem at hand, and work with the society as it existed. Instead of creating a sustainable, right-sized, and politically viable force, we just assumed we were the good guys and anything we did was good. There was an intrinsic tension between leaving the society as it was, thereby just funding a reboot of a Taliban-like (or northern alliance-like) force to keep the country pacified, and forcing some change, on social, political, economic, and technological levels, by changing the form of government and associated institutions. The US clearly did not invade Afghanistan to keep everything the same. But by overreaching, we essentially achieved nothing, allowing precisely the group we dethroned to come back into power, and casting the country back into its pre-invasion economic and social abyss. At least, thanks to other technological bequests of the US and the West, the Afghans now have cell phones.

So our military and other institutions do not come off well in any of their recent engagements. It is a case of losing every battle, while winning the war. For we still enjoy a hegemonic position, not thanks to our incompetent and technology-bedazzled military, but thanks to our friends, with whom we still lead the world. The core groups of the anglophone countries, NATO, and the East Asian alliances with Japan, South Korea, and Taiwan remain the core of the developed world, enjoying peaceful relations, democracy, and prosperous economies. China is advancing mightily to displace that grouping, but can not do so alone, and has little hope of doing so with streadfast friends like Russia and North Korea by its side.

Tiers of development. Blue is the developed world, yellow the middle-tier (developing), and red, the lower tiers of development (desperately developing, one might say).

The advantages of joining this developed core are so evident, that one wonders why it is under threat, both from the spoiler countries like Russia, and from endogenous authoritarians in the US, Poland, Hungary, India, and elsewhere. Two decades ago, we were looking at the end of history, when a futuristic society of peace and contentment would inherit the post-cold war earth, Russia would join NATO, and we would live happily ever after. But democracy is a cultural pattern that not everyone can easily understand, especially people who run (or want to run) undemocratic countries. As our framers understood so well, sovereign power is dangerous, and needs to be diluted among publicly competing branches, candidates, officers, and voters for it to be durably controlled, a bit like an atomic chain reaction. It takes wisdom and humility to figure that out and abide by such fundamental (constitutional) rules. 

It is tempting to take that power directly in hand, to satisfy a burning desire to "do something". In the US, a Republican minority has progressively lost its commitment to popular rule and the viability of contemporary governmental institutions. This is, incidentally, only possible because of their special relationship with sources of money and of media influence, without which they would have little popular purchase. In China, the communist party figured that, despite its own history of ravaging its country, it had developed a stable enough system of governance, and had obtained implicit popular support ... reflecting either brainwashing or acquiescence ... that it did not need actual elections or Western-style divided government. And in Russia, the bitterness of its descent into kleptocracy, under the poisoned banner of "capitalism", combined with various snubs from the West and general historical and cultural distance, rendered the idea of becoming a Western country too much to bear.

Each authoritarian system has, like an unhappy family, its own reasons, while the happy families of the West seem to, think along similar lines almost involuntarily, at least until some authoritarian mountebank comes along to solve all our problems by doing away with our safeguards. We are in a grand race to find out which systems are more stable. Those that rely on one person, such as the aging Vladimir Putin, for their decisions, or those that rely on popular will and a controlling set of institutions. The lessons of history could not be more stark, telling us that the former is the bigger crapshoot. Sometimes it turns out well, but more often not. That is why liberalism and deliberative democracy developed in the first place.

There remains a great deal of middle ground around the world. The muslim countries, for example, form a middle tier of populous and developing countries comprising, between Pakistan, Egypt, Indonesia, Bangladesh, Turkey, Iran, the Gulf states and others, well over a billion people. Our wars in Iraq and Afghanistan didn't help our relations there, but on the other hand, China is hardly making itself loved either, with its extermination campaign in Xinjiang. The cultural patterns of the Islamic world make it a particularly hard sell for Western democracy vs authoritariansim. Thus the brief Arab Spring came to a painful and inglorious end, mostly in whimpers, sometimes in horror. The liberatlization process took a long time in the West as well, measured perhaps from the French revolution, through the revolutions of 1848, culminating the aftermath of World War 2, with developmental delays in the Eastern European deep freeze. Ideas and new social patterns take a long time to take root, even when the templates (Switzerland, the US, ancient Greece) are at hand.

The American hegemony is little more than an agreement among like-minded and friendly nations to maintain their democratic systems, their prosperous (if environmentally rapacious and unsustainable) economies, and to largely offload their military responsibilities on the US. Whether those responsibilities have been well-stewarded is certainly doubtful. But up to this point, the agreement has been highly successful, mostly because the US has been a willing, stable, and vigorous anchor. Can the EU take our place? It is conceivable, but the EU is structurally less decisive. Bodies like the UN or the G20 are even less capable, in any executive sense. So, until we come up with something better, with a hot war against Russia and a cold one developing against China, and while other cultures are slowly chewing over their various problems with authoritarianism, it is critical that the US remain that anchor for the democratic developed world.

• What are the rules, anyhow?
• Bad intelligence.
• History is important to authoritarians, at least.
• Argentina is in the throes of inflation.
• The totalitarian speakership is bad for democracy, as well as being unworkable with thin majorities.

Empty Skepticism at the Discovery Institute

What makes a hypothesis scientific, vs a just-so story, or a religious fixation?

"Intelligent" design has fallen on hard times, after a series of court cases determined that it was, after all, a religious idea and could not be foisted on unsuspecting schoolchildren, at least in state schools and under state curricula. But the very fact of religious motivation leads to its persistence in the face of derision, evidence, and apathy. The Discovery Institute, (which, paranthetically, does not make any discoveries), remains the vanguard of intelligent design, promoting "skepticism", god, alternative evolutionary theories, and, due to the paucity of ways to attack evolution, tangential right-wingery such as anti-vaccine agitation. By far their most interesting author is Günter Bechly, who delves into the paleontological record to heap scorn on other paleontologists and thereby make room for the unmentioned alternative hypothesis ... which is god.

A recent post discussed the twists and turns of ichthyosaur evolution. Or should we say biological change through time, with unknown causes? Ichthyosaurs flourished from about 250 million years ago (mya) to 100 mya, with the last representatives dated to 90 mya. They were the reptile analogs of whales and dophins, functioning as apex predators in the ocean. They were done in by various climate crises well-prior to the cometary impact that ended the Cretaceous and the reign of dinosaurs in general.

Bechly raises two significant points. First is the uncertain origins of Ichthyosaurs. As is typical with dramatic evolutionary transitions like that from land to water in whales, the time line is compressed, since there are a lot of adaptations that are desirable for the new environment that might have been partially pre-figured, but get fleshed out extensively with the new ecological role and lifestyle. Selection is presumably intense and transitional fossils are hard to find. This was true for whales, though beautiful transitional fossils have been found more recently. And apparently this is true for the Ichthyosaurs as well, where none have been found, yet. There is added drama stemming from the time of origin, which is right after the Permian exinction, perhaps the greatest known extinction event in the history of the biosphere. Radiations after significant extinction events tend to be rapid, with few transitional fossils, for the same reason of new niches opening and selection operating rapidly.

Ichthyosaur

Bechly and colleagues frequently make hay out of gaps in the fossil record, arguing that something (we decline to be more specific!) else needs to be invoked to explain such lack of evidence. It is a classic god of the gaps argument. But since the fossils are never out of sequence, and we are always looking at millions of years of time going by with even the slimmest layers of rock, this is hardly a compelling argument. One thing that we learned from Darwin's finches, and the whole argument around punctuated equilibrium, is that evolution is typically slow because selection is typically not directional but conservative. But when selection is directional, evolution by natural selection can be startlingly fast. This is an argument made very explicitly by Darwin through his lengthy discussions of domestic species, whose changes are, in geological terms, instant. 

But Bechly makes an additional interesting argument- that a specific hypothesis made about ichthyosaurs is a just-so story, a sort of hypothesis that evolutionary biologists are very prone to make. Quite a few fossils have been found of ichthyosaurs giving birth, and many of them find that the baby comes out not only live (not as an egg, as is usual with reptiles), but tail-first. Thus some scientists have made the argument that each are adaptations to aquatic birth, allowing the baby to be fully borne before starting to breathe. Yet Bechly cites a more recent scientific review of the fossil record that observes that tail-first birth is far from universal, and does not follow any particular phylogenetic pattern, suggesting that it is far from necessary for aquatic birth, and thus is unlikely to be, to any significant extent, an adaptation. 

Ha! Just another story of scientists making up fairy tales and passing them off as "science" and "evolutionary hypotheses", right?  

"Evolutionary biology again and again proves to be an enterprise in imaginative story-telling rather than hard science. But when intelligent design theorists question the Darwinist paradigm based on empirical data and a rational inference to the best explanation, they are accused of being science deniers. Which science?" ... "And we will not let Darwinists get away with a dishonest appeal to the progress of science when they simply rewrite their stories every time conflicting evidence can no longer be denied."

Well, that certainly is a damning indictment. Trial and sentencing to follow! But let's think a little more about what makes an explanation and a hypothesis, on the scientific, that is to say, empirical, level. Hypotheses are always speculative. That is the whole point. They try to connect observations with some rational or empirically supported underlying mechanism / process to account for (that is, explain) what is observed. Thus the idea that aquatic birth presents a problem for mammals who have to breathe represents a reasonable subject for an hypothesis. Whether headfirst or tailfirst, the baby needs to get to the surface post haste, as soon as its breathing reflex kicks in. While the direction of birth doesn't seem to the uninitiated (and now, apparently to experts with further data at hand) to make much difference, thinking it does is a reasonable hypothesis, based on obvious geometric arguments and biological assumptions, that it is possible that the breathing reflex is tied to emergence of the head during birth, in which case coming out tailfirst might delay slightly the time it takes between needing to breathe and being able to breathe. 

This argument combines a lot of known factors- the geometry of birth, the necessity of breathing, the phenomenon of the breathing reflex initiating in all mammals very soon after birth, by mechanisms that doubtless are not entirely known, but at the same time clearly the subject of evolutionary tuning. And also the paleontological record. Good or bad, the hypothesis is based on empirical data. What characterizes science is that it follows a disciplined road from one empirically supported milestone to the next, using hypotheses about underlying mechanisms, whether visible or not, which abide by all the known/empirical mechanisms. Magic is only allowed if you know what is going on behind the curtain. Unknown mechanisms can be invoked, but then immediately become subjects of further investigation, not of protective adulation and blind worship.

In contrast, the intelligent design hypothesis, implicit here but clear enough, is singularly lacking in any data at all. It is not founded on anything other than the sentiment that what has clearly happened over the long course of the fossil record operates by unknown mechanisms, by god operating pervasively to carry out the entire program of biological evolution, not by natural selection (a visible and documented natural process) but by something else, which its proponents have never been able to demonstrate in the least degree, on short time scales or long. Faith does not, on its own, warrant novel empirical mechanisms, and nor does skeptical disbelief warrant them. Nor does one poor, but properly founded, hypothesis that is later superceded by more careful analysis of the data impugn the process of science generally or the style of evolutionary thinking specifically.

Imagine, for example, if our justice system operated at this intellectual level. When investigating crimes, police could say that, if the causes were not immediately obvious, an unnamed intelligent designer was responsible, and leave it there. No cold cases, no presumption of usual natural causality, no dogged pursuit of "the truth" by telegenic detectives. Faith alone would furnish the knowledge that the author of all has (inscrutibly) rendered "his" judgement. It would surely be a convenient out for an over-burdened and under-educated police force!

Evolution by natural selection requires a huge amount of extrapolation from what we know about short time scales and existing biology to the billions of years of life that preceeded us. On the other hand, intelligent design requires extrapolation from nothing at all- from the incredibly persistent belief in god, religion, and the rest of the theological ball of wax not one element of which has ever been pinned down to an empirical fact. Believers take the opposite view solely because religious propaganda has ceaselessly drilled the idea that god is real and "omnipotent" and all-good, and whatever else wonderful, as a matter of faith. With this kind of training, then yes, "intelligent" design makes all kinds of sense. Otherwise not. Charles Darwin's original hypothesis was so brilliant because it drew on known facts and mechanisms to account (with suitable imagination and extrapolation) for the heretofore mysterious history of biology, with its painfully slow yet inexorable evolution from one species to another, one epoch to another. Denying that one has that imagination is a statement about one's intelligence, no matter how it was designed.

• Only god can give us virulent viruses.
• The priest who knew it so well, long ago.
• A wonderful Native American Film- Dance me outside.
• With a wonderful soundtrack, including NDN Kars.
• We need to come clean on Taiwan.
• Appeasers, cranks, and fascist wannabes.
• Vaccines for poor people are not profitable.
• California is dumbing down math, and that will not help any demographic.

Are we all the Same, or all Different?

Refining diversity.

There has been some confusion and convenient logic around diversity. Are we all the same? Conventional wisdom makes us legally the same, and the same in terms of rights, in an ever-expanding program of level playing fields- race, gender, gender preference, neurodiversity, etc. At the same time, conventional wisdom treasures diversity, inclusion, and difference. Educational conventional wisdom assumes all children are the same, and deserve the same investments and education, until some magic point when diversity flowers, and children pursue their individual dreams, applying to higher educational institutions, or not. But here again, selectiveness and merit are highly contested- should all ethnic groups be equally represented at universities, or are we diverse on that plane as well?

It is quite confusing, on the new political correctness program, to tell who is supposed to be the same and who different, and in what ways, and for what ends. Some acute social radar is called for to navigate this woke world and one can sympathize, though not too much, with those who are sick of it and want to go back to simpler times of shameless competition; black and white. 

The fundamental tension is that a society needs some degree of solidarity and cohesion to satisfy our social natures and to get anything complex done. At the same time, Darwinian and economic imperatives have us competing with each other at all levels- among nations, ethnicities, states, genders, families, work groups, individuals. We are wonderfully sensitive to infinitesimal differences, which form the soul of Darwinian selection. Woke efforts clearly try to separate differences that are essential and involuntary, (which should in principle be excluded from competition), from those that are not fixed, such as personal virtue and work ethic, thus forming the proper field of education and competition.

But that is awfully abstract. Reducing that vague principle to practice is highly fraught. Race, insofar as it can be defined at all, is clearly an essential trait. So race should not be a criterion for any competitive aspect of the society- job hunting, education, customer service. But what about "diversity" and what about affirmative action? Should the competition be weighted a little to make up for past wrongs? How about intelligence? Intelligence is heritable, but we can't call it essential, lest virtually every form of competition in our society be brought to a halt. Higher education and business, and the general business of life, is extremely competitive on the field of intelligence- who can con whom, who can come up with great ideas, write books, do the work, and manage others.

These impulses towards solidarity and competition define our fundamental political divides, with Republicans glorying in the unfairness of life, and the success of the rich. Democrats want everyone to get along, with care for unfortunate and oppressed. Our social schizophrenia over identity and empathy is expressed in the crazy politics of today. And Republicans reflect contemporary identity politics as well, just in their twisted, white-centric way. We are coming apart socially, and losing key cooperative capacity that puts our national project in jeopardy. We can grant that the narratives and archetypes that have glued the civic culture have been fantasies- that everyone is equal, or that the founding fathers were geniuses that selflessly wrought the perfect union. But at the same time, the new mantras of diversity have dangerous aspects as well.

Each side, in archetypal terms, is right and each is an essential element in making society work. Neither side's utopia is either practical or desirable. The Democratic dream is for everyone to get plenty of public services and equal treatment at every possible nexus of life, with morally-informed regulation of every social and economic harm, and unions helping to run every workplace. In the end, there would be little room for economic activity at all- for the competition that undergirds innovation and productivity, and we would find ourselves poverty-stricken, which was what led other socialist/communist states to drastic solutions that were not socially progressive at all.

On the other hand is a capitalist utopia where the winners take not just hundreds of billions of dollars, but everything else, such as the freedom of workers to organize or resist, and political power as well. The US would turn into a moneyed class system, just like the old "nobility" of Europe, with serfs. It is the Nietzschian, Randian ideal of total competition, enabling winners to oppress everyone else in perpetuity, and, into the bargain, write themselves into the history books as gods.

These are not (and were not, historically) appetizing prospects, and we need the tension of mature and civil political debate between them to find a middle ground that is both fertile and humane. Nature is, as in so many other things, an excellent guide. Cooperation is a big theme in evolution, from the assembly of the eukaryotic cell from prokaryotic precusors, to its wonderous elaboration into multicellular bodies and later into societies such as our own and those of the insects. Cooperation is the way to great accomplishments. Yet competition is the baseline that is equally essential. Diversity, yes, but it is competition and selection among that diversity and cooperative enterprise that turns the downward trajectory of entropy and decay (as dictated by physics and time) into flourishing progress.

• Identity, essentialism, and postmodernism.
• Family structure, ... or diversity?
• Earth in the far future.
• Electric or not, cars are still bad.
• Our non-political and totally not corrupt supreme court.
• The nightmare of building in California.

Cellular Package Logistics

Some new insights on how vesicle fusion occurs with target membranes.

Membranes were one of the founding inventions of life. Every cell has a membrane, and many viruses do as well. Whether they were present from the start, or were a later innovation when the nascent chemical reactions of life, begun in some rocky pore, freed themselves into the open ocean, the fatty bilayer membrane is now fundamental. And from a proper perspective, it is a formidable barrier. If you were a water molecule, a typical membrane would be a sixty-five foot wide mass of repellent goo.

A typical cellular membrane, with the fatty bilayer core and a few proteins and other molecules sprinkled about, all of which move freely in the plane of the membrane.

Eukaryotes, as usual, took this innovation to whole new level, developing a variety of internal membranes and organelles that were entirely unknown to their bacterial forebears. Foremost of which is the mitochondrion- the symbiotic bacterium that turned into a powerful organelle. But there are many others, like the endoplasmic reticulum, the nucleus, the lysosome, phagosome, and the golgi apparatus. There is constant traffic among these organelles, with small membrane vesicles being emitted, traveling around, and finding and then fusing with their target destination membranes. It is like a tiny FedEx system within each cell, complete with addresses, carriers, cargoes, and grateful recipients.

A cartoon about the some of the internal membranes of eukaryotic cells. Note all the traffic going about. The lysosome, for instance, receives incoming vesicles from the plasma membrane, as things to digest, and from the golgi apparatus, as packages of new enzymes to do its work- enzymes that only turn on in the acidic environment inside the lysosome. This traffic requires a great deal of vesicle formation, transportation and fusion with targets, whose molecular detail is being gradually revealed. The golgi apparatus is a central sorting and distribution center.

Vesicles can exist because they are generally not prone to fuse with each other. Each membrane has a electrical charge-rich exterior that keeps it happily hydrated and slightly stand-offish vs other membranes. So something extra is needed to provide the push to fuse with a target membrane. And this barrier also provides the possibility of regulation, getting the right vesicle to fuse with the right target. A recent paper discussed one small part of this quite complicated process- the structure of tethering proteins that bring cargo vesicles and target membranes together. The research group focused on vesicles destined for the lysosome. The lysosome is the target of two major types of vesicles. One type brings in the enzymes needed for the lysosome to digest food for the cell. The other type are endosomes coming from the plasma membrane, and other sources of cellular garbage, which go to the lysosome to be digested, much like food is digested in our stomachs.

A schematic of the SNARE proteins that operate at the core of membrane fusion. One (here, synaptobrevin) is attached to the cargo vesicle. Another (here, syntaxin) is attached to the target membrane. A third, SNAP-25, supplies two more alpha helices to the 4-helix structure that winds up and brings the two membranes ever closer. The extra protein (synaptotagmin) is a regulator, in this case at the neuronal synapse, which directs fusion to happen in response to electrical neural activation, thereby helping secrete a neurotransmitter and thus propagate the neural signal.

Vesicle fusion is, at core, conducted by proteins called SNARE proteins. One extends from the cargo vesicle, another extends from the target membrane, and a third joins in, complexed with the second. Their alpha helical structures strongly and progressively inter-twine together to drive the membranes together, forcing fusion. Energetic studies show that at least three of these complexes are needed to get two membranes fused. After the fusion event, the SNARE proteins are recovered by special chaperone proteins that expend ATP to unwind the SNARE helices and reset them for another round of action.

Part of the regulation of this process (of which a great deal remains unknown) is provided by "tethering" complexes- proteins that grab hold of membranes of the right sort, extend across the gap to the target membrane, and also bind the SNARE proteins to orchestrate the fusion process. This research group studied one such tethering complex called HOPS, from yeast cells, which is composed of six proteins, Vps11, 16, 18, 39, 41, fall named for vacuole protein sorting. In yeast cells, the lysosome is called the vacuole, and these were all picked up by genetic screens for defects in getting proteins to the vacuole. Thus HOPS is essential for the fusion process, even though it plays a helping, orchestrating role.

New structures of the HOPS complex, which helps direct cargo vesicles to lysosomes. It is composed of six Vps proteins, all similar, which reach in three directions- to each membrane, and to the SNARE proteins as well. A three-handed helper, as it were.

The researchers found that the HOPS complex is fundamentally a triangle. Two of the ends (green, above) extend to the membranes to be fused, while the third end (brown) engages the SNARE proteins and helps them do their thing when the right geometry has been attained. The shape almost tells the story of what is going on, with the SNARE proteins sitting right in the middle, at the presumptive cleft between the two membranes. The structure has an interesting profusion of beta-propeller structures on all its ends. These are bulky protein domains very commonly used for protein-protein interactions. The shared structures also show that these proteins are deeply related to each other, probably all evolved from a single ancestor. 

Model of HOPS function, as it joins the two membranes, and also orchestrates SNARE action.

The HOPS complex tethers to Ypt7 proteins on both membranes. But Ypt7 is itself highly regulated, and not always "on", i.e. receptive for docking. It is turned on by other proteins that specify that it is in the right place and near the right partner to activate. But that is another story, and one still developing.

• Our lethal roads.
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• Veganism on the march.
• Can there be a science of consciousness? Is there one? Or will AI get there first?

Why do we Put up with the Specter of Unemployment?

A post by Paul Krugman got me thinking... why do we allow unemployment at all?

Paul Krugman has been ruminating a lot about inflation- why it went up, and why it is back down. One insight is that, asssuming that interest rate increases are supposed to work by raising unemployment, they have not evidently accomplished anything, yet inflation is back down and has been at 2-3 % for the last year, on a month to month basis. Perhaps the rate increases operated through other channels, like dampening the real estate market or general confidence. Or perhaps the rate increases had as much inflationary as deflationary effect, which is to say none at all, and our current state is simply due to the working-out of all the supply chain disruptions, emergency federal spending, and opportunistic profit-making brought on by the pandemic. As was, incidentally, supposed by the MMT school from the start.

But why make workers the focus of inflation policy in the first place? And why use unemployment as the index of inflation-fighting effectiveness? Why have unemployment at all? Unemployment is a central and classic feature of capitalism, certainly not of our natural state. Chimpanzees never experience unemployment- there is always something to do. But when it comes to capitalism, once workers have bought into the labor-rental scheme, they are dependent on the specific employer for pay, and on the employer class as a whole for the existence of a labor market. While employers like nothing better than to "discipline" workers with the prospect of sleeping on the streets, we can do better.

The Phillips curve, of unemployment related to inflation (the non-accelerating inflation rate level of unemployment, or NAIRU). A somewhat mythical and protean concept that used to be taken as a "law" of economics, that low unemployment drives higher inflation, via hotter labor market and wage increases. Even the Fed doesn't take this seriously any more.

Capitalists manage to pay themselves pretty well, to the point that our whole economy and social life (and politics) has been deranged by whole new classes of super-rich and their lackeys. So an allergy to income is not generally the problem- merely parting with money to pay others fairly. It is clear from the recent minimum wage increases that paying the lower end more has very little inflationary effect- it is peanuts on top of peanuts. But is immensely meaningful for those on the receiving end.

Similarly, the provision of a job guarantee, (as previously posted), thereby eliminating involuntary unemployment, would help workers on the low end of the scale with much greater security. The government would be the employer of last resort, at a decent wage, offering a wide range of work, from street cleaning and park maintenance to non-profit collaborations and technical operations appropriate to whatever skills are on offer. Looking around the country, there is no end of work that needs doing. The Great Depression, which gave us so much innovative legislation, also gave us a model of public works and public jobs programs- something well worth learning from and using on a permanent basis.

Such a job guarantee would automatically provide a floor for the minimum wage, (and also a floor for work conditions, hours, and benefits), and replace most unemployment insurance and other benefit programs. If a person didn't want the jobs offered, they could take a lower basic welfare-type income. But the work would not be designed to either onerous or easy- the point is to get some useful work done for society, and take in the bottom level of the labor market as needed from fluctuations in the private market. It is an insurance system, just as we have for health, for property hazards, and, as embodied in the Federal Reserve, for the banks and US capitalism writ large. Such a guarantee of work is, I think, far superior to the current unemployment insurance system, which is grudgingly funded by employers, pays people to not work, which is morally perverse and heavily abused. Private employers would naturally be able to bid workers off the system with higher pay.

Such a system would have little effect on the Fed's interest rate policies, (assuming they are effective in the first place), since unemployment is really just an index of economic activity, not the point of interest rate increases. Economic slowing would be reflected in higher numbers of people thrown into the job guarantee, and presumably getting lower (but still decent) pay. (A pay scale that would, incidentally, be more anti-cyclical than current policies.) And would be reflected in a myriad of other slowdowns that would contribute, if needed, to inflation control. 

The irony is that welfare reform of the last few decades focused relentlessly on "work requirements", and of the decades prior to that on "job training". The latter was a boondoggle, and the former forced the poor into appalling, coercive, and low-paying jobs- the very bottom end of the capitalist system. Which was the design, no doubt. I can imagine that capitalists would yell "communism" about a program where governments give decent work with decent income and benefits to anyone willing to work. Well, if that is communism, we need more of it.

Unemployment is currently used as a potent weapon- both by capitalists, given its dire consequences, and paradoxically by unions as well, which walk off the job and strike as a way to pressure employers who may find it inconvenient to hire scabs in a short time. A job guarantee could transform such conflict by taking the most dire consequences off the table. Everyone could maintain their livelihoods, and negotiations could proceed with less drama and coercion. And that is what our society should be about, promoting freedom and civility by removing forms of unjust and pernicious coercion, whether political, criminal, military, or economic.

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• Some statistics.
• When insurrection becomes policy.
• Think of the children...

Keeping Cellular Signals Straight

Cells often use the same signaling systems for different inputs and purposes. Scaffolds come to the rescue.

Eukaryotic cells are huge, at least compared with their progenitors, bacteria. Thanks to their mitochondria and other organizational apparatus, the typical eukaryotic cell has about 100,000 times the volume of a bacterium. These cells are virtual cities- partially organized by their membrane organelles, but there is a much more going on, with tremendous complexity to manage. One issue that was puzzling over the decades was how signals were kept straight. Eukaryotic cells use a variety of signaling systems, proto-typicaly starting with a receptor at the cell surface, linking to a kinase (or series of kinases) that then amplifies and broadcasts the signal inside the cell, ending up with the target phosphorylated proteins entering the nucleus and changing the transcription program of the cell. 

While our genome does have roughly 500 kinases, and one to two thousand receptors, a few of them (especially some kinases and their partners, which form "intracellular signaling systems") tend to crop up frequently in different systems and cell types, like the MAP kinase cascade, associated with growth and stress responses, and the AKT kinase, associated with nutrient sensing and growth responses. Not only do many different receptors turn these cellular signaling hubs on, but their effects can often be different as well, even from unrelated signals hitting the same cell.

If all these proteins were diffusable all over the cell, such specificity of signaling would be impossible. But it turns out that they are usually tethered in particular ways, by organizational helpers called scaffold proteins. These scaffolds may localize the signaling to some small volume within the larger cell, such as a membrane "raft" domain. They may also bind multiple actors of the same signaling cascade, bringing several proteins (kinases and targets) together to make signaling both efficient and (sterically) insulated from outside interference. And, in a recent paper, they can also tweak their binding targets allosterically to insulate them from outside interference.

What is allostery vs stery? If one protein (A) binds another (B) such that a phosphorylation or other site is physically hidden from other proteins, such as a kinase (C) that would activate it, that site is said to be sterically hidden- that is, by geometry alone. On the other hand, if that site remains free and accessible, but the binding of A re-arranges protein B such that it no longer binds C very well, blocking the kinase event despite the site of phosphorylation being available, then A has allosterically regulated B. It has altered the shape of B in some subtle way that alters its behavior. While steric effects are dominant and occur everywhere in protein interactions and regulation, allostery comes up pretty frequently as well, proteins being very flexible gymnasts. 

GSK3 is part of insulin signaling. It is turned off by phosphorylation, which affects a large number of downstream functions, such as turning on glycogen synthase.

The current case turns on the kinase GSK3, which, according to Wikipedia... "has been identified as a protein kinase for over 100 different proteins in a variety of different pathways. ... GSK-3 has been the subject of much research since it has been implicated in ... diseases, including type 2 diabetes, Alzheimer's disease, inflammation, cancer, addiction and bipolar disorder." GSK3 was named for its kinase activity targeting glycogen synthase, which inactivates the synthase, thus shutting down production of glycogen, which is a way to store sugar for later use. Connected with this homeostatic role, the hormone insulin turns GSK3 off by phosphorylation by a pathway downstream of the membrane-resident insulin receptor called the PI3 kinase / protein kinase B pathway. Insulin thus indirectly increases glycogen synthesis, mopping up excess blood sugar. The circuit reads: insulin --> kinases --| GSK3 --| glycogen synthase --> more glycogen.

GSK3 also functions in this totally different pathway, downstream of WNT and Frizzled. Here, GSK3 phosphorylates beta-catenin and turns it off, most of the time. WNT (like insulin) turns GSK3 off, which allows beta-catenin to accumulate and do its gene regulation in the nucleus. Cross-talk between these pathways would be very inopportune, and is prevented by the various functions of Axin, a scaffold protein. 

Another well-studied role of GSK3 is in a developmental signal, called WNT, which promotes developmental decisions of cells during embryogenisis, wound repair, and cancer, cell migration, proliferation, etc. GSK3 is central here for the phosphorylation of beta-catenin, which is a transcription regulator, among other things, and when active migrates to the nucleus to turn its target genes on. But when phosphorylated, beta-catenin is diverted to the proteosome and destroyed, instead. This is the usual state of affairs, with WNT inactive, GSK3 active, and beta-catenin getting constantly made and then immediately disposed of. This complex is called a "destruction" complex. But an incoming WNT signal, typically from neighboring cells carrying out some developmental program, alters the activity of a key scaffold in this pathway, Axin, which is destroyed and replaced by Dishevelled, which turns GSK3 off.

How is GSK3 kept on all the time for the developmental purposes of the WNT pathway, while allowing cells to still be responsive to insulin and other signals that also use GSK3 for their intracellular transmission? The current authors found that the Axin scaffold has a special property of allosterically preventing the phosphorylation of its bound GSK3 by other upstream signaling systems. They even re-engineered Axin to an extremely minimal 26 amino acid portion that binds GSK3, and this still performed the inhibition, showing that the binding doesn't sterically block phosphorylation by insulin signals, but blocks allosterically. 

That is great, but what about the downstream connections? Keeping GSK3 on is great, but doesn't that make a mess of the other pathways it participates in? This is where scaffolds have a second job, which is to bring upstream and downstream components together, to keep the whole signal flow isolated. Axin also binds beta-catenin, the GSK3 substrate in WNT signaling, keeping everything segregated and straight. 

Scaffold proteins may not "do" anything, as enzymes or signaling proteins in their own right, but they have critical functions as "conveners" of specific, channeled communication pathways, and allow the re-use of powerful signaling modules, over evolutionary time, in new circuits and functions, even in the same cells.

• The oceans need more help, less talk.
• Is Trump your church?
• Can Poland make it through?

The Curious Path of German Socialism

From Marx to Hitler to Honecker, and beyond.

As I was listening to a podcast about the Civil War, a character jumped out- August Willich. Willich was a Union general, both loved and respected, who had been born as a Prussian aristocrat and attended the Prussian military academy. But then he took a turn, along with many Germans of his generation, and fell in with the socialists and communists (including, later in England, Karl Marx), and the revolutionaries of 1848, going to far as to command a revolutionary corps with fellow-Prussian Friederich Engels at his side. This era was a confused mess of motivations, (maybe a bit like the 1960's), inspired by the nationalist and socialist/ liberal ideals of the French revolution, while fighting against the monarchies that the Napoleonic era had ultimately, by its defeat, propped up all over Germany. The simultaneous nationalistic revolution in Italy was a template, as was the prosperous development of democracy in the US. The philospher Georg Hegel had even chimed in, a few decades before, putting the progressive and liberal spirit of the French revolution into sufficiently turgid terms to inspire a generation of German philosophers and social reformers.

The revolutions of 1848 in Germany were crushed, but the reformers found other outlets. Willich fled through Switzerland to England, as had his fellow-Prussian, Karl Marx. This communist league was concerned with far more than nationalism, finding in the new capitalist system another, and perhaps even worse, feudalism spreading across the continent, crushing traditional cultures as it ground workers to dust. While one branch of this movement continued to plot and feud and agitate in Europe, (with Vladimir Lenin as its ultimate expression), others became social democrats and found ways to work within the gradually loosening political systems. Many German socialists (as did Willich) went to America, a fertile territory for self-government as well as the battle with capitalism. And they saw the fight for the Union as the same old pattern- of the joined forces of the planter aristocracy (plus a particularly soul-less form of capitalism) fighting liberal progress and social justice. Several prominent generals of the Civil war, and many whole regiments, were of German origin.

August Willich, during the Civil War.

In fact, there was a large influx of prominent and educated Germans to the US around this time, which led to to a heavy concentration of Germans in the Midwest, especially Wisconsin. Milwaukee became a stronghold of (democratic) socialism in the later 1800's and early 1900's. Like the democratic socialists of Germany, they introduced the old age pensions, health and unemployment insurance, public housing, and other public works that typify the reform era. It is something of a lost story, how these reforms that we take for granted today had significant origins in the migration of progressive-spirited Germans in the wake of the 1848 revolutions. For example, they propagated the Turnverein, sometimes now named Turner halls, which were early gyms and community centers.

Naturally, all this innovation came under a cloud when Germany turned into the enemy of the US and much of the rest of the world, not once, but twice, in the 20th century. I often marvel at the growing practice of pronouncing Hispanic names and words properly in the media these days. If such care were devoted to German names, the media would sound quite different! All that is to say that there is another inheritance to appreciate.

Ethnic composition of the US.

Back in Europe, socialists took various paths, as noted. The extreme and involuted form that became communism and bolshevism was successful only once- in Russia, to cataclysmic consequences. Elsewhere, democratic socialists were the dominant type, with a great deal of popular support. Bismark, no socialist himself, put forth the first national health insurance system, and old age and accident insurance, as ways to coopt the socialists in Germany at the time. The continuing superiority of labor laws and practices in Germany today, compared with the US, speaks to the strong historical influence of socialism. This influence also led to the curious choice by Hitler's party to call itself national socialism, though we would regard them today as quite on another end of the political spectrum. But socialism was held in high esteem and spoke strongly to the solidarity that Germany needed in the wake of economic and military disaster, so that it apparently could be twisted to fascist ends. They just discarded the politically liberal elements, and focused on the economically (and militarily) communal ones. One can conjecture that socialism generally hearkens back in somewhat atavistic fashion to the tribal and village societies/economies that, while doubtless harsh, were highly personal and arguably more humane than the pitiless and impersonal operations of modern capitalism.

The sad irony is that German-originated socialism, in the form of communism that had filtered through Russian theory and experience, came back in force over Eastern Germany after World War 2, back to its Prussian homeland, more or less. And boy, what a system it had turned into by that point. Its rhetoric of solidarity had turned into empty propaganda, its nationalist aspirations into a Russian prison, and its hope of freeing workers into a state of the most stringent surveillance and terror.

Socialism today remains variable and amorphous, depending on where and who you are. Its formal definition of public ownership of the means of production (as opposed to communism, where everything is owned communally and distributed centrally) seems nowhere in sight in the West. That part of the program seems a dead letter, and what is left, for the democratic socialists, is more in line with the Social Democratic reform movements in Germany and the US; progressive reform to sand some edges off the capitalist system. That program has been stunningly successful in making capitalism both reasonably humane and highly productive, but it took place, historically, under the impetus of great extremism at the fringes- the labor wars, the bombings, and most of all, the spectre of communism looming over the early 20th century. Can we find a reasonable and reasoned path to reform now, without the fires of a revolution glowing in the distance?

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Better Red Than Dead

Some cyanobacteria strain for photosynthetic efficiency at the red end of the light spectrum.

The plant world is green around us- why green, and not some other color, like, say, black? That plants are green means that they are letting green light through (or out by reflection), giving up some energy. Chlorophyll absorbs both red light and blue light, but not green, though all are near the peak of solar output. Some accessory pigments within the light-gathering antenna complexes can extend the range of wavelenghts absorbed, but clearly a fair amount of green light gets through. A recent theory suggests that this use of two separated bands of light is an optimal solution to stabilize power output. At any rate, it is not just the green light- the extra energy of the blue light is also thrown away as heat- its excitation is allowed to decay to the red level of excitation, within the antenna complex of chlorophyll molecules, since the only excited state used in photosynthesis is that at ~690 nm. This forms a uniform common denominator for all incoming light energy that then induces charge separation at the oxygen reaction center, (stripping water of electrons and protons), and sends newly energized electrons out to quinone molecules and on into the biosynthetic apparatus.

The solar output, which plants have to work with.

Fine. But what if you live deeper in the water, or in the veins of a rock, or in a mossy, shady nook? What if all you have access to is deeper red light, like at 720 nm, with lower energy than the standard input? In that case, you might want to re-engineer your version of photosynthesis to get by with slightly lower-energy light, while getting the same end results of oxygen splitting and carbon fixation. A few cyanobacteria (the same bacterial lineage that pioneered chlorophyll and the standard photosynthesis we know so well) have done just that, and a recent paper discusses the tradeoffs involved, which are of two different types.

The chlorophylls with respective absorption spectra and partial structures. Redder light is toward the right. Chlorophyll a is one used most widely in plants and cyanobacteria. Chlorophyll b is also widely used in these organisms as an additional antenna pigment that extends the range of absorbed light. Chlorophylls d and f are red-shifted and used in specialized species discussed here. 

One of the species, Chroococcidiopsis thermalis, is able to switch states, from bright/white light absorbtion with normal array of pigments, to a second state where it expresses chlorophylls d and f, which absorb light at the lower energy 720 nm, in the far red. This "facultative" ability means that it can optimize the low-light state without much regard to efficiency or photo-damage protection, which it can address by switching back to the high energy wavelength pigment system. The other species is Acaryochloris marina, which has no bright light system, but only chlorophyll d. This bacterium lives inside the cells of bigger red algae, so has a relatively stable, if shaded, environment to deal with.

What these and prior researchers found was that the ultimate quantum energy used to split water to O2, and to send energized electrons off the photosystem I and carbon compound synthesis, is the same as in any other chlorophyll a-using system. The energetics of those parts of the system apparently can not be changed. The shortfall needs to be made up in the front end, where there is a sharp drop in energy from that absorbed- 1.82 electron volts (eV) from photons at 680 nm (but only 1.72 eV from far-red photons)- and that needed at the next points in the electron transport chains (about 1.0 eV). This difference plays a large role in directing those electrons to where the plant wants them to go- down the gradient to the oxygen-evolving center, and to the quinones that ferry energized electrons to other synthetic centers. While it seems like more waste, a smaller difference allows the energized electrons to go astray, forming chemical radicals and other products dangerous to the cell. 

Summary diagram, described in text. Energy levels are described for photon excitation of chlorophyll (Chl, left axis, and energy transitions through the reaction center (Phe- pheophytin), and quinones (Q) that conduct energized electrons out to the other photosynthetic center and biosynthesis. On top are shown the respective system types- normal chlorophyll a from white-light adapted C. thermalis, chlorophyll d in A. marina, and chlorophyll f in red-adapted C. thermalis. 

What these researchers summarize in the end is that both of the red light-using cyanobacteria squeeze this middle zone of the power gradient in different ways. There is an intermediate event in the trail from photon-induced electron excitation to the outgoing quinone (+ electron) and O2 that is the target of all the antenna chlorophylls- the photosynthetic reaction center. This typically has chlorophyll a (called P680) and pheophytin, a chlorophyll-like molecule. It is at this chlorophyll a molecule that the key step takes place- the excitation energy (an electron bumped to a higher energy level) conducted in from the antenna of ~30 other chlorophylls pops out its excited electron, which flits over to the pheophytin, then thence to the carrier quinone molecules and photosystem I. Simultaneously, an electron comes in to replace it from the oxygen-evolving center, which receives alternate units of photon energy, also from the chlorophyll/pheophytin reaction center. The figure above describes these steps in energetic terms, from the original excited state, to the pheophytin (Phe-, loss of 0.16 eV) to the exiting quinone state (Qa-, loss of 0.385 eV). In the organisms discussed here, chlorophyll d replaces a at this center, and since its structure is different and absorbance is different, its energized electron is about 0.1 eV less energetic. 

In A. marina, (center in the diagram above), the energy gap between the pheophytin and the quinone is squeezed, losing about 0.06 eV. This has the effect of losing some of the downward "slope" on the energy landscape that prevents side reactions. Since A. marina has no choice but to use this lower energy system, it needs all the efficiency it can get, in terms of the transfer from chlorophyll to pheopytin. But it then sacrifices some driving force from the next step to the quinone. This has the ultimate effect of raising damage levels and side reactions when faced with more intense light. However, given its typically stable and symbiotic life style, that is a reasonable tradeoff.

On the other hand, C. thermalis (right-most in the diagram above) uses its chlorophyll d/f system on an optional basis when the light is bad. So it can give up some efficiency (in driving pheophytin electron acceptance) for better damage control. It has dramatically squeezed the gap between chlorophyll and pheophytin, from 0.16 eV to 0.08 eV, while keeping the main pheophytin-to-quinone gap unchanged. This has the effect of keeping the pumping of electrons out to the quinones in good condition, with low side-effect damage, but restricts overall efficiency, slowing the rate of excitation transfer to pheophytin, which affects not only the quinone-mediated path of energy to photosystem I, but also the path to the oxygen evolving center. The authors mention that this cyanobacterium recovers some efficiency by making extra light-harvesting pigments that provide more inputs, under these low / far-red light conditions.

The methods used to study all this were mostly based on fluorescence, which emerges from the photosynthetic system when electrons fall back from their excited states. A variety of inhibitors have been developed to prevent electron transfer, such as to the quinones, which bottles up the system and causes increased fluorescence and thermoluminescence, whose wavelengths reveal the energy gaps causing them. Thus it is natural, though also impressive, that light provides such an incisive and precise tool to study this light-driven system. There has been much talk that these far red-adapted photosynthetic organisms validate the possibility of life around dim stars, including red dwarves. But obviously these particular systems developed evolutionarily out of the dominant chlorophyll a-based system, so wouldn't provide a direct path. There are other chlorophyll systems in bacteria, however, and systems that predate the use of oxygen as the electron source, so there are doubtless many ways to skin this cat.

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• "The top 1% of households are responsible for more emissions (15-17%) than the lower earning half of American households put together (14% of national emissions)."