In the Depths, Antennas for Light

Coccolithophores are beautiful, inside and out.

As we pump out ever more carbon, burned from fossil sources, we are relying on the great geochemical and biological cycles to take in this waste and clear the air. At the same time, we are impairing these cycles by chopping down forests and acidifying the oceans. Half of photosynthetic productivity happens in the oceans, thanks to phytoplankton. While plants on land grow large and store carbon in their vast root and branch systems, plants in the ocean- the diatoms, algae, and of interest this week, coccolithophores- are all small and short-lived. They sequester carbon as a rain of detritus that falls into the deep ocean from the upper, planktonic regions. Coccolithophores, which are related to red algae, particularly make calcium carbonate shells that fix and remove a billion tons of carbon each year. Chalk landscapes like the cliffs of Dover- those are piles of coccolithophores from ancient seas.

These photosynthetic protists, which adopted a red algal symbiont somewhere in the mists of the past, are beautiful on the outside, with tough shells that are, ingeniously, transparent to the light they live from, just as are the silicate shells of their cousins the diatoms. These shells protect them from the physical buffeting of the ocean, from viruses and other pathogens, and the shell also buffers them from harsh chemicals and toxins. 

Coccolithophores make up roughly ten percent of oceanic phytoplankton, and specialize in more nutrient poor areas, relative to diatoms. One such area is deeper water, where light is relatively dim. A recent paper revealed structures for the light antenna complexes that allow these organisms to maximize their energy collection. All photosynthetic organisms have photosynthetic reaction centers where the key reactions happen- using light energy to crack the bonds of water molecules to liberate the hydrogens that are later stored in carbohydrates and fats. Complementary to that process is the re-union of two oxygen molecules into the waste product, oxygen gas, and also the fixation of carbon molecules from carbon dioxide, using those hydrogens to displace additional oxygen molecules.

But photosynthetic reaction centers are expensive to make, with requirements for obscure elements like manganese, and are highly reactive. Solar energy is diffuse, as we know from the somewhat painful, landscape-hogging process we use to collect it for our own electrical needs, so it turns out to be helpful to surround these reaction centers with light antennas that funnel energy in from a larger area. This only works because of quantum mechanics- the ability of electronic excitations to travel through a properly structured and electronically tuned pathway by Förster resonance energy transfer.

Full light harvesting complex and photoreaction center, of Emiliania huxleyi. A is a view from the top or outside of the (thylakoid) membrane, while C shows edge-on views. There are 38 antenna subunits in all.

All eukaryotic photosynthetic organisms use light antennas, but the ones developed by coccolithophores turn out to be particularly large and ornate. They form beautiful pinwheels of linked proteins, up to six per spoke, adding up to 38 antenna proteins in all, that conduct light from the outside in. They are packed with chlorophyl molecules, which are the pigments that receive light energy, and also with caroteniods, which are additional pigments that receive light and transfer it to nearby chlorophylls. They measured the time it took to transfer energy from an incoming light pulse to the reaction center at about 100 picoseconds. And this happens with an efficiency of 95%- amazing! An image of the antenna complex emphasizing the chlorophylls shows that they are lines up quite precisely from one unit to the next, making for an easy, even beautiful, path from the outer reaches into the center.

Each of the light harvesting proteins is loaded with chlorophylls, (blue, green), and with carotenoids (yellow).

Whereas land plants have only about five antenna complexes associated with their reaction centers, this coccolithophore has 38, making it the largest light harvesting complex ever found. This represents either a vast increase in light gathering capacity, or else an admission of a special cost of some kind in making or operating reaction centers, compared with antenna complexes. The authors do not delve into this issue, but one can imagine several constraints, such as a design optimum for keeping a reaction center busy at a certain high rate, or for minimizing the oxidative off-reactions that can occur in these centers. At any rate, the design, refined over hundreds of millions of years, is impressive indeed.

Emphasizing the chlorophylls in the light harvesting units shows how they are lined up, forming quantum wires for the conduction of excitation.

• It is unbelievable, and culpable, that Lysenkoism is being revived in the US in 2026.
• And abroad.
• Not to mention Neanderthal climate and energy policy.
• More in the kowtowing department.
• Cuba is in the dark.
• Surrender, at the end of a disastrous war.
• Novel solar financing.

Dalio on Debt

Review of Ray Dalio's "How Countries Go Broke". 

It is difficult to focus on important policy issues, as the national media is led around by the president's revolving fixations like a cat by a laser pointer. But focus we must, if we are not going to decline faster than we already are due to incompetent and corrupt leadership. One looming area is the federal budget. As a card-carrying acolyte of MMT economics, it is hard to say this, but there are limits to federal borrowing. 

A recent book by super-investor Ray Dalio lays out a set of patterns, which he calls the big cycle, that tracks government solvency over roughly eighty year cycles, which typically start out tight and solvent, using relatively hard money, and end up overextended and in crises that are resolved by some mix of inflation, depreciation, and restructuring / reneging on debts. It is a perpetual and international set of cycles. As an investor, he is not much of a writer or economist, so the book is repetitive, poorly written, and markedly incurious about the origins of the patterns he finds. But still, it makes some significant points. 

First is that the cycle happens for all monetary systems, whether fiat and borrowing domestically, or hard currency and borrowing in foreign currencies. But the consequences are far more severe for the latter than the former. Having your own currency, as MMT economists well know, is a blessing when you want to borrow and manage a domestic economy. Second is that even with a fiat currency, the limits are different, but there still are limits to government borrowing, which we are gradually running into. 

Trajectory of US government debt.

Trajectory of interest compared to other US government spending.

At the beginning of a big cycle, the foregoing crisis has scared everyone into hard currencies, like gold, or some properly revalued local currency backed by a solvent government. Probity is everything. Later on in the cycle, the money is softened up due to increased borrowing and laxer standards. Eventually, there are private debt crises, where the central bank is obliged to take on a large part of the private debt and expand its balance sheet. Eventually, the central bank no longer bothers to unwind its balance sheet after such crises, and holds on to both private debts and government debt that it monetizes. And at the far end of the cycle, the debt service paid by the government threatens to become so onerous that a crisis develops- investors flee, interest rates go up, inflation goes up, and the debts, fiat though they are, become unsustainable. There is "restructuring".

This is a big cycle because it is superimposed on the regular business cycle that takes much shorter time- something like five to ten years. And it concerns the government's management of the money, not the private sector's vacillating enthusiasm about business conditions. Turkey is currently in the far end of such a cycle, plunged into high inflation and struggling to find a way to put itself back on a sound basis after massive mismanagement. And obviously the US is somewhere late in the same continuum. The issue is not the size of the federal debt, or its relation to GDP, but the amount we have to pay in interest from the annual budget. That is heading towards one trillion dollars, and if interest rates remain where they are, (given the inflationary pressures from the current administration's bad policies such as tariffs, oil shortages, and tax cuts), there is danger of a growing spiral of higher revenues going to interest, and less money available for government functions, increased monetization by the central bank, and ultimately, loss of faith in the currency. 

A fascinating case is that of Japan, which both Dalio and MMT economists focus on for its unique approach to monetary policy. Since its debt bubble in the 90's, Japan has shifted lots of private debt and public debt to the central bank's balance sheet, which stands at about three times GDP- far beyond what other countries would deem acceptable. This can be sustained because the bank of Japan has kept interest rates very low- in the zero to one percent range. Thus the cost of all this debt is manageable, and will remain so unless and until interest rates go up. But this also means that the bank can not use interest rates to manage the economy and foreign exchange. In consequence, Japan's currency has weakened enormously on the international currency markets, making imports (such as of oil, significantly) much more expensive, while improving the competitive position of Japanese export manufacturers. Additionally, Japanese banks and businesses have been reluctant to unwind bad debts, which leads to the stagnation and lack of overheating that the low interest rates would otherwise foster. Everyone kicks the can down the road, waiting for either a crisis, or a resolution, neither of which seem in the offing. 

But more interesting than the economic drama is the larger cultural cycle which Dalio alludes to as well. For this is not just an economic big cycle, but something deeper. For the US, Dalio starts with the civil war, but I think it is much more instructive to include the cycle before, which started with the Revolutionary War. These wars, plus World War 2, mark the three big cycles that the US has been through. Each started with war, and with currency disruption. The Continental Congress issued reams of Continental currency that had, by the end of the war, become worthless. So, one big objective of the ensuing constitutional order was to put the newly minted dollar on a sound footing, as also the finances of the federal government. This led to decades of growth, prosperity, and (the war of 1812, and various Native American extermination campaigns aside) peace. The middle of this period also saw a progressive cultural flowering, with the transcendentalists, various experimental communes like Brook Farm, and the Great Awakening. All this stability allowed people to envision a better society. However, what happened instead was increased division and conflict, leading to the Civil War. 

Here again, paper money was issued and resulted in significant inflation, as the accumulated hatred tore the country apart. But in its wake, prosperity again reigned, with rapid technological advancement, peace, and, eventually, and progressive movements for women's suffrage, temperance, anti-corruption and anti-monopoly, and the Settlement movement. All this was reset in the Depression and ensuing world war, which then began a new cycle of conflict avoidance enshrined by the US role in the UN, NATO, and a very sedate and conventional media environment. As peace and stability took hold, a new progressive movement rose- the hippies, the anti-war, civil rights, and feminist movements. Did these foster peace and togetherness? Not exactly. One can sense that the culture was eager for truth, for not sugar-coating things anymore, for honesty and, indeed, for conflict. Humor shows became more cutting, movies more biting, tinged with horror and apocalypse. And here we are, in a country where the two parties can't stand each other and are headed towards something that smells distinctly martial.

All this conflict has smothered discussions of actual policy, which anyway has gone to the dogs in the new administration. For example, a high level of federal borrowing is more defensible if it builds US productive capacity, through investments in future-oriented technology and education. But the current adminstration is spending billions to cancel renewable energy contracts that had already been entered into. This is money not just down the drain, but subtracted from future productive capacity. 

Is Dalio sanguine about our prospects? Not particularly. But nor does he view them as terribly dire. In the first place, the gulf between sovereign, fiat-issuing countries and others comes out starkly in his many graphs and analyses. The latter get into much more difficult straits when they borrow too much of someone else's money. Secondly, rather modest adjustments now, to federal spending, to taxation, and to interest rate policy, can change the trajectory we are on, from spiraling to sustainable. I would focus particularly on the tax side, which has so egregiously been attacked by the current administration, in its contempt for making the rich pay anything. Dalio mentions, however, that the most consequential lever is that of interest rates, which, as Japan shows, can, if low enough, make eye-watering debts quite easy to carry. But given a system where we want to retain the interest rate as a lever of macro-economic policy, (and capitalist motivation), it would be best to approach rates not by fiat, as Japan has done, but by good policy on the other fronts, which will naturally lead to lower interest rates, if properly handled. 

• Are we headed into the China century?
• A pathetic spectacle of weakness and decline.

Reading the Eloquent Brain Regions

Telling the difference between inner and outer speech.

As we understand more about how the brain works, we can decode what is going on inside. But sometimes, the result is oversharing! A recent paper discussed how one lab is filtering out inner speech from intentional outer-directed speech in their BCI: brain-computer-interface. 

After a very long road of brain research, we understand a great deal of its computational mechanism. There is no soul, no mystery other than the amazingly intricate interdigitation of billions of neurons, painstakingly architected during evolution to make a rapid learning and response machine. A recent paper described progress on a brain-computer interface, whereby people with brain damage can be helped to communicate from undamaged portions. They found that unspoken thoughts were also detectable, in addition to the attempted speech they were trying to help their subjects express. This led the researchers to provide a switchable interface where the subject could turn that part off or on, at will!

Updated view of speech production areas in the brain. v stands for ventral, PrCG stands for precentral gyrus, the general motor control area. Wernicke's area is known to participate in general language construction / comprehension.

The human facility for speech is unique among animals, and while many animals vocalize and communicate with some complexity, none have been found with the richness of human speech. As a recent evolutionary innovation, there have been some rough edges, but we have quickly become utterly dependent on speech for all aspects of social life. In the brain, speech production happens in motor areas, which reside in a vertical stripe of the cortex forward of the sensory map. It had been thought that Broca's area was the main region and was purely a motor conduit, constructing from the sensory and higher regions the signals sent to innervate the larynx, tongue, lips, and other vocal apparatus. But it turns out to be more complicated. More of the pre-central gyrus (the motor cortex) is involved, and also, when one records from these regions, one gets many kinds of signals, including speech perception, not just production, and other aspects of audio perception and premotor thoughts about communication- phonological working memory, silent rehearsal, etc. Indeed, Broca's area appears to have higher-level roles more in sentence construction rather than in detailed motor control and articulation.

The current authors took off from these recent insights and placed high-density electrodes (about 60 electrodes in each of several locations) up and down the pre-central gyrus in patients that had been rendered inarticulate due to stroke or ALS. Even though this sampling is unbelievably crude compared to the brain's own density of computation, it was enough to generate recognizable speech.

"We discovered that inner speech is robustly represented and demonstrated a proof-of-concept real-time inner-speech BCI that can decode self-paced imagined sentences from a large vocabulary (125,000 words). We also found that aspects of free-form inner speech could be decoded even during tasks where participants were not explicitly instructed to use inner speech. ... To prevent unintended output during inner-speech BCI use, we also demonstrate a system where an internally spoken “keyword” can be detected with high accuracy, enabling a user to “lock” and “unlock” the system."

Outline of the experiments. Electrode micro-arrays were implanted in several place up and down the motor area, or precentral gyrus (C). The computer, using large language models to make sense of the array signals, then interpreted as the user was prompted (or not prompted) for attempted speech.

Given enough computer power, even these patchy signals from the subject's brains could be processed into something useful. The researchers found that the same algorithms that recover attempted speech also detect silent speech, reading, and even listening. This implies perhaps that we listen sympathetically, struggling in our speech production areas when a speaker struggles, and are prone to following / copying other speakers. Or else it just reiterates that these areas are not pure motor control regions, but participate in a more integrated way in the hearing/thinking/speaking circuit. Fortunately, the signals differ significantly in amplitude, so can be told apart. The accuracy of all this is not great, a shown below, but it is surely better than being locked in.

The results (C) of interpretation of inner speech, as opposed to more strongly attempted speech, are far from perfect, but give some indication of what the subject is thinking about.

• Galloping inequality.
• Corruption in Puerto Rico.
• Just because you are knocked out does not mean that your brain isn't working at a more local level.
• Gross malpractice at the NIH.
• The racism is ever louder on the right.

Peak Carbon?

Are we at peak oil, perhaps even peak burning? Thanks to Donald Trump, renewables are looking better than ever.

It turns out that using the oil weapon opens people's eyes to the alternatives. The Saudis have recognized for a long time that stability in oil pricing and supply was the way to keep the world addicted. But in the current wars, Russia has used the natural gas weapon, and Iran has used the oil weapon. Now the addicts realize what a thin needle it is that brings them the fossil fix. After two months of closure on the Strait of Hormuz, the economic responses around the world have been surprisingly muted. While Paul Krugman rang the alarm of $200/barrel oil, prices have stabilized around $110 or so. It turns out that demand is more elastic than anticipated, at least it has been while supplies are still in transit. However, as physical shortages begin to hit, prices may rise again.

As a matter of strategy, the US administration is clearly flailing, unwilling to recognize a loss, and callous about the worldwide harms being imposed by its fruitless dithering. Is a blockade of Iran going to break its government? That is highly unlikely. They have been through much worse, such as during their war with Iraq. Trump's attacks and insults have rallied the population, entirely contrary to the administration's intention, but entirely foreseeably. Iran's sensitivity to economic pain is much lower than ours. And, as the administration was already doing on an ongoing basis prior to its war, it continues to make enemies of the US around the world, more so with each passing day that shipping in the Persian Gulf is stalled.

Paul Krugman bemoaned the "demand destruction" that continued shortages and high prices would cause, which may lead to economic slowdowns, perhaps recession. However I welcome it. It represents conservation of this precious resource, and, one might say, more realistic pricing that brings in, at least to a small degree, the widespread harms of fossil fuels. When one adds volatility and geostrategic dependencies, on top of the gross environmental harms, and what is now an economic disadvantage of fossil fuels when compared with renewable energy, the solution is clear, if not easy. The transition to renewable energy is going to accelerate.

Trend of world-wide carbon emissions.

Currently, the world is at the cusp of still-rising carbon emissions. This means that, even after all the climate conferences, and the reports, the activism, and the technological development, humanity as a whole is still burning more fossil carbon every year than the year before, and thus increasing the CO2 concentration in the atmosphere ever faster, and driving the climate crisis to ever-accelerating harms and disasters. Is it possible that this strategic-economic crisis, brought on by the blundering of a demented US administration- one that has done all in its power to deny climate change and scuttle the energy transition- will finally turn the tide? Could we be at peak carbon? And if so, will the downslope of emissions be faster than the upslope, in this slow-motion catastrophe? One can see that the US is already past peak carbon, and the state of California stands at 75% of the peak carbon emissions, which happened back in 2004. The upslope has been driven by highly uneven, and gradual, technological development and increased population. The downslope will be driven by the much more globally integrated rise of renewable technologies, so it has a chance of happening at a faster pace, despite the challenges of transitioning difficult economic sectors like trucking and aviation.

With the economic tailwinds of cheaper energy storage technologies, coupled with other advances in geothermal, solar, and wind power collection, the transition is inevitable. But public policy can make it faster or slower. The Biden administration worked towards the future, while the current administration works against it. Outside the US, China is enabling both its own transition and those of all other countries by leading extremely efficient solar and storage manufacturing. Those economics are going to eliminate new coal plant construction, and eventually use of all fossil fuels. China now sells more EV than fossil-based automobiles. While it has a prodigious fleet of coal-burning power plants, and is still building new ones, the overall level of coal power generation has leveled off, as it closes plants close to reduce pollution in sensitive urban areas.

While ironies abound, the important part of the story is that the biosphere is baking and needs help as fast as possible. If that help comes through the narcissism of small-minded tyrants, so be it. 

• Caesar, King, tomato, tomahto.
• Coding is toast.
• Renewable energy has beaten methane in the US electricity generation.
• Krugman chimes in.

The History and Future of a Single Mutation

The CCR5delta32 confers resistance to HIV. Where did it come from?

We are edging into an age of precision medicine, where the causes of our maladies will be known in molecular detail, allowing treatments that address them at the root. Given the parlous state of medicine today, in the midst of financial breakdown and a continued mediocre level of basic diagnosis, it is hard to believe this is a corner we can turn. But vaccines have long been in this category, of addressing the precise pathogenic causes of disease, and oncology is fitfully getting there, given advances in DNA sequencing and in treatments based on specific mutations.

HIV is also a beneficiary of this approach, since the discovery of its pathogen led directly to a variety of effective (if not yet permanent) treatments. A researcher in China created gene-edited humans with a specific mutation that will render them resistant to HIV. The mutation he chose for this work is called CCR5delta32, and it does not naturally exist in Chinese populations. 

But it does exist in European populations, at a roughly 10% rate in single copy. When present in two copies, it provides complete immunity to HIV, while if present in one copy, it slows infection substantially. A recent paper rooted through the available ancient and present genomes to figure out where this mutation came from. 

CCR5 is a cell surface receptor for cytokines 3, 4, and 5. These are all pro-inflammatory cytokines, and they interact with multiple receptors. Here, as in so many other respects, the immune system is riven with redundancy, so that it can grapple with as many contingencies as possible. Cytokines are signaling molecules for the immune system, which is an unusual organ, being dispersed all over the body with numerous cell types all patrolling around, and communicating with each other by long- and short-range chemical messages. It turns out that the major form of HIV uses the CCR5 protein to get into our immune cells, explaining why CCR5delta32, which is totally non-functional, has such a dramatic effect on HIV susceptibility. 

While people carrying CCR5delta32 are generally fine, this defect does confer a variety of subtle changes to their susceptibility to other infectious diseases and cancers. That explains why this mutation has settled at its low level in the European populations, probably balancing the occasional benefit against a specifically CCR5-seeking pathogen against its natural functions that form the basis of its existence in the first place as a part of immune system that is conserved in all mammals. The Chinese gene-editing researcher came under withering criticism not only for breaching the generally agreed moratorium on human germline gene editing, but also because the net effect of this mutation is, on the whole, negative, raising risks of numerous diseases, despite its beneficial effect on HIV. 

The authors run several models and populations in an attempt to time the origin of the CCR5delta32 mutation, and portray its positive selection over the ensuing millenia.  CHG- Caucasus hunter-gatherer; EHG- Eastern hunter-gatherer; WHG- Western hunter-gatherer; ANA- Anatolian Neolithic ancestry. The bottom axis is time, and the Y axis is the frequency of the mutation in these populations. "Modern DAF" refers to the inclusion of the data set of current (not ancient) population frequencies, (top), which the authors claim leads to continued rates of selection (last 2,000 years) that are artifactual.

So where did it come from? The new authors gather up a large variety of population samples from around the world, and from ancient humans, back to about ten thousand years ago. They find the first instance of the mutation in one sample at 5.8 thousand years ago. After that, its frequency rises dramatically, up to about two thousand years ago, when it levels off. They conclude that this mutation originated about seven to nine thousand years ago, in the steppes of Eastern Europe / Western Asia, and was under strong positive selection at first, spreading to the current frequency of about 10% of the population / alleles. All occurrences on other continents can be accounted by the spread from this source.

Does this mean that HIV was prevalent long, long before the current pandemic? Hardly. The authors can not say anything about it, but one theory would be that some other disease had a similar profile. It certainly was not the Black Death, as the authors show that this mutation had no change in frequency over that gruesome pandemic. Another hypothesis is that general reduction in inflammatory response might be beneficial in some settings, as has been found for Covid-19, though here again, this mutation does not have any known positive or negative net effect on Covid-19 susceptibility or course. 

It is amazing that we have enough sequences of ancient DNA to be able to reconstruct this kind of thing- to be able to trace where and when some influential mutation occurred, and how it traveled and spread. It is a tour-de-force of bio-archeological reconstruction.

• When you escape reality, and morality.
• Some environmental benefits are flowing from the current war.
• We may be at peak oil, courtesy of the US.

The Death of Boredom and the Future of Politics

Can politics work without a civic sphere?

How can we have a loneliness epidemic when we are connected like never before? It is a problem that perplexed Robert Putnam in "Bowling Alone". He put it mostly down to TV, internet, and the growth of passive and isolated forms of entertainment generally. When you read between the lines of history of any time before about one hundred years ago, you realize that people were, before the modern age, bored out of their minds. Who plays cards? Who puts on operas, or runs numbers, or goes bowling? Who needs an Easter pageant, or a three-to-four-hour baseball game? Only people with nothing better to do. If you wanted music, you had to make it. If you wanted conversation, you had to share it. Human society was built on simple quid pro quos- social rewards and resolution of boredom and isolation for personal participation.

But that deal has broken down dramatically in the modern age. We have a thousand channels, talk radio, recorded music. With AI, we are getting personal chatbots and bespoke romantasy partners. Sports have slid tectonically from participation to spectation. Boredom is a thing of the past, though if you do want to play cards, plenty of computers are willing to take a hand.

An interesting article in the New Republic knit this together very nicely with the problems we are having in politics. In the US, political engagement is increasingly shallow, leaving the field to extremists who can still call up foot soldiers to storm the ramparts. What happened to the Occupy movement? For all its inherent logic and flash organization, it fizzled into nothing because it gave little thought to its own institutionalization (indeed, was allergic to organization) and durable engagement, all the while railing against the overwhelming organization and deep pockets of the entrenched systems of capitalism. The Left is notoriously inable to herd itself into an effective, organized force. While capitalism is naturally organized and institutionalized by virtue of naked self-interest and corporate structures, civic groups grow out of far more disparate, and evanescent, motivations. Unions have been an attempt to organize around a countervailing, while still self-interested logic, which inherently limits their reach and coherence. The true civic sphere, however, is threadbare.

Political parties have similarly shallow roots. In California, the governor's race has 61 candidates, and little control by the party establishment, particularly by the Democratic establishment that supposedly runs the state. Like other non-profits, parties ask little of their adherents, other than possibly a monetary contribution, and wouldn't dream of holding truly social events that could deepen civic engagement. Expectations of civic engagement have hit rock bottom, mostly because people have tuned out across the civic spectrum. The testimonial dinner is a relic. The ice cream social is unheard of. Service organizations like Rotary and Elks are fossils, unions are on life support. Events and organizations that previously kept people entertained and involved in a civic way are scarce. These traditions both trained people for common action, and led to the kind of networking and contact that fed political consciousness and activity. They also helped to vet people directly for office holding (see the recent Swalwell case). 

Bernie Sanders can draw a crowd, but do those crowds go out, organize, and persist?

Republicans have found a partial solution to these problems by ginning up endless outrage through their propaganda outlets, predominantly talk radio and hate TV. While motivating, the results have, naturally, been intellectually disastrous and have us teetering on the edge of fascism. Democrats, as the more level-headed and progressive temperament, have not used the same tools effectively, and shouldn't. What should they do? Well, the field for civic engagement is pretty wide open. For example, one could imagine a tax on political advertisements, say 10%, which is collected by the government / FEC, and sent to counties or municipalities for civic engagement purposes, either election-related or not. This would create a fund for local talks, events, civic education, and the like that would, in theory, complement the advertising that is increasingly vacuous and meretricious. 

Another approach is direct action, where Democrats could use some of their energy and resources to build civic engagement, outside of straight campaigns. Just as the Republicans have harnessed ancillary issues like abortion and tax cuts that energized specific segments of their base, Democrats have to be a bit more canny about asking for more engagement and offering more involvement. Climate change is a great example, where a wide spectrum of individual action (trash pickups, solar panel installation, water quality testing) could be integrated into civic engagement that builds party alignment and ultimately, institutional strength. All great religions know that the more you ask, the more you get, and the deeper the commitment of followers. Additionally, the left already has a bewildering array of non-profits, whose efforts would ideally be more closely integrated with the Democratic umbrella to generate more organizational power- synergy or leverage, in business-speak.

On the other hand, how could civic disengagement be accommodated rather than fought? One approach might be to enhance the vetting and exposure of candidates by having nominating conventions at the local level. Even though California has an open primary, and thus does not grant each party automatic spots on each ticket, the parties should not shy away from selecting, testing, and promoting candidates. This should not be a central commitee operation hidden in the dark, the province of interested apparatchiks, but open forums that promote philosophies as well as people.

We are in a tough position, trying to keep politics alive in a world where its underpinnings- of civic engagement, communal organization and leadership, and simple conviviality- are fading in a deluge of individualized enjoyments. Political parties are at the forefront of this change, and need to think very deeply about how to keep themselves relevant and effective.

• Tax reform
• Is power based on insults?
• Everybody has deterrence these days.
• Who is being served here?
• Patient, heal thyself.
• Norway is going electric.

Pumping Calcium

An ornate ion pump manages rapid outflow of calcium.

In the beginning, the egg cell experienced a wave of calcium release, triggered by union with a sperm cell. This blocked other sperm from entering, and prepared the egg to become a zygote and embark on embryogenesis. It is but one example of the pervasive role of calcium signaling among animals. Another is the muscle activation cycle, which relies on calcium release from the specialized sarcoplasmic reticulum (in response to a nerve activation) to get the cell as a whole contracting. Generally, calcium is kept very low in the cytoplasm, and high in the endoplasmic reticulum and outside the cell. Thus, channels gated by electrical activation or other signals can cause rapid cytoplasmic calcium spikes and signal widely within a cell. 

On the flip side, there have to be pumps that keep the cytoplasmic concentration low, and a recent paper elucidates the structure of one such pump that is remarkably fast, while also closely regulated. It is an impressive machine. PMCA2 is an ATP-using calcium pump that sits in the plasma membrane and carries out what is called the Post-Albers cycle. This is a flip-switch mechanism for pumping ions, where ATP drives conformational switches alternately exposing ion binding sites to each side of the membrane. When the pore is open to the cytoplasm, there is no competition from higher concentrations outside, so the active site can bind one internal calcium, given a high-affinity site. Then, after the conformational switch, the pore is exposed to the outside, and at the same time the site is reconfigured to be lower-affinity, releasing the calcium ion into a high concentration environment. Neurons especially use calcium signaling extensively to operate synapses and regulate growth and development. Their rapid and frequent signaling requires a pump that has especially high capacity. PMCA2 operates at a maximal rate of several thousands of Ca2+ ions pumped per second.

Cartoon of the Post-Albers cycle, which is shared by a large family of active ATP-using pumps that transfer ions against their chemical concentration gradient. M is the main transmembrane domain of the pump, where the ions traverse the membrane. The N, P, and A domains are regulatory, especially binding and cleaving ATP  at an interface between the N, P, and A domain. The cycle links power steps (1,2) with conformational changes that carefully gate the pumping process.

And that is not all. Since calcium has a charge of 2+ and this pump does not intend to alter charge across the membrane, the pump simultaneously has binding sites for counter-ions (generally two OH-) that are transferred in the opposite direction from the calcium. Not only that, but every pump of this kind requires regulation of various kinds. PMAC2 is activated by phosphatidyl inositol 4,5 bisphosphate (PIP2), which is another important signaling molecule generated by specific PI kinases in response to activation of G-protein coupled receptors or protein kinase C, which may respond to external signals. In very general terms, these tend to be pro-growth or stress-induced pathways. These regulatory processes can tune the overall rate of recovery from rapid Ca2+ signaling events, by adjusting the level and activity of pumps like PMAC2. 

ATP binds at the N/P/A domain interface, and its hydrolysis (and loss of ADP) generates extensive shape changes, including into the transmembrane M domain. At the very bottom, the calcium ion is shown in green, bound inside the M domain pumping channel. The motions here are subtle, but enough to dramatically reshape the calcium channel.

The authors, using various substrate variants and other tricks, were able to develop structures of PMAC2 in several steps of the pumping cycle, using cryo-electron microscopy. The ATPase site in the N domain (red) is far from the channel that conducts the calcium ion (brown, far bottom). They show extensive shape changes from binding or losing the ATP molecule, though they mostly concern the intracellular domains (red, blue, yellow). The effects on the transmembrane pore domain are rather subtle, shown on right. The authors claim that, compared to other pumps of this large family, the structural changes are significantly less, suggesting that evolution for speed has caused the mechanism to become more efficient, with less wasted motion per conduction event, at least in the channel region itself.

Relation of the PIP2 binding domain (orange/red stick figures) to the calcium core binding site. PIP2 appears to be essential for rapid pump operation. At bottom is shown some schematics of the gating provided by PIP2 in bound and unbound states, especially via the D873 side chain (negatively charged aspartic acid).

They also find that the activating molecule PIP2 is neatly parked right next to the main calcium binding and conduction region, and is more or less essential for enzyme activity. In the graph above (e), they show that several single mutations made in the calcium binding high affinity site, for example switching the negatively charged D873 for the positively charged K (lysine), kills ion pumping activity. Mutation of the PIP2 binding pocket (KKQ->TLL, around position 347) likewise kills enzyme activity.

Relation of the counter-ion channel (red dots) with the calcium channel. Both are essential parts of the mechanism. Closeups with the coordinating protein side chains shown on the right.

The whole mechanism is alluded to in the last figure, where the central calcium binding site is shown, with the general direction of calcium pumping. The counter-ion transport area is shown nearby as a flurry of red dots (standing for water molecules, which at this scale are interchangeable with OH ions). Specific single mutations in either area, either changing negatively charged E412 to positively charged lysine at the calcium binding pocket, or changing polar S877 in the water/hydroxy binding area to the bulky and hydrophobic F (phenylalanine), each kill pumping activity (graph). 

While it would be ideal to have a more dynamic representation of what is going on, the new structures give tremendous detail, including the associated ATP, PIP2, calcium, and water molecules. The mutations also nail down several functional points. Obviously a rather intricate and well-oiled machine that keeps its bit of cellular calcium homeostasis on an even keel. It is hard to believe that the sum of thousands of machines like this one is life, but the deeper we look the more true that appears to be.

• Gullibility-maxxing.
• There is a serious bifurcation in Catholic thought.
• Reality has a well-known liberal bias.
• Well, that didn't work out so great.
• Is the internet going to collapse?

Not Every Transcript is Golden

 Reflections on junk DNA, and junk transcripts.

Some time ago, a large project in molecular biology determined that most regions of the genome are transcribed. The authors and most observers took this to mean that most regions are functional, quite in contrast to the reigning theory up to that point, that our genomes host a smattering of genes floating in a sea of "junk" DNA. That theory was based on the now-ancient observations of reannealing curves for bulk DNA from humans and other species which found that most of our DNA re-anneals very quickly, due to the fact that it is repetitive. Most of our genomes (60%) are taken up with LINE repeats, SINE repeats, old retro-transposons, stray duplications, and other repetitive material that, at a first glance, seems like junk. There has been a battle ever since, between proponents of junk DNA and those who see function around every corner. As we learn more about the genome, many more functions have indeed come to light, like distant enhancers and regulatory RNAs of many flavors. But overall, there still seems to be a lot of junk. 

A recent paper took an oblique shot at this field, looking at the profusion of alternative gene transcripts, which can number into the hundreds for a single gene. (This was also reviewed.) These are generally called isoforms, and arise due to variable ways one gene's RNA products can be initiated, terminated, and spliced. So not only are most regions of the genome transcribed in some form, actively transcribed regions can be transcribed and processed in myriad ways to lead to different RNA products. Here again, there has been an analogous argument, about whether every such isoform has a function, or whether isoforms might arise from more or less sporadic processes, often as unintended and non-functional sparks coming out of the machinery. The importance of isoforms is very well documented in many cases, so the possibility of function, sometimes highly conserved, is not in question. Only the importance of every last variation in combinatorial collections of isoforms that can number into the hundreds.

Here is an image from the first page (of about six pages) of RNA transcripts coming off the notorious BRCA1 gene, which is intensely studied for its role in breast cancer. Each line is a distinct mRNA transcript. Each darker bar is an exon, which are separated by introns. The darker colored exons are in the protein coding region, while the lighter exons signify the untranslated upstream and downstream ends. I count about 315 transcripts described for this genetic locus. The idea that each of these has some evolutionarily constrained and important function is, on the face of it, absurd.

The authors took an interesting evolutionary approach, reasoning that species with larger population sizes experience more stringent purifying selection, and thus should (in theory) show tighter control over stray genomic products such as isoforms, if most transcript isoforms are neutral (or even deleterious) accidents, rather than intentional and functional forms. Thankfully, animals come in a wide range of population sizes, from insects to crocodiles and primates; very large to very small. While population size is hard to calculate, several convenient proxies are known, like lifespan, body size, etc. When they totted everything up, they saw clear correlations between these proxies and the number of alternative RNA products per gene- also termed transcript diversity. They sliced up the data by organ where the RNA was expressed, and by the source of the RNA variation- either different initiation, different termination, different splicing. In all cases the trend was the same. In species with larger population sizes, the diversity of transcripts was lower, agreeing with their hypothesis that when greater selecive force is available, the slop from the transcription and transcript processing machinery declines.

The authors draw correlations between alternative splicing (AI) diversity in an organism's cells and its population size. 

The authors additionally note that there is a similar relationship between alternative splice site usage and expression level of a gene. That is, the higher the gene expression, the less likely that minor splice sites are used, indicating that here again, higher selective pressure helps to clear out non-functional off-products of the transcription apparatus.

The correlations found here are only that- correlations. While significant, they are not terribly strong, let alone stark. So it is evident that our gene expression machinery has a lot of play in it, and this falls on a spectrum from deleterious to critically functional. It is, after all, machinery, not divine. It is also grist for evolution itself- it is useful to have some slop so that there is always some diversity in the gearing to accommodate new selective pressures. But the idea that just because a distinct transcript exists, it is biologically functional, or that, similarly, because a genomic region is transcribed, it is a "gene" rather than junk DNA.. that does not hold water. Every nucleotide in the genome has its own unique selective constraints, and for many of them, that constraint is zero.

• The world order, and our position in it, is crumbling.
• Whence Hungary?
• Another AI tax, as if gobbling up power wasn't bad enough.
• Mindless.

Death and Resurrection ... Of a Gene

The SLAMF9 gene became non-functional in the human lineage, and then later was re-activated. Why?

Biology is amazingly intricate, but it is often also needlessly complex- evidence for the haphazard, if eventually pointed, mechanisms of the evolutionary process. We will take up the discussion of "junk" DNA again next week, but molecular biology is full of redundant and excessive processes, which should certainly be mystifying from a "design" perspective. At the frontier of natural selection are neutral and near-neutral genetic elements, which change over time due to chance, lacking selection pressure towards conservation. Pseudogenes (of which we have about 20,000- almost as many as functional genes) are one form of neutral element. They are typically remnants of functional genes that have been duplicated and inactivated by mutation. They are a lively area of genome annotation because it is hard to be sure that they are really dead. Despite what looks like an inactivating mutation, they typically still produce RNA transcripts, and may produce partial or alternative proteins as well. The literature is full of experiments finding products and activities from genes annotated elsewhere as pseudogenes. And what looks like a pseudogene from one sample might just be an allele, the same gene being whole and active in other people.

So, it is hard to know what any particular genetic region is doing without a lot of evolutionary, functional, and even population analysis. A recent paper looked deeply at one gene- a gene that seems to have flipped back and forth between functional and non-functional states in the human lineage. It is a rare example of a gene coming back from what is usually a one-way trip into mutational oblivion, once its function- and thus selective pressure for conservation- have disappeared.

SLAMF9 is one of a family (signaling lymphocyte activation molecule family) of surface receptors that occur in many cells of the immune system, help activate responses in these cells, and also recognize some viruses and bacteria. They bind to each other and to other components of the immune system, creating complex signaling networks. Genes involved in our immune systems are commonly subject to rapid evolution, the arms race against our many pathogens being relentless. Sometimes that takes the form of gene inactivation, if a particular receptor, for instance, has been turned against us by a pathogen that uses it for binding and cell entry. 

This week's authors were facing a conundrum. They were studying SLAMF9, and found the mouse version easy to clone and express in the lab. But the human version ... that was another story, frustratingly impossible to express in usable amounts. When they looked at the protein sequence, they were in for a big surprise:

At the front end of SLAMF9, there is very strong conservation across mammals... except when it comes to humans! The signal peptide is what directs this protein to be inserted into the plasma membrane, and is cleaved off the mature protein. In red is highlighted the region starkly different in humans, which naturally affects (not in a good way) the signal cleavage process. "a" and "b" point to important domains of the cytoplasmic side of the final protein, which are just barely preserved/conserved in the human form.

This alignment among various mammalian versions (orthologs) of SLAMF9 shows that they are all pretty much the same... except for the human version. All the way from mouse to chimpanzee nothing has changed at the front end of this protein. That is amazing in itself, showing very strong conservation. But then after our lineage split from chimpanzees, something weird. A small segment at the front of this protein is totally different. This area is important because it carries the cleavage site of the signal sequence. The signal sequence directs the protein to be sent to the membrane (as this is a trans-membrane receptor), and this cleavage site is bad, explaining why the author's attempt to express this protein went so poorly. It might be enough for modest expression in the natural setting, but not enough for their investigations.

At the DNA level, it is clear that what happened to the protein was a double frame shift in translation, out of frame at the front, then recovered frame at the second mutation. The mutations must have been independent events, but the order of their occurrence is not known. The first intron trails off to the left, while the coding sequence tails off to the right.

When they looked at the DNA sequence, the reason for this change in the protein sequence became clearer. There was a frame shift, with only small changes in the DNA sequence that led to the bigger change in the protein sequence. On the left, there is a shift in the splice site at the end of the first intron (splice acceptor). This shifts the mRNA product by four bases (vs the start site of translation), creating a frame shift in translation, as portrayed in the amino acid codes given. On the right, there is a one nucleotide deletion, causing another frame shift that brings the translation back into the normal frame. 

They sampled all the available archeological samples from the human lineage- Neanderthals and Denisovans, and each were the same as the current human sequence. So, whatever happened did so between the split from chimpanzees and the advent of these available homo species. And what happened were two distinct events- the second frame shift and the first frame shift are independent genetic mutations. 

Which happened first? That is uncertain, but the authors show that the right-most frame shift (called g.621delT) did not influence the change in the splice site. The splice site change was caused by a series of about six mutations within the first intron, (not shown), which shifted the pattern of mRNA self-hybridization that helps direct splice site selection. So it is likely that the splice site change happened first, essentially killing the gene. And then the downstream frameshift happened later on to rescue it in a partial, not very well-expressed way. However, either mutation could have happened first to functionally kill off this gene, and then further mutation(s) to recover its function. In any case, both events happened within this roughly six-million-year time span that generated our immediate lineage, becoming firmly fixed as the only version of this gene now in our collective genome.

What might cause these events? It all goes back to the function of SLAMF9. As shown above, it is very highly conserved. But, being part of the immune system and the interface we show to pathogens, it is also on the front line of the bio-warfare arms race. As humans started ranging far beyond their original habitats, they doubtless encountered many new pathogens. It seems likely that killing off this gene might have resolved one such fight, at least for a little while, perhaps by removing a pathogen entry point. But later on, it became beneficial to recover it, which is to say that new mutations that restored its function even a little bit were evidently selected for, and spread in the population. There was a race at this point between the accumulation of more (now neutral) mutations that would have permanently inactivated this gene, and the advent of that one special mutation that could save it. The overall conservation of SLAMF9 argues that saving it must have conferred significant benefits.

• "A single long-haul flight per year over the past decade leads to about $25k ($6,000–77,000) in future damages by 2100."
• These people run our lives?
• Update on the cerebellum.
• Cuba and capitalism, of a sort.

Dreaming Our Way Out of Capitalism

Review of "Understanding Capitalism", by Richard Wolff.

When I picked up this book, I thought it was going to be a sober analysis of capitalism, by a real economist. But what I was met with was something quite different- a Marxist screed with the most flaccid intellectual grounding, disingenuous and dishonest by turns. Wolff apparently has been paid to teach economics at liberal institutions, but this book is evidence that they have little idea what they are buying. 

Not that I am unsympathetic. Capitalism is a highly problematic system. But it hardly helps to make statements like: "Given China's huge influence on poverty measures, one could claim that reduced global poverty in recent decades results from an economic system that insists that it is not capitalist, but socialist." Note the squirrely way this is phrased, not defining the economic system, but noting only the wholly outdated self-description. China is one of the most capitalist countries in the world right now, having harnessed naked capitalism (and a lot of stolen IP) to raise its industries and living standard dramatically. 

Or how about this, in a discussion of why the idea that capitalism is highly innovative is a myth: "Yet the USSR, for example, exhibited much small business formation on its collective farms, in its service sector, and in its black markets, all replete with competition and innovations." If black markets are evidence of the innovative capacity of socialist economies, then the US is surely headed for Marxism forthwith.

It is almost funny how poorly this book is argued, and how formulaic its critiques and nostrums. But it provides a jumping-off point for a discussion that is a bit more grounded. Wolff casually describes capitalism as just another system, like feudalism and mercantilism, having its day and sure to pass on to some other, better system. He ends up promoting worker-owned cooperatives that are democratically run, where every action is voted on. Needless to say, such ideas have not, and will not, go anywhere. They are simply not practical. For we are, at base, dealing with human nature and the imperatives of existence. 

The state of nature (in larger societies) is organized crime- the strong rule the weak, and call themselves noble. Workers are managed by aristocrats (and priests), who make a fetish of not doing any work themselves. The feudal system was an attempt to give some order to this system of relations, by raising the serfs from mere slavery, and mandating some notional reciprocal duties. Capitalism, as even Marx appreciated, was an enormous advance over feudalism, putting the workers and businesses both on firmer legal footing, with a (labor) market intermediating between them. Labor markets have all sorts of problems and biases, but with advances in regulation and labor agitation, it has become for most people a relatively civilized way to exchange labor for money. 

Is capitalism still unfair? Yes, grossly so. But let's look two of its most basic injustices. First is that it takes money to make money. If one is born rich, one can be a capitalist and not work a day on one's life. Capitalism puts a high value on using that money to take risks and create businesses. But most rich people are content to buy bonds and sit on their money. What kind of capitalism is that? On the other hand, there is a large industry of venture capital that exists to lure money from the pockets of dentists and other rich people, promising high returns from risky ventures. This is the kind of essential engine that classical capitalism envisions- a tireless hunt for new business opportunities and technologies that will, in the end, make the economy more efficient and raise the standard of living. 

Wolff offers a telling example of capricious unfairness in management, where a business brings in a machine that replaces half of its workers, who are fired. He decries the loss of jobs, and suggests that the machine be used instead to fund continuing pay for all the workers. But just in the section before, he had decried the much-vaunted efficiency of capitalism as a myth. It does not sound like a myth here, where more work is done by fewer workers, and those fired workers are then freed to go off into other (presumably) productive forms of work.

Maybe China does a better job using state capitalism to deploy large amounts of capital. Maybe the USSR did a reasonable job, for a couple of decades, in deploying capital to build its heavy industry and arm for World War 2. And maybe free capital markets tend to vacillate between over-enthusiasm and credit contraction. But over the long term, it is clear that relatively free capital markets (with lots of government regulation!) do a good job of finding innovative business prospects and driving efficiency increases over the whole economy. So ... we should definitely think about taxing wealth, and finding ways to make the rich use their money in socially beneficial ways. But the idea that voters, or the state, can do a better job of general capital deployment is not realistic.

A second gross unfairness is management and surplus production. Why are workers still treated like slaves, told what to do, and then underpaid? Sadly, the fact is that management is a difficult job too. We had a worker-run bakery down the street in our city, and it only lasted a few years, because of the inherent problems of not having someone in charge of a business organization. The leading methods of worker-owned corporation now are oriented to giving workers ownership (like the Publix supermarket chain), but not management roles. Workers are on the board, but they do not run the day-to-day operations, because there simply has got to be decisiveness, accountability, and responsibility up the chain of a productive organization. Whether these roles have to be paid a lot more is open to question. But they do have to exist. Even in socialism, political commissars were part of management.

It is worth noting here that while management and unemployment are the disciplining factors for workers, competition is the disciplining mechanism for capitalists (in addition to government regulation). Without competition across the gamut, for labor, for markets, and for inputs, capitalists can abuse their workers and their customers. That is why a renewed focus on antitrust enforcement is an essential part of any progressive program of state oversight over the capitalist system.

As the example of black markets shows, market capitalism is a natural way of organizing human activities and satisfying our desires. But capitalism has plenty of problems. Capital and credit markets can not be left to their own devices. Glaring market failures, like in medicine, show that whole sectors of the economy have no business being capitalist businesses. Capitalism is an engine for turning "externalities", like minerals, air, and creativity, into money, heedless of destructive effects. So capitalism needs heavy regulation and continual reform to tame it into something that provides us with a civilized life. But at its core, it merely expresses our desires, needs, and ambitions, and that core engine needs to be preserved as well.

• When your Tesla crashes, it's your fault.
• Cheap e-vehicles are all the rage.. scooters, bikes, trikes.

Just Whose Foreign Policy Is This?

Our foreign policy appears to be led by people whom Trump gets weak in the knees for. Does that serve US or world interests?

US foreign policy serves not only US interests. We share an interest in the peaceful, prosperous, and sustainable future of the whole world, and as the leading nation, have an outsize role in its development. That is why Barack Obama got a Nobel peace prize, and why Donald Trump will not. As with most bullies, Trump puts on a show of strength and enjoys humiliating the weak. But there is also a curious weakness. He also loves humiliating himself at the feet of bigger and tougher bullies, for reasons that I frankly do not understand. 

The current war on Iran is not really in the US interest. Iran had already been boxed in by last year's attacks, which had supposedly obliterated any nuclear ambition. It is Israel that, in the person of Bibi Netanyahu, has been beating the drum about attacking Iran for several decades. It is Netanyahu who has been whispering in Trump's ear about how easy all this would be, including how the Iranian government would crumple under sustained assault. But I am sure our own intelligence knew better- that the Islamic state of Iran is a tough customer, having lived through the original takeover and US hostage crisis, then the brutal war with Iraq. It has legions of loyal IRGC and Basij all over the country. 

Unlike Netanyahu's view of things focused on its tactical defense, the US interest is in the long-term positive evolution of Iran, not in its tactical weakening. The bombing campaign is not only not going to break the government, but will make it stronger vs its people internally. The two likely paths it will lead to are, (at best) a civil war breaking out among the current actors in power, if they are not happy with the new supreme leader and the defense the Islamic leadership takes in this war. Or second, and more likely, the continued involution and isolation of the Iranian government, heading towards a North Korean model in a culture of suffering and perpetual resistance. And also, incidentally, the acquisition of a nuclear bomb at any cost. The idea that the powerless masses will somehow march their way into power during a bombing campaign is ridiculous.

So it is obvious that Trump was sweet-talked into this war, with no request from congress, no clamor from the American people, and no precipitating threat abroad, by none other than Netanyahu. And he was not smart enough to realize that he would not have a way out that serves US interests. Now oil prices are up, stocks are down, and those economic interests who really have the president's ear are going to be urging surrender after what, strategically speaking, has been a futile and immiserating affair. 

Even worse has been our policy towards Russia and Ukraine. It is evident that Trump loves to talk with Vladimir Putin, and Putin knows how to manipulate Trump. Just this week, the US dropped sanctions on Russian oil, in a bid to clean up its catastrophe in the Persian Gulf. Not seize Russian oil and sell it into world markets to benefit Ukraine, not block shipments of Russia's shadow fleet, but outright dropping sanctions. It is unbelievable, in any world where US interests drive US policy.

The Ukraine fight would have benefited from more decisiveness from the start, obviously. At least the Biden administration was rhetorically consistent, on the side of Ukraine, its position in Europe, and supporting our European allies. Our strategic interest is firstly in keeping Europe free of military conflict (as we keep the North American region). And secondly in containing Russia, in its new guise of anti-NATO imperialist revanchist power. Now all these aims are subordinated to getting a bad real-estate deal in Eastern Ukraine, and giving Russia what it wants. 

All through the second Trump administration, the US has been following Russian desires, reducing our support for Ukraine to nothing, berating Volodimir Zelensky in person, and bad-mouthing our European allies and alliance structures. How is all this in the US interest, when our core power stems from leadership of a community of like-minded and like-valued allies that have particularly and especially foresworn making Europe a battlefield? It is making the US weaker by the day. All due to the mental weakness of Donald Trump.

• Or perhaps other influences were at work.