Shape-Shifting: The New Phrenology

Anatomical and connectivity patterns in brains correlate with behavior patterns.

Remember phrenology? This was the reading of people's traits and destinies in the shape of their skulls. While the motivation made sense, the brain being the seat of our traits and character, along with consciousness and all other mental functions, the science didn't. It turns out that the brain is far more plastic within its vault than we ever see from the outside - a skull that hardens during early childhood, long before the rest of brain and mental development is complete.

Brain visualization methods have long battled with variability. To do studies using many subjects to find some area of the brain that is "activated" during some task, the brains of those subjects need to be correlated, even though they may be shaped differently. The major landmarks of human brains are quite uniform, but on smaller scales they are not, making comparisons difficult.

But what if that variability is functional, and reflective of our capabilities and personalities? That is the subject of a recent paper, which used a style of MRI called resting state fMRI, which compares brains when they are not doing anything in particular, to see how different areas fire in relation to each other. We have what is called a "default network", which hums along even when we are consciously not doing anything. As any meditator knows, emptying the mind is virtually impossible.. there is always something going on, and these stray activities, not to mention the vast amount of unconscious processing, is the target of this rfMRI. And not just the activity per se, but the correlations between activity in different locations, which, when suitably processed, can tell us about the actual locations of functional modules of brain anatomy, and the strength of their connection.

An illustration/map of the author's data, showing variable and behavior-correlating regions by color. For example, the yellow region bottom left/right, rear of the brain, is in the parietal-occipital sulcus, associated with visually-guided behavior and planning. 

The authors devised measures of variation of region size, and correlated them with behavioral measures. Some of these were remarkably strong, indicating that small increases in a particular brain areas can have strong association with phenotypes like susceptibility to addiction and other vices, intelligence, and self-discipline. The authors focus on the technical implications of their work, which shows that inter-individual variation in functional brain structure is substantial, and makes merging/averaging for many kinds of brain studies more perilous than previously realized. It also implies that previous conclusions about variations in "coupling strength" between regions might be better interpreted as a signal of mass action caused by physically larger regions devoted to a given function.

Functions correlated with anatomical variation in the brain.

It is not surprising that, as we understand the brain better, its evident variations in effect will start to be reflected in corresponding variations in its structure and function. But it is rather disturbing as well, as this work implies that, someday down the road, brain scans may be able to tell others significant secrets about our personal lives and prospects. A "pre-crime" kind of scenario, indeed. It is, of course, one more reason to definitively separate health care from employment. It is also part of a general trend making of our lives, inside and out, an open book.

"Our results indicate that spatial variation in the topography of functional regions across individuals is strongly associated with behaviour. ... Furthermore, recent work has shown that resting state spatial maps can be used to predict task activation maps from individual subjects very accurately, and that interdigitated and highly variable subnetworks can be identified within individuals."

• TED talk on Russian information warfare.
•  ... which becomes our contemporary intelligence test.
• Arming teachers? Right.
• Why not mix a little political corruption with your business corruption?
• Supreme court says it is OK.
• Want a free AR15?
• Some people are naturally more important than other people.
• When reasonable people become socialists....
• Where do tax cuts go? Into stock buybacks.
• Our new feudal reality.

"Taken together, this evidence casts doubt on the idea that more rapid technological progress alone has been the primary driver of rising inequality over recent decades, and tends to lend support to more institutional and structural explanations."

"I Think the Second Amendment is There For a Reason."

A Senator alludes to insurrection against the state he is sworn to uphold.

This is not a new phenomenon. Before the Civil war, many senators and other politicians from the South tried their best to undermine the federal government, going so far as to capture armories and other supplies for the looming conflict. Today, a similar mind-set arises from similar sources- the Southern and Southern-inspired strategists of "State's rights" and a new decentralized feudalism. On guns, their argument is that the free ownership of guns allows the insurrectionists a fair chance against a totalitarian state, much as the original colonists waged a guerrilla war against Britain.

One first question is - in what way is our democracy defective? Does it over-represent the totalitarian, state-centered interests? Only if one construes those to be represented by the Republican party, ironically. Does it over-regulate and construct collective and long-term interests against the wishes of short-term greed and small-minded ideologues? Yes, it certainly does, but we have the "democratic" process to thank for a dramatic pushback, in the form of unchecked spending by corporate and other greedy interests, flame-throwing conservative media, plus the Russian government. It is hard to see where these complaints can find purchase, in such an atmosphere.

A second question is, even supposing that our state is or could be tyrannical in some irremediable way, where does one draw the line on armaments? What arms are valid for this hypothetical use, and which are not? We all seem to agree that nuclear bombs are not proper for civilian use. But why? Is it that the danger they pose is far beyond what is reasonable to put into the hands of one person, without some organized institutional oversight? Is it that we do not want to live in a MAD society, each armed to the teeth, in a petrified defensive crouch, waiting to see what the next madman will do?

This logic applies down the line to other military weapons, naturally, given that our fellow citizens (even presidents) are not to be relied upon to be uniformly sane and good-natured. Great firepower implies great danger and great responsibility. Where do machine guns fall in this scale, for that is what the semi-automatic and other assult-style weapons amount to? Obviously, in light of the many mass shootings in the US over recent years, they fall into the dangerous class of weapons that should be restricted to organizations with structured oversight. That, of course, was the original meaning of the second amendment, with its justification through an organized, state-supporting milita, something which has been lost on our Supreme Court, not to mention our rabid gun nuts.

The Civil war should have disabused our home-grown insurrectionists from any notion of armed resistance against whatever bogeyman they make the "guvmint" out to be. People power is the only effective power. They can never win without a political movement. Their arms are merely a fascistic decoration, not an effective form of policy. That we let off the Bundy gang so lightly was a travesty, both legally and politically. But their intended revolution against government control of government lands never took off on a popular, armed basis, and now is being accomplished from the inside, in the new administration, via the "democratic" process.

There is a mental health issue afoot, and it is that people with military-grade guns are mentally ill, as are open-carriers and other maximalist acolytes of the NRA. These attitudes are uncivil, insurrectionary, and deranged. The idea that others will be politically and socially intimidated by their weapons and various forms of rage is absurd and insulting, apart from spineless politicians, who don't seem to understand the first thing about our constitution, their duties, or statehood in general.

• Pakistan is still at it. Not even Trump lies quite like the Pakistanis lie.
• An infrastructure nothing burger.

Too Damn Many People

We are in a population crisis.

Virtually every serious crisis we are experiencing now, from anti-immigrant attitudes, to climate change, lack of housing, homelessness, inequality, warfare, drought, desertification, traffic, scarcity of natural resources, and loss of wildlife, share a common root cause of overpopulation. Like any wonderful thing, it is the dose that makes something great turn into something less great.

The top line of damage is of course environmental destruction. In the last 50 years, the population of wild animals has fallen by half. CO2 in the atmosphere has doubled, which promises an eon of pain for the biosphere. The oceans are awash with trash, and all habitats from the arctic, to prairies, coral reefs, and rainforests are either being directly destroyed by humans and / or are being impaired indirectly by our global effects.

Summer arctic sea ice in dramatic decline.

Politically and socially, the idea that Europe should welcome millions of refugees from Africa and the Middle East, driven themselves by environmenal degradatation and overpopulation, and the conflicts they generate, is creating an understandable backlash. Just as global heating is reducing water and arable land, populations are growing all over these regions due to a modicum of medical and agricultural technology, combined with lack of human development. But is further human development the answer? From an environmental perspective, hardly- while development typically reduces birth rates, it explodes appetites and capacities to degrade the ultimate resource- the Earth- its minerals and biosphere.

An example is China. China carried out one of the most important environmental policies of all time when it instituted the one-child policy. It was, thanks to its draconian nature, effective in keeping population growth under control. Now China has a billion more people than the US, but it could easily have been two billion, in far more miserable condition. It played a big role in enabling the ensuing economic development, which has made China the biggest emitter of CO2 in the world, and generated countless other environmental problems, of global as well as local scope. They are building coal-fired power plants at a breakneck pace, and will be almost doubling worldwide coal-fired power capacity over the next decade or two. This is not driven by population, but by development of existing populations.

We are living far beyond the carrying capacity of the Earth, and our long-term choice is to either live sustainably or to have fewer people. Both seem impossible options, given that true sustainability is far more arduous than what any country has attempted to date, and is very hard to envision. Carrying capacity has many different aspects, from aesthetic features that come with a healthy biosphere, to critical minerals, water supply and agricultural capacity. Each of these has different relations to human population, and different elasticities based on our needs and technology. But we can safely say from the many ways we are degrading the global environment that we are well beyond many individual capacities, especially those that pertain to the biopshere in general, and animals other than ourselves.

Population is unfortunately, precisely the area where we care least about others. Our desires for family and legacy are very personal, often construed as a human right of some sacred or sovereign nature. But summed over the globe, it amounts to another tragedy of the commons, where my chastity merely makes room for someone else's profligacy.

There is no population bomb in the traditional sense. The agricultural technology we have, and the economic systems that drives its use, will insure all can be fed to some degree. There is a bomb, however, in a larger environmental sense. The degradation of the biosphere by humans is a slow-motion attack, as though several nuclear bombs were unleashed every year, rendering large areas uninhabitable, and sprinkling the rest of the globe with all sorts of trashy, choking fallout. These bombs are going off steadily and silently, year in and year out, till we will end up living in a global trailer park.

• Sectarianization?
• Economic injustice? We are great again.
• Very little wage growth here. Economic graph of the week:

Touch the Pressure Sensor

The revealing structure of one pressure-sensing protein complex.

The sensation of touch is perhaps the most elemental, and the most wide-spread, in nature. And detecting pressure doesn't just function in conscious sensation, but in all sorts of other processes such as, proprioception in muscles and joints, kidney function, red blood cell shape maintenance, blood pressure regulation, pain, bone maintenance, cancer cell invasion, neural development, and embryonic development generally, where bulging, shape changes, and migration are all guided by mechanisms that sense pressure inside and between cells.

Thus it is no surprise that we have numerous pressure sensors in our genomes, of various types. The sensors involved in hearing (TMC1 and TMC2) are different from a series of sensors involved in touch, (TREK-1), which are different from those responsible for organ shape and development. One thing they all share, however, is that they are cation channels. That means that deformations in the membrane they lie in, or other attachments they may have, get translated into a rush of potassium or calcium ions, out of or into the cell, respectively. This leads either to direct membrane depolarization (potassium ions), or signal propagation (calcium) via other proteins and channels.

A recent paper (review) detailed the interesting structure of PIEZO1, which is in a recently-discovered family of mechano-sensors that function in organ development and maintenance, conduct cations, mostly potassium, when activated, and directly (though briefly) depolarize membranes they reside in. While all membrane proteins are affected by membrane stretching, and there are simpler ways to translate mechanical stress into channel opening, PIEZO1 shows a rather intricate structure that allows exquisite sensitivity and control of its channel.

Top view, and side views of the PIEZO1 mechanosensory ion channel. In cells, the top faces the cytoplasm.

The first thing to notice is the dramatic, classic, maybe even Star-Treky, triskelion structure adopted by the trimeric protein. The authors note that they did not even see the entire protein, and that there should be twelve more helices extending out on each arm beyond those here that we can see, which are flapping in the breeze, so to speak. Second is the knot of protein in the center, above the plane of the rest of the structure. The actual channel is deep within the convergence zone of the three arms, so is far away from the protein knot, which extends intracellularly. This structure was derived from electron microscopy, which has begun to overtake X-ray crystallography as a method for structure determination, and the authors provide an averaged overview of what they were looking at, below.

Averaged electron micrographic view, without the inferred atomic modeling shown above. Scale bar is 10 nm.

Here, the arms are looking much more like a membrane interface, and the structure as whole clearly forms a cup that pre-deforms the membrane in a way that then makes the detection of membrane stretching even more sensitive than it would otherwise be. The authors spend much of the paper showing that this is the case- that in artificial vesicles, one can see PIEZO1 deforming the local membrane quite dramatically. One can easily see how this would make membrane stresses easier to sense.

Model of the channel (gray) surrounded by key protein structures, including negatively charged Glutamic acid (E) at the most constricted point, where opening is predicted upon membrane tension.

As for the actual channel, they provide a structure that narrows down to nothing at the bottom (E2537, showing the red negatively charged ends of glutamic acid). Clearly their model is of a closed version, which makes sense given the relaxed conditions used for visualization. Opening awaits some stretch on the overall structure that will pull these protein structures apart slightly, but not too much- enough to allow a four Ångstrom opening, as estimated from studies of the channel's conductance.

Another key part of the structure is the long helix running from the bottom, near the ion channel to about halfway along each triskelion arm. They seem to be key "beams" that transmit leverage from tension-induced membrane flattening towards the center nexus where this channel constriction is so obvious. As the authors put it ("TM" refers to transmembrane alpha helix domain, of which there are 38 in all per monomer):

"At first consideration a force directed along the triskelion arms toward the center of the trimer, associated with flattening of Piezo’s arms, might be expected to constrict the pore further. However, given that TM37-38 are domain-swapped relative to TM1-36, such a force will more likely push the ‘swapped’ pore-lining helices away from the center and open the pore."

That is to say, the beam helices at so long and subtly connected to the pore that they push cross-wise from the three directions, pulling the channel open instead of pushing it closed. This putative mechanism helps to some degree also to isolate the pore from the activating force, limiting its opening so that it can be ion-selective and have high, but limited, conductivity while open, all with super-high sensitivity. There are examples of stretch activated channels from bacteria whose function is to relieve turgor pressure stress, and whose opening is virtually unlimited under stress, becoming completely non-selective in what they allow through, which is very effective for their stress-relieving role.

This is a beautiful and informative structure. It shows yet again that underlying the magic and mysteries of biology is always structure and chemistry. Defects in these types of channels are responsible for a wide range of problems. Complete deletion of this gene (PIEZO1) in mice is rapidly lethal soon after the heart begins to beat, since the nascent vasculature is deranged, not being able to sense fluid pressures. The same gene is key for neural cell development and pathfinding. It also plays a central role in helping red blood cells know and regulate their pressure status, which is key to their function and survival as they squeeze through tight spots and get jostled by turbulent flows.

• On neoliberalism. With an example.
• Afghanistan- not going so well. Reminiscent of Vietnam, the countryside is slipping away, due to pervasive corruption.
• Things are not working so well here, either.