Showing posts with label insects. Show all posts
Showing posts with label insects. Show all posts

Saturday, May 6, 2023

The Development of Metamorphosis

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

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

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


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

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

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

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

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

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

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

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


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


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  • "China has arguably been the biggest beneficiary of the U.S. security system in Asia, which ensured the regional stability that made possible the income-boosting flows of trade and investment that propelled the country’s economic miracle. Today, however, General Secretary of the Chinese Communist Party Xi Jinping claims that China’s model of modernization is an alternative to “Westernization,” not a prime example of its benefits."

Saturday, April 1, 2023

Consciousness and the Secret Life of Plants

Could plants be conscious? What are the limits of consciousness and pain? 

Scientific American recently reviewed a book titled "Planta Sapiens". The title gives it all away, and the review was quite positive, with statements like: 

"Our senses can not grasp the rich communicative world of plants. We therefore lack language to describe the 'intelligence' of a root tip in conversation with the microbial life of the soil or the 'cognition' that emerges when chemical whispers ripple through a lacework of leaf cells."

This is provocative indeed! What if plants really do have a secret life and suffer pain with our every bite and swing of the scythe? What of our vaunted morals and ethics then?

I am afraid that I take a skeptical view of this kind of thing, so let's go through some of the aspects of consciousness, and ask how widespread it really is. One traditional view, from the ur-scientific types like Descartes, is that only humans have consciousness, and all other creatures, have at best a mechanism, unfeeling and mechanical, that may look like consciousness, but isn't. This, continued in a sense by B. F. Skinner in the 20th century, is a statement from ignorance. We can not fully communicate with animals, so we can not really participate in what looks like their consciousness, so let's just ignore it. This position has the added dividend of supporting our unethical treatment of animals, which was an enormous convenience, and remains the core position of capitalism generally, regarding farm animals (though its view of humans is hardly more generous).

Well, this view is totally untenable, from our experience of animals, our ability to indeed communicate with them to various degrees, to see them dreaming, not to mention from an evolutionary standpoint. Our consciousness did not arise from nothing, after all. So I think we can agree that mammals can all be included in the community of conscious fellow-beings on the planet. It is clear that the range of conscious pre-occupations can vary tremendously, but whenever we have looked at the workings of memory, attention, vision, and other components assumed to be part of or contributors to conscious awareness, they all exist in mammals, at least. 

But what about other animals like insects, jellyfish, or bacteria? Here we will need a deeper look at the principles in play. As far as we understand it, consciousness is an activity that binds various senses and models of the world into an experience. It should be distinguished from responsiveness to stimuli. A thermostat is responsive. A bacterium is responsive. That does not constitute consciousness. Bacteria are highly responsive to chemical gradients in their environment, to food sources, to the pheromones of fellow bacteria. They appear to have some amount of sensibility and will. But we can not say that they have experience in the sense of a conscious experience, even if they integrate a lot of stimuli into a holistic and sensitive approach to their environment. 


The same is true of our own cells, naturally. They also are highly responsive on an individual basis, working hard to figure out what the bloodstream is bringing them in terms of food, immune signals, pathogens, etc. Could each of our cells be conscious? I would doubt it, because their responsiveness is mechanistic, rather than being an independent as well as integrated model of their world. Simlarly, if we are under anaesthesia and a surgeon cuts off a leg, is that leg conscious? It has countless nerve cells, and sensory apparatus, but it does not represent anything about its world. It rather is built to send all these signals to a modeling system elsewhere, i.e. our brain, which is where consciousness happens, and where (conscious) pain happens as well.

So I think the bottom line is that consciousness is rather widely shared as a property of brains, thus of organisms with brains, which were devised over evolutionary time to provide the kind of integrated experience that a neural net can not supply. Jellyfish, for instance, have neural nets that feel pain, respond to food and mates, and swim exquisitely. They are highly responsive, but, I would argue, not conscious. On the other hand, insects have brains and would count as conscious, even though their level of consciousness might be very primitive. Honey bees map out their world, navigate about, select the delicacies they want from plants, and go home to a highly organized hive. They also remember experiences and learn from them.

This all makes it highly unlikely that consciousness is present in quantum phenomena, in rocks, in bacteria, or in plants. They just do not have the machinery it takes to feel something as an integrated and meaningful experience. Where exactly the line is between highly responsive and conscious is probably not sharply defined. There are brains that are exceedingly small, and neural nets that are very rich. But it is also clear that it doesn't take consciousness to experience pain or try to avoid it, (which plants, bacteria, and jellyfish all do). Where is the limit of ethical care, if our criterion shifts from consciousness to pain? Wasn't our amputated leg in pain after the operation above, and didn't we callously ignore its feelings? 

I would suggest that the limit remains that of consciousness, not that of responsiveness to pain. Pain is not problematic because of a reflex reaction. The doctor can tap our knee as often as he wants, perhaps causing pain to our tendon, but not to our consciousness. Pain is problematic because of suffering, which is a conscious construct built around memory, expectations, and models of how things "should" be. While one can easily see that a plant might have certain positive (light, air, water) and negative (herbivores, fungi) stimuli that shape its intrinsic responses to the environment, these are all reflexive, not reflective, and so do not appear (to an admittedly biased observer) to constitute suffering that rises to ethical consideration.

Saturday, April 2, 2022

E. O. Wilson, Atheist

Notes on the controversies of E. O. Wilson.

E. O. Wilson was one of our leading biologists and intellectuals, combining a scholarly career of love for the natural world (particularly ants) with a cultural voice of concern about what we as a species are doing to it. He was also a dedicated atheist, perched in his ivory tower at Harvard and tilting at various professional and cultural windmills. I feature below a long quote from one of his several magnum opuses, Sociobiology (1975). This was putatively a textbook by which he wanted to establish a new field within biology- the study of social structures and evolution. This was a time when molecular biology was ascendent, in his department and in biology broadly, and he wanted to push back and assert that truly important and relevant science was waiting to be done at higher levels of biology, indeed the highest level- that of whole societies. It is a vast tome, where he attempted to synthesize everything known in the field. But it met with significant resistance across the board, even though most of its propositions are now taken as a matter of course ... that our social instincts and structures are heavily biological, and have evolved just as our physical features have.

Saturday, October 30, 2021

Genetics and Non-Genetics of Temperament

Some fish are shy, some honeybees are outgoing. What makes individuals out of a uniform genetic background?

Do flies have personalities? Apparently so. Drosophila have a long and storied history as perhaps the greatest model organism for genetic research. They have brains, intricate development, complex bodies and behaviors, but also rapid generation time, relatively easy handling, and mass rearing. A new paper describes a quest to define their personalities- behavioral traits that vary despite a uniform genetic background. Personality is a trait that may be genetically influenced, but may just as well have environmental or sporadic causes (that is, not determined by outside factors). Importantly, this kind of trait tends to recur in a population, indicating that while it may not be determined, it follows certain canalized pathways in development, which might themselves be amenable to genetic investigation. Human personality studies have a long history, with various systems trying to make sense of the typical forms and range of variation.

A recent paper did a massive screen of uniformly inbred flies for personality variations. Computerization and automation have revolutionized the animal screening field, as it has so many others, so now flies can be indivually put through a battery of tests with minimal effort to humans, looking for their individual responses to light, to maze choices, spontaneous activity, circadian preferences, sensitivity to odors, etc. These tests were compiled for hundreds of genetically identical flies from birth to death, followed by sequencing of their mRNA expression to see which genes were active. Another batch of more diverse wild-type flies were tested as well to compare what variable genetic influences might be afoot.

Firstly, the differences they observed in these flies were stable over time. They represent true "types" of behavior, despite the lack of genetic input. Secondly, they are limited in landscape. Those flies more active in one test tend to be more active in other tests as well. So the variations in behavior seem to flow from deep-seated categorical types that follow typical patterns within fly development. Which tests should yield correlated scores, and which other ones are more orthogonal, is a little hard to figure out and a matter of subjective taste, so these conclusions about wide-spread correlations in disparate behaviors reflecting personality types is based largely on these researchers knowing their flies on a pretty intimate basis.

A matrix of videos of flies just strolling along, captured by these researchers. Not all flies walk the same way.

For example, they emphasize correlations where they would not have expected them- between, say light sensitivity and overall activity- and non-correlations where they would have expected correlation- say between activity measures of maze walking and free activity. The main observation is that there were a lot of variations among these identical-twin flies. So, just as identical humans can have different personalities, sensitivities, and outlooks, so can flies. 

Is there anything one can say about this genetically? The behavioral variations were themselves not genetically based, but rather due to alternate paths taken down developmental pathways, via either sporadic or experience-based differences. The flies were raised in the same homes, so to speak, but as we know from humans, however similar things may seem on the outside, the individual subjective experience can be very different. At any rate, the developmental pathways leading to the variations are themselves genetically determined, so this exercise was really about learning about how they work, and what range of variation they support/allow.

This analysis of course boils down to how informative the behavioral traits are that the researchers are testing. And obviously, they were not very informative- how does one connect a propensity to turn left when going down a maze with some developmental process? These researchers threw a bunch of statistics at their data, including from the gene expression analysis performed in the sacrificed flies after their mortal trials were over. For instance, among known molecular pathways, metabolic pathway gene expression correlated with activity assays of behavior- not a big surprise. Expression of photo-transduction related genes also correlated with response to light. The biggest correlation was between oxidative phosphorylation gene expression (i.e. mitochondrial activity) with their various activity measurements, which were, after all, the essence of all their assays. In humans, some people are just high-energy, which informs everything they do.

"We found that in all cases, behavioral variation has high dimensionality, that is, many independent axes of variation."

In the end, they conclude that, yes, flies of identical genetic background grow up to have distinct behavioral profiles, or one can say, personalities. Many of these behavioral profiles or traits are independent of each other, indicating several, or even numerous, axes of development where such differences can arise. The researchers estimate 27 dimensions of trait variability, in fact, just from this smattering of tests. But others vary together, forming a sort of personality type, though the choice of assays was obviously very influential in these cross-correlations. These results give a very rough start to the project of figuring out where animal development is less than fully determined, and can thus give rise to the non-genetic variation that provides rich fodder for environmental and social adaptation / specialization. While genes are not directly responsible for this variation, they are responsible for the available range, and thus set the parameters of possible adaptation.

It is sadly typical that these researchers disposed of about 1/3 of their flies at the outset of the study for being insufficiently active. While they are surely correct that these flies would continue to be less active through the rest of the assays, thus giving less data to their automated tests, they did not ask themselves why some flies might choose to think before they leap - so to speak. Were they genetically defective? The flies were identical to a matter of a handful of single nucleotide variations. If inbreeding was a problem, all the flies would have been equally affected. So it is likely that one of the most significant personality traits was summarily excluded out of raw institutionalized bias against the more introverted fly, conveniently veiled by claims of technical limitations. Hey hey, ho ho!

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Saturday, July 3, 2021

How a Nervous System is Maintained

Researchers have mapped how transcriptional programming specifies C. elegans neurons.

Model systems in biology have led the way into knowledge of body development. Fruit flies have been the target of intensive work on the genetic origins of morphogenesis and body plan specification, finding successive action by maternally deposited proteins or mRNAs, gap genes, pair rule genes, and homeotic genes to specify ever finer segments of the body. 

An even simpler model system was later developed, in the tiny worm C. elegans, a nematode, which is smaller, faster-developing than the fruit fly, and also transparent. This organism is attractive for some neurobiology studies, (despite lacking a brain), since its nervous system is both simple and stereotypical- every worm has 302 neurons, of 118 types, laid out in pretty much the same pattern, all easily visible. 

The neurons of C. elegans, in overview. Only the cell body locations are shown, not their various axonal and dendritic processes.

A recent paper therefore looked into the question of how these neurons are specified- how they maintain their identity through the life of the worm, after their original development. The fruit fly genes mentioned above that lay out the body plan are almost all transcription regulators- proteins that regulate the expression of other genes by binding near them and turning on (or off) transcription. A cascade of such regulators allows complex programs of refinement and specification to be carried out, to the point that individual cells are told what they are supposed to be and what features they are supposed to express. These patterns of transcription eventually get cast in stone by the durable repression of unneeded genes, and feedback loops that perpetuate the expression of whatever ones at the end are required to maintain the particular specified type. These are also transcription regulators acting at the end of the line of the developmental pathway, and are called "terminal selectors", since they regulate /select the final sets of genes to be expressed in that cell type which manifest whatever it is supposed to be. 

So a question is- what kind of terminal selectors are active in the stereotyped neurons of C. elegans? Are there just a few for each neuron, used broadly to control all its distinctive genes, or are there many different ones deployed in a complex combinatorial code of transcription regulators to control the final gene expression and the cell type? What they found was that these worms use mostly the former method, and much less the latter. But there can be over 20 such regulators deployed in combination to set up some of these neuronal cells.

For each neuron type (top graph, bottom axis), the associated transcriptional regulators are either common (blue) or rare and particular (green). Common regulators are used to broadly bind to and activate many or most of that neuron's specifically expressed genes. The bottom graph shows the various regulators (bottom axis), and counts how many neuron types they operate in (Y-axis). Some of these regulators are used by many neurons, yet by their cooperation with other regulators can be relied on to specify a particular cell type.

The methods these researchers use are two-fold. One is to sequence all the RNAs of each specific neuron (generally called single cell sequencing). This was used to find all the specifically (differentially) expressed genes of each neuronal cell type, whose upstream regions were then investigated to find the binding sites for all the known transcription regulators of C. elegans. This catalog of target binding sites, genes and their binding regulators could then be compiled to ask whether each cell type had a characteristic pattern ... and generally they do. A second method was to consult a previously developed collection of many "reporter" genes, which had each been fused to bit of DNA encoding a fluorescent protein, which then were screened as being expressed specifically in one or another neuron of C. elegans. This collection of 1000 genes was likewise scanned for its regulatory sites and binding transcription regulators, and the authors found completely concordant results- that here too. the same combinations of regulators were used time and again to activate the specific genes of each neuron. 


Analysis of one gene, and one regulator, through evolutionary time. One key analysis to find regulator sites on a gene was to ask whether its sites were conserved in related species. Here, the ODR-7 DNA-binding regulator has binding sites both upstream and within the olrn-1 gene. Sites are shown in purple, the gene transcription start is shown with the big arrow at top, and the gene's coding exons are shown in black blocks downstream of the start site. The locations of the sites are not well conserved, but their presence is quite well conserved, here on a gene that is expressed in AWS neurons, and necessary for them to occur. 

So development, specification, and maintenance of the body are encoded by the genome largely via a program of regulators that are placed where they are supposed to be, and then successively activate, out of the genome, further parts of the control series in defined regions, and finally regulate the genes required to manifest the body plan in particular places, by expressing (or repressing) genes for the ion channels, cytoskeletal formation, neurotransmitters, and all other specific bric-a-brac of each cell type.


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  • Voting has been a big constitutional issue, with at least five relevant amendments. But now the federal government has no role in enforcing the constitution. Just how many more amendments are needed?
  • Covid graph of the week- Where were covid deaths undercounted?

Saturday, November 30, 2019

Metrics of Muscles

How do the microstructures of the muscle work, and how do they develop to uniform sizes?

Muscles are gaining stature of late, from being humble servants for getting around, to being a core metabolic organ and playing a part in mental health. They are one of the most interesting tissues from a cell biology and cytoarchitectural standpoint, with their electrically-activated activity, and their complex and intensely regimented organization. How does that organization happen? There has been a lot of progress on this question, one example of which is a recent paper on the regulation of Z-disc formation, using flies as a model system.

A section of muscle, showing its regimented structure. Wedged in the left middle is a cell nucleus. The rest of these cells are given over to sarcomeres- the repeating structure of muscles, with dark myosin central zones, and the sharp Z-lines in the light regions that anchor actin and separate adjacent sarcomeres.

The basic repeating unit of muscle is the sarcomere, which occurs end-to-end within myofibrils, which are bundled together into muscle fibers, which constitute single muscle cells. Those cells are then in turn bundled into fascicles, bundles, and whole muscles. The sarcomere contains end-plates called the Z-disk, which attach actin filaments that travel lengthwise into the sarcomere (to variable distances depending on contraction). In the center of the sarcomere, interdigitated with the actin filaments, are myosin filaments, which look much thicker in the microscope. Myosin contains the ATP-driven motor which pulls along the actin, causing the whole sarcomere to contract. The two assemblies contact each other like two combs with interdigitated teeth.

Some molecular details of the sarcomere. Myosin is in green, actin in red. Titin is in blue, and nubulin in teal. The Z-disks are in light blue at the sides, where actin and titin attach. Note how the titin molecules extend from the Z-disks right through the myosin bundles, meet in the middle. Titin is highly elastic, unfolding like an accordion, and also has stress sensitivity, containing a protein kinase domain (located in the central M-band region) that can transmit mechanical stress signals. The diagram at bottom shows the domain structure of nebulin, which has the significant role of metering the length of the actin bundles. It is also typical in containing various domains that interact with numerous other proteins, in addition to repetitive elements that contribute to its length.

There are over a hundred other molecules involved in this structure, but some of more notable ones are huge structural proteins, the biggest in the genome, which provide key guides for the sizes of some sarcomeric dimensions. Nubulin is a ~800 kDa protein that wraps around the actin filaments as they are assembled out from the Z-disk and sets the length of the actin polymer. The sizes of all the components of the sarcomere are critical, so that the actin filaments don't run into each other during contraction, the myosins don't run into the Z-disk wall, etc. Everything naturally has to be carefully engineered. Conversely, titin is a protein of ~4,000 kDa (over 34,000 amino acids long) that is highly elastic and spans from the Z-disk, through the myosin bundles, and to a pairing site at the M-line. In addition to forming the core around which the myosin motors cluster, thus determining the length of the myosin region, it appears to set the size of the whole sarcomere, and forms a spring that stores elastic force, among much else.

Many of these proteins come together at the Z-disk. Actin attaches to alpha-actinin there, and to numerous other proteins. One of these is ZASP, the subject of the current paper. ZASP joins the Z-disk very early, and contains domains (PDZ) that bind to alpha actinin, a key protein that anchors actin filaments, and other domains that bind to each other (ZM and LIM). To make things interesting, ZASP comes in several forms, from a couple of gene duplications and also from alternative splicing that includes or discards various exons during the processing of transcripts from these genes. In humans, ZASP has 14 exons and at least 12 differently spliced forms. Some of these forms include more or fewer of the self-interacting LIM domains. These authors figured that if the ZASP protein plays an early and guiding role in controlling Z-disk size, it may do so by arriving in its full-length, fully interlocking version early in development, and then later arriving in  shorter "blocking" versions, lacking self-interacting domains, thereby terminating growth of the Z-disks.

Overexpression of the ZASP protein (bottom panels) causes visibly larger, yet also somewhat disorganized, Z-disks in fly muscles. Note how beautifully regular the control muscle tissue is, top. Left sides show fluorescence labels for both actin and ZASP, while right sides show fluorescence only from ZASP for the same field.

The authors show (above) that overexpressing ZASP makes Z-disks grow larger and somewhat disorganized, while conversely, overexpressing truncated versions of ZASP leads to smaller Z-disks. They then show (below) that in the wild-type state, the truncated forms (from a couple of diverged gene duplicates) tend to reside at the outsides of the Z-disks, relative to the full length forms. They also show in connection with this that the truncated forms are also expressed later in development in flies, in concordance with the theory.

Images of Z-disks, end-on. These were not mutant, but are expressing fluorescently labelled ZASP proteins from the major full length form (Zasp52, c and d), or from endogenous gene duplicates that express "blocking" shortened forms (Zasp66 and Zasp67, panels in d). They claim by their merged image analysis (right) to find that full length ZASP resides with higher probability near the centers of the disks, while the shorter forms reside more towards the outsides.

Compared with what else is known, (and unknown), this is a tiny step. It also begs a lot of questions- could gene expression be so finely controlled as to create the extremely regimented Z-disk pattern? (Unlikely) And if so, what controls all this gene expression and alternative splicing, both in normal development, and in wound repair and other times when muscle needs to be rebuilt, which can not be solely time-dependent, but appears, from the regularity of the pattern, to follow some independent metric of ideal Z-disk size? It is likely that there is far more to this story that will come out during further analysis.

It is notable that the Z-disk is a hotbed of genes that cause myopathies of various sorts when mutated. Thus the study of these structures, while fascinating in its own right and a window into the wonders of biology and our own bodies, is also informative in medical terms, and while unlikely to lead to significant treatments until the advent of gene therapy, may at least provide understanding of syndromes that might otherwise be though of as acts of a cruel god.


Saturday, May 18, 2019

What Happened to the Monarchs?

Monarch butterflies are in crisis.

Flying over the Midwest, it is easy to see the impact of humans. The land is neatly tiled into monoculture farms, with hardly a wild spot in sight. Unseen is the chemical crusade that has happened over the same time period, making insects and weeds sparse on this land as well. All this has contributed to a phenomenally productive agriculture, making our food with almost factory-like consistency using a variety of high-tech machinery, chemicals, and plenty of CO2 emissions. But each of these assaults on nature has also multiplied the plight of (among many others) the Monarch butterfly, which eats weeds, is an insect, and migrates over astonishing distances in a multigenerational trek to communal wintering sites. While Eastern populations of Monarchs are in decline and in peril, the condition of the separate Western population, which circulates up the Sierra and back down the Pacific coast, is dire, headed towards extinction.
"... the Midwest lost more than 860 million milkweeds between 1999 and 2014, mostly in agricultural fields" -Entomology Today
Monarch butterflies have a curious method of migration. While birds live several years, and thus may commute several times over their lifespan, (for instance from Northern breeding grounds to Carribean or South American wintering sites), Monarch butterflies live only roughly a month. But they also migrate over long distances, either from Mexico up through the Eastern US and Midwest, or from Coastal California across Central California, to the Sierras, then North to Oregon and Washington, then back down in fall. Like birds, the Monarchs use these routes to move through optimal habitats as the Northern Hemisphere goes through its seasons. But the migration must encoded in their genes, not learned from experience or from others, since it takes several generations to make the trek, somewhat like the colonization space ships of science fiction, which would go through many generations to get to, say, Alpha Centauri.

Now a rare sight.

It also means that Monarchs rely on suitable environments (which is to say, the milkweed) every step of the way. And our technologies of weed, insect and physical habitat extermination are making enormous swathes of their routes uninhabitable, not to say lethal. The Western population is down from millions in the 1980's to 30,000 today. This is not sustainable, and likely to drop to zero unless big changes happen to render the landscape less lethal. Thankfully, there are many milkweed species, many of which can grow widely in the region, if allowed to.

But this is just a small example of the harm humans are doing to the natural world. We are a plague, and have initiated a new age in biology- the Anthropocene, complete with our own mass extinction event. While the process is well underway here in California, it is only beginning in regions like the Amazon and Africa, whose human populations are growing steadily and whose natural environments are being decimated and whose wildlife is declining, including being directly killed and eaten. Climate heating will kill off far more species, until we end up in a world of mega-cities separated by monoculture croplands and nature reserves that will be faint shadows of a vanished, and richer, world.