Biology

how-do-brainless-creatures-control-their-appetites?

How do brainless creatures control their appetites?

apetite, Behavioral science, Biology, hunger, hydras, neurobiology, Science / /

Feed me! —

Separate systems register when the animals have eaten and control feeding behaviors.

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Image of a greenish creature with a long stalk and tentacles, against a black background.

The hydra is a Lovecraftian-looking microorganism with a mouth surrounded by tentacles on one end, an elongated body, and a foot on the other end. It has no brain or centralized nervous system. Despite the lack of either of those things, it can still feel hunger and fullness. How can these creatures know when they are hungry and realize when they have had enough?

While they lack brains, hydra do have a nervous system. Researchers from Kiel University in Germany found they have an endodermal (in the digestive tract) and ectodermal (in the outermost layer of the animal) neuronal population, both of which help them react to food stimuli. Ectodermal neurons control physiological functions such as moving toward food, while endodermal neurons are associated with feeding behavior such as opening the mouth—which also vomits out anything indigestible.

Even such a limited nervous system is capable of some surprisingly complex functions. Hydras might even give us some insights into how appetite evolved and what the early evolutionary stages of a central nervous system were like.

No, thanks, I’m full

Before finding out how the hydra’s nervous system controls hunger, the researchers focused on what causes the strongest feeling of satiety, or fullness, in the animals. They were fed with the brine shrimp Artemia salina, which is among their usual prey, and exposed to the antioxidant glutathione. Previous studies have suggested that glutathione triggers feeding behavior in hydras, causing them to curl their tentacles toward their mouths as if they are swallowing prey.

Hydra fed with as much Artemia as they could eat were given glutathione afterward, while the other group was only given only glutathione and no actual food. Hunger was gauged by how fast and how often they opened their mouths.

It turned out that the first group, which had already glutted themselves on shrimp, showed hardly any response to glutathione eight hours after being fed. Their mouths barely opened—and slowly if so—because they were not hungry enough for even a feeding trigger like glutathione to make them feel they needed seconds.

It was only at 14 hours post-feeding that the hydra that had eaten shrimp opened their mouths wide enough and fast enough to indicate hunger. However, those that were not fed and only exposed to glutathione started showing signs of hunger only four hours after exposure. Mouth opening was not the only behavior provoked by hunger since starved animals also somersaulted through the water and moved toward light, behaviors associated with searching for food. Sated animals would stop somersaulting and cling to the wall of the tank they were in until they were hungry again.

Food on the “brain”

After observing the behavioral changes in the hydra, the research team looked into the neuronal activity behind those behaviors. They focused on two neuronal populations, the ectodermal population known as N3 and the endodermal population known as N4, both known to be involved in hunger and satiety. While these had been known to influence hydra feeding responses, how exactly they were involved was unknown until now.

Hydra have N3 neurons all over their bodies, especially in the foot. Signals from these neurons tell the animal that it has eaten enough and is experiencing satiety. The frequency of these signals decreased as the animals grew hungrier and displayed more behaviors associated with hunger. The frequency of N3 signals did not change in animals that were only exposed to glutathione and not fed, and these hydra behaved just like animals that had gone without food for an extended period of time. It was only when they were given actual food that the N3 signal frequency increased.

“The ectodermal neuronal population N3 is not only responding to satiety by increasing neuronal activity, but is also controlling behaviors that changed due to feeding,” the researchers said in their study, which was recently published in Cell Reports.

Though N4 neurons were only seen to communicate indirectly with the N3 population in the presence of food, they were found to influence eating behavior by regulating how wide the hydras opened their mouths and how long they kept them open. Lower frequency of N4 signals was seen in hydra that were starved or only exposed to glutathione. Higher frequency of N4 signals were associated with the animals keeping their mouths shut.

So, what can the neuronal activity of a tiny, brainless creature possibly tell us about the evolution of our own complex brains?

The researchers think the hydra’s simple nervous system may parallel the much more complex central and enteric (in the gut) nervous systems that we have. While N3 and N4 operate independently, there is still some interaction between them. The team also suggests that the way N4 regulates the hydra’s eating behavior is similar to the way the digestive tracts of mammals are regulated.

“A similar architecture of neuronal circuits controlling appetite/satiety can be also found in mice where enteric neurons, together with the central nervous system, control mouth opening,” they said in the same study.

Maybe, in a way, we really do think with our gut.

Cell Reports, 2024. DOI: 10.1016/j.celrep.2024.114210

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IV infusion enables editing of the cystic fibrosis gene in lung stem cells

Biology, CRISPR, Cystic Fibrosis, gene editing, gene therapy, Genetics, medicine, Science / /

Right gene in the right place —

Approach relies on lipid capsules like those in the mRNA vaccines.

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Abstract drawing of a pair of human hands using scissors to cut a DNA strand, with a number of human organs in the background.

The development of gene editing tools, which enable the specific targeting and correction of mutations, hold the promise of allowing us to correct those mutations that cause genetic diseases. However, the technology has been around for a while now—two researchers were critical to its development in 2020—and there have been only a few cases where gene editing has been used to target diseases.

One of the reasons for that is the challenge of targeting specific cells in a living organism. Many genetic diseases affect only a specific cell type, such as red blood cells in sickle-cell anemia, or specific tissue. Ideally, to limit potential side effects, we’d like to ensure that enough of the editing takes place in the affected tissue to have an impact, while minimizing editing elsewhere to limit side effects. But our ability to do so has been limited. Plus, a lot of the cells affected by genetic diseases are mature and have stopped dividing. So, we either need to repeat the gene editing treatments indefinitely or find a way to target the stem cell population that produces the mature cells.

On Thursday, a US-based research team said that they’ve done gene editing experiments that targeted a high-profile genetic disease: cystic fibrosis. Their technique largely targets the tissue most affected by the disease (the lung), and occurs in the stem cell populations that produce mature lung cells, ensuring that the effect is stable.

Getting specific

The foundation of the new work is the technology that gets the mRNAs of the COVID-19 mRNA vaccines inside cells. The nucleic acids of an mRNA are large molecules with a lot of charged pieces, which makes it difficult for them to cross a membrane to get inside of a cell. To overcome that problem, the researchers package the mRNA inside a bubble of lipids, which can then fuse with cell membranes, dumping the mRNA inside the cell.

This process, as the researchers note, has two very large advantages: We know it works, and we know it’s safe. “More than a billion doses of lipid nanoparticle–mRNA COVID-19 vaccines have been administered intramuscularly worldwide,” they write, “demonstrating high safety and efficacy sustained through repeatable dosing.” (As an aside, it’s interesting to contrast the research community’s view of the mRNA vaccines to the conspiracies that circulate widely among the public.)

There’s one big factor that doesn’t matter for vaccine delivery but does matter for gene editing: They’re not especially fussy about what cells they target for delivery. So, if you want to target something like blood stem cells, then you need to alter the lipid particles in some way to get them to preferentially target the cells of your choice.

There are a lot of ideas on how to do this, but the team behind this new work found a relatively simple one: changing the amount of positively charged lipids on the particle. In 2020, they published a paper in which they describe the development of selective organ targeting (SORT) lipid nanoparticles. By default, many of the lipid particles end up in the liver. But, as the fraction of positively charged lipids increases, the targeting shifts to the spleen and then to the lung.

So, presumably, because they know they can target the lung, they decided to use SORT particles to send a gene editing system specific to cystic fibrosis, which primarily affects that tissue and is caused by mutations in a single gene. While it’s relatively easy to get things into the lung, it’s tough to get them to lung cells, given all the mucus, cilia, and immune cells that are meant to take care of foreign items in the lung.

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to-kill-the-competition,-bacteria-throw-pieces-of-dead-viruses-at-them

To kill the competition, bacteria throw pieces of dead viruses at them

bacteria, Biology, evolution, phages, Science / /

Murderous —

A network of mutual murder ensures that diverse populations of bacteria survive.

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A green, lawn like background with an orange item consisting of legs, a narrow shaft, and a polygonal head.

Enlarge / This is an intact phage. A tailocin looks like one of these with its head cut off.

Long before humans became interested in killing bacteria, viruses were on the job. Viruses that attack bacteria, termed “phages” (short for bacteriophage), were first identified by their ability to create bare patches on the surface of culture plates that were otherwise covered by a lawn of bacteria. After playing critical roles in the early development of molecular biology, a number of phages have been developed as potential therapies to be used when antibiotic resistance limits the effectiveness of traditional medicines.

But we’re relative latecomers in terms of turning phages into tools. Researchers have described a number of cases where bacteria have maintained pieces of disabled viruses in their genomes and converted them into weapons that can be used to kill other bacteria that might otherwise compete for resources. I only just became aware of that weaponization, thanks to a new study showing that this process has helped maintain diverse bacterial populations for centuries.

Evolving a killer

The new work started when researchers were studying the population of bacteria associated with a plant growing wild in Germany. The population included diverse members of the genus Pseudomonas, which can include plant pathogens. Normally, when bacteria infect a new victim, a single strain expands dramatically as it successfully exploits its host. In this case, though, the Pseudomonas population contained a variety of different strains that appeared to maintain a stable competition.

To learn more, the researchers obtained over 1,500 individual genomes from the bacterial population. Over 99 percent of those genomes contained pieces of virus, with the average bacterial strain having two separate chunks of virus lurking in their genomes. All of these had missing parts compared to a functional virus, suggesting they were the product of a virus that had inserted in the past but had since picked up damage that disabled them.

On its own, that’s not shocking. Lots of genomes (including our own) have plenty of disabled viruses in them. But bacteria tend to eliminate extraneous DNA from their genomes fairly quickly. In this case, one particular viral sequence appeared to date back to the common ancestor of many of the strains since all of them had the virus inserted at the same location of the genome, and all instances of this particular virus had been disabled by losing the same set of genes. The researchers termed this sequence VC2.

Many phages have a stereotypical structure: a large “head” that contains their genetic material, perched on top of a stalk that ends in a set of “legs” that help latch on to their bacterial victims. Once the legs make contact, a stalk contracts, an action that helps transfer the virus’ genome into the bacterial cell. In VC2’s case, all copies of it lacked the genes for producing the head section, as well as all the genes needed for processing its genome during infection.

This made the researchers suspect VC2 was something called a “tailocin.” These are former phages that have been domesticated by bacteria so they can be used to harm the bacteria’s potential competition. Bacteria with a tailocin can produce partial phages that consist only of the legs and stalk. These tailocins can still find and latch on to other bacteria, but when the stalk contracts, there’s no genome to inject. Instead, this just opens a hole in the membrane of their victim, partially eliminating the boundary of the cell and allowing some of its contents to leak out, leading to its death.

An evolutionary free-for-all

To confirm that the VC2 sequence encodes a tailocin, the researchers grew some bacteria that contained the sequence, purified proteins from it, and used electron microscopy to confirm that they contained headless phages. Exposing other bacteria to the tailocin, they found that while the strain that produced it was immune, many other strains growing in the same environment were killed by it. When the team deleted the genes that encode key parts of the tailocin, the killing went away.

The researchers hypothesize that the system is used to kill off potential competition but that many strains have evolved resistance to the tailocin.

When the researchers did a genetic screen to identify resistant mutants, they found that resistance was provided by mutations that interfered with the production of complex sugar molecules that are found on proteins that end up on the exterior of cells. At the same time, most of the genetic differences among the VC2 genes occur in the proteins that encode the legs, which latch on to these sugars.

So it appears that every bacterial strain is both an aggressor and a victim, and there’s an evolutionary arms race that leads to a complex collection of pairwise interactions among the strains—think of a rock/paper/scissors game with dozens of options. And the arms race has a history. Using old samples, the researchers show that many of the variations in these genes have been around for at least 200 years.

Evolutionary competitions are often viewed as a simple one-against-one fight, probably because it’s an easy way to think about them. But the reality is that most are more akin to a chaotic bar room brawl—one where it’s rare for any faction to obtain a permanent advantage.

Science, 2024. DOI: 10.1126/science.ado0713  (About DOIs).

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bizarre-egg-laying-mammals-once-ruled-australia—then-lost-their-teeth

Bizarre egg-laying mammals once ruled Australia—then lost their teeth

Biology, echidna, evolution, fossils, monotremes, paleontology, Platypus, Science / /

Eggs came first, no chickens involved —

Finds may indicate what the common ancestor of the platypus and echidna looked like.

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A small animal with spiky fur and a long snout strides over grey soil.

Enlarge / The echidna, an egg-laying mammal, doesn’t develop teeth.

Outliers among mammals, monotremes lay eggs instead of giving birth to live young. Only two types of monotremes, the platypus and echidna, still exist, but more monotreme species were around about 100 million years ago. Some of them might possibly be even weirder than their descendants.

Monotreme fossils found in refuse from the opal mines of Lightning Ridge, Australia, have now revealed the opalized jawbones of three previously unknown species that lived during the Cenomanian age of the early Cretaceous. Unlike modern monotremes, these species had teeth. They also include a creature that appears to have been a mashup of a platypus and echidna—an “echidnapus.”

Fossil fragments of three known species from the same era were also found, meaning that at least six monotreme species coexisted in what is now Lightning Ridge. According to the researchers who unearthed these new species, the creatures may have once been as common in Australia as marsupials are today.

“[This is] the most diverse monotreme assemblage on record,” they said in a study recently published in Alcheringa: An Australasian Journal of Paleontology.

The Echidnapus emerges

Named Opalios spendens, the “echidnapus” shows similarities to both ornithorhynchoids (the platypus and similar species) and tachyglossids (echidna and similar species). It is thought to have evolved before the common ancestor of either extant monotreme.

The O. splendens holotype had been fossilized in opal like the other Lightning Ridge specimens, but unlike some, it is preserved so well that the internal structure of its bones is visible. Every mammalian fossil from Lightning Ridge has been identified as a monotreme based partly on their peculiarly large dental canals. While the fossil evidence suggests the jaw and snout of O. splendens are narrow and curved, similar to those of an echidna, it simultaneously displays platypus features.

So what relates the echidnapus to a platypus? Despite its jaw being echidna-like at first glance, its dentary, or the part of the jaw that bears the teeth, is similar in size to that of the platypus ancestor Ornithorhynchus anatinus. Other features related more closely to the platypus than the echidna have to do with its ramus, or the part of the jaw that attaches to the skull. It has a short ascending ramus (the rear end) and twisted horizontal ramus (the front end) that are seen in other ornithorhynchoids.

Another platypus-like feature of O. splendens is the flatness of the front of its lower jaw, which is consistent with the flatness of the platypus snout. The size of its jaw also suggests a body size closer to that of a platypus. Though the echidnapus had characteristics of both surviving monotremes, neither of those have the teeth found on this fossil.

My, what teeth you don’t have

Cretaceous monotremes might not have had as many teeth as the echidnapus, but they all had some teeth. The other two new monotreme species that lived among the Lightning Ridge fauna were Dharragarra aurora and Parvopalus clytiei, and the jaw structure of each of these species is either closer to the platypus or the echidna. D. aurora has the slightly twisted jaw and enlarged canal in its mandible that are characteristic of an ornithorhynchoid. It might even be on the branch that gave rise the platypus.

P. clytiei is the second smallest known monotreme (after another extinct species named Teinolophos trusleri). It was more of an echidna type, with a snout that was curved and deep like that of a tachyglossid rather than flat like that of an ornithorhynchoid. It also had teeth, though fewer than the echidnapus. Why did those teeth end up disappearing altogether in modern monotremes?

Monotremes without teeth came onto the scene when the platypus (Ornithorhynchus anatinus) appeared during the Pleistocene, which began 2.6 million years ago. The researchers think competition for food caused the disappearance of teeth in the platypus—the spread of the Australo-New Guinean water rat may have affected which prey platypuses hunted for. Water rats eat mostly fish and shellfish along with some insects, which are also thought to have been part of the diet of ancient ornithorhynchoids. Turning to softer food to avoid competition may explain why the platypus evolved to be toothless.

As for echidnas, tachyglossids are thought to have lost their teeth after they diverged from ornithorhynchoids near the end of the Cretaceous. Echidnas are insectivores, grinding the hard shells of beetles and ants with spines inside their mouths, so have no need for teeth.

Although there is some idea of what happened to their teeth, the fate of the diverse species of Cretaceous monotremes, which were not only toothy but mostly larger than the modern platypus and echidna, remains unknown. The end of the Cretaceous brought a mass extinction triggered by the Chicxulub asteroid. Clearly, some monotremes survived it, but no monotreme fossils from the time have surfaced yet.

“It is unclear whether diverse monotreme fauna survived the end-Cretaceous mass extinction event, and subsequently persisted,” the researchers said in the same study. “Filling this mysterious interval of monotreme diversity and adaptive development should be a primary focus for research in the future.”

Alcheringa: An Australasian Journal of Palaeontology, 2024. DOI: 10.1080/03115518.2024.2348753

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nitrogen-using-bacteria-can-cut-farms’-greenhouse-gas-emissions 

Nitrogen-using bacteria can cut farms’ greenhouse gas emissions 

agriculture, bacteria, Biology, climate change, fertilizer, nitrogen, Science / /

Keeping crops from the greenhouse —

Nitrogen fertilizers get converted to nitrous oxide, a potent greenhouse gas.

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A tractor amidst many rows of small plants, with brown hills in the background.

Fritz Haber: good guy or bad guy? He won the Nobel Prize in Chemistry in 1918 for his part in developing the Haber-Bosch process, a method for generating ammonia using the nitrogen gas in air. The technique freed agriculture from the constraint of needing to source guano or manure for nitrogen fertilizer and is widely credited for saving millions from starvation. About half of the world’s current food supply relies on fertilizers made using it, and about half of the nitrogen atoms in our bodies can be traced back to it.

But it also allowed farmers to use this newly abundant synthetic nitrogen fertilizer with abandon. This has accentuated agriculture’s role as a significant contributor to global warming because the emissions that result from these fertilizers is a greenhouse gas—one that has a warming potential almost 300 times greater than that of carbon dioxide and remains in the atmosphere for 100 years. Microbes in soil convert nitrogen fertilizer into nitrous oxide, and the more nitrogen fertilizer they have to work with, the more nitrous oxide they make.

Agriculture also leaks plenty of the excess nitrogen into waterways in the form of nitrate, generating algal blooms that create low-oxygen ‘dead zones’ where no marine life can live.

One way to reduce nitrogen emissions from farms would be to simply use fertilizer more efficiently. But—as we’ve seen with fossil fuels (and antibiotics and plastics)—when humans have a miraculous substance on our hands, we just can’t seem to use it at levels that minimize its impact. We instead seem compelled to throw around as much of the stuff as we can. But even if we were to start using less fertilizer now, we are past time to choose a single technique to curb greenhouse gas emissions; we need to put them all into action.

Denitrifying bacteria reduces levels of nitrous oxide in soil by converting it to the molecular form of nitrogen found in air. They use it as an oxidizer for respiration under conditions with low or no oxygen. So adding these nitrogen-respiring bacteria to soil could help decrease nitrous oxide emissions.

Modifying the microbiome of soil is just as hard as modifying the microbiome in our bodies. So instead of trying to promote the growth of any denitrifying bacteria that might happen to already be in soil, researchers decided to grow them externally and then add them in. Their source was partially treated sewage, called digestate, that was destined as organic fertilizer anyway. Keeping the digestate in oxygen-free conditions enriched their levels of one strain of nitrogen-respiring bacteria.

The researchers homed in on this particular strain because it has the enzyme needed to break down nitrous oxide, but not the enzymes used to make it from other nitrogen compounds. And although it is not the fastest, most efficient strain at nitrogen respiration, it won because it is the most tenacious: It grows to high concentrations even when oxygen is present, and it works well in soil.

When this digestate was mixed into soil, fertilizer-induced emissions were reduced by 50–95 percent, depending on the pH and organic carbon content of the soils. The effect lasted over the entire growing season. The presence of the added nitrogen-respiring bacteria did not seem to affect the indigenous microbiota already present in the soil, and the added bacteria did not carry genes for antibiotic resistance or pathogenicity, which is obviously essential if they are to be used in farming. What hasn’t been tested yet, however, is whether the presence of these bacteria influence the growth of crops.

Using mathematical modeling of future emissions, the researchers concluded that adding these bacteria to soil could reduce nitrous oxide emissions by 60 percent, and if they are added to all liquid manure systems in Europe, Europe could reduce its anthropogenic nitrous oxide emissions by 3 to 4 percent.

Nature, 2024.  DOI: 10.1038/s41586-024-07464-3

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mutations-in-a-non-coding-gene-associated-with-intellectual-disability

Mutations in a non-coding gene associated with intellectual disability

Biology, developmental disorders, Genetics, neurobiology, neurodevelopment, RNA, Science, spacing / /

Splice of life —

A gene that only makes an RNA is linked to neurodevelopmental problems.

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Colored ribbons that represent the molecular structure of a large collection of proteins and RNAs.

Enlarge / The spliceosome is a large complex of proteins and RNAs.

Almost 1,500 genes have been implicated in intellectual disabilities; yet for most people with such disabilities, genetic causes remain unknown. Perhaps this is in part because geneticists have been focusing on the wrong stretches of DNA when they go searching. To rectify this, Ernest Turro—a biostatistician who focuses on genetics, genomics, and molecular diagnostics—used whole genome sequencing data from the 100,000 Genomes Project to search for areas associated with intellectual disabilities.

His lab found a genetic association that is the most common one yet to be associated with neurodevelopmental abnormality. And the gene they identified doesn’t even make a protein.

Trouble with the spliceosome

Most genes include instructions for how to make proteins. That’s true. And yet human genes are not arranged linearly—or rather, they are arranged linearly, but not contiguously. A gene containing the instructions for which amino acids to string together to make a particular protein—hemoglobin, insulin, serotonin, albumin, estrogen, whatever protein you like—is modular. It contains part of the amino acid sequence, then it has a chunk of DNA that is largely irrelevant to that sequence, then a bit more of the protein’s sequence, then another chunk of random DNA, back and forth until the end of the protein. It’s as if each of these prose paragraphs were separated by a string of unrelated letters (but not a meaningful paragraph from a different article).

In order to read this piece through coherently, you’d have to take out the letters interspersed between its paragraphs. And that’s exactly what happens with genes. In order to read the gene through coherently, the cell has machinery that splices out the intervening sequences and links up the protein-making instructions into a continuous whole. (This doesn’t happen in the DNA itself; it happens to an RNA copy of the gene.) The cell’s machinery is obviously called the spliceosome.

There are about a hundred proteins that comprise the spliceosome. But the gene just found to be so strongly associated with neurodevelopmental disorders doesn’t encode any of them. Rather, it encodes one of five RNA molecules that are also part of the spliceosome complex and interact with the RNAs that are being spliced. Mutations in this gene were found to be associated with a syndrome with symptoms that include intellectual disability, seizures, short stature, neurodevelopmental delay, drooling, motor delay, hypotonia (low muscle tone), and microcephaly (having a small head).

Supporting data

The researchers buttressed their finding by examining three other databases; in all of them, they found more people with the syndrome who had mutations in this same gene. The mutations occur in a remarkably conserved region of the genome, suggesting that it is very important. Most of the mutations were new in the affected people—i.e. not inherited from their parents—but there was one case of one particular mutation in the gene that was inherited. Based on this, the researchers concluded that this particular variant may cause a less severe disorder than the other mutations.

Many studies that look for genes associated with diseases have focused on searching catalogs of protein coding genes. These results suggest that we could have been missing important mutations because of this focus.

Nature Medicine, 2024. DOI: 10.1038/s41591-024-03085-5

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dinosaurs-needed-to-be-cold-enough-that-being-warm-blooded-mattered

Dinosaurs needed to be cold enough that being warm-blooded mattered

Biology, climate change, dinosaurs, evolution, paleontology, Science, warm blooded / /

Some like it less hot —

Two groups of dinosaurs moved to cooler climes during a period of climate change.

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Image of a feathered dinosaur against a white background.

Enlarge / Later theropods had multiple adaptations to varied temperatures.

Dinosaurs were once assumed to have been ectothermic, or cold-blooded, an idea that makes sense given that they were reptiles. While scientists had previously discovered evidence of dinosaur species that were warm-blooded, though what could have triggered this adaptation remained unknown. A team of researchers now think that dinosaurs that already had some cold tolerance evolved endothermy, or warm-bloodedness, to adapt when they migrated to regions with cooler temperatures. They also think they’ve found a possible reason for the trek.

Using the Mesozoic fossil record, evolutionary trees, climate models, and geography, plus factoring in a drastic climate change event that caused global warming, the team found that theropods (predators and bird ancestors such as velociraptor and T. rex) and ornithischians (such as triceratops and stegosaurus) must have made their way to colder regions during the Early Jurassic. Lower temperatures are thought to have selected for species that were partly adapted to endothermy.

“The early invasion of cool niches… [suggests] an early attainment of homeothermic (possibly endothermic) physiology in [certain species], enabling them to colonize and persist in even extreme latitudes since the Early Jurassic,” the researchers said in a study recently published in Current Biology.

Hot real estate

During the Mesozoic Era, which lasted from 230 to 66 million years ago, proto-dinosaurs known as dinosauromorphs began to diversify in hot and dry climates. Early sauropods, ornithischians, and theropods all tended to stay in these regions.

Sauropods (such as brontosaurus and diplodocus) would become the only dinosaur groups to bask in the heat—the fossil record shows that sauropods tended to stay in warmer areas, even if there was less food. This suggests the need for sunlight and heat associated with ectothermy. They might have been capable of surviving in colder temperatures but not adapted enough to make it for long, according to one hypothesis.

It’s also possible that living in cooler areas meant too much competition with other types of dinosaurs, as the theropods and ornithiscians did end up moving into these cooler areas.

Almost apocalypse

Beyond the ecological opportunities that may have drawn dinosaurs to the cooler territories, it’s possible they were driven away from the warm ones. Around 183 million years ago, there was a perturbation in the carbon cycle, along with extreme volcanism that belched out massive amounts of methane, sulfur dioxide, and mercury. Life on Earth suffered through scorching heat, acid rain, and wildfires. Known as the Early Jurassic Jenkyns Event, the researchers now think that these disruptions pushed theropod and ornithischian dinosaurs to cooler climates because temperatures in warmer zones went above the optimal temperatures for their survival.

The theropods and ornithischians that escaped the effects of the Jenkyns event may have had a key adaptation to cooler climes; many dinosaurs from these groups are now thought to have been feathered. Feathers can be used to both trap and release heat, which would have allowed feathered dinosaurs to regulate their body temperature in more diverse climates. Modern birds use their feathers the same way.

Dinosaur species with feathers or special structures that improved heat management could have been homeothermic, which means they would have been able to maintain their body temperature with metabolic activity or even endothermic.

Beyond the dinosaurs that migrated to high latitudes and adapted to a drop in temperature, endothermy might have led to the rise of new species and lineages of dinosaurs. It could have contributed to the rise of Avialae, the clade that includes birds—the only actual dinosaurs still around—and traces all the way back to their earliest ancestors.

“[Our findings] provide novel insights into the origin of avian endothermy, suggesting that this evolutionary trajectory within theropods… likely started in the latest Early Jurassic,” the researchers said in the same study.

That really is something to think about next time a sparrow flies by.

Current Biology, 2024.  DOI: 10.1016/j.cub.2024.04.051

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whale-songs-have-features-of-language,-but-whales-may-not-be-speaking

Whale songs have features of language, but whales may not be speaking

animal behavior, Biology, language, Science, whale song, whales / /
A group of sperm whales and remora idle near the surface of the ocean.

Whales use complex communication systems we still don’t understand, a trope exploited in sci-fi shows like Apple TV’s Extrapolations. That show featured a humpback whale (voiced by Meryl Streep) discussing Mahler’s symphonies with a human researcher via some AI-powered inter-species translation app developed in 2046.

We’re a long way from that future. But a team of MIT researchers has now analyzed a database of Caribbean sperm whales’ calls and has found there really is a contextual and combinatorial structure in there. But does it mean whales have a human-like language and we can just wait until Chat GPT 8.0 to figure out how to translate from English to Sperm-Whaleish? Not really.

One-page dictionary

“Sperm whales communicate using clicks. These clicks occur in short packets we call codas that typically last less than two seconds, containing three to 40 clicks,” said Pratyusha Sharma, a researcher at the MIT Computer Science and Artificial Intelligence Laboratory and the lead author of the study. Her team argues that codas are analogues of words in human language and are further organized in coda sequences that are analogues of sentences. “Sperm whales are not born with this communication system; it’s acquired and changes over the course of time,” Sharma said.

Seemingly, sperm whales have a lot to communicate about. Earlier observational studies revealed that they live a fairly complex social life revolving around family units forming larger structures called clans. They also have advanced hunting strategies and do group decision-making, seeking consensus on where to go and what to do.

Despite this complexity in behavior and relationships, their vocabulary seemed surprisingly sparse.

Sharma’s team sourced a record of codas from the dataset of the Dominica Sperm Whale Project, a long-term study on sperm whales that recorded and annotated 8,719 individual codas made by EC-1, a sperm whale clan living in East Caribbean waters. Those 8,719 recorded codas, according to earlier research on this database, were really just 21 coda types that the whales were using over and over.

A set of 21 words didn’t look like much of a language. “But this [number] is exactly what we found was not true,” Sharma said.

Fine-grained changes

“People doing those earlier studies were looking at the calls in isolation… They were annotating these calls, taking them out of context, shuffling them up, and then tried to figure out what kind of patterns were recurring,” Sharma explained. Her team, by contrast, analyzed the same calls in their full context, basically looking at entire exchanges rather than at separate codas. “One of the things we saw was fine-grained changes in the codas that other whales participating in the exchange were noticing and reacting to. If you looked at all these calls out of context, all these fine-grained changes would be lost; they would be considered noise,” Sharma said.

The first of those newly recognized fine-grained changes was termed “rubato,” borrowed from music, where it means introducing slight variations in the tempo of a piece. Communicating sperm whales could stretch or shrink a coda while keeping the same rhythm (where rhythm describes the spacing between the clicks in a coda).

The second feature the researchers discovered was ornamentation. “An ornament is an extra click added at the end of the coda. And when you have this extra click, it marks a critical point, and the call changes. It either happens toward the beginning or at the end of the call,” said Sharma.

The whales could individually manipulate rubato and ornamentation, as well as previously identified rhythm and tempo features. By combining this variation, they can produce a very large variety of codas. “The whales produce way more combinations of these features than 21—the information-carrying capacity of this system is a lot more capable than that,” Sharma said.

Her team identified 18 types of rhythm, three variants of rubato, five types of tempo, and an ability to add an ornament or not in the sperm whale’s communication system. That adds up to 540 possible codas, of which there are roughly 150 these whales frequently used in real life. Not only were sperm whales’ calls built with distinctive units at a coda level (meaning they were combinatorial), but they were compositional in that a call contained multiple codas.

But does that get us any closer to decoding the whale’s language?

“The combinatoriality at the word level and compositionality at the sentence level in human languages is something that looks very similar to what we found,” Sharma said. But the team didn’t determine whether meaning was being conveyed, she added. And without evidence of meaning, we might be barking up the wrong tree entirely.

Whale songs have features of language, but whales may not be speaking Read More »

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Beethoven likely didn’t die from lead poisoning, new DNA analysis reveals

Biology, DNA analysis, forensic DNA, human genetics, Ludwig von Beethoven, Science / /

get the lead out —

There was also mercury and arsenic but none of the toxins likely caused composer’s death.

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(7) Portrait of Beethoven by Joseph Karl Stieler, 1820

Enlarge / Portrait of Beethoven by Joseph Karl Stieler, 1820. Toxocology analysis of the composer’s locks of hair showed high levels of lead.

Beethoven-Haus Bonn

Last year, researchers sequenced the genome of famed composer Ludwig van Beethoven for the first time, based on authenticated locks of hair. The same team has now analyzed two of the locks for toxic substances and found extremely high levels of lead, as well as arsenic and mercury, according to a recent letter published in the journal Clinical Chemistry.

“It definitely shows Beethoven was exposed to high concentrations of lead,” Paul Janetto, co-author and director of the Mayo Clinic’s Department of Laboratory Medicine and Pathology, told The New York Times. “These are the highest values in hair I’ve ever seen. We get samples from around the world, and these values are an order of magnitude higher.” That said, the authors concluded that the lead exposure was not sufficient to actually kill the composer, although Beethoven very likely did suffer adverse health effects because of it.

As previously reported, Beethoven was plagued throughout his life by myriad health problems. The composer began losing his hearing in his mid- to late 20s, experiencing tinnitus and the loss of high-tone frequencies in particular. He claimed the onset began with a fit in 1798 induced by a quarrel with a singer. By his mid-40s, he was functionally deaf and unable to perform public concerts, although he could still compose music.

Beethoven on his deathbed: lithograph by Josef Danhauser after his own drawing.

Enlarge / Beethoven on his deathbed: lithograph by Josef Danhauser after his own drawing.

Beethoven-Haus Bonn

Beethoven also had lifelong chronic gastric ailments, including persistent abdominal pains and prolonged stretches of diarrhea. By 1821, the composer showed signs of liver disease, marked by the first of two severe attacks of jaundice. These issues certainly affected his career and emotional state, so much so that Beethoven requested—via a letter addressed to his brothers—that his favorite physician examine his body after his death to determine the cause of all his suffering.

By December 1826, Beethoven was quite ill, suffering from a second bout of jaundice and swollen limbs, fever, dropsy, and labored breathing. His doctor performed several operations to remove excess fluid from the composer’s abdomen. On March 24, 1827, he purportedly said to visitors, “Plaudite, amici, comoedia finita est” (“Applaud, friends, the comedy is over”). Two days later, he died. According to his good friend Anselm Hüttenbrenner, who was present, lightning and a loud clap of thunder briefly woke Beethoven, who “opened his eyes, lifted his right hand and looked up for several seconds with his fist clenched… not another breath, not a heartbeat more.”

An autopsy identified severe liver damage (evidence of cirrhosis) as the likely cause of death and significant dilation of the auditory nerve. But what caused that liver damage or his hearing loss—or his chronic stomach complaints, for that matter? Medical detectives have been debating possible causes for nearly two centuries, drawing on the composer’s letters, diaries, and physicians’ notes for evidence, as well as reports on skeletal remains from when his body was exhumed in 1863 and 1888. But no general consensus emerged.

Beethoven likely didn’t die from lead poisoning, new DNA analysis reveals Read More »

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Chemical tweaks to a toad hallucinogen turns it into a potential drug

biochemistry, Biology, hallucinogen, health, neurobiology, psychedelic, Science, toads / /

No licking toads! —

Targets a different serotonin receptor from other popular hallucinogens.

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Image of the face of a large toad.

Enlarge / The Colorado River toad, also known as the Sonoran Desert Toad.

It is becoming increasingly accepted that classic psychedelics like LSD, psilocybin, ayahuasca, and mescaline can act as antidepressants and anti-anxiety treatments in addition to causing hallucinations. They act by binding to a serotonin receptor. But there are 14 known types of serotonin receptors, and most of the research into these compounds has focused on only one of them—the one these molecules like, called 5-HT2A. (5-HT, short for 5-hydroxytryptamine, is the chemical name for serotonin.)

The Colorado River toad (Incilius alvarius), also known as the Sonoran Desert toad, secretes a psychedelic compound that likes to bind to a different serotonin receptor subtype called 5-HT1A. And that difference may be the key to developing an entirely distinct class of antidepressants.

Uncovering novel biology

Like other psychedelics, the one the toad produces decreases depression and anxiety and induces meaningful and spiritually significant experiences. It has been used clinically to treat vets with post-traumatic stress disorder and is being developed as a treatment for other neurological disorders and drug abuse. 5-HT1A is a validated therapeutic target, as approved drugs, including the antidepressant Viibryd and the anti-anxiety med Buspar, bind to it. But little is known about how psychedelics engage with this receptor and which effects it mediates, so Daniel Wacker’s lab decided to look into it.

The researchers started by making chemical modifications to the frog psychedelic and noting how each of the tweaked molecules bound to both 5-HT2A  and 5-HT1A. As a group, these psychedelics are known as “designer tryptamines”—that’s tryp with a “y”, mind you—because they are metabolites of the amino acid tryptophan.

The lab made 10 variants and found one that is more than 800-fold selective about sticking to 5-HT1A as compared to 5-HT2A. That makes it a great research tool for elucidating the structure-activity relationship of the 5-HT1A receptor, as well as the molecular mechanisms behind the pharmacology of the drugs on the market that bind to it. The lab used it to explore both of those avenues. However, the variant’s ultimate utility might be as a new therapeutic for psychiatric disorders, so they tested it in mice.

Improving the lives of mice

The compound did not induce hallucinations in mice, as measured by the “head-twitch response.” But it did alleviate depression, as measured by a “chronic social defeat stress model.” In this model, for 10 days in a row, the experimental mouse was introduced to an “aggressor mouse” for “10-minute defeat bouts”; essentially, it got beat up by a bully at recess for two weeks. Understandably, after this experience, the experimental mouse tended not to be that friendly with new mice, as controls usually are. But when injected with the modified toad psychedelic, the bullied mice were more likely to interact positively with new mice they met.

Depressed mice, like depressed people, also suffer from anhedonia: a reduced ability to experience pleasure. In mice, this manifests in not taking advantage of drinking sugar water when given the opportunity. But treated bullied mice regained their preference for the sweet drink. About a third of mice seem to be “stress-resilient” in this model; the bullying doesn’t seem to phase them. The drug increased the number of resilient mice.

The 5-HT2A receptor has hogged all of the research love because it mediates the hallucinogenic effects of many popular psychedelics, so people assumed that it must mediate their therapeutic effects, too. However, Wacker argues that there is little evidence supporting this assumption. Wacker’s new toad-based psychedelic variant and its preference for the 5-HT1A receptor will help elucidate the complementary roles these two receptor subtypes play in mediating the cellular and psychological effects of psychedelic molecules. And it might provide the basis for a new tryptamine-based mental health treatment as well—one without hallucinatory side effects, disappointing as that may be to some.

Nature, 2024.  DOI: 10.1038/s41586-024-07403-2

Chemical tweaks to a toad hallucinogen turns it into a potential drug Read More »

the-wasps-that-tamed-viruses

The wasps that tamed viruses

Biology, entomology, Parasitic wasps, Science, syndication, virology, viruses / /
Parasitoid wasp

Enlarge / Xorides praecatorius is a parasitoid wasp.

If you puncture the ovary of a wasp called Microplitis demolitor, viruses squirt out in vast quantities, shimmering like iridescent blue toothpaste. “It’s very beautiful, and just amazing that there’s so much virus made in there,” says Gaelen Burke, an entomologist at the University of Georgia.

M. demolitor  is a parasite that lays its eggs in caterpillars, and the particles in its ovaries are “domesticated” viruses that have been tuned to persist harmlessly in wasps and serve their purposes. The virus particles are injected into the caterpillar through the wasp’s stinger, along with the wasp’s own eggs. The viruses then dump their contents into the caterpillar’s cells, delivering genes that are unlike those in a normal virus. Those genes suppress the caterpillar’s immune system and control its development, turning it into a harmless nursery for the wasp’s young.

The insect world is full of species of parasitic wasps that spend their infancy eating other insects alive. And for reasons that scientists don’t fully understand, they have repeatedly adopted and tamed wild, disease-causing viruses and turned them into biological weapons. Half a dozen examples already are described, and new research hints at many more.

By studying viruses at different stages of domestication, researchers today are untangling how the process unfolds.

Partners in diversification

The quintessential example of a wasp-domesticated virus involves a group called the bracoviruses, which are thought to be descended from a virus that infected a wasp, or its caterpillar host, about 100 million years ago. That ancient virus spliced its DNA into the genome of the wasp. From then on, it was part of the wasp, passed on to each new generation.

Over time, the wasps diversified into new species, and their viruses diversified with them. Bracoviruses are now found in some 50,000 wasp species, including M. demolitor. Other domesticated viruses are descended from different wild viruses that entered wasp genomes at various times.

Researchers debate whether domesticated viruses should be called viruses at all. “Some people say that it’s definitely still a virus; others say it’s integrated, and so it’s a part of the wasp,” says Marcel Dicke, an ecologist at Wageningen University in the Netherlands who described how domesticated viruses indirectly affect plants and other organisms in a 2020 paper in the Annual Review of Entomology.

As the wasp-virus composite evolves, the virus genome becomes scattered through the wasp’s DNA. Some genes decay, but a core set is preserved—those essential for making the original virus’s infectious particles. “The parts are all in these different locations in the wasp genome. But they still can talk to each other. And they still make products that cooperate with each other to make virus particles,” says Michael Strand, an entomologist at the University of Georgia. But instead of containing a complete viral genome, as a wild virus would, domesticated virus particles serve as delivery vehicles for the wasp’s weapons.

Here are the steps in the life of a parasitic wasp that harbors a bracovirus.

Enlarge / Here are the steps in the life of a parasitic wasp that harbors a bracovirus.

Those weapons vary widely. Some are proteins, while others are genes on short segments of DNA. Most bear little resemblance to anything found in wasps or viruses, so it’s unclear where they originated. And they are constantly changing, locked in evolutionary arms races with the defenses of the caterpillars or other hosts.

In many cases, researchers have yet to discover even what the genes and proteins do inside the wasps’ hosts or prove that they function as weapons. But they have untangled some details.

For example, M. demolitor  wasps use bracoviruses to deliver a gene called glc1.8  into the immune cells of moth caterpillars. The glc1.8  gene causes the infected immune cells to produce mucus that prevents them from sticking to the wasp’s eggs. Other genes in M. demolitor’s bracoviruses force immune cells to kill themselves, while still others prevent caterpillars from smothering parasites in sheaths of melanin.

The wasps that tamed viruses Read More »

deepmind-adds-a-diffusion-engine-to-latest-protein-folding-software

DeepMind adds a diffusion engine to latest protein-folding software

AI, biochemistry, Biology, deepmind, Google, protein folding, Science / /

Added complexity —

Major under-the-hood changes let AlphaFold handle protein-DNA complexes and more.

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image of a complicated mix of lines and ribbons arranged in a complicated 3D structure.

Enlarge / Prediction of the structure of a coronavirus Spike protein from a virus that causes the common cold.

Google DeepMind

Most of the activities that go on inside cells—the activities that keep us living, breathing, thinking animals—are handled by proteins. They allow cells to communicate with each other, run a cell’s basic metabolism, and help convert the information stored in DNA into even more proteins. And all of that depends on the ability of the protein’s string of amino acids to fold up into a complicated yet specific three-dimensional shape that enables it to function.

Up until this decade, understanding that 3D shape meant purifying the protein and subjecting it to a time- and labor-intensive process to determine its structure. But that changed with the work of DeepMind, one of Google’s AI divisions, which released Alpha Fold in 2021, and a similar academic effort shortly afterward. The software wasn’t perfect; it struggled with larger proteins and didn’t offer high-confidence solutions for every protein. But many of its predictions turned out to be remarkably accurate.

Even so, these structures only told half of the story. To function, almost every protein has to interact with something else—other proteins, DNA, chemicals, membranes, and more. And, while the initial version of AlphaFold could handle some protein-protein interactions, the rest remained black boxes. Today, DeepMind is announcing the availability of version 3 of AlphaFold, which has seen parts of its underlying engine either heavily modified or replaced entirely. Thanks to these changes, the software now handles various additional protein interactions and modifications.

Changing parts

The original AlphaFold relied on two underlying software functions. One of those took evolutionary limits on a protein into account. By looking at the same protein in multiple species, you can get a sense for which parts are always the same, and therefore likely to be central to its function. That centrality implies that they’re always likely to be in the same location and orientation in the protein’s structure. To do this, the original AlphaFold found as many versions of a protein as it could and lined up their sequences to look for the portions that showed little variation.

Doing so, however, is computationally expensive since the more proteins you line up, the more constraints you have to resolve. In the new version, the AlphaFold team still identified multiple related proteins but switched to largely performing alignments using pairs of protein sequences from within the set of related ones. This probably isn’t as information-rich as a multi-alignment, but it’s far more computationally efficient, and the lost information doesn’t appear to be critical to figuring out protein structures.

Using these alignments, a separate software module figured out the spatial relationships among pairs of amino acids within the target protein. Those relationships were then translated into spatial coordinates for each atom by code that took into account some of the physical properties of amino acids, like which portions of an amino acid could rotate relative to others, etc.

In AlphaFold 3, the prediction of atomic positions is handled by a diffusion module, which is trained by being given both a known structure and versions of that structure where noise (in the form of shifting the positions of some atoms) has been added. This allows the diffusion module to take the inexact locations described by relative positions and convert them into exact predictions of the location of every atom in the protein. It doesn’t need to be told the physical properties of amino acids, because it can figure out what they normally do by looking at enough structures.

(DeepMind had to train on two different levels of noise to get the diffusion module to work: one in which the locations of atoms were shifted while the general structure was left intact and a second where the noise involved shifting the large-scale structure of the protein, thus affecting the location of lots of atoms.)

During training, the team found that it took about 20,000 instances of protein structures for AlphaFold 3 to get about 97 percent of a set of test structures right. By 60,000 instances, it started getting protein-protein interfaces correct at that frequency, too. And, critically, it started getting proteins complexed with other molecules right, as well.

DeepMind adds a diffusion engine to latest protein-folding software Read More »