Now the lab is back with important results that build on that discovery. New findings published in Molecular Cell provide details about the hidden organization of the cytoplasm — the soup of liquid, organelles, proteins, and other molecules inside a cell. The research shows it makes a big difference where in that cellular broth that messenger RNA (mRNA) get translated into proteins.

“You know the old real estate saying, ‘location, location, location.’ It turns out it applies to how proteins get made inside of cells, too,” says Dr. Mayr, a molecular and cell biologist at the Sloan Kettering Institute, a hub for basic and translational research within MSK. “If it’s translated over here, you get twice as much protein as if it’s translated over there.”

This first-of-its-kind study highlights the degree to which the cytoplasm is “beautifully organized,” rather than being just a big jumble of stuff, she says.

Not only do the findings shed new light on fundamental cellular biology, but the knowledge also holds promise for increasing or altering the production of proteins in mRNA vaccines and therapies, the researchers note.

The study was led by former lab member Ellen Horste, PhD, whom Mayr tapped for the daunting but exciting project when she joined the lab several years ago. Dr. Horste received her doctorate from the Gerstner Sloan Kettering Graduate School in June and now works for a gene therapy company.

“When we started, we had a hard time getting funding for this project,” Dr. Mayr says. “Everyone thought isolating the individual components would be totally impossible. This was really Ellen’s project from her first day in the lab to her last day. It was quite challenging, and I couldn’t be more proud of her.”

Adapting an approach commonly used by immunologists, the team was able to color-code individual particles within cells using antibodies and then sort them by color. They used RNA sequencing to identify which RNAs were associated with which particles.

“And it was really striking to see that in each of these intracellular neighborhoods, very different types of mRNAs were being translated,” Dr. Mayr says.

Welcome to the Cellular Neighborhood

Most of the well-known components inside a cell have a defined shape and come wrapped in an exterior membrane: the nucleus, mitochondria, lysosomes, the Golgi apparatus.

Two of the key components at the heart of the Mayr team’s study don’t have membranes — which is what has made them so hard to find in the first place, and a challenge to isolate and study in the lab.

A quick biology review: Cells build proteins using instructions encoded in DNA. Those DNA sequences are transcribed into mRNA inside the cell nucleus. These messenger RNA then move out into the cytoplasm where they are translated into a useful protein.

The new study demonstrated that where in the cytoplasm this translation step happens isn’t random, and that there’s an underlying logic or “code” that directs mRNAs to specific neighborhoods within the cell.

“The whole cytoplasm is nicely compartmentalized,” Dr. Mayr says. “We were able to demonstrate there is a code at work that’s based on the mRNA’s biophysical features — their size and shape — and the particular RNA-binding proteins they partner with. This code directs the mRNAs to different locations for translation.”

Investigating Translation in 3 Locations Inside the Cell

Through a painstaking series of experiments, the research team was able to show that mRNAs of different lengths and shapes tend to gravitate to specific neighborhoods. And that if you intervene to redirect them to a different location, it can have a profound impact on the amount of protein that gets produced and on the protein’s function.

The researchers looked at mRNAs that locate to the surface of the endoplasmic reticulum (an organelle involved in protein synthesis and other cellular functions). It’s well established that proteins associated with cellular membranes and those that get secreted by the cell for use elsewhere are translated there. The research revealed that nearly 15% of mRNAs that encode non-membrane proteins are also translated at the ER — and they encode large and highly expressed proteins.

Meanwhile, the mRNAs that get translated in the cytosol (the liquid part of the cytoplasm) tend to be very small proteins.

And mRNAs that locate to TIS granules tend to be transcription factors (proteins that regulate the transcription of genes). TIS granules are a membrane-less cellular component Mayr’s lab discovered in 2018. They form a network of interconnected proteins and mRNAs, and are closely allied with the endoplasmic reticulum, forming a distinct space where mRNA and proteins can collect and interact.

A fluorescent microscopy image of a cell, with TIS granules shown in red and the endoplasmic reticulum is shown in green. The central black area is the cell’s nucleus.

Cracking the Code

Cracking the code for how mRNA localize to different locations revealed some surprising findings.

After discovering the TIS granule network five years ago, the lab had turned its attention to understanding which of the many thousands of mRNAs in a cell localize there, and whether they have shared characteristics.

The team homed in on one part of the mRNA that doesn’t usually get much attention — the tail. It’s separate from the middle part of the mRNA, which contains the instructions for building the protein. Scientists call the tail the three prime untranslated region (3? UTR), and it turns out to be critical for the localization process.

“The tail usually contains a longer sequence than the part of the RNA that’s actually used to make the protein,” Dr. Mayr says. “But for a long time, people didn’t pay that much attention to the tail regions since you can still make the protein without them.” (They’re also important in other ways, as Dr. Mayr outlined in a 2019 review article.)

It turns out that the tail is essential for partnering with RNA-binding proteins so that, together, the mRNA goes to the correct translation region within the cell. (RNA-binding proteins are a type of protein that attaches to RNA molecules and can modulate various aspects of their activity.)

At first the team thought it was primarily these RNA-binding proteins that directed the action — guiding the mRNAs to neighborhood one, neighborhood two, and so forth, Dr. Mayr says.

“But the really surprising finding was that the RNA-binding proteins actually play a secondary role rather than a primary role in the process,” she says.

The default sorting of mRNA to a location, the researchers found, is based on the overall size and shape of the mRNAs. But being in partnership with a binding protein can override this default and redirect them.

“Our data show that if you translate an mRNA in the TIS granules, the resulting protein will perform one function, and if you translate it outside of the TIS granules, it will perform a different function,” she says. “And this is how, in higher organisms like us, one protein can have more than one function.”

Toward Future Applications

One specific protein the team examined during the study is MYC. The MYC gene is one of the more famous oncogenes, and mutations in MYC underlie the development of many cancers.

“We observed that several MYC protein complexes were only formed when MYC mRNA was translated in the granules and not when it was translated in the cytosol,” Dr. Mayr says. “Our results show there’s an important biological relevance to these neighborhoods, even when only about 20% of mRNAs get translated in the TIS granules.”

Together, these insights suggest that mRNA could be targeted to achieve different functions, as well as to vary the amount of a protein that gets produced, she adds.

“So, we hope that in the future we can make smarter medicines by making more or less of a particular factor, and also by manipulating its function,” Dr. Mayr says. “This probably won’t happen in the next five years, but it’s something we are paving the way to do.”

But how these complex structures, known as apical extracellular matrices (aECMs) are assembled into elaborately woven architectures has remained an elusive question.

Now, following years of research and the power of a technologically advanced instrument, University of California San Diego scientists have unraveled the underpinnings of such matrices in a tiny nematode. The roundworm Caenorhabditis elegans has been studied extensively for decades due to its transparent structure that allows researchers to peer inside its body and examine its skin.

Described in the journal Nature Communications, School of Biological Sciences researchers have now deciphered the assemblage of aECM patterns in roundworms at the nanoscale. A powerful, super-resolution microscope helped reveal previously unseen patterns related to columns, known as struts, that are key to the proper development and functioning of aECMs.

“Struts are like tiny pillars that connect the different layers of the matrix and serve as a type of scaffolding,” said Andrew Chisholm, a professor in the School of Biological Sciences and the paper’s senior author.

Although roundworms serve as a model organism for laboratory studies due to their simple, transparent bodies, below the surface they feature intricate architectures. They also have nearly 20,000 genes, not unlike the number of human genes, and therefore provide lessons on structure and function of more advanced organisms.

Focusing on the roundworm exoskeleton known as the cuticle, the researchers found that defects in struts result in unnatural layer swelling, or “blistering.” Within the cuticle layer, the research study focused on collagens, which are the most abundant family of proteins in our bodies and help keep bodily materials conjoined.

“The struts hold the critical layers together,” said Chisholm. “Without them, the layers separate and cause disorders such as blistering. In blistering mutants you don’t see any struts.”

Conventional laboratory instruments had previously imaged struts without detail, often resulting in undefined blobs. But through Biological Sciences Assistant Professor Andreas Ernst’s laboratory they accessed advanced instrumentation — known as 3D-structured illumination super resolution microscopy (3D-SIM) — which put the struts into stunning focus and allowed their functions to be more easily defined. The researchers were then able to solve the nanoscale organization of struts and previously undocumented levels of patterning in the cuticle layer.

“We could see exactly where these proteins were going in the matrix,” said Chisholm. “This is potentially a paradigm for how the matrix assembles into very complex structures and very intricate patterning.”

A flu vaccine prompts the immune system to make antibodies that can bind to a viral protein called hemagglutinin on the outside of an invading flu virus, blocking it from entering a person’s cells. Different antibodies bind to different parts of hemagglutinin in different ways, and hemagglutinin itself evolves over time, resulting in the emergence of new flu strains that can evade old antibodies. New flu vaccines are offered each year based on predictions of whatever the most dominant strains will be.

Extensive research efforts are paving the way to development of flu vaccines that are better at protecting against multiple strains at once. Many scientists are focused on antibodies that can simultaneously protect against flu subtypes known as H1 and H3, which come in multiple strains and are responsible for widespread infection.

Simmons and colleagues homed in on a particular challenge in this endeavor — a small change found in some H1 strains in the sequence of building blocks that makes up hemagglutinin. Certain antibodies capable of neutralizing H3 can also neutralize H1, but not if its hemagglutinin has this change, known as the 133a insertion.

Now, in a series of experiments conducted with blood samples from patients, the researchers have identified a novel class of antibodies capable of neutralizing both certain H3 strains and certain H1 strains with or without the 133a insertion. Distinct molecular characteristics set these antibodies apart from other antibodies capable of cross-neutralizing H1 and H3 strains via other means.

This research expands the list of antibodies that could potentially contribute to development of a flu virus that achieves broader protection through an assortment of molecular mechanisms. It also adds to growing evidence supporting a move away from flu vaccines grown in chicken eggs — currently the most common manufacturing approach.

The authors add, “We need annual influenza virus vaccines to keep pace with continuing viral evolution. Our work suggests that the barriers to eliciting more broadly protective immunity may be surprisingly low. Given the right series of influenza virus exposures/vaccinations, it is possible to for humans to mount robust antibody responses that neutralize divergent H1N1 and H3N2 viruses, opening new avenues to design improved vaccines.”

Early life stages of insects fulfill important functions in our ecosystems. They decompose dead bodies and wood, forming soil and returning various elements into material cycles. Not least, they are a major food source for many larger animals such as birds and mammals. This has led to many insect larvae developing structures and strategies for reducing the danger of being eaten. These include features like spines and hairs, but also camouflage and concealment. Over millions of years, a wide variety of such adaptation strategies have developed.

Researchers at LMU and the universities of Greifswald and Rostock have studied particularly well preserved fossils from Burmese amber and have been able to demonstrate that such anti-predator mechanisms had already evolved very diverse forms in insect larvae during the Cretaceous period 100 million years ago. This includes well-known strategies such as that employed by lacewing larvae, which carry various plant and animal materials on their back to give them camouflage, or the ploy of mimicking the appearance of certain plant parts.

“A particularly spectacular example is by far the oldest larva of a scorpionfly to have been discovered, which is the second fossil ever found to have special hairs on its back for attaching camouflage material,” says Professor Carolin Haug, lead author of the article and zoologist at the Faculty of Biology. “Also, I could mention sawfly larvae that lived in leaves and created tunnels in them as they ate their way through the thin layer of the leaf interior.” Overall, the article, which has been published in the journal iScience, shows that a large variety of different strategies already existed 100 million years ago for insect larvae to defend themselves against predators. “Observing the diversity of the past and the emergence and disappearance of various morphologies helps us better understand these processes, which is particularly important in view of the ongoing biodiversity crisis,” says Haug.

The research on management strategies and use of animal resources in high mountain areas during the Early Neolithic, approximately 6,500 to 7,500 years ago, was conditioned by the presumption that human occupancy of these regions were mainly seasonal and that economic practices focused greatly on making use of wild resources. With regards to livestock rearing, the role of sheep and goat transhumance in high mountain areas has stood out traditionally, while only a marginal role has been given to other livestock activities, in which the temporary maintenance of these animal flocks has been highlighted.

Researchers from the Archaeozoology Laboratory and the High Mountain Archaeology Group of the Universitat Autònoma de Barcelona (UAB), the University of Évora (HERCULES Laboratory), the Milà i Fontanals Institution-CSIC and the General Directorate of Cultural Heritage of the Government of Aragon, have now for the first time managed to characterise the livestock practices and feeding strategies of domesticated animals in high mountain regions during the Early Neolithic, specifically in the archaeological site of Coro Trasito, located in the region of Sobrarbe, Aragon. Their research has yielded new elements to be used in the study of the complexity of neolithisation processes in the Central Pyrenees.

The study conducted by the research team focused on assessing animal ecology, livestock management strategies and feeding practices implemented by the first societies settling in high mountain regions (over 1,500 metres above sea level). To do so, the team became the first to apply to high mountain contexts a combination of analysis of stable carbon and nitrogen isotopes in bone collagen — the study of these two isotopes can be used to determine the diet and the position in the food chain of the animals — and the archaeozoological analysis of the remains of animals from that period. Thanks to this combination, researchers were able to document that management and feeding strategies differed among flocks.

The results obtained showed that flocks belonging to these first settlers were small and formed by a few number of each species: cows, goats, sheep and pigs (Bos taurus, Capra hircus, Ovis aries and Sus domesticus), and were mainly used for their meat and milk production. In addition, researchers were able to document the rise in the economic importance of pigs (Sus domesticus) during the Neolithic.

The presence in some of the cases studied of different ways of managing the feeding of animals, with access to different pastures and the possible provision of forage, mainly from surplus agricultural products, shows that livestock practices developed at the Coro Trasito site were consolidated practices at the start of the Neolithic and related to agricultural practices. The study also demonstrates how flocks were adapted to the environmental conditions of the cave.

The results of the archaeozoological, isotopic and archaeological analyses reveal that the inhabitants of the Coro Trasito cave made use mainly of domestic resources. In addition, the presence of transformation activities related to dairy products and fat, as well as the existence of storage structures within the cave, point to the complexity of neolithisation processes in the Central Pyrenees and how these areas were rapidly integrated into an even wider and more complex economic system.

“Our high-resolution data provide a new interpretation for the formation of tens of thousands of pits on the North Sea seafloor, and we predict that the underlying mechanisms occur globally, but have been overseen until now,” Schneider von Deimling adds. For the study, Schneider von Deimling and researchers from the Alfred Wegener Institute, the Helmholtz Centre for Polar and Marine Research (AWI), the University of Veterinary Medicine Hannover, Foundation (TiHo) as well as the Leibniz Institute for Baltic Sea Research Warnemünde (IOW) examined the seafloor in the North Sea off Heligoland down to centimeters. They also included the behavior of vertebrates such as porpoises in their analyses.

Vertebrates leave pits in the seabed of the North Sea

Most of the depressions in the seafloor in the German Bight, the team suspects, are created by porpoises and other animals in search of food, and then scoured out by bottom currents. The sand eel, a small eel-like fish that spends most of the year buried in shallow sediments, plays a key role in this process. Sand eels are not only popular with the fishing industry, but are also consumed in large quantities by porpoises. “From analyses of the stomach contents of stranded porpoises, we know that sand eels are an important food source for the North Sea population,” says Dr Anita Gilles of the TiHo-Institute for Terrestrial and Aquatic Wildlife Research (ITAW), who has long studied the biology of marine mammals. In their study, the researchers showed that the marine mammals leave pits in the seafloor when they hunt for buried sand eels. Although these pits resemble the familiar pockmarks, they are much shallower.

Advanced multibeam echosounder technology provides information on pit condition

The detection of the pits has only become possible in recent years with the help of modern multibeam echosounder technology, which is taught and practiced intensively at Kiel University. “The formation mechanism of these pits, as we call them, probably also explains the existence of numerous crater-like depressions on the seafloor worldwide, which have been misinterpreted as the result of methane gas leaks,” says geoscientist Schneider von Deimling. In the North Sea, the researchers identified 42458 of these enigmatically shaped, shallow pits with an average depth of just eleven centimeters, which differ in their morphology from the more conical craters of the pockmarks.

Schneider von Deimling works in the Kiel Marine Geophysics and Hydroacoustics working group at the Institute of Geosciences and the Kiel Marine Science (KMS) priority research area at Kiel University, and is vice chairman of the German Hydrographic Society (DHyG). As an expert in seafloor mapping, methane gas seepage and seafloor pockmarks, he never believed that the depressions in the German Bight were caused by rising fluids. “We had to come up with an alternative hypothesis for the formation. This allowed us to predict where potential porpoise feeding sites are, and that is exactly where we found the pits — always close to sandeel habitats. Our extensive and multidisciplinary data analysis now provides a conclusive explanation for our harbor porpoise pits hypothesis.”

An interdisciplinary approach leads to the harbor porpoise pits hypothesis

The key to the new findings was an interdisciplinary approach that brought together geological studies, geophysical sonar measurements, vertebrate behavior and feeding biology, satellite evaluation, and oceanographic analysis. By precisely analyzing millions of echosoundings collected by German research vessels, the researchers were able to locate the unusual pits. “Using special echosounding methods, we can now measure the seafloor with centimeter precision and thus find the shallow pits. We can also look into the seafloor and see, for example, whether there is free methane gas,” explains AWI researcher Dr Jasper Hoffmann.

Analyzing the data, collected by research vessels over thousands of nautical miles, was a mammoth task. “With modern methods, such structures can be automatically detected and characterized in acoustic data sets and automatically analyzed in large data sets,” says Dr. Jacob Geersen, co-author of the study.

From the North Sea into the world: results with far-reaching effects

The research team currently believes that the initial feeding pits serve as a nucleus for scouring and eventually develop into larger pits. This finding also has global implications. The scouring of sediments by vertebrates in the ocean could modulate the seafloor on a global scale and influence benthic ecosystems. In the study area alone, pits cover nine percent of the seafloor. Initial volume estimates indicate that 773369 tons of sediment have been deposited over an area of 1581 km². This is roughly equivalent to the weight of half a million cars. “Our results have far-reaching implications from a geological and biological perspective. They can help to assess the ecological risks associated with the expansion of renewable energies in the offshore sector and thus improve marine environmental protection,” concludes Schneider von Deimling.

Quasar light reveals clues about the large-scale structure of the universe as it shines through enormous clouds of neutral hydrogen gas formed shortly after the Big Bang on the scale of 20 million light years across or more.

Using quasar light data, the National Science Foundation (NSF)-funded Frontera supercomputer at the Texas Advanced Computing Center (TACC) helped astronomers develop PRIYA, the largest suite of hydrodynamic simulations yet made for simulating large-scale structure in the universe.

“We’ve created a new simulation model to compare data that exists at the real universe,” said Simeon Bird, an assistant professor in astronomy at the University of California, Riverside.

Bird and colleagues developed PRIYA, which takes optical light data from the Extended Baryon Oscillation Spectroscopic Survey (eBOSS) of the Sloan Digital Sky Survey (SDSS). He and colleagues published their work announcing PRIYA October 2023 in the Journal of Cosmology and Astroparticle Physics (JCAP).

“We compare eBOSS data to a variety of simulation models with different cosmological parameters and different initial conditions to the universe, such as different matter densities,” Bird explained. “You find the one that works best and how far away from that one you can go without breaking the reasonable agreement between the data and simulations. This knowledge tells us how much matter there is in the universe, or how much structure there is in the universe.”

The PRIYA simulation suite is connected to large-scale cosmological simulations also co-developed by Bird, called ASTRID, which is used to study galaxy formation, the coalescence of supermassive black holes, and the re-ionization period early in the history of the universe. PRIYA goes a step further. It takes the galaxy information and the black hole formation rules found in ASTRID and changes the initial conditions.

“With these rules, we can we take the model that we developed that matches galaxies and black holes, and then we change the initial conditions and compare it to the Lyman-𝛼 forest data from eBOSS of the neutral hydrogen gas,” Bird said.

The ‘Lyman-𝛼 forest’ gets its name from the ‘forest’ of closely packed absorption lines on a graph of the quasar spectrum resulting from electron transitions between energy levels in atoms of neutral hydrogen. The ‘forest’ indicates the distribution, density, and temperature of enormous intergalactic neutral hydrogen clouds. What’s more, the lumpiness of the gas indicates the presence of dark matter, a hypothetical substance that cannot be seen yet is evident by its observed tug on galaxies.

PRIYA simulations have been used to refine cosmological parameters in work submitted to JCAP September 2023 and authored by Simeon Bird and his UC Riverside colleagues, M.A. Fernandez and Ming-Feng Ho.

Previous analysis of the neutrino mass parameters did not agree with data from the Cosmic Microwave Background radiation (CMB), described as the afterglow of the Big Bang. Astronomers use CMB data from the Plank space observatory to place tight constraints on the mass of neutrinos. Neutrinos are the most abundant particle in the universe, so pinpointing their mass value is important for cosmological models of large-scale structure in the universe.

“We made a new analysis with simulations that were a lot larger and better designed than anything before. The earlier discrepancies with the Planck CMB data disappeared, and were replaced with another tension, similar to what is seen in other low redshift large-scale structure measurements,” Bird said. “The main result of the study is to confirm the σ8 tension between CMB measurements and weak lensing exists out to redshift 2, ten billion years ago.”

One well-constrained parameter from the PRIYA study is on σ8, which is the amount of neutral hydrogen gas structures on a scale of 8 megaparsecs, or 2.6 million light years. This indicates the number of clumps of dark matter that are floating around there,” Bird said.

Another parameter constrained was ns, the scalar spectral index. It is connected to how the clumsiness of dark matter varies with the size of the region analyzed. It indicates how fast the universe was expanding just moments after the Big Bang.

“The scalar spectral index sets up how the universe behaves right at the beginning. The whole idea of PRIYA is to work out the initial conditions of the universe, and how the high energy physics of the universe behaves,” Bird said.

Supercomputers were needed for the PRIYA simulations, Bird explained, simply because they were so big.

“The memory requirements for PRIYA simulations are so big you cannot put them on anything other than a supercomputer,” Bird said.

TACC awarded Bird a Leadership Resource Allocation on the Frontera supercomputer. Additionally, analysis computations were performed using the resources of the UC Riverside High Performance Computer Cluster.

The PRIYA simulations on Frontera are some of the largest cosmological simulations yet made, needing over 100,000 core-hours to simulate a system of 3072^3 (about 29 billion) particles in a ‘box’ 120 megaparsecs on edge, or about 3.91 million light years across. PRIYA simulations consumed over 600,000 node hours on Frontera.

“Frontera was very important to the research because the supercomputer needed to be big enough that we could run one of these simulations fairly easily, and we needed to run a lot of them. Without something like Frontera, we wouldn’t be able to solve them. It’s not that it would take a long time — they just they wouldn’t be able to run at all,” Bird said.

In addition, TACC’s Ranch system provided long-term storage for PRIYA simulation data.

“Ranch is important, because now we can reuse PRIYA for other projects. This could double or triple our science impact,” Bird said. “

“Our appetite for more compute power is insatiable,” Bird concluded. “It’s crazy that we’re sitting here on this little planet observing most of the universe.”

Researchers at iDiv looked at long-term trends of land-based insects, such as beetles, moths, and grasshoppers, and found that decreases in the number of the formerly most common species have contributed most to local insect declines. Common or abundant insect species are those species that are locally found in the highest numbers, but which species these are differ among locations. The study’s findings challenge the idea that changes in insect biodiversity result from rarer species disappearing.

The study follows the recent sounding of alarm bells about insect loss, as researchers note dramatic declines in the total number of insects in many parts of the world. However, little is known about the general trends among locally rare and abundant species over long periods. “It was obvious this needed exploring,” says Roel van Klink, lead author of the study and senior scientist at iDiv and MLU. “We had to know whether observations about declines in total abundances of insects differed among common and rare species, and how this translated into changes in the overall insect diversity.”

More common species are losing out

Van Klink and colleagues set out to better understand trends in insect numbers by diving into past studies. They compiled a database on insect communities using data collected over periods between 9 and 64 years from 106 studies. For example, one Dutch study on ground beetles was started in 1959 and continues today.

With this updated database, the researchers confirmed that despite variation among the data, on the whole, land-based insects from these long-term surveys are declining by 1.5% each year. To better understand this pattern, they compared the trends of species in different abundance categories and found that species that were the most abundant at the start of the time series showed the strongest average decline — around 8% annually — while rarer species declined less.

Importantly, the losses of previously dominant species were not compensated for by rises in other species, which has far-reaching implications: Abundant species are a staple food for birds and other insect-eating animals, making them essential for ecosystems. “Food webs must already be rewiring substantially in response to the decline of the most common species,” explains van Klink. “These species are super important for all kinds of other organisms and for the overall functioning of the ecosystem.”

Winners and Losers

The analysis clearly shows that the formerly abundant species are consistently losing the most individuals compared to the less abundant insect species. However, less abundant and rare species are also taking losses, driving declines in local species numbers. The study found a modest decrease in the overall number of species of just under 0.3% annually. This decline indicates that in addition to significant losses of common species, some rare species are going locally extinct.

Coming out on top are new arrivals who managed to successfully establish themselves. Most of these new arrivals stay locally rare and replace other formerly rare insects, but occasionally they become very abundant. The invasive Asian Ladybeetle (Harmonia axyridis), which is now common throughout Europe, the Americas and South Africa, is one such example.

According to the paper’s authors, further research is necessary to determine the underlying causes of these trends. Although this study did not explicitly investigate possible causes, the declines are likely linked to recent human-related impacts, such as climate change and urbanisation, which are considered major drivers of biodiversity loss. “Insects seem to be taking a heavier hit than many other species as humans continue to dominate the planet,” explains Professor Jonathan Chase, senior author of the study and professor at iDiv and MLU. “Other studies, including those our team has worked on, have not found such diversity declines at local scales from many other groups of animals and plants.”

While the study’s results are striking, these trends are strongly biased to data on insect communities in Europe and North America. As such, they should not be interpreted as a global phenomenon. Chase adds: “The patterns we observed might be a best-case scenario for quantifying the real impact of people on insects,” referring to what scientists have called the lifeboat effect. “These declines were observed in long-term data from areas that have remained largely intact, sort of like a lifeboat, rather than in areas where massive conversion of natural areas into human-dominated landscapes has occurred, such as malls and parking lots.”

Today, in the journal Nature, a research team led by scientists at Columbia’s Zuckerman Institute describes a previously undetected mechanism in mice — starring the genetic molecule RNA — that could explain how each sensory cell, or neuron, in mammalian noses becomes tailored to detect a specific odor chemical.

For example, there are sensory neurons in our noses that bear receptors uniquely tuned to detect ethyl vanillin, the main odorant in vanilla, and other cells with receptors for limonene, lemon’s signature odorant.

“How sensory cells in the nose make their receptor choices has been one of the most vexing mysteries about olfaction,” said Stavros Lomvardas, PhD, a Roy and Diana Vagelos Professor and Chair of Biochemistry and Molecular Biophysics and Herbert and Florence Irving Professor of Neuroscience at Columbia’s Zuckerman Institute and the Vagelos College of Physicians and Surgeons, and corresponding author on the paper. “Now, the story behind our sense of smell, or olfaction, is becoming clearer, and also more dramatic.”

The sense-refining drama he is referring to unfolds entirely within the minuscule confines of each olfactory neuron’s nucleus, where the cell’s chromosomes and genes reside. There, in a Squid Games-style, winner-takes-all competition, a developing cell’s myriad olfactory receptor genes vie with each other in a process that winnow them down, in stages, first to handful of finalists and then to a single winner. The prevailing gene is the one that determines the cell’s odorant sensitivity. In their study, Dr. Lomvardas and his team uncover details of the final stage of this process when the winner emerges from the finalist genes.

“It’s basically a battle between a 1000 contenders,” said Ariel Pourmorady, the paper’s first author and an M.D.-Ph.D. candidate at the Zuckerman Institute in the Lomvardas lab.

The action is exceedingly complex and involves a dizzying cast of molecular characters. Playing roles that either dial up or down each gene’s ability to produce olfactory receptors are a variety of gene-regulating molecules. By gathering into various alliances within the genome, these molecular players help turn specific genes on or off.

Also in the fray is another set of molecular hubs that reshape portions of the genome in ways that favor specific receptor genes. When his team first observed these in the genome in 2014, Dr. Lomvardas dubbed them “Greek Islands” because they reminded him of islands in the Aegean Sea.

“It turns out that the genome has a certain spatial organization in the nucleus and changes in this structure are pivotal when it comes to which genes are expressed into proteins, like olfactory receptors,” said Pourmorady. “We are learning just how important this process is within maturing olfactory cells.”

In their new Nature paper, the researchers summon a trove of data from mouse studies pointing toward RNA as the linchpin molecule in the olfactory system’s gene-choosing mechanism. RNA is most known as the go-between molecule that translates the genetic code embodied in DNA into protein molecules with specific cellular jobs, like detecting odorants. Using sophisticated techniques for analyzing changes in genome structure as cells mature, however, the researchers say their evidence points to a pivotal second role for the RNA.

“It looks like the RNA the cell makes during gene expression also is altering the genome’s architecture in ways that bolster the expression of one olfactory receptor gene while also shutting down all the others,” Pourmorady said.

Big gaps in this genome-controlling story remain, but the researchers say the outline

is becoming more defined. It starts with maturing olfactory cells, which initially express many receptor genes at those genomic hubs where gene-regulating molecules and complexes, including Greek Islands, converge.

Then the RNA winnows the contending olfactory-receptor genes down to one. The particular hub in each cell where the molecular stars align to produce the highest amount of RNA wins the competition. At this hub, receptor-gene expression soars. But, like a slinky saboteur, RNA from that same hub may wind its way to all the other hubs. In those locations, the RNA causes shape changes in the genome that shut down gene expression. The result is a nose’s worth of mature olfactory neurons, each of which bears on its surface only one odorant receptor.

“We are reaching the edge of science fiction when it comes to the molecular and genomic details we now can observe inside a single cell’s nucleus,” said Dr. Lomvardas. “We need to keep going back in to figure out the rest of this olfaction puzzle.”