But surprising new research published in Nature is adding a new, early chapter to the evolutionary story of gills.

“Our work suggests that the early, simplified gills of our worm-like ancestors played an important role in ion regulation. And that role might have originated as early as the very inception of gills, well before they played any role in breathing,” says Dr. Michael Sackville, a zoologist who led the study while with the University of British Columbia (UBC).

“This really does flip the script on our understanding of how gills and gill function evolved.”

The evolution of gills and lungs has fascinated biologists, including Darwin, for more than 100 years. Prior to this study, gills were thought to be first used for breathing and ion regulation near the very beginning of vertebrate life. In this traditional timeline, these two functions shifted from the skin to the gills in tandem, helping vertebrates transition from small, worm-like creatures to larger, active fishes. This transition from “small and wormy” to “big and fishy” is an iconic event in vertebrate evolution.

The study traced the evolutionary journey of gills by comparing three animals that are alive today, but belong to different lineages: lampreys, which are vertebrates, and amphioxus and acorn worms, which are close relatives of vertebrates. The researchers assumed that any gill functions shared between the animals were inherited from a common ancestor, which is believed to be when simple gills first appeared well over 500 million years ago.

“We found that gills were used for breathing in only our vertebrate representative, and only with increasing body size and activity,” says Dr. Colin Brauner, a UBC zoologist and senior author on the paper.

“But we found ion regulating cells in the gills of all three of our animals. This allowed us to trace the origin of ion regulation at gills all the way back to early deuterostome animals, when very simple gill structures are thought to have first evolved. The finding supports the classic story that gills were first used for breathing in early vertebrates, but adds an exciting new, earlier chapter to the story, clearly worthy of further study.”

The study was conducted in collaboration with researchers at the University of Montreal and Cambridge University, and funded by the Natural Sciences and Engineering Council of Canada and Royal Society.

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Last year, a team led by Jill Banfield discovered DNA structures within a methane-consuming microbe called Methanoperedens that appear to supercharge the organism’s metabolic rate. They named the genetic elements “Borgs” because the DNA within them contains genes assimilated from many organisms. In a study published today as the cover item in Nature, the researchers describe the curious collection of genes within Borgs and begin to investigate the role these DNA packages play in environmental processes, such as carbon cycling.

First contact

Methanoperedens are a type of archaea (unicellular organisms that resemble bacteria but represent a distinct branch of life) that break down methane (CH₄) in soils, groundwater, and the atmosphere to support cellular metabolism. Methanoperedens and other methane-consuming microbes live in diverse ecosystems around the world but are believed to be less common than microbes that use photosynthesis, oxygen, or fermentation for energy. Yet they play an outsized role in Earth system processes by removing methane — the most potent greenhouse gas — from the atmosphere. Methane traps 30 times more heat than carbon dioxide and is estimated to account for about 30 percent of human-driven global warming. The gas is emitted naturally through geological processes and by methane-generating archaea; however, industrial processes are releasing stored methane back into the atmosphere in worrying quantities.

Banfield, a faculty scientist at Lawrence Berkeley National Laboratory (Berkeley Lab) and professor of Earth & Planetary Science and Environmental Science, Policy & Management at UC Berkeley, studies how microbial activities shape large-scale environmental processes and how, in turn, environmental fluctuations alter the planet’s microbiomes. As part of this work, she and her colleagues regularly sample microbes in different habitats to see what interesting genes microbes are using for survival, and how these genes might affect global cycles of key elements, such as carbon, nitrogen, and sulfur. The team looks at the genomes within cells as well as the portable packets of DNA known as extra-chromosomal elements (ECEs) that transfer genes between bacteria, archaea, and viruses. These elements allow microbes to quickly gain beneficial genes from their neighbors, including those that are only distantly related.

While studying Methanoperedens sampled from seasonal wetland pool soil in California, the scientists found evidence of an entirely new type of ECE. Unlike the circular strands of DNA that make up most plasmids, the most well-known type of extra-chromosomal element, the new ECEs are linear and very long — up to one-third the length of the entire Methanoperedens genome. After analyzing additional samples from underground soil, aquifers, and riverbeds in California and Colorado that contain methane-consuming archaea, the team uncovered a total of 19 distinct ECEs they dubbed Borgs. Using advanced genome analysis tools, the scientists determined that many of the sequences within the Borgs are similar to the methane-metabolizing genes within the actual Methanoperedens genome. Some of the Borgs even encode all the necessary cellular machinery to eat methane on their own, so long as they are inside a cell that can express the genes.

“Imagine a single cell that has the ability to consume methane. Now you add genetic elements within that cell that can consume methane in parallel and also add genetic elements that give the cell higher capacity. It basically creates a condition for methane consumption on steroids, if you will,” explained co-author Kenneth Williams, a senior scientist and Banfield’s colleague in Berkeley Lab’s Earth and Environmental Sciences Area. Williams led research at the Rifle, Colorado site where the best characterized Borg was recovered, and is also chief field scientist of a research site on the East River, near Crested Butte, Colorado, where some of Banfield’s current sampling takes place.

The East River field site is part of the Department of Energy’s Watershed Function Scientific Focus Area, a multidisciplinary research project led by Berkeley Lab that aims to link microbiology and biochemistry with hydrology and climate science. “Our expertise is bringing together what are often thought of and treated as completely disparate fields of inquiry — big science that links everything from genes all the way up to watershed and atmospheric processes.”

Resistance is futile a disadvantage

Banfield and her fellow researchers at UC Berkeley’s Innovative Genomics Institute, including co-author and longtime collaborator Jennifer Doudna, hypothesize that the Borgs could be residual fragments of entire microbes that were engulfed by Methanoperedens to aid metabolism, similar to how plant cells harnessed formerly free-living photosynthetic microbes to gain what we now call chloroplasts, and how an ancient eukaryotic cell consumed the ancestors of today’s mitochondria. Based on the similarities in sequences, the engulfed cell could have been a relative of Methanoperedens, but the overall diversity of genes found in the Borgs indicates that these DNA packages were assimilated from a wide range of organisms.

No matter the origin, it is clear that Borgs have existed alongside these archaea, shuttling genes back and forth, for a very long time.

Notably, some Methanoperedens were found with no Borgs. And, in addition to recognizable genes, the Borgs also contain unique genes encoding other metabolic proteins, membrane proteins, and extracellular proteins almost certainly involved in electron conduction required for energy generation, as well as other proteins that have unknown effects on their hosts. Until the scientists can culture Methanoperedens in a laboratory environment, they won’t know for sure what capabilities the different Borgs confer, why some microbes use them, and why others don’t.

One likely explanation is that Borgs act as a storage locker for metabolic genes that are only needed at certain times. Ongoing methane monitoring research has shown that methane concentrations can vary significantly throughout the year, usually peaking in the fall and dropping to the lowest levels in early spring. The Borgs therefore provide a competitive advantage to methane-eating microbes like Methanoperedens during periods of abundancewhen there is more methane than their native cellular machinery can break down.

Plasmids are known to serve a similar purpose, quickly spreading genes for resistance to toxic molecules (like heavy metals and antibiotics) when the toxins are present in high enough concentrations to exert evolutionary pressure.

“There is evidence that different types of Borgs sometimes coexist in the same host Methanopreredens cell. This opens the possibility that Borgs could be spreading genes across lineages,” said Banfield.

Boldly exploring the (microbial) universe

Since posting their article as a pre-print last year, the team has begun follow-up work to better understand how Borgs may affect biological and geological processes. Some researchers are combing through data sets of genetic material from other microorganisms, looking for evidence that Borgs exist in association with other species.

While her colleagues are using lab-based methods, co-author Susan Mullen, a graduate student in Banfield’s lab, will be getting her feet wet with some very picturesque field work. She recently started a project to sample microbes from the floodplains of the East River throughout the year to assess how seasonal changes in Borg abundance and other microbes known to be involved in methane cycling correlate to seasonal fluxes of methane.

According to the authors, years down the line, carefully cultured microbes chock full of Borgs could be used to reduce methane and curb global warming. It’s all to benefit the collective — life on Earth.

Opiates cause addiction, new substances do not

They are a blessing for patients suffering from severe pain, but they also have serious side effects: Opioids, and above all morphine, can cause nausea, dizziness and constipation and can also often cause slowed breathing that can even result in respiratory failure. In addition, opiates are addictive — a high percentage of the drug problem in the USA is caused by pain medication, for example.

In order to tackle the unwanted medical and social effects of opioids, researchers all over the world are searching for alternative analgesics. Prof. Dr. Peter Gmeiner, Chair of Pharmaceutical Chemistry is one of these researchers. “We are focusing particularly on the molecular structures of the receptors that dock onto the pharmaceutical substances,” says Gmeiner. “It is only when we understand these on the atomic level that we can develop effective and safe active substances.” Collaborating with an international team of researchers, Prof. Gmeiner discovered an active substance in 2016 that bonds to known opioid receptors and that offers the same level of pain relief as morphine, even though it has no chemical similarity to opiates.

New approach: Adrenaline receptors instead of opioid receptors

Peter Gmeiner is currently following a lead that seems very promising: “Many non-opioid receptors are involved in pain processing, but only a small number of these alternatives have as yet been validated for use in therapies,” he explains. Gmeiner and a team of researchers from Erlangen, China, Canada and the USA have now turned their attention to a new receptor that is responsible for binding adrenaline — the alpha 2A adrenergic receptor. There are already some analgesics that target this receptor such as brimonidine, clonidine and dexmedetomidine. Gmeiner: “Dexmedetomidine relieves pain, but has a strong sedative effect, which means its use is restricted to intensive care in hospital settings and is not suitable for broader patient groups.”

The aim of the research consortium is to find a chemical compound that activates the receptor in the central nervous system without a sedative effect. In a virtual library of more than 300 million different and easily accessible molecules, the researchers looked for compounds that physically match the receptor but are not chemically related to known medication. After a series of complex virtual docking simulations, around 50 molecules were selected for synthesis and testing and two of these fulfilled the desired criteria. They had good bonding characteristics, activated only certain protein sub-types and thus a very selective set of cellular signal pathways, whereas dexmedetomidine responds to a significantly wider range of proteins.

Pain relief without sedation in animal models

By further optimizing the identified molecules, for which extremely high-resolution cryo-electron microscopic imaging was used, the researchers were able to synthesize agonists that produced high concentrations in the brain and reduced the sensation of pain effectively in investigations with animal models. “Various tests confirmed that docking on the receptor was responsible for the analgesic effect,” explains Gmeiner. “We are particularly pleased about the fact that none of the new compounds caused sedation, even at considerably higher doses than those that would be required for pain relief.”

The successful separation of analgesic properties and sedation is a milestone in the development of non-opioid pain medication, especially as the newly-identified agonists are comparatively easy to manufacture and administer orally to patients. However, Prof. Gmeiner has to dampen any hopes of rapid widespread use in human medicine: “We are currently still talking about basic research. The development of medication is subject to strict controls and in addition to significant amounts of funding, it takes a long time. However, these results still make us very optimistic.”

The starting point was data from 58 randomised controlled trials (RCTs) of over 10,000 patients worldwide with chronic low back pain. First, the data relevant to the topic were filtered out of the original manuscripts and then evaluated in groups. When evaluating these data, the researchers examined on the one hand whether and to what extent standard forms of treatment and individualised treatment differ in terms of the result. “Individualised” means that there is some type of personal coaching, where therapists specifically target the potentials and requirements of each patient and decide together with them how their therapy should look.

The study concluded that individualised treatment for chronic back pain led to a significantly increased effect in comparison to standard exercise therapies. The success rate in pain relief was 38 percent higher than with standard treatment. “The higher effort required for individual treatment is worthwhile because patients benefit to an extent that is clinically important,” says lead author Dr Johannes Fleckenstein from the Institute of Sport Sciences at Goethe University Frankfurt.

However, the study went even further. The research team in Frankfurt compared a third group of treatment methods alongside the standard and individualised ones. In this group, individualised training sessions were combined with cognitive behavioural therapy (CBT). This procedure — a type of talk therapy — is based on the assumption that negative thoughts and behaviours surrounding pain tend to exacerbate it. Through CBT, pain patients learn to change the way they handle it. They stop being afraid to move or are taught tactics for coping with pain. This makes them realise that they are by no means helpless. But what does the psychotherapeutic support through CBT actually contribute to the success of the treatment? Analysis of the data revealed the following: When an individualised approach and CBT were combined, the success rate in terms of pain relief was an impressive 84 percent higher than with standard treatment. The combined therapy, also called multimodal therapy, thus led to the best result by far.

Fleckenstein sees in the study “an urgent appeal to public health policy” to promote combined therapies both in terms of patient care and remuneration. “Compared to other countries, such as the USA, we are in a relatively good position in Germany. For example, we issue less prescriptions for strong narcotic drugs such as opiates. But the number of unnecessary X-rays, which, by the way, can also contribute to pain chronicity, and inaccurate surgical indications is still very high.” This is also due, according to Fleckenstein, to economic incentives, that is, the relatively high remuneration for such interventions. The situation is different for organisations working in the area of pain therapy, he says. Although these are not unprofitable, they are not a cash cow for investors either. In his view, it is important here to improve the economic conditions. After all, pain therapy saves a lot of money in the long run as far as health economics are concerned, whereas tablets and operations rarely lead to medium and long-term pain relief.

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It means spending hours in the field listening for calls. Or leaving a recording device in the field to catch what sounds are made — only to spend hours later listening to that audio. Then, repeating this process until there’s enough information to start making population estimates.

But a new model developed by researchers at the University of Georgia aims to streamline this process. By using artificial intelligence to analyze terabytes of recordings for quail calls, the process gives wildlife managers the ability to gather the data they need in a matter of minutes.

“The model is very accurate, picking up between 80% and 100% of all calls even in the noisiest recordings. So, you could take a recording, put it through our model and it will tell you how many quail calls that the recorder heard,” said James Martin, an associate professor at the UGA Warnell School of Forestry and Natural Resources who has been working on the project, in collaboration with the Georgia Department of Natural Resources, for about five years. “This new model allows you to analyze terabytes of data in seconds, and what that will allow us to do is scale up monitoring, so you can literally put hundreds of these devices out and cover a lot more area and do so with a lot less effort than in the past.”

The software represents about five years of work by Martin, postdoctoral researcher Victoria Nolan and numerous key contributors who have worked with a code writer to create the model. It’s also part of a larger shift taking place in the field of wildlife research, where computer algorithms are now assisting with work that once took humans thousands of hours to complete.

Increasingly, computers are getting smarter at, for example, identifying specific noises or certain traits in photos and sound recordings. For researchers such as Martin, it means hours once spent on tasks such as listening to audio or looking at game camera images can now be done by a computer, freeing up valuable time to focus on other aspects of a project.

The new tool can also be a valuable resource for state and federal agencies looking for information on their quail populations, but with limited funds to spend on any one project. “So, I think this is something states might jump on as far as replacing their current monitoring with acoustic recording devices,” added Martin.

The software’s success was recently documented by the Journal of Remote Sensing in Ecology and Conservation.

As the software gets more use and is exposed to sounds from new geographic areas, Martin said, it gets even “smarter.” As it is, quail offer several different kinds of calls. But when the software is exposed to a variety of sounds that aren’t quail, he said, it’s better able to distinguish the correct calls from the ambient noises of the grasses and trees around them.

Over time, the software will grow more discerning.

“So that’s why you have to keep giving it training data, and when you move geographies, you encounter new sounds that you didn’t train the model for,” he added. “It’s always about adaption.”

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Materials provided by University of Georgia. Original written by Kristen Morales. Note: Content may be edited for style and length.