“When I first saw a video of the cockatoos opening the bins I thought it was such an interesting and unique behavior and I knew we needed to look into it,” says lead author Barbara Klump, a behavioral ecologist at the Max Planck Institute of Animal Behavior.

The cockatoos’ motivation is food waste. “They really like bread,” she says. “Once one gets a bin open all the cockatoos in the vicinity will come and try to get something nice to eat.”

The birds typically pry the bins open with their beaks and then maneuver themselves onto a small rim and flip the lid open. It’s a community affair. “We could actually show that this is a cultural trait,” says Klump. “The cockatoos learn the behavior from observing other cockatoos and within each group they sort of have their own special technique, so across a wide geographic range the techniques are more dissimilar.”

Human residents trying to keep the cockatoos out can’t simply secure the bin lids completely closed because the lids need to open when tipped by an automated arm on the garbage truck. A survey given by the researchers found that people put bricks and stones on their bin lids, strap water bottles to the top, rig ropes to prevent the lid from flipping, use sticks to block the hinges, and switch tactics once the cockatoos figure them out. “There are even commercially available cockatoo locks for bins,” says Klump.

“It’s not just a social learning on the cockatoo side, but it’s also social learning on the human side,” she says. “People come up with new protection methods on their own, but a lot of people actually learn it from their neighbors or people on their street, so they get their inspiration from someone else.”

Klump won’t say who she expects to win the race for control of the bins, but she and her colleagues plan to look at how the cockatoos’ behavior varies from season to season.

Klump expects we will see more of these kinds of human-wildlife interactions in the future. “As cities expand, we will have more interactions with wildlife,” she says. “I’m hoping that there will be a better understanding and more tolerance for the animals that we share our lives with.”

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In a new study, researchers led by Serge Y. Fuchs of the School of Veterinary Medicine, have uncovered a detailed mechanism by which tumors can skirt both the immune system and cancer therapies that leverage its power, such as genetically engineered CAR T cells.

Their investigation, published in the journal Cell Metabolism, revealed how tumor-derived factors stimulate trogocytosis — a process derived from the Greek word trogo, which means “to gnaw” or “to chew.” When T cells interact with cancer cells, they can sometimes “nibble” a piece of the cancer cell membrane. When that membrane segment includes an antigen, a molecule specific to the cancer, the T cells may then begin expressing that antigen on their own cell surface, making it appear to other T cells like a cancer cell.

Trogocytosis can affect a patient’s own T cells and those modified to become CAR T cells, an approach in which a patient’s T cells are genetically engineered to specifically target cancer cells, grown in a lab, and then delivered back to the patient.

“Trogocytosis can lead to three different things, and all three are bad for a person with a tumor,” says Fuchs, the senior author on the work. “First of all, the tumor cell did not get killed and has lost an antigen, which may mean that even if another, better equipped T cell comes along, it will not recognize it, giving cancer cells a window of opportunity to grow unchecked. The second problem is, for reasons we still don’t understand, once a T cell takes a piece of the tumor cell membrane, it becomes much less active. And the third problem is very ironic. Because now, a T cell that displays tumor antigen, this ‘sheep in wolf’s clothing,’ may then become victim to ‘fratricide,’ killed by another T cell.” Overall, the result is a decline in killer T cell numbers and activity and a bump in opportunities for the cancer cells to escape detection and grow.

“What we see is that only a small number of cells undergo trogocytosis and then they disappear quickly because they’re killed. So we’re studying a vanishing act. It is hard to do — very expensive and very tedious — but it appears to be very important,” says Fuchs.

With a longstanding interest in how receptors on the surface of immune cells guide anti-cancer immunity, Fuchs and colleagues have made a variety of discoveries showing how tumors can manipulate T cells to escape being targeted and killed.

A particular area of interest is what’s known as tumor-derived factors, or the concoction of proteins, lipids, and other materials that cancer cells secrete into the body. In the current study, the Penn researchers found that collecting these secretions and exposing the resulting solution to T cells hampered the cells’ ability to do their cancer-fighting job.

“Just exposing them to this tumor-conditioned media caused them to kill fewer cancer cells, trogocytose more, and get killed more,” Fuchs says.

Trogocytosis was previously believed to have something to do with cancer’s ability to hinder anti-cancer immunity, but the Penn-led team pinned down the mechanism, showing that T cells exposed to tumor-derived factors experienced a notable decline in levels of the gene CH25H. This gene is known to be involved in altering cell’s lipid membranes and can inhibit two cell membranes from fusing together — an essential process for trogocytosis to occur. When they added back a metabolite produced by CH25H, they could block trogocytosis.

“That was an ‘aha’ moment,” Fuchs says.

Further characterization of the pathway helped the team identify another player, the gene ATF3, which opposes the activity of CH25H. Eliminating AFT3 prevented trogocytosis from occurring and restored the ability of T cells to kill tumor cells.

Not only do the new insights suggest novel targets for anti-cancer therapies, but they may have immediate significance for CAR T therapy. Since trogocytosis could impair the effectiveness of the engineered T cells delivered in CAR T, the researchers surmised that blocking this could improve CAR T performance. “We figured, why don’t we use what is cleverly known as an ‘armored CAR’ approach, and co-express CH25H in the CAR T,” Fuchs says. “This turned out to be more efficient than the old CAR T cells.”

Indeed, delivering the CAR T cells adorned with CH25H improved the survival of mice with cancer compared to the unarmored CAR T cells.

Though only a small percentage of T cells are involved in trogocytosis, Fuchs says it may be an underappreciated process when it comes to cancer immunity and other processes, such as those involved in autoimmunity. With future work, he and colleagues intend to explore the roles of ATF3 and CH25H and other molecules in trogocytosis. And he’s hopeful that other researchers will pick up on these lines of work, bringing the findings closer to clinical application.

“I can see this going into use in CAR T therapy quickly,” Fuchs says. “It’s ready to play.”

Serge Fuchs is the Elizabeth and William Whitney Clark Professor of Oncology at the University of Pennsylvania School of Veterinary Medicine.

Fuchs’ coauthors on the work were Penn Vet’s Zhen Lu, Noreen McBrearty, Jinyun Chen, Vivek S. Tomar, Hongru Zhang, Gianluca De Rosa, and Daniel P. Beiting; the Perelman School of Medicine’s Aiwen Tan, Aalim M. Weljie, Zhen Miao, Subin S. George, and Constantinos Koumensis; Takeda Development Center’s Allison Berger and Gurpanna Saggu; and Case Western Reserve University’s J. Alan Diehl.

The study was supported in part by the National Institutes of Health (grants CA247803, CA240814, CA165997, and CA115299).

The 10^th oocyte collection in northern white rhinos (NWR) was performed by a team of scientists and conservationists from the Leibniz Institute for Zoo and Wildlife Research (Leibniz-IZW), Ol Pejeta Conservancy, Safari Park Dvůr Králové, Kenya Wildlife Service (KWS) & Wildlife Research and Training Institute (WRTI) on July 28, 2022, at Ol Pejeta Conservancy in Kenya. The BioRescue team was able to collect 23 oocytes from Fatu, the younger of the two remaining NWR females. Oocyte collections from Najin, Fatu’s mother, were ceased in 2021 following an in-depth ethical risk assessment. The oocytes were immediately air-lifted to the Avantea laboratory in Cremona, Italy. Following maturation, 7 of the oocytes were fertilized using cryopreserved, thawed semen from the deceased NWR male Angalifu. Eventually, 5 embryos of Fatu were successfully produced and cryopreserved in liquid nitrogen.

This collection followed on from the 9^th oocyte collection held at the same location and by the same team on April 24^th. Out of 16 collected oocytes, 3 embryos were produced in the Avantea laboratory, again using the semen of Angalifu. Successful results of both procedures raised the total number of NWR embryos produced to 22 — all of them from female Fatu, with half of them sired by the deceased male Suni who was born in Safari Park Dvůr Králové, Czech Republic, and the other half sired by Angalifu who lived in San Diego Zoo Safari Park, USA.

Once the protocol to transfer the embryos to surrogate southern white rhino (SWR) female recipients is optimized, the embryos will be the foundation of a new NWR population, eventually destined to step back into their ecological role as keystone grazers in Central Africa.

To set up suitable conditions for a successful embryo transfer, the team has been carefully following the interactions of the sterilized SWR bull Owuan, who serves as the oestrus detector, with the possible surrogate females that share an enclosure with him. Once the conditions allow it, the BioRescue team will attempt to conduct an embryo transfer — first with SWR embryos to demonstrate that the whole procedure works properly before the team uses the extremely valuable NWR embryos. The team is currently considering whether adding more SWR females to the program might increase the chance of achieving the first successful embryo transfer.

Thomas Hildebrandt, BioRescue project leader and head of Department of Reproduction Management at Leibniz-IZW: “In 2019, one day before our worldwide first oocyte collection in NWR I said — tomorrow we will change the world. Today I can say, we did: The 5 new NWR embryos created in one set of procedures are a new record in our mission to save the NWR from the brink of extinction. In total, we managed to produce and cryopreserve 22 pure NWR embryos from 158 oocytes collected during 10 collections: 148 from Fatu and 10 from Nájin. Our next aim is to successfully produce viable offspring by inventing and using new scientific embryo transfer methods and techniques. The ground breaking scientific work we are establishing here will lay the groundwork for future conservation rescue initiatives.”

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The discovery, published in Nature, describes the skeletal remains of a young adult found in a cave in Borneo, who had part of the left lower leg and left foot amputated, probably as a child, at least 31,000 years ago. The person survived the surgical procedure, living for at least another six to nine years.

The find presents a remarkable feat. It is notoriously difficult to prevent infections in surgical amputations, even to this day. Yet 30,000 years ago a community was able to successfully navigate veins, arteries, nerves, and tissue, and keep the wound clean so that it healed successfully. The individual went on the live into adulthood where an unknown cause eventually led to their death.

Bioarchaeologist and an expert in ancient skeletons, Dr Melandri Vlok, at University of Sydney said the find is “incredibly exciting and unexpected.”

“The discovery implies that at least some modern human foraging groups in tropical Asia had developed sophisticated medical knowledge and skills long before the Neolithic farming transition,” said Dr Vlok, who is co-lead author of the paper and a postdoctoral research associate in Sydney Southeast Asia Centre.

Studying bones

The skeleton of the young adult, possibly in their 20s when they died, was carefully buried within LiangTebo cave — located Borneo in East Kalimantan, in a limestone karst area that harbours some of the world’s earliest dated rock art.

The bones were uncovered by archaeologists from Griffith University and University of Western Australia (UWA) just days before borders closed for the COVID-19 pandemic in March 2020. The team was led by Professor Maxime Aubert and Dr Tim Maloney (Griffith University), Dr India Dilkes-Hall (UWA) and Mr Andika Priyatno from the Kalimantan Timur Cultural Heritage Preservation Centre.

The University of Sydney’s Dr Vlok was invited to study the bones when they were brought back to Australia.

“No one told me they had not found the left foot in the grave,” Dr Vlok said. “They kept it hidden from me to see what I would find.”

As Dr Vlok laid the bones out, the left leg looked withered, and was the size of a child’s, but the individual was an adult. She unwrapped the part of the leg that contained the stump and noticed the cut was clean, well healed and had no evidence of any infection. “The chances the amputation was an accident was so infinitely small,” Dr Vlok said. “The only conclusion was this was stone age surgery.”

Dr Vlok ran to the office to tell her research colleagues what she had found. “I told them I thought it looked like a surgical amputation,” she said. “It wasn’t until then that they said they already knew the foot was missing.” Dr Vlok had just confirmed their suspicions. The foot was never placed in the grave to begin with.

An accident

While it is not entirely clear what led to the amputation, the individual also had a very well healed neck fracture and trauma to their collar bone that may have occurred during the same event, said Dr Vlok.

“An accident, such as a rock fall may have caused the injuries, and it was clearly recognised by the community that the foot had to be taken off for the child to survive,” she said.

“It is an extremely rugged environment with steep mountains dotted with caves containing some of the oldest paintings created by our species,” said Professor Aubert.

Archaeologists including excavation lead Dr Tim Maloney had to kayak into the valley and scale the enormous cliff to get into the cave, proving just how remarkable it was for someone with only one leg to have survived in such challenging terrain.

“This unique find challenges assumptions of humanity’s capabilities in the past and is set to significantly advance our understanding of human lifeways in tropical rainforests,” said Dr Dilkes-Hall.

Nature has evolved these structures to harness the sun’s energy through photosynthesis, but these sunlight receivers don’t belong to plants. They’re found in microbes known as cyanobacteria, the evolutionary descendants of the first organisms on Earth capable of taking sunlight, water and carbon dioxide and turning them into sugars and oxygen.

Published Aug. 31 in the journal Nature, the findings immediately shed new light on microbial photosynthesis — specifically, how light energy is captured and sent to where it’s needed to power the conversion of carbon dioxide into sugars. Going forward, the insights could also help researchers remediate harmful bacteria in the environment, develop artificial photosynthetic systems for renewable energy and enlist microbes in sustainable manufacturing that starts with the raw materials of carbon dioxide and sunlight.

“There’s a lot of interest in using cyanobacteria as solar-powered factories that capture sunlight and convert it into a kind of energy that can be used to make important products,” said Cheryl Kerfeld, Hannah Distinguished Professor of structural bioengineering in the College of Natural Science. “With a blueprint like the one we’ve provided in this study, you can start thinking about tuning and optimizing the light-harvesting component of photosynthesis.”

“Once you see how something works, you have a better idea of how you can modify it and manipulate it. That’s a big advantage,” said Markus Sutter, a senior research associate in the Kerfeld Lab, which operates at MSU and Berkeley Lab in California.

The cyanobacterial antenna structures, which are called phycobilisomes, are complex collections of pigments and proteins, which assemble into relatively massive complexes.

For decades, researchers have been working to visualize the different building blocks of phycobilisomes to try to understand how they’re put together. Phycobilisomes are fragile, necessitating this piecemeal approach. Historically, researchers have been unable to get the high-resolution images of intact antennae needed to understand how they capture and conduct light energy.

Now, thanks to an international team of experts and advances in a technique known as cryo-electron microscopy, the structure of a cyanobacterial light harvesting antenna is available with nearly atomic resolution. The team included researchers from MSU, Berkeley Lab, the University of California, Berkeley and the University of South Bohemia in the Czech Republic.

“We were fortunate to be a team made up of people with complementary expertise, people who worked well together,” said Kerfeld, who is also a member of the MSU-DOE Plant Research Laboratory, which is supported by the U.S. Department of Energy. “The group had the right chemistry.”

‘A long journey full of nice surprises’

“This work is a breakthrough in the field of photosynthesis,” said Paul Sauer, a postdoctoral researcher in Professor Eva Nogales’ cryogenic electron microscopy lab at Berkeley Lab and UC Berkeley.

“The complete light-harvesting structure of a cyanobacteria’s antenna has been missing until now,” Sauer said. “Our discovery helps us understand how evolution came up with ways to turn carbon dioxide and light into oxygen and sugar in bacteria, long before any plants existed on our planet.”

Along with Kerfeld, Sauer is a corresponding author of the new article. The team documented several notable results, including finding a new phycobilisome protein and observing two new ways that the phycobilisome orients its light-capturing rods that hadn’t been resolved before.

“It’s 12 pages of discoveries,” said María Agustina Domínguez-Martín of the Nature report. As a postdoctoral researcher in the Kerfeld Lab, Domínguez-Martín initiated the study at MSU and brought it to completion at the Berkeley Lab. She is currently at the University of Cordoba in Spain as part of the Marie Sk?owdoska-Curie Postdoctoral Fellowship. “It’s been a long journey full of nice surprises.”

One surprise, for example, came in how a relatively small protein can act as a surge protector for the massive antenna. Before this work, researchers knew the phycobilisome could corral molecules called orange carotenoid proteins, or OCPs, when the phycobilisome had absorbed too much sunlight. The OCPs release the excess energy as heat, protecting a cyanobacterium’s photosynthetic system from burning up.

Until now, there’s been debate about how many OCPs the phycobilisome could bind and where those binding sites were. The new research answers these fundamental questions and offers potentially practical insights.

This kind of surge-protecting system — which is called photoprotection and has analogs in the plant world — naturally tends to be wasteful. Cyanobacteria are slow to turn their photoprotection off after it has done its job. Now, with the complete picture of how the surge protector works, researchers can design ways to engineer “smart,” less wasteful photoprotection, Kerfeld said.

And, despite helping make the planet habitable for humans and countless other organisms that need oxygen to survive, cyanobacteria have a dark side. Cyanobacteria blooms in lakes, ponds and reservoirs can produce toxins that are deadly to native ecosystems as well as humans and their pets. Having a blueprint of how the bacteria not only collect the sun’s energy, but also protect themselves from too much of it could inspire new ideas to attack harmful blooms.

Beyond the new answers and potential applications this work offers, the researchers are also excited about the new questions it raises and the research it could inspire.

“If you think of this like Legos, you can keep building up, right? The proteins and pigments are like blocks making the phycobilisome, but then that’s part of the photosystem, which is in the cell membrane, which is part of the entire cell,” Sutter said. “We’re climbing up the ladder of scale in a way. We’ve found something new on our rung, but we can’t say we’ve got the system settled.”

“We’ve answered some questions, but we’ve opened the doors on others and, to me, that’s what makes it a breakthrough,” Domínguez-Martín said. “I’m excited to see how the field develops from here.”

This work was supported by the U.S. Department of Energy Office of Science, the National Institutes of Health, the Czech Science Foundation and the European Union’s Horizon 2020 research and innovation program.