To Cure Gout, Scientists Are Bringing Back A 20-M Year-Old Gene

Gout is considered as one of the most well-represented (and oldest) diseases in human history, primarily because this "disease of kings" impacted the most affluent of any given society. Alexander the Great, Charlemagne, and King Henry VIII all suffered from this pernicious form of arthritis. Benjamin Franklin even wrote letters to "Madame Gout," pleading as to why he must withstand these "cruel sufferings."

With the dawn of modern medicine in the 19th century, scientists found an answer to Franklin’s painful inquiries. Put simply, rich diets of meats, alcohol, and sugar (common on the tables of the rich and powerful throughout history) are all high in chemical compounds known as purines, which produce uric acid when metabolized. When these uric levels climb too high, crystals can form in the liver and kidneys, leading to joint pain and kidney disease.

Today, a variety of treatments exist, including Nonsteroidal Anti-Inflammatory Drugs (NSAIDs). But a new study revived a very old strategy for treating gout—like, 20 to 29 million years old.

In this study, published in the journal Scientific Reports, scientists used the gene-editing technology CRISPR-Cas9 (also sometimes referred to as 'molecular scissors') to bring back the uricase gene, which evolved out of primates during the Neogene period. It’s likely that our distant ancestors used uric acid to turn fruit sugars into fats, which is a pretty effective survival strategy during periods of food shortage. However, without the uricase gene, what once kept early primates alive became a primary vector for gout.

"Without uricase, humans are left vulnerable," Eric Gaucher, the co-author of the study from Georgia State University, said in a press statement. "By reactivating uricase in human liver cells, we lowered uric acid and stopped the cells from turning excess fructose into triglycerides—the fats that build up in the liver."

To test this idea, Gaucher and his team first tested the restored gene function in human liver cells and found that uric acid dropped dramatically, and fructose-driven fat buildup in those cells was prevented entirely. To up the ante a bit, they tested this same method on 3D liver spheroids—essentially collections of tissues that mimic miniature organs. Uric acid levels were lowered within these systems as well.

While uric acid is the key driver behind Franklin’s "cruel sufferings," hyperuricemia (excess uric acid in the blood) can cause a variety of different diseases, including hypertension and cardiovascular disease. According to the authors, a quarter of patients with high blood pressure also have elevated uric levels, and when it comes to hypertension, that overlap jumps to a staggering 90 percent.

However, the scientists aren’t celebrating yet. Gene-editing therapies still have safety hurdles to overcome, and this particular approach will need rigorous human trials. But if the results hold, the "disease of kings" will have finally met its match.

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These Queen Ants Can Clone Ants From Other Species

Queen ants in southern Europe can produce male clones of an entirely different species — tearing up the playbook of reproductive biology and suggesting we need to rethink our understanding of species barriers.

The workers in Iberian harvester ant (Messor ibericus) colonies are all hybrids, with queens needing to mate with males from a distantly related species, Messor structor, to keep the colony functioning. But researchers found that some Iberian harvester ant populations have no M. structor colonies nearby.

"That was very, very abnormal. I mean, it was kind of a paradox," study co-author Jonathan Romiguier, an evolutionary biologist at the University of Montpellier, told Live Science. The team initially believed there was a sampling issue, but they went on to find 69 regions where this was the case.

"We had to face the facts and try to see if there is something special within Messor ibericus colonies," Romiguier said.

In setting out to resolve this paradox, Romiguier and his team found that queen Iberian harvester ants also lay eggs containing male M. structor ants, with these males ultimately fathering the workers. This discovery, published Sept. 3 in the journal Nature, is the first time any animal has been recorded producing offspring from another species as part of their normal life cycle.

"In the early stages, it was kind of a joke in the team," Romiguier said. "But the more we got results, the more it became a hypothesis and not a joke anymore."

Ants are eusocial insects, meaning their colonies form cooperative super-organisms predominantly made up of infertile females, called workers, and a small number of reproductive females, called queens. Males solely exist to fertilize queens during their mating flight and die soon after.

Queens only mate once in their lives and store the sperm from this meeting in a special organ. She then draws from this sperm stash to lay new eggs containing one of three types of offspring: queens, workers or males.

However, Iberian harvester ants mating with males of their own species can only produce new queens. This is thought to be a result of selfish queen genes, where the DNA from male M. ibericus guarantees its survival across generations by biasing larvae to produce fertile queens rather than infertile workers — known as "royal cheaters."

To avoid this, queens must use sperm from male M. structor ants to produce their workers.

This was why the presence of thriving isolated M. ibericus colonies was such a conundrum.

To find answers, the researchers first sampled 132 males from 26 Iberian harvester ant colonies to figure out whether there were M. structor males present. They found that 58 were covered in hair and 74 were hairless. A closer inspection of the nuclear genomes of a subset of these ants revealed that all hairy ones were M. ibericus and all bald ones were M. structor.

But this was not proof that the queens were laying male eggs of two different species — there could have been some hidden M. structor queens producing the odd male. So the team sequenced the mitochondrial DNA, which is passed down by the mother, of 24 of the M. structor males, and found it came from the same mother as the M. ibericus male nestmates.

"This was the detail that made me realize that 'maybe we are on to something very, very, very big,'" Romiguier said.

The team then separated 16 queens from laboratory colonies and looked at the genetic sequences of their freshly laid eggs. They found that 9 percent of their eggs contained M. structor ants. They then directly observed a single queen producing males of both species by monitoring its broods weekly over an 18-month period.

Together, all these findings show that Iberian harvester ant queens are cloning M. structor males and not passing on any of their own nuclear DNA. Researchers now need to pinpoint the exact mechanism underlying this cloning, Romiguier said, and find out at what point the maternal DNA is removed.

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Stone Age Women Buried With Tools And Weapons

Researchers discovered that some 6,000 years ago in the northern reaches of modern Latvia, a young woman died. Afterwards, a group of early humans buried her in an ancient, sacred place along a lakeshore. They carefully lowered her small teenage frame into the ground, gently placing a stone ax, 28 flint flakes, 15 blades, and a stone scraper beside her.

Stained with ochre, the stone implements were part of her last rites. This young woman remained there thousands of years, until, when archaeologists discovered her along with more than 300 others in the 20th century. The site, known as Zvejnieki cemetery, is one of Europe’s largest Stone Age cemeteries.

Research conducted at Zvejnieki has often challenged longheld assumptions about gender roles in prehistoric Europe. For instance, the young woman interred in burial 211 described above is one of several women and children buried with stone axes at the site, upending the notion that axes only belonged to Stone Age men.

Now, a new study published September 10 in the journal PLOS One again upends gender stereotypes, demonstrating that women and children were just as likely to be buried with stone tools as men. The woman in burial 211 alone was laid to rest with a staggering 45 different stone objects.

Nestled along the northern shore of Lake Burtnieks in northern Latvia, Stone Age communities used the Zvejnieki burial site for more than 5,000 years. Archeologists estimate that it was first used around 7,500 BCE, and was abandoned sometime around 2,500 BCE.

Zvejnieki remained untouched for more than 4,000 years, a veritable treasure trove of the Stone Age waiting to be discovered. Then in the 1960s, Lake Burtnieks’s northern shore was used as a gravel quarry. Latvian workers harvested rock from the small hill along the lake, eventually discovering a human skull amongst the rubble in 1964.

Archaeologists soon swooped in, and immediately noticed Stone Age graves exposed along the quarry’s walls. The quarry was closed and a team of archaeologists carried out an extensive dig between 1964 and 1978. In 2005, another large dig was conducted and lasted four years. So far, a total of 330 individuals have been found at the Zvejnieki cemetery, making it one of the largest sites of its kind in Europe.

Led by Dr. Aimée Little from the University of York’s archaeology department, the new study takes a closer look at the stone tools found at Zvejnieki. As part of the Stone Dead project, the new research demonstrates how tools played an important role in Stone Age funerary rites. While some tools seemed specifically made for gravesites, others were broken into pieces as part of intricate rituals.

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Lasker Prize Goes To Scientists Who Discovered Treatment To Cystic Fibrosis

Cystic fibrosis was once a dire, likely deadly diagnosis, destroying a patient's ability to breathe and digest food -- but a revolutionary new treatment offers reason for hope.

Last 10 September, the three scientists who developed the clinical advance were awarded America's most prestigious scientific award, taking home the Lasker prize. The top honorees are pulmonologist Michael Welsh along with researchers Jesus Gonzalez and Paul Negulescu from the US laboratory Vertex.

Their research has shed light on the causes of the disease and given rise to a new class of innovative drugs, including the flagship treatment Kaftrio -- known as Trikafta in the United States -- which are capable of stabilizing the otherwise debilitating condition.

"It's unbelievable. It's better than I ever hoped," Welsh told AFP. "You see these kids and they look healthy and they're not coughing. They're running around and playing."

"I almost can't believe it. Then they go, and they're getting married and they're having kids, and they're getting on with their lives."

That reality stands in sharp contrast to Welsh's memories from the early days of his career, when a cystic fibrosis diagnosis was a likely death sentence in childhood or adolescence.

The new award-winning treatment has been hailed as "revolutionary" by patient advocacy organizations.

It works by addressing the underlying causes of the inherited disease -- which wreaks havoc on the lungs and digestive system -- rather than its symptoms.

Some 100,000 people worldwide are estimated to suffer from cystic fibrosis, in which sticky mucus builds up in the lungs, digestive tract and other parts of the body.

After the 1989 discovery of the CFTR gene -- whose mutation was identified as the cause of the disease -- Welsh began dissecting the problem with fellow researchers.

"We thought, if we understand how CFTR works, we have a chance of fixing it," he said.

Gaining a better understanding of how the protein that the gene codes for led the pulmonologist down a path seeking how genetic mutations impaired its function.

Welsh identified two major anomalies caused by the most common mutation: a trapping of sorts of the protein within the cell, and its reduced performance.

The medical breakthrough resulted from experiments, notably some that showed how lowering temperature could help release the trapped protein.

"That meant it was not totally broken," Welsh remembered enthusiastically.

Armed with these discoveries, the American Cystic Fibrosis Foundation then approached researchers Gonzalez and Negulescu, who began studying the possibility of chemically reversing the identified malfunctions.

The notion of gene therapy -- which would aim to directly reverse the gene mutations -- had seemed on paper to be the simplest route.

But when it didn't work as hoped, patient organizations began to explore other options.

Gonzalez developed an innovative research technique using dyes that allowed for testing thousands of chemical compounds in record times.

"Without the screening, we would never have found these molecules," he said.

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Toxic Barrels At The Bottom Of LA Coast Leaks Waste

Barrels of toxic waste dumped into the Pacific Ocean decades ago are still affecting the deep seafloor off the Los Angeles coast, a new study has found.

The discarded industrial-grade barrels, which have for years been encircled by mysterious white halos, have likely been leaking a caustic alkaline waste product into the marine environment, according to the study, published last 9 September in the Proceedings of the National Academy of Sciences Nexus.

Scientists had initially linked the halos, observed in images captured in 2020, to the toxic pesticide DDT, whose manufacturing processes unleashed copious amounts of acidic waste into the ocean from the 1930s through the 1970s.

Although DDT manufacturing did produce alkaline byproducts in addition to the acidic waste, other major industries such as oil refining generated significant alkaline residuals as well, the study authors noted.

"One of the main waste streams from DDT production was acid and they didn’t put that into barrels," lead author Johanna Gutleben, a postdoctoral scholar at the University of California San Diego’s Scripps Institution of Oceanography, said in a statement.

"It makes you wonder: What was worse than DDT acid waste to deserve being put into barrels?" Gutleben asked.

The researchers found that the caustic, alkaline waste emanating from these barrels was so powerful that it transformed parts of the seafloor into extreme environments reminiscent of natural hydrothermal vents. These vents contain specialized bacteria that thrive in conditions where most life cannot survive, the authors noted.

The severity and extent of this mystery waste’s impacts, however, depend on just how many of the barrels are planted on the seafloor and the specific chemicals they contain, the researchers explained.

Yet senior author Paul Jensen, an emeritus marine microbiologist at Scripps, said in a statement that he would have expected the alkaline waste to dissipate quickly in seawater.

Instead, he observed, the contaminants have persisted for more than half a century — indicating that this waste "can now join the ranks of DDT as a persistent pollutant with long-term environmental impacts."

While the number of barrels remains unknown, the researchers deployed a remotely operated vehicle to collect sediment cores adjacent to five of the containers. They then analyzed the sediment samples and hardened pieces of halo barrel crust, to assess DDT levels, mineral content and microbial DNA.

As for DDT, the scientists found that concentrations of the chemical and its byproducts were highly elevated relative to control sites but did not change with distance from the barrels — leading the researchers to conclude that the DDT was not linked to this contamination.

On the other hand, they discovered that the pH levels of the microbial DNA were remarkably high, indicating that the halos contained waste that was very alkaline, also known as a base.

These sediments, the researchers observed, had low bacterial diversity compared to other surrounding sediments, and the bacteria came from families habituated to alkaline environments, such as deep-sea hydrothermal vents or alkaline hot springs.

Although the researchers were not able to identify the specific chemicals present inside the barrels, they stressed the importance in now using white halos to help track alkaline waste — and thereby determine the extent of the contamination in this region.

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