Embryos kill off male tissue to become female

Add a new ingredient to the sugar, spice and everything nice needed to make girls.

A protein called COUP-TFII is necessary to eliminate male reproductive tissue from female mouse embryos, researchers report in the Aug. 18 Science. For decades, females have been considered the “default” sex in mammals. The new research overturns that idea, showing that making female reproductive organs is an active process that involves dismantling a primitive male tissue called the Wolffian duct.
In males, the Wolffian duct develops into the parts needed to ejaculate sperm, including the epididymis, vas deferens and seminal vesicles. In females, a similar embryonic tissue called the Müllerian duct develops into the fallopian tubes, uterus and vagina. Both duct tissues are present in early embryos.

A study by French endocrinologist Alfred Jost 70 years ago indicated that the testes make testosterone and an anti-Müllerian hormone to maintain the Wolffian duct and suppress female tissue development. If those hormones are missing, the Wolffian duct degrades and an embryo by default develops as female, Jost proposed.

That’s the story written in textbooks, says Amanda Swain, a developmental biologist at the Institute of Cancer Research in London. But the new study “demonstrates that females also have a pathway to make sure you don’t get the wrong ducts,” says Swain, who wrote a commentary in the same issue of Science.

Testing Jost’s hypothesis wasn’t what reproductive and developmental biologist Humphrey Yao and colleagues set out to do. Instead, the researchers wanted to learn how tissues on the outside of the early ducts communicate with the tubes’ lining, says Yao, of the National Institute of Environmental Health Sciences in Research Triangle Park, N.C.

The COUP-TFII protein is produced in that outer layer, and Yao suspected it was involved in talking with the lining. The researchers blocked the communication in early female mouse embryos’ reproductive tissue by removing the gene that produces COUP-TFII.
To the team’s surprise, the Wolffian duct remained in the female mice along with the female Müllerian duct. That shouldn’t happen, according to the textbooks. “We were just scratching our heads,” Yao says.

Searching for an explanation, Yao and colleagues first tested whether removing COUP-TFII changed the ovaries to produce testosterone like testes do. Testosterone could feed the male tissue and allow it to persist, the researchers thought.

“No, the ovary is just like an ovary. There’s nothing wrong with it,” Yao says. “We were just shocked. This can’t be happening.” Further experiments demonstrated that no stray testosterone was responsible for the male tissue sticking around.

Instead, COUP-TFII appears to be the foreman of a biochemical wrecking crew that demolishes the Wolffian duct in females. Without the protein barking orders, the demolition crew is idle and the male duct isn’t torn down. Signals that trigger COUP-TFII production and activity aren’t yet understood.

“This study fills a void in our understanding of the mechanism of regression of the Wolffian duct,” reproductive biologists Patricia Donahoe and David Pepin of Harvard Medical School said in an e-mail. More research is needed to understand how the protein interacts with male hormones to regulate reproductive tract development, they say.

While the study used mice, COUP-TFII probably works the same way in other mammals, including humans, Donahoe says. Females rarely still carry Wolffian duct remnants, sometimes leading to tumors. The opposite sometimes happens, too, resulting in males with female reproductive organs. Those men may be infertile and have other problems, such as cysts. Researchers should look for defects in COUP-TFII in patients with reproductive problems, Donahoe says.

Wild yeasts are brewing up batches of trendy beers

Craft brewers are going wild. Some of the trendiest beers on the market are intentionally brewed to be sour and funky. One of the hottest new ingredients in the beverages: Yeast scavenged from nature.

Unlike today’s usual brewing, which typically relies on carefully cultivated ale or lager yeast and rejects outsider microbes, some brewers are returning to beer’s roots. Those beginnings go back thousands of years and for most of that time, the microbes fermenting grain into alcohol were probably wild yeast and bacteria that fell into the brew. Now local microbes — in some cases with the help of scientists — are being welcomed back into breweries.

Wild and sour beers are a niche, but growing segment of the craft brewing market, says Bart Watson, chief economist of the Brewers Association. Last year, more than 245,000 cases of wild and sour beers were sold and sales are up 9 percent so far this year.

For geneticist Maitreya Dunham, wild, funky and sour beers aren’t just a market trend; they are ecological microcosms. Dunham’s lab group at the University of Washington in Seattle uses yeast to study genetic variation and evolution. She got interested in beer when her husband took up home brewing.
In the bottom of his five-gallon fermentation bucket, the yeast formed a thick mat that bubbled rapidly. “That’s not how we grow yeast in the lab,” Dunham said. She wanted to test a new technique her lab had developed to identify wild yeast in their natural habitat. And what better habitat to explore than a barrel of beer?
Dunham teamed up with a brewer who made a wild beer with microbes from a warehouse. “Whatever is living in the old warehouse ended up in the beer,” she says. On a lab outing to the brewery, Dunham and her team took samples from beer barrels, marveling at the thriving mass of microbes gurgling inside. “You could see it being alive in there.”
DNA tests revealed that four kinds of bacteria and four kinds of yeast, including a newly identified hybrid yeast, lived in the wild brew, Dunham and colleagues reported June 15 on bioRxiv.org. The hybrid doesn’t have a name yet, because Dunham is still trying to identify its parents. One is Pichia membranifaciens, but the other is an unknown fungus P. membranifaciens is a food spoiler, and no lightweight: It can handle up to 11 percent alcohol. The other parent’s identity and attributes aren’t known, and that ID can take time. People have known for a long time that lager yeast Saccharomyces pastorianus is a hybrid, but scientists didn’t identify both of its parents until 2011.

As excited as Dunham is to find a hybrid yeast, she’s not sure that it will take beer brewing by storm. Her lab brewed a small batch of “science beer” with the hybrid yeast. The yeast didn’t make much ethanol or other flavor compounds. “It didn’t do much on its own,” she laments. But she hasn’t given up hope. Sometimes a yeast needs bacteria or other fungi to really shine. Maybe, she says, “when it’s mixed in with all its friends, it may bring something interesting to the party.”

A Facebook group of home brewers called Milk the Funk is about to help her find out. People from the group saw Dunham’s study on bioRxiv.org and volunteered to ferment beers with and without the hybrid. “I’m about to have a couple dozen people doing experiments for me,” Dunham says. “In fact, they’re going to send me free beer, although it may be weird beer.” (“Funk is one of the flavors they go for in these weirdo beers,” Dunham explains. Descriptions of funk encompass barnyard tastes and smells such as goat, horse blanket, urine, sweat, cheese and manure, as well as spicy notes and complex flavors of clove, smoke, Band-Aid, bacon and bitter, says fellow scientist and yeast hunter Matthew Bochman. “Funk basically covers anything ‘weird’ in beer that might be interesting or pleasant in small amounts but off-putting at higher concentrations.”)
Bochman, a biochemist at Indiana University Bloomington and a self-professed yeast whisperer, is also bagging new kinds of wild yeast. Bochman, who studies how cells keep their DNA intact, was a home brewer for years before moving to Indiana. He soon made friends with many local craft brewers there.
In 2014, he met brewer Robert Caputo, who wanted to make an all-Indiana beer. There were farmers in the state growing hops and malt grains. Indiana water was plentiful. “The missing ingredient was the Indiana yeast,” Bochman says. Caputo asked Bochman to help him find the missing microbe. “So we went yeast hunting.”

That spring and summer, Bochman collected about 100 strains of yeast. “Whenever I was out and about I would grab something — a piece of a bark, a berry — bring it back to the lab and get yeast from it.” The microbes are everywhere, he says. “It’s hard not to find yeast.”

But not just any yeast will do. For beer brewing, he needed to find yeast that eat the sugar maltose in the wort — the liquid extracted from grain mash that will be fermented into beer. Yeasts used for brewing also have to be tolerant of hops, which make weak acids that might slow yeast growth. The yeast must be able to live in 4 to 5 percent alcohol. In addition, the microbes have “to smell and taste at least neutral, if not good,” Bochman said.

Not all yeast can pass the sniff test. For instance, eight strains of Saccharomyces paradoxus “all smelled and tasted heavily of adhesive bandages,” Bochman and colleagues reported August 7 on bioRxiv.org.

But in 2015, a batch of wild beer brewed in an open vat in a vacant lot in Indianapolis by Bochman’s friends at Black Acre Brewing Co., yielded a winner. Among the four species and six strains of yeast in the beer was a Saccharomyces cerevisiae strain called YH166. S. cerevisiae is the species of yeast used to brew ales and wine and to make bread. YH166 lends beer an aroma that is “an amazing pineapple, guava something. Like an umbrella drink,” says Bochman.

He doesn’t yet know what chemicals the yeast makes to produce the tropical fruit scent. He puts his money on one of the sweet-smelling esters yeast use to attract the fruit flies that can give the fungi a lift — sort of a microbial version of a ride-hailing app.
Sour beer brewers may also benefit from Bochman’s bio-prospecting. Sour beers generally contain lactic acid bacteria in addition to yeast. Brewers need separate equipment for brewing sour beers, because it’s difficult to get rid of all the bacteria in order to brew a nonsour beer.
Among 54 species of yeasts Bochman and colleagues investigated, he found five strains that can make both alcohol and lactic acid to brew sour beers without troublesome bacteria. The researchers described the five sourpusses — Hanseniaspora vineae, Lachancea fermentati, Lachancea thermotolerans, Schizosaccharomyces japonicus and Wickerhamomyces anomalus — July 28 on bioRxiv.org. Bochman and Caputo formed Wild Pitch Yeast, a company to sell the strains, in part, to fund his yeast research. The company supplied yeasts isolated from cobwebs, trees and other spots to brewers for making all-Indiana beers, dubbed “Bicentenni-ales” in honor of the state’s 200th anniversary.

Both Bochman and Dunham are relying on brewers to tell them how their newfound yeast perform in the real world. “The proof is in the brewing,” Bochman says. “You can do as many lab tests as you want, but you’re never going to know how something will act until you throw it into some wort and let it bubble away for a couple of weeks.”

The results from a slew of experiments are in: Dark matter remains elusive

Patience is a virtue in the hunt for dark matter. Experiment after experiment has come up empty in the search — and the newest crop is no exception.

Astronomical observations hint at the presence of an unknown kind of matter sprinkled throughout the cosmos. Several experiments are focused on the search for one likely dark matter candidate: weakly interacting massive particles, or WIMPs. But those particles are yet to be spotted.

New results, posted online at arXiv.org in recent months, continue the trend. The PandaX-II experiment, based in China, found no hint of the particles, scientists reported August 23. The XENON1T experiment in Italy also came up WIMPless according to a May 18 paper. Scientists with the DEAP-3600 experiment in Sudbury, Canada, reported their first results on July 25. Signs of dark matter? Nada. And the SuperCDMS experiment in the Soudan mine in Minnesota likewise found no WIMP hints, scientists reported August 29.

Another experiment, PICO-60, also located in Sudbury, reported its contribution to the smorgasbord of negative results June 23 in Physical Review Letters.

Scientists haven’t given up hope. Researchers are building ever-larger detectors, retooling their experiments and expanding the search beyond WIMPs, in hopes of glimpsing a dark matter particle.

The Cassini probe dies tomorrow. Here’s how to follow its end

It’s not every day that a spacecraft gets vaporized by the very planet it sought to explore.

After 13 years studying Saturn and its moons, NASA’s Cassini spacecraft will plunge into the ringed gas giant’s atmosphere. The mission will come to a close at about 7:55 a.m. EDT (4:55 a.m. PDT) Friday, when Saturn’s atmosphere pushes Cassini’s antenna away from Earth, terminating the signal. Shortly thereafter, the spacecraft will disintegrate.

If you want to keep tabs on the action, you’ve got a few options. Science News astronomy writer Lisa Grossman is at the Jet Propulsion Laboratory in Pasadena, Calif. — home of mission control for the Cassini probe. She’ll be popping on to the Science News Facebook page throughout the day Thursday with live updates, and she (@astrolisa) and Science News (@ScienceNews) will have details for you on Twitter as well.

Cassini’s death won’t be captured on film. But thanks to the internet, you can watch NASA scientists react to the probe’s impending doom live. In the early hours of Friday morning (7-8:30 a.m. EDT/4-5:30 a.m. PDT), NASA plans to stream a live video feed from the control room, which you can watch here:
And, you can also watch on NASA JPL’s YouTube channel and NASA’s Facebook page.

For more on Cassini’s exploits, check out all of our past coverage of the mission.

Radioactive material from Fukushima disaster turns up in a surprising place

Six years after the Fukushima nuclear reactor disaster in Japan, radioactive material is leaching into the Pacific Ocean from an unexpected place. Some of the highest levels of radioactive cesium-137, a major by-product of nuclear power generation, are now found in the somewhat salty groundwater beneath sand beaches tens of kilometers away, a new study shows.

Scientists tested for radioactivity at eight different beaches within 100 kilometers of the plant, which experienced three reactor meltdowns when an earthquake and tsunami on March 11, 2011, knocked out its power. Oceans, rivers and fresh groundwater sources are typically monitored for radioactivity following a nuclear accident, but several years following the disaster, those weren’t the most contaminated water sources. Instead, brackish groundwater underneath the beaches has accumulated the second highest levels of the radioactive element (surpassed only by the groundwater directly beneath the reactor), researchers report October 2 in the Proceedings of the National Academy of Sciences.

In the wake of the 2011 accident, seawater tainted with high levels of cesium-137 probably traveled along the coast and lapped against these beaches, proposes study coauthor Virginie Sanial, who did the work while at Woods Hole Oceanographic Institution in Massachusetts. Some cesium stuck to the sand and, over time, percolated down to the brackish groundwater beneath. Now, the radioactive material is steadily making its way back into the ocean. The groundwater is releasing the cesium into the coastal ocean at a rate that’s on par with the leakage of cesium into the ocean from the reactor site itself, Sanial’s team estimates.

Since this water isn’t a source of drinking water and is underground, the contamination isn’t an immediate public health threat, says Sanial, now a geochemist at the University of Southern Mississippi in Hattiesburg. But with about half of the world’s nuclear power plants located on coastlines, such areas are potentially important contamination reservoirs and release sites to monitor after future accidents.

Using high-nicotine e-cigarettes may boost vaping and smoking in teens

Vaping e-cigarettes with high amounts of nicotine appears to impact how often and how heavily teens smoke and vape in the future, a new study finds.

In 2016, an estimated 11 percent of U.S. high school students used e-cigarettes. Past research has found that that teen vaping can lead to smoking (SN: 9/19/15, p. 14). The new study, published online October 23 in JAMA Pediatrics, is the first look at whether vaping higher amounts of nicotine is associated with more frequent and more intense vaping and cigarette use in the future.
Researchers at the University of Southern California surveyed 181 10th-graders from 10 high schools in the Los Angeles area who had reported vaping in the previous 30 days, then followed up six months later, when the students were 11th-graders. The teens answered questions about how much and how often they had smoked and vaped in the past 30 days and about the amount of nicotine in their vaping liquid. The researchers categorized the amount of nicotine as none, low (up to 5 milligrams per milliliter), medium (6 to 17 mg/mL) or high (18 mg/mL or more).

With each step up in nicotine concentration, teens were about twice as likely to report frequent smoking versus no smoking at the six-month follow-up. Teens who vaped a high-nicotine liquid smoked seven times as many cigarettes per day as those who vaped without nicotine.

Also with each nicotine level increase, teens were about 1½ times as likely to report frequent vaping than no vaping at all. Vaping high-nicotine liquid led to almost 2½ times as many episodes of vaping per day compared with no-nicotine vaping, and kids took more puffs each time they vaped.

“This study is important because it begins to chip away at the ‘black box’ that links e-cigarette use with later use of regular cigarettes,” says sociologist Richard Miech of the University of Michigan in Ann Arbor. “Ideally, studies like this will encourage government agencies to develop policies that will make it very difficult for youth to obtain e-liquids with nicotine.”
In 2016, then-U.S. Surgeon General Vivek Murthy released a report on e-cigarettes, concluding that using nicotine-containing products in any form is not safe for youth. Studies find an association between nicotine use in teens and problems with learning, attention and impulse control, as well as addiction (SN: 7/11/15, p. 18).

A sandy core may have kept Enceladus’ ocean warm

A soft heart keeps Enceladus warm from the inside. Friction within its porous core could help Saturn’s icy moon maintain a liquid ocean for billions of years and explain why it sprays plumes from its south pole, astronomers report November 6 in Nature Astronomy.

Observations in 2015 showed that Enceladus’ icy surface is a shell that’s completely detached from its rocky core, meaning the ocean spans the entire globe (SN: 10/17/15, p. 8). Those measurements also showed that the ice is not thick enough to keep the ocean liquid.
Other icy moons, like Jupiter’s Europa, keep subsurface oceans warm through the energy generated by gravitational flexing of the ice itself. But if that were Enceladus’ only heat source, its ocean would have frozen within 30 million years, a fraction of the age of the solar system, which formed roughly 4.6 billion years ago.

Planetary scientist Gaël Choblet of the University of Nantes in France and his colleagues tested whether friction in the sand and gravel thought to make up Enceladus’ core could heat things up.

The team made computer simulations of water circulating through the spongy core using data from the Cassini spacecraft and geoengineering experiments with sand and gravel on Earth. They found that, depending on the core’s makeup, the ocean should get enough heat to stay liquid for tens of millions to billions of years.

The simulations also showed that certain hot spots in the core, including at the poles, correspond to regions where the ice shell is thinner.
“That was quite cool,” Choblet says. “It explains the internal structure and the way things are organized and the dynamics interior to Enceladus.”

And that could explain why the moon spews plumes of water from its south pole: More heat from the core at that spot could melt the ice and let water out. It doesn’t explain why the north pole is plume-free, though.

Crocs take a bite out of claims of ancient stone-tool use

Recent reports of African and North American animal fossils bearing stone-tool marks from being butchered a remarkably long time ago may be a crock. Make that a croc.

Crocodile bites damage animal bones in virtually the same ways that stone tools do, say paleoanthropologist Yonatan Sahle of the University of Tübingen in Germany and his colleagues. Animal bones allegedly cut up for meat around 3.4 million years ago in East Africa (SN: 9/11/10, p. 8) and around 130,000 years ago in what’s now California (SN: 5/27/17, p. 7) come from lakeside and coastal areas. Those are places where crocodiles could have wreaked damage now mistaken for butchery, the scientists report online the week of November 6 in the Proceedings of the National Academy of Sciences.
Larger samples of animal fossils, including complete bones from various parts of the body, are needed to begin to tease apart the types of damage caused by stone tools, crocodile bites and trampling of bones by living animals, Sahle’s team concludes. “More experimental work on bone damage caused by big, hungry crocs is also critical,” says coauthor Tim White, a paleoanthropologist at the University of California, Berkeley.

In a field where researchers reap big rewards for publishing media-grabbing results in high-profile journals, such evidence could rein in temptations to over-interpret results, says archaeologist David Braun of George Washington University in Washington, D.C., who did not participate in the new study or the two earlier ones. “There’s a push to publish extraordinary findings, but evolutionary researchers always have to weigh what’s interesting versus what’s correct.”

Authors of the ancient butchery papers agree that bone marks made by crocodiles deserve closer study and careful comparison with proposed stone-tool marks. But the researchers stand their ground on their original conclusions.

Microscopic investigations in the 1980s led some researchers to conclude that carnivores such as hyenas leave U-shaped marks on bones. In contrast, they argued, stone tools leave V-shaped incisions with internal ridges. And hammering stones create signature pits and striations.
Sahle’s group expanded on research previously conducted by paleoanthropologist Jackson Njau of Indiana University Bloomington. In his 2006 doctoral dissertation, Njau reported that bone damage produced by feeding crocodiles looks much like stone-tool incisions and pits, with a few distinctive twists such as deep scratches. Njau retrieved and studied cow and goat bones from carcasses that had been eaten by crocodiles housed at two animal farms in Tanzania.

In the new study, the scientists used Njau’s findings to reassess marks on fossils previously excavated in Ethiopia and dating to around 4.2 million, 3.4 million and 2.5 million years ago. Damage to these fossils has generally been attributed to butchery with stone tools.

Incisions and pits on arm bones from an ancient hominid, Australopithecus anamensis, and similar marks on a horse’s leg bone likely resulted from crocodile bites and not stone-tool use, as initially suspected, the investigators say. If stone tools had indeed damaged the A. anamensis remains, that would raise the possibility of cannibalism — a difficult behavior to confirm with fossils. Tellingly, Sahle’s team argues, these bones come from what were once waterside areas. Some were found in the same sediment layer as crocodile remains. Marks on these bones include deep scratches consistent with crocodile bites.

The horse fossil comes from a spot along an ancient lakeshore where no stone tools have been found, a further clue in favor of damage from croc bites.

Jagged pits, incisions and other marks scar a leg fragment and lower jaw from an ancient hoofed animal. But microscopic analyses could not definitively attribute the damage to stone tools or crocodile bites.

In light of these findings, the ancient California and 3.4-million-year-old East Africa bones should also be reexamined with the possibility of croc damage in mind, White says. For now, the earliest confirmed stone-tool marks occur on animal bones from two East African sites dating to around 2.5 million years ago (SN: 4/17/04, p. 254), he adds.

The range of crocodile marks described in the new study doesn’t look “especially like” damage to the 130,000-year-old mastodon bones on California’s coast, says paleontologist Daniel Fisher of the University of Michigan in Ann Arbor, a coauthor of the ancient California bones paper. No fossil evidence indicates crocodiles lived there at that time, he adds. Several lines of evidence, including pounding marks and damage near joints, point to stone-tool use at the West Coast site, says archaeologist Richard Fullagar of the University of Wollongong in Australia, also a coauthor of the mastodon paper.

Further studies of the 3.4-million-year-old African bones previously reported as probable examples of animal butchery will statistically compare the probability of various causes for particular marks, including crocodile bites, says Shannon McPherron, the lead author of the earlier study and an archaeologist at the Max Planck Institute for Evolutionary Anthropology in Leipzig, Germany. In that way, researchers can assess whether any one cause stands out as the strongest candidate.

This ancient marsupial lion had an early version of ‘bolt-cutter’ teeth

A skull and other fossils from northeastern Australia belong to a new species in the extinct family of marsupial lions.

This newly named species, Wakaleo schouteni, was a predator about the size of a border collie, says vertebrate paleontologist Anna Gillespie of the University of New South Wales in Sydney. At least 18 million years ago (and perhaps as early as 23 million years ago), it roamed what were then hot, humid forests. Its sturdy forelimbs suggest it could chase possums, lizards and other small prey up into trees. Gillespie expects W. shouteni — the 10th species named in its family — carried its young in a pouch as kangaroos, koalas and other marsupials do.
Actual lions evolved on a different fork in the mammal genealogical tree, but Australia’s marsupial lions got their feline nickname from the size and slicing teeth of the first species named, in 1859. Thylacoleo carnifex was about as big as a lion. And its formidable teeth could cut flesh. But unlike other pointy-toothed predators, marsupial lions evolved a horizontal cutting edge. A bottom tooth stretched back along the jawline on each side, its slicer edge as long as four regular teeth. An upper tooth extended too, giving this marsupial lion a bite like a “bolt cutter,” Gillespie says.

The newly identified species lived some 17 million years before its big bolt-cutter relative. Though the new species’ tooth number matched those of typical early marsupials, W. schouteni already had a somewhat elongated tooth just in front of the molars, Gillespie and colleagues report December 7 in the Journal of Systematic Paleontology. W. schouteni is “pushing the history of marsupial lions deeper into time,” she says.

Protein helps old blood age the brains of young mice

Old blood can prematurely age the brains of young mice, and scientists may now be closer to understanding how. A protein located in the cells that form a barrier between the brain and blood could be partly to blame, experiments on mice suggest.

If something similar happens in humans, scientists say, methods for countering the protein may hold promise for treating age-related brain decline.

The preliminary study, published online January 3 at bioRxiv.org, focused on a form of the protein known as VCAM1, which interacts with immune cells in response to inflammation. As mice and humans age, levels of that protein circulating in the blood rise, Alzheimer researcher Tony Wyss-Coray at Stanford University and colleagues found.
After injecting young mice behind an eye with plasma from old mice, the team discovered that VCAM1 levels also rose in certain parts of the blood-brain barrier, a mesh of tightly woven cells that protect the brain from harmful factors in the blood. The young mice showed signs of brain deterioration as well, including inflammation and decreased birthrates of new nerve cells. Plasma from young mice had no such effects.

Interfering with VCAM1 may help prevent the premature aging of brains. Plasma from old mice didn’t have a strong effect when injected into young mice genetically engineered to lack VCAM1 in certain blood-brain barrier cells. Nor did it affect mice treated with antibodies that blocked the activity of VCAM1. Those antibodies also seemed to help the brains of older mice that had aged naturally, the team found.

The results suggest that anti-aging treatments targeting specific aspects of the blood-brain barrier may hold promise.