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.

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.

Seeds coated in a common pesticide might affect birds’ migration

MINNEAPOLIS — Pesticides that kill insects can also have short-term effects on seed-eating birds. Ingesting even small amounts of imidacloprid, a common neonicotinoid pesticide, can disorient migratory white-crowned sparrows, researchers report.

Neonicotinoid pesticides were designed to be safer than traditional pesticides: toxic to insects, but comparatively harmless to other animals. But the new findings add to evidence suggesting that the widely used pesticides, which are chemically similar to nicotine, might be sending ecological ripples beyond the intended targets.
In lab studies, researchers captured wild white-crowned sparrows, Zonotrichia leucophrys, that were migrating north and fed them small doses of imidacloprid for three days — the amount that birds would get from eating a few pesticide-coated wheat seeds. The birds that ate the pesticides lost weight, study coauthor Margaret Eng reported November 15 at the annual meeting of the Society of Environmental Toxicology and Chemistry North America.

And when placed in a large, inverted funnel used to study birds’ migratory orientations, the neonic-fed birds tried to fly in directions other than north. Birds that consumed sunflower oil instead showed no ill effects.

For the birds that ate pesticides, the damage was temporary — after two weeks, the birds regained normal function and body weight, Eng, a toxicologist at the University of Saskatchewan in Saskatoon, Canada, and her colleagues also reported November 9 in Scientific Reports.

The fact that the effects reverse after a period of time is “good news,” says Thomas Bean, a toxicologist at the University of Maryland in College Park who wasn’t part of the study. The short-term malaise might incentivize birds to avoid that food in the future. Bean has found that Japanese quail, Coturnix japonica, also show similar temporary behavioral effects in response to neonicotinoids.
Preliminary results from field studies also appear to confirm the published lab findings. Eng’s team outfitted white-crowned sparrows in the wild with tiny tracking tags. The scientists gave the birds small amounts of pesticides, held the birds for six hours, and then released them.

When released, the birds still had traces of the chemicals in their blood plasma, the researchers reported at the November meeting. On average, there wasn’t a difference between groups in how long the birds hung around before resuming migration, but all of the birds that waited an abnormally long time had eaten neonics. Those animals’ flight paths also appeared to be slightly skewed from the route favored by the control birds.

Those analyses are preliminary, cautions Eng, and a closer look at the data could change the story.

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.

The wiring for walking developed long before fish left the sea

These fins were made for walking, and that’s just what these fish do — thanks to wiring that evolved long before vertebrates set foot on land.

Little skates use two footlike fins on their undersides to move along the ocean floor. With an alternating left-right stride powered by muscles flexing and extending, the movement of these fish looks a lot like that of many land-based animals.

Now, genetic tests show why: Little skates and land vertebrates share the same genetic blueprint for development of the nerve cells needed for limb movement, researchers report online February 8 in Cell. This work is the first to look at the origins of the neural circuitry needed for walking, the authors say.
“This is fantastically interesting natural history,” says Ted Daeschler, a vertebrate paleontologist at the Academy of Natural Sciences in Philadelphia.

“Neurons essential for us to walk originated in ancient fish species,” says Jeremy Dasen, a neuroscientist at New York University. Based on fossil records, Dasen’s team estimates that the common ancestor of all land vertebrates and skates lived around 420 million years ago — perhaps tens of millions of years before vertebrates moved onto land (SN: 1/14/12, p. 12).
Little skates (Leucoraja erinacea) belong to an evolutionarily primitive group. Skates haven’t changed much since their ancestors split from the fish that evolved into land-rovers, so finding the same neural circuitry in skates and land vertebrates was surprising.

The path to discovery started when Dasen and coauthor Heekyung Jung, now at Stanford University, saw YouTube videos of the little skates walking.

“I was completely flabbergasted,” Dasen says. “I knew some species of fish could walk, but I didn’t know about these.”

Most fish swim by undulating their bodies and tails, but little skates have a spine that remains relatively straight. Instead, little skates move by flapping pancake-shaped pectoral fins and walking on “feet,” two fins tucked along the pelvis.

Measurements of the little skates’ movements found that they were “strikingly similar” to bipedal walking, says Jung, who did the work while at NYU. To investigate how that similarity arose, the researchers looked to motor nerve cells, which are responsible for controlling muscles. Each kind of movement requires different kinds of motor nerve cells, Dasen says.

The building of that neural circuitry is controlled in part by Hox genes, which help set the body plan, where limbs and muscles and nerves should go. For instance, snakes and other animals that have lost some Hox genes have bodies that move in the slinky, slithery undulations that many fish use to swim underwater.

By comparing Hox genes in L. erinacea and mice, researchers discovered that both have Hox6/7 and Hox10 genes and that these genes have similar roles in both. Hox6/7 is important for the development of the neural circuitry used to move the skates’ pectoral fins and the mice’s front legs; Hox10 plays the same role for the footlike fins in little skates and hind limbs in mice. Other genes and neural circuitry for motor control were also conserved, or unchanged, between little skates and mice. The findings suggest that both skates and mice share a common ancestor with similar genetics for locomotion.

The takeaway is that “vertebrates are all very similar to each other,” says Daeschler. “Evolution works by tinkering. We’re all using what we inherited — a tinkered version of circuitry that began 400-plus million years ago.”

In Borneo, hunting emerges as a key threat to endangered orangutans

Orangutan numbers on the Southeast Asian island of Borneo plummeted from 1999 to 2015, more as a result of human hunting than habitat loss, an international research team finds.

Over those 16 years, Borneo’s orangutan population declined by about 148,500 individuals. A majority of those losses occurred in the intact or selectively logged forests where most orangutans live, primatologist Maria Voigt of the Max Planck Institute for Evolutionary Anthropology in Leipzig, Germany, and colleagues report February 15 in Current Biology.
“Orangutan killing is likely the number one threat to orangutans,” says study coauthor Serge Wich, a biologist and ecologist at Liverpool John Moores University in England. Humans hunt the forest-dwelling apes for food, or to prevent them from raiding crops, the investigators say. People also kill adult orangutans to steal their babies for the international pet trade.

Between 70,000 and roughly 100,000 orangutans currently live on Borneo, Wich says. That’s substantially higher than previous population estimates. The new figures are based on the most extensive survey to date, using ground and air monitoring of orangutans’ tree nests. Orangutans live only on Borneo and the island of Sumatra and are endangered in both places.

Still, smaller orangutan populations in deforested areas of Borneo — due to logging or conversion to farm land — experienced the severest rates of decline, up to a 75 percent drop in one region.

Satellite data indicate that Borneo’s forest area has already declined by about 30 percent from 1973 to 2010. In the next 35 years, Voigt’s team calculates that further habitat destruction alone will lead to the loss of around 45,000 more of these apes. “Add hunting to that and it’s a lethal mix,” Wich says. But small groups of Bornean orangutans living in protected zones and selectively logged areas will likely avoid extinction, the researchers say.

50 years ago, early organ transplants brought triumph and tragedy

While the drama of human heart transplants has grasped the public interest, kidney transplants are ahead in the field…. Although only three little girls are now surviving liver transplants, the liver is a promising field for replacement…. The donor, of course, must be dead; no one can live without his liver. — Science News, March 2, 1968

Update
Kidney patients, who could receive organs from family members, had up to a 75 percent one-year survival rate in 1968. Liver recipients were less lucky, having to rely on unrelated, postmortem donations. Liver patients’ immune systems often attacked the new organ and one-year survival was a low 30 percent. Cyclosporine, an immune-suppressing drug available since 1983, has made a big difference. Now, about 75 percent of adults are alive three years after surgery, and children’s odds are even better. The liver is still a must-have organ, and the need for donor livers has climbed. Today, the options have expanded, with split-liver transplants and partial transplants from living donors.