上海千花419论坛

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.

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.”

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.