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.
For some poison dart frogs, gaining resistance to one of their own toxins came with a price.
The genetic change that gives one group of frogs immunity to a particularly lethal toxin also disrupts a key chemical messenger in the brain. But the frogs have managed to sidestep the potentially damaging side effect through other genetic tweaks, researchers report in the Sept. 22 Science.
While other studies have identified genetic changes that give frogs resistance to particular toxins, this study “lets you look under the hood” to see the full effects of those changes and how the frogs are compensating, says Butch Brodie, an evolutionary biologist at the University of Virginia in Charlottesville who wasn’t involved in the research. Many poison dart frogs carry cocktails of toxic alkaloid molecules in their skin as a defense against predators (SN Online: 3/24/14). These toxins, picked up through the frogs’ diets, vary by species. Here, researchers studied frogs that carry epibatidine, a substance so poisonous that just a few millionths of a gram can kill a mouse.
Previous studies have shown that poisonous frogs have become resistant to the toxins the amphibians carry by messing with the proteins that these toxins bind to in the body. Switching out certain protein building blocks, or amino acids, changes the shape of the protein, which can prevent toxins from latching on. But making that change could have unintended side effects, too, says study coauthor Rebecca Tarvin, an evolutionary biologist at the University of Texas at Austin.
For example, the toxin epibatidine binds to proteins that are usually targeted by acetylcholine, a chemical messenger that’s necessary for normal brain function. So Tarvin and her colleagues looked at how this acetylcholine receptor protein differed between poison frog species that are resistant to epibatidine and some of their close relatives that aren’t. Identifying differences between the frogs in the receptor protein’s amino acids allowed researchers to systematically test the effects of each change. To do so, the scientists put the genetic instructions for the same protein in humans, who aren’t resistant to epibatidine, into frog eggs. The researchers then replaced select amino acids in the human code with different poison frog substitutions to find an amino acid “switch” that would make the resulting receptor protein resistant to epibatidine.
But epibatidine resistance wasn’t a straightforward deal, it turned out. “We noticed that replacing one of those amino acids in the human [protein] made it resistant to epibatidine, but also affected its interaction with acetylcholine,” says study coauthor Cecilia Borghese, a neuropharmacologist also at the University of Texas at Austin. “Both are binding in the exact same region of the protein. It’s a very delicate situation.” That is, the amino acid change that made the receptor protein resistant to epibatidine also made it harder for acetylcholine to attach, potentially impeding the chemical messenger’s ability to do its job.
But the frogs themselves don’t seem impaired. That’s because other amino acid replacements elsewhere in the receptor protein appear to have compensated, Borghese and Tarvin found, creating a protein that won’t let the toxin latch on, but that still responds normally to acetylcholine.
The resistance-giving amino acid change appears to have evolved three separate times in poison frogs, Tarvin says. Three different lineages of the frogs have resistance to the poison, and all of them got that immunity by flipping the same switch. But the amino acid changes that bring back a normal acetylcholine response aren’t the same across those three groups.
“It’s a cool convergence that these other switches weren’t identical, but they all seem to recover that function,” Brodie says.
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.
Two days before plunging into Saturn, the Cassini spacecraft took one last look around the planet it had orbited for more than 13 years.
The view of Saturn above, released November 21, is actually made from 42 images that have been stitched together. Six moons — Enceladus, Epimetheus, Janus, Mimas, Pandora and Prometheus — are faintly visible as dots surrounding the gas giant (see the annotated image below). Cassini was about 1.1 million kilometers away from Saturn when it took the images on September 13. The whole observation took a little over two hours.
On September 11, Cassini set itself on a collision course with Saturn, and on September 15, the probe ended its mission by burning up in Saturn’s atmosphere, taking data all the way down.
Wikipedia: The settler of dinnertime disputes and the savior of those who cheat on trivia night. Quick, what country has the Nile’s headwaters? What year did Gershwin write “Rhapsody in Blue”? Wikipedia has the answer to all your burning trivia questions — including ones about science.
With hundreds of thousands of scientific entries, Wikipedia offers a quick reference for the molecular formula of Zoloft, who the inventor of the 3-D printer is and the fact that the theory of plate tectonics is only about 100 years old. The website is a gold mine for science fans, science bloggers and scientists alike. But even though scientists use Wikipedia, they don’t tend to admit it. The site rarely ends up in a paper’s citations as the source of, say, the history of the gut-brain axis or the chemical formula for polyvinyl chloride. But scientists are browsing Wikipedia just like everyone else. A recent analysis found that Wikipedia stays up-to-date on the latest research — and vocabulary from those Wikipedia articles finds its way into scientific papers. The results don’t just reveal the Wiki-habits of the ivory tower. They also show that the free, widely available information source is playing a role in research progress, especially in poorer countries.
Teachers in middle school, high school and college drill it in to their students: Wikipedia is not a citable source. Anyone can edit Wikipedia, and articles can change from day to day — sometimes by as little as a comma, other times being completely rewritten overnight. “[Wikipedia] has a reputation for being untrustworthy,” says Thomas Shafee, a biochemist at La Trobe University in Melbourne, Australia.
But those same teachers — even the college professors — who warn students away from Wikipedia are using the site themselves. “Academics use Wikipedia all the time because we’re human. It’s something everyone is doing,” says Doug Hanley, a macroeconomist at the University of Pittsburgh.
And the site’s unreliable reputation may be unwarranted. Wikipedia is not any less consistent than Encyclopedia Britannica, a 2005 Nature study showed (a conclusion that the encyclopedia itself vehemently objected to). Citing it as a source, however, is still a bridge too far. “It’s not respected like academic resources,” Shafee notes. Academic science may not respect Wikipedia, but Wikipedia certainly loves science. Of the roughly 5.5 million articles, half a million to a million of them touch on scientific topics. And constant additions from hundreds of thousands of editors mean that entries can be very up to date on the latest scientific literature.
How recently published findings affect Wikipedia is easy to track. They’re cited on Wikipedia, after all. But does the relationship go the other way? Do scientific posts on Wikipedia worm their way into the academic literature, even though they are never cited? Hanley and his colleague Neil Thompson, an innovation scholar at MIT, decided to approach the question on two fronts.
First, they determined the 1.1 million most common scientific words in published articles from the scientific publishing giant Elsevier. Then, Hanley and Thompson examined how often those same words were added to or deleted from Wikipedia over time, and cited in the research literature. The researchers focused on two fields, chemistry and econometrics — a new area that develops statistical tests for economics.
There was a clear connection between the language in scientific papers and the language on Wikipedia. “Some new topic comes up and it gets exciting, it will generate a new Wikipedia page,” Thompson notes. The language on that new page was then connected to later scientific work. After a new entry was published, Hanley and Thompson showed, later scientific papers contained more language similar to the Wikipedia article than to papers in the field published before the new Wikipedia entry. There was a definite association between the language in the Wikipedia article and future scientific papers.
But was Wikipedia itself the source of that language? This part of the study can’t answer that. It only observes words increasing together in two different spaces. It can’t prove that scientists were reading Wikipedia and using it in their work.
So the researchers created new Wikipedia articles from scratch to find out if the language in them affected the scientific literature in return. Hanley and Thompson had graduate students in chemistry and in econometrics write up new Wikipedia articles on topics that weren’t yet on the site. The students wrote 43 chemistry articles and 45 econometrics articles. Then, half of the articles in each set got published to Wikipedia in January 2015, and the other half were held back as controls. The researchers gave the articles three months to percolate through the internet. Then they examined the next six months’ worth of published scientific papers in those fields for specific language used in the published Wikipedia entries, and compared it to the language in the entries that never got published.
In chemistry, at least, the new topics proved popular. Both the published and control Wikipedia page entries had been selected from graduate level topics in chemistry that weren’t yet covered on Wikipedia. They included entries such as the synthesis of hydrastine (the precursor to a drug that stops bleeding). People were interested enough to view the new articles on average 4,400 times per month.
The articles’ words trickled into to the scientific literature. In the six months after publishing, the entries influenced about 1 in 300 words in the newly published papers in that chemical discipline. And scientific papers on a topic covered in Wikipedia became slightly more like the Wikipedia article over time. For example, if chemists wrote about the synthesis of hydrastine — one of the new Wikipedia articles — published scientific papers more often used phrases like “Passarini reaction,” a term used in the Wikipedia entry. But if an article never went on to Wikipedia, the scientific papers published on the topic didn’t become any more similar to the never-published article (which could have happened if the topics were merely getting more popular). Hanley and Thompson published a preprint of their work to the Social Science Research Network on September 26.
Unfortunately, there was no number of Wikipedia articles that could make econometrics happen. “We wanted something on the edge of a discipline,” Thompson says. But it was a little too edgy. The new Wikipedia entries in that field got one-thirtieth of the views that chemistry articles did. Thompson and Hanley couldn’t get enough data from the articles to make any conclusions at all. Better luck next time, econometrics.
The relationship between Wikipedia entries and the scientific literature wasn’t the same in all regions. When Hanley and Thompson broke the published scientific papers down by the gross domestic product of their countries of origin, they found that Wikipedia articles had a stronger effect on the vocabulary in scientific papers published by scientists in countries with weaker economies. “If you think about it, if you’re a relatively rich country, you have access at your institution to a whole list of journals and the underlying scientific literature,” Hanley notes. Institutions in poorer countries, however, may not be able to afford expensive journal subscriptions, so scientists in those countries may rely more heavily on publicly available sources like Wikipedia.
The Wikipedia study is “excellent research design and very solid analysis,” says Heather Ford, who studies digital politics at the University of Leeds in England. “As far as I know, this is the first paper that attributes a strong link between what is on Wikipedia and the development of science.” But, she says, this is only within chemistry. The influence may be different in different fields.
“It’s addressing a question long in people’s minds but difficult to pin down and prove,” says Shafee. It’s a link, but tracking language, he explains, isn’t the same as finding out how ideas and concepts were moving from Wikipedia into the ivory tower. “It’s a real cliché to say more research is needed, but I think in this case it’s probably true.”
Hanley and Thompson would be the first to agree. “I think about this as a first step,” Hanley says. “It’s showing that Wikipedia is not just a passive resource, it also has an effect on the frontiers of knowledge.”
It’s a good reason for scientists get in and edit entries within their expertise, Thompson notes. “This is a big resource for science and I think we need to recognize that,” Thompson says. “There’s value in making sure the science on Wikipedia is as good and complete as possible.” Good scientific entries might not just settle arguments. They might also help science advance. After all, scientists are watching, even if they won’t admit it.
