新上海龙凤后花园

Don’t blame lab mice for shortfalls in their ability to mimic human immune systems — blame their upbringing.

Mice with more experience fighting pathogens have immune system reactions more like humans’, conclude two studies published online April 20. “Dirty” mice bought from pet stores or caught in the wild have more humanlike immune systems than clean lab mice do, researchers report in Nature. And in Cell Host & Microbe, scientists find that infecting lab mice with a series of viruses and parasites alters their immune responses to be similar to those of dirty mice and humans.
In recent years, scientists have debated whether mice are adequate stand-ins for humans. Some say mice are poor substitutes, and that money should instead be spent on bolstering human studies (SN: 3/23/13, p. 10). Others look at the same data and conclude that mice do a pretty good job of representing humans (SN: 9/20/14, p. 14). Plus, many important studies could not be done with humans, so mice are a necessity.

But even mouse fans recognize there is room for improvement. “All science is an approximation of the real situation,” says immunologist Andrew Macpherson of the University Hospital of Bern, Switzerland, who relies on mice models. “I don’t think anybody doubts that the models don’t always accurately recapitulate what is happening in humans.” The new papers show where mice fall short and suggest ways to improve their ability to mimic people, he says.

Lab mice’s immune system responses “really do look different” from that of humans’, says immunologist David Masopust, coauthor of both studies. Masopust, of the University of Minnesota in Minneapolis, and colleagues wondered whether those dissimilarities are due to irreconcilable differences in the genetic makeup of mice and humans or if the environment plays a role.

His group counted immune cells in blood from adult lab mice, adult humans and human umbilical cords. Of special interest were “memory CD8+ T cells,” which cull body cells that are infected with viruses or bacteria or that have become cancerous. Lab mice and human infants have few of these memory cells, while adult humans have a plethora. That indicates that lab mice have inexperienced immune systems, much like human babies.

The finding, “is one of those things that once you know it, it’s incredibly obvious,” says E. John Wherry, an immunologist at the University of Pennsylvania. “Mice are like humans raised in a bubble.”
Masopust agrees. “They live a preposterously hygienic existence.” Even mice with severe immune deficiencies can thrive in immaculately clean labs.

Ultraclean lab mice can’t emulate the sort of history most human immune systems experience, says Tiffany Reese, a viral immunologist at the University of Texas Southwestern Medical Center in Dallas. Adults carry an average of eight to 12 chronic viruses, such as Epstein-Barr virus (the cause of mononucleosis). Worm parasites infect about 2 billion people worldwide. And by adulthood, people have usually fought off multiple colds, flus and other infections.

Masopust’s team found that the memory T cell profiles of wild and pet-store mice more closely resembled that of adult humans than lab mice’s did. Housing lab mice next to pet-store mice for a month caused their immune system to change, making the lab mice resemble the dirty mice, the researchers reported in Nature. In discrepancies between studies of lab mice and humans, “the mouse may not be at fault,” Masopust says. “It’s the way that they are cared for.”

An experienced immune system not only looks different, it also works differently from an inexperienced one, Reese and colleagues report in Cell Host & Microbe. Reese infected lab mice with two types of herpesviruses, gave them the flu and inoculated them with an intestinal parasite. She then compared how uninfected mice reacted to a yellow fever vaccine with how chronically infected mice reacted. Uninfected mice made more antibodies against the vaccine. The result might help explain why some vaccines that look promising in animal studies don’t pan out in human trials.

Controlled infections may increase understanding of how pathogens interact with each other, with friendly microbes that live in the body and with the host’s immune system, says Reese’s coauthor Herbert Virgin, a viral immunologist at Washington University School of Medicine in St. Louis.

Researchers have a bias that mice are not humans, says Virgin, “But I think that’s too simplistic a view. We shouldn’t be asking whether the mouse is a perfect model for humans, but whether we can make the mouse emulate more closely the basic nature of human physiology.”

Years ago, when I visited the Daintree Rainforest in northeastern Australia, I couldn’t help but notice the signs — several of them — warning of crocodiles. Australia is home to two species of the ferocious reptiles, freshwater and saltwater — the latter of which can be found in the Daintree River. And the signs are no joke. Croc attacks aren’t common, but a few do happen every year, and some result in deaths.

Crocodiles aren’t terrifying just because they have huge teeth and a deadly bite, though. It’s that an attack appears to come from nowhere. The animals lurk just beneath the water, with only their eyes keeping a lookout for something tasty — like one of us. Now, new research shows that, while a croc may not see as well as you or I, its eyesight is quite good and well adapted for lying in wait at the water’s surface.

Nicolas Nagloo and colleagues from the University of Western Australia in Crawley took a detailed look at eyes from three young saltwater and two young freshwater crocodiles. “Both Australian species possess a bright yellow iris, a slit pupil and a relatively large lens,” the team notes May 4 in the Journal of Experimental Biology. Such features, which were known before this study, are helpful for seeing in dim light. (The animals, though, don’t have great vision underwater.) Crocs are also equipped with a “mobile slit retina” that helps the animals control how much light reaches the eye during daylight.
Dissections and examinations of the cells of the eyes revealed that both species have three types of single cones, a type of double cone and one type of rod. This means that the animals can see colors well. But the freshwater crocs appear to be a bit more sensitive to red than their saltwater counterparts (known as “salties” in Australia); that may help the freshies see in streams and rivers where there is more red light. Both species also have a horizontal streak of high spatial acuity, which allows the reptiles to scan back and forth for prey without ever moving their heads.
That the two species have eyes that are so similar is somewhat surprising given that they are separated by some 12 million years of evolution, live in different habitats and prefer different prey, with the freshwater crocs preferring smaller animals and more fish. But both species have adopted a similar hunting style in which the animals hide just beneath the water and scan the flat environment for a suitable meal. Their eyes, this study shows, are specialized to aid in such attacks.

In 2013, nearly three times as many U.S. high school students smoked cigarettes as vaped electronic cigarettes. By 2015, the trend reversed. Nearly twice as many vaped as smoked, a new study finds. For middle school students, the preference for vaping over smoking cigarettes was even stronger (2.3-fold).

Federal researchers analyzed data from the National Youth Tobacco Survey and found that some 2.39 million U.S. high school kids vaped in 2015. Fewer high schoolers, about 1.37 million, smoked cigarettes, the researchers report in the April 15 Morbidity and Mortality Weekly Report.
Since 2011, teen use of tobacco products has fallen for all categories but two: e-cigarettes and hookahs (although even hookah use has dropped since 2014). In fact, the federal researchers conclude, the steep growth in vaping seems to be keeping overall teen tobacco use stable.
The vast majority of U.S. states have banned sales of vaping supplies to minors, according to the National Conference of State Legislatures. Yet “minors do not face any significant barrier in purchasing liquid nicotine over the Internet” to vape in e-cigs, a second new study shows.

Last summer, Dmitriy Nikitin of the University of California, Irvine and his colleagues recruited three teens to buy e-liquids from 120 different U.S. online vaping-supply vendors. Only four stores did not sell e-liquids to the 16- and 17-year-olds. “I was really blown away,” Nikitin says. His team published its findings online March 19 in Nicotine & Tobacco Research.

Some of the stores packaged their e-liquids with child-friendly bonuses: toy frogs, stickers, little green army men or candy such as SweeTarts. On May 5, the U.S. Food and Drug Administration announced sweeping new regulations for e-cigs, hookahs and other tobacco products.

When scientist George Yancopoulos speaks about his experience with the Science Talent Search, he uses words like “life-changing.” Named a finalist in the competition decades ago, he credits it with helping him launch a career in medical research. Now, Yancopoulos, chief scientific officer at Regeneron Pharmaceuticals Inc., of Tarrytown, N.Y., and his fellow STS alum Leonard Schleifer, Regeneron CEO and president, want to give back to the competition.

On May 26, Regeneron and Society for Science & the Public, which created the STS program in 1942 and publishes Science News, announced that the biotechnology company will take over as the third lead sponsor of the Science Talent Search. The competition was sponsored by Westinghouse for more than five decades; in 1998, Intel became the lead sponsor.
“We are honored to be the new sponsors of the Science Talent Search, a national treasure that highlights the critical role science plays in advancing society,” Yancopoulos said in a press release. “For me, participating in the Science Talent Search was a life-changing experience that inspired my future scientific career.”
The sponsorship will include $100 million in support over 10 years, increasing the value of the scholarships and other awards offered to winners of the competition to $3.1 million annually. Regeneron will also dedicate $30 million of the total to growing the Society’s efforts in outreach and equity, designed to encourage more young people to engage in original research as part of their explorations of science.

Regeneron, founded in 1988, developed the cholesterol-fighting drug Praulent that went on sale last year and Eylea, a treatment for the vision disease wet macular degeneration, among other products. It also has a $1.7 billion deal to develop new immunotherapies for cancer with Sanofi, the French pharmaceutical firm.

To Maya Ajmera, CEO and president of Society for Science & the Public and publisher of Science News, the expansion of the competition and related outreach efforts is particularly exciting. “Through the dedication of Regeneron not only to continue but to advance the Science Talent Search, we will be expanding the program’s reach like never before,” she said.

At the end of the last Ice Age, humans undertook an epic American road trip — trekking from a northern land bridge into interior of North America. But details about the route and timing of that trip are hotly debated.

Some researchers think that humans followed a so-called “ice-free corridor” along the eastern Rocky Mountains. Studies have suggested, though, that the corridor froze over and became impassable around 21,000 years ago. Now, a bread crumb trail of fossils showing the movement of ancient bison indicates that the corridor may have reopened a few thousand years later, researchers report in the Proceedings of the National Academy of Sciences the week of June 6.

Analyzing DNA samples from 78 bison fossils unearthed in Canada, a team led by Beth Shapiro of the University of California, Santa Cruz, found that genetically distinct northern and southern populations moved north and south along the corridor by 13,000 years ago. That means humans may have also hiked along the slopes of the Rockies at the same time.

These probably weren’t the first humans to head south. Recent archaeological evidence points to early Americans trekking as far as Chile more than 15,000 years ago. But the corridor could have served as a later route, the team argues.

Kids are fascinated by fireflies. So are scientists, who, despite decades of research, are still perplexed by many of the mysteries posed by “lightning bugs.” In Silent Sparks, biologist Sara Lewis explores both the cultural and scientific fascination with these marvelous beetles.

Many creatures can manufacture their own glow, Lewis notes, but fireflies are some of the few that can readily turn their lamps on and off. Not all of the world’s nearly 2,000 firefly species light up as adults. But all of their larvae do, which suggests that the bioluminescence may have first evolved in a dinosaur-era ancestor as a “Don’t eat me! I’m toxic!” signal to predators. Only later would adults have co-opted this glimmer for the mating displays that most people are familiar with.
Some of the most impressive firefly shows involve the synchronous flashing of thousands of insects. Each mating season, these Christmas tree–like spectacles draw thousands of tourists to locales as diverse as Tennessee and Malaysia. Although researchers have a fairly good idea of how the fireflies synchronize their flashings — in some species, males continually adjust their flashing rate based on their neighbors’ activity — scientists still haven’t figured out why they do so.

Fireflies aren’t just pretty; they’re useful. For instance, food inspectors monitor food contamination by taking advantage of the chemical reactions that the insects use to signal their mates. These reactions occur only in the presence of ATP, an energy-storing chemical found in all living cells, making the glowing substances a keen detector for food-tainting bacteria such as Salmonella or E. coli.

Silent Sparks is at its best when Lewis describes her own experiences in the field, such as lying on her back on the forest floor while flickering fireflies wafted mere inches above her nose. For readers who would like their own experience, Lewis includes a field guide to the most common species found in the southeastern United States (the hot spot of North American firefly diversity).

So grab a copy of the book, along with a net, jar and kid you love, and relive fond childhood memories while inspiring a few new ones.

In the years after the animated movie Finding Nemo was released by Pixar in 2003, sales of clownfish spiked as fans, little and big, rushed to buy their own “Nemo.” So many Nemos were purchased that the sales actually depleted some wild stocks of the fish. Pressure on those wild populations has since dropped, thanks to efforts to increase captive clownfish breeding. But now there are worries that Nemo’s sequel, Finding Dory, may have a similar effect on Dory’s species, the blue tang — and an even bigger impact on the coral ecosystems in which these fish are found.

Despite concerted efforts, scientists have been unable to convince blue tangs to breed in captivity. That means that every blue tang, every Dory, sold has to be captured from the wild. And a surprisingly large number of those fish are captured with cyanide, new research shows.

Most of the 11 million fish sold in the U.S. aquarium trade come from coral reefs in the Indo-Pacific. In some places, like Hawaii and Australia, there are decent rules and enough enforcement of them that fish can be collected without too much harm to ecosystems. But in others, there aren’t enough laws or enforcers to prevent disturbing, destructive practices, such as fishing with explosives or cyanide.

For the aquarium trade, cyanide fishing is “cheap and easy to do,” says Craig Downs, executive director of the Haereticus Environmental Laboratory in Clifford, Va. A diver adds a pellet of cyanide to a bottle and squirts a bit on a target fish. Or they may use larger quantities pumped down from their boat. The poison quickly stuns the fish, which can then be captured and later sold.

But cyanide is deadly. Coral exposed to cyanide bleaches and dies. Other fish and organisms left behind can die. Even the fish that enter the aquarium trade may die within a few weeks or months of being caught. “If you survive [exposure], you’re messed up for the rest of your life,” Downs says. And while there are laws that should prevent divers from employing this fishing method — and from wholesalers in the United States from being able to purchase fish caught this way — “this practice happens all through the Indo-Pacific,” says Downs. As many as 30 million fish may be caught this way every year, and 90 percent of those may die.

There is no way for someone purchasing a fish in a pet store to tell if the animal had been exposed to cyanide. “You have to be a fish pathologist” to see the signs, Downs says. But after a fish, human or other organism is exposed to the toxin, it will excrete a cyanide metabolite, thiocyanate, in its urine. And this can be detected in the water in which a captive fish is living.

Recently, Downs and Rene Umberger, director of the nonprofit organization For the Fishes, wanted to get an idea of how many fish sold in pet stores were caught with cyanide. They purchased 89 fish from shops in California, Hawaii, Maryland, North Carolina and Virginia, collected water samples and sent them off to an independent laboratory. More than half came back positive for cyanide exposure, including many of the blue tangs. None of the fish from companies that breed fish in captivity came back positive, though. The results of this initial study will be presented later this month at the International Coral Reef Symposium in Hawaii.

A 2008 report from NOAA estimated that 90 percent of the aquarium fish imported into the United States were captured with cyanide or other illegal methods. And Downs suspects that cyanide use for the fish in his study may be higher than he and his colleague are now reporting. The fish only excrete detectable levels of thiocyanate for a short time after exposure. Plus, initial runs of a more sensitive method for detecting the chemical show that many of the negatives may really be positives for exposure, he says.

He is hoping that this method might be turned into an easy tool that can be used by consumers, citizen scientists and enforcement agencies to quickly detect fish that have been illegally caught with cyanide, which would hopefully drive down the trade.

This doesn’t mean that all saltwater fish are off limits for consumers, though. “If consumers really want to have coral reef fish, then going the cultured route is the way to go,” Downs says. There aren’t many of those fish — only 42 or so species among the more than 1,800 currently traded in the United States — but identifying them is easy. Umberger’s group has a free iOS app, Tank Watch, that lists them all. And even though the app doesn’t list every species that may be in a store, if a species isn’t on their good list, it can be assumed to be bad.

So go ahead and buy Nemo, if you must, but leave Dory and most of her fishy cousins where they belong — in the ocean.

BOSTON — New studies find a rise in drug-resistant urinary tract infections in pets, raising concerns that companion animals may serve as microbe reservoirs that could contribute to the spread of potential superbugs. About four in 10 U.S. households own dogs, which sleep with us, eat off our plates, lick our faces and leave plenty of poop to scoop. Cat ownership is nearly as prevalent.

It’s not clear whether pets are picking up the resistant microbes from their owners, or vice versa, said Cátia Marques, a veterinary medicine doctoral candidate. She presented the research, conducted by scientists from the University of Lisbon in Portugal, June 20 at a joint meeting of the American Society for Microbiology and the Interscience Conference on Antimicrobial Agents and Chemotherapy. More research is needed to answer that question, she said.
Either way, scientists worry that companion animals provide another haven for bacteria to mingle and pick up genes that give them resistance to drugs, said Michael Schmidt of the Medical University of South Carolina in Charleston, who was not involved in the new work. “It is a substantial issue,” he said.

Other research has examined human-pet sharing of bacteria, but the subject has been little explored for urinary tract infections, which are extremely common. The new research found a growing resistance in veterinary infections to antibiotics critical for treating human illness. In one study, samples of the bacterium Proteus mirabilis taken over 16 years in Portugal showed a steady climb in the prevalence of resistant strains. An example: Resistance to a class of drugs known as third-generation cephalosporins grew from 2 percent of samples in 2004 to 20 percent today. Other research found worrisome multidrug resistance in infections caused by Klebsiella. In a third study, which tested for resistance in urinary tract infections in pets across Europe, patterns of drug resistance in dogs and cats tracked that of humans, the researchers found.

In humans, doctors have watched warily as resistance to urinary tract infections has grown. In May, scientists reported the discovery of a woman with a urinary infection resistant to colistin, a rarely used drug of last resort (SN Online: 5/27/16). It’s not clear how the patient contracted the resistance, but given colistin’s role as a last-ditch drug, it raised the specter of an unstoppable microbe.

While the new research is broader, it isn’t the first study to raise concerns about the role of companion animals in difficult-to-treat urinary infections. In 2013, German researchers writing in the Journal of Antimicrobial Therapy described finding carbapenem-resistant Escherichia coli and Klebsiella urinary infections in six dogs — a discovery later called a phenomenon “of great concern” in a commentary in the same journal. E. coli and P. mirabilis are the two biggest causes of urinary tract infections. Carbapenem, which the researchers in Portugal did not test for, is also considered a drug of last resort for urinary infections.

Whether humans are giving resistant organisms to their animals or vice versa, the findings emphasize that the battle against resistance needs a global strategy that involves veterinarians along with human doctors and patients, Marques said. “We need to have a common public health approach,” she said.

Schmidt also cautioned that people who are particularly vulnerable to urinary infections, such as pregnant women, take extra care around their pets, especially when cleaning up after them. “If you do have a companion animal and you’re prone to these infections,” he said, “be very strict with your hand hygiene before you eat.”