Newfound airway cells may breathe life into tackling cystic fibrosis

Meet the ionocyte. This newly discovered cell may be the star of future cystic fibrosis therapies. Researchers have found that the gene tied to the disease is very active in the cells, which line the air passages of the lungs.

While the cells are rare, making up only 1 to 2 percent of cells that line the airways, they seem to play an outsized role in keeping lungs clear. The identification of the ionocyte “provides key information for targeting treatments,” says medical geneticist Garry Cutting of Johns Hopkins School of Medicine in Baltimore, who was not involved in the research. Two teams, working independently, each describe the new cell online August 1 in Nature.
The ionocyte shares its name with similar cells found in fish gills and frog skin. This type of cell regulates fluid movement at surfaces — skin, gills, airways — where air and water meet. In people, special proteins that tunnel across cell membranes lining the airways allow chloride ions (half of what makes salt) to move into the airway. This causes water to move into the airway through a different channel to moisten mucus along the lining, which helps it remove bacteria and inhaled particles from the body.

The tunnel protein that allows chloride ions through is made by a gene called CFTR. In cystic fibrosis patients, that gene is flawed. Airways can’t regulate water movement properly and get clogged with thick mucus that traps bacteria and leads to persistent infections and lung damage. The genetic disease affects at least 70,000 people worldwide, according to the Cystic Fibrosis Foundation in Bethesda, Md.

Researchers had suspected CFTR was most active in ciliated cells — cells with brushlike projections that work along with the mucus in airways to move invaders out. But the new work found very little gene activity in those cells, compared with the ionocytes.

In experiments with laboratory samples of mouse cells from the airway lining, cell biologist Jayaraj Rajagopal of Massachusetts General Hospital in Boston and his colleagues found that the gene was very active in ionocytes: out of all the instructions for building the tunnels detected in the cells, 54 percent came from ionocytes. Aron Jaffe, a respiratory disease researcher at Novartis Institutes for Biomedical Research in Cambridge, Mass., and his colleagues reported that, in laboratory samples of human airways cells, ionocytes were the source of 60 percent of the activity of the tunnels.
The discovery of the new cells raises a lot of questions. Jaffe wonders where ionocytes are positioned in the lining of the airways, and how that placement supports the coordination of water movement and mucus secretion by other cells. “You can imagine the distribution [of ionocytes] is really important,” he says.

A question Rajagopal has: “How does a rare cell type do all of this work?” In fish and frogs, ionocytes are loaded with mitochondria, the so-called cellular energy factories, he notes. Maybe that will be true for human ionocytes, too, giving them lots of energy to do the lion’s share of regulating the movement of water.

Both researchers say the ionocyte’s discovery should lead to a better understanding of cystic fibrosis. “It will let us think about creative new ways to approach the disease,” Rajagopal says.

Google Glass could help children with autism socialize with others

Google Glass may have failed as a high-tech fashion trend, but it’s showing promise as a tool to help children with autism better navigate social situations.

A new smartphone app that pairs with a Google Glass headset uses facial recognition software to give the wearer real-time updates on which emotions people are expressing. In a pilot trial, described online August 2 in npj Digital Medicine, 14 children with autism spectrum disorder used this program at home for an average of just over 10 weeks. After treatment, the kids showed improved social skills, including increased eye contact and ability to decode facial expressions.
After her son Alex, now 9, participated in the study, Donji Cullenbine described the Google Glass therapy as “remarkable.” She noticed within a few weeks that Alex, who was 7 years old at the time, was meeting her eyes more often — a behavior change that’s stuck since treatment ended, she says. And Alex enjoyed using the Google Glass app. Cullenbine recalls her son telling her excitedly, “Mommy, I can read minds.”
Unlike most children, who naturally learn to read facial expressions by interacting with family and friends, children with autism often have to hone these skills through behavioral therapy. That typically involves a therapist leading the child through structured activities, like exercises with flash cards that depict faces wearing different expressions. But therapists are so few and far between that a child diagnosed with autism can spend 18 months on a waiting list before starting treatment.
Dennis Wall, a biomedical data scientist specializing in pediatrics at Stanford University, and colleagues built the new Google Glass program to offer children with autism at-home, on-demand behavioral therapy. The headset’s camera records the faces of people in the child’s field of view and feeds that information to a smartphone app. The app, trained on hundreds of thousands of face photos, is designed to recognize eight core expressions: happiness, sadness, anger, disgust, surprise, fear, contempt and calm. When the app recognizes an expression of one of these feelings, it sends the information to the Google Glass wearer — either by naming the emotion through the headset speaker or by displaying an emoticon on a small screen in the corner of the right spectacle frame.

In the pilot trial, children ages 3 to 17 with autism used this Google Glass program around their families for at least three 20-minute sessions per week. Before and after treatment, parents completed questionnaires that rated their children’s social skills. On this Social Responsiveness Scale, scores below 60 fall within the “normal” range, whereas scores 60 to 65, 65 to 75, and above 75 indicate mild, moderate and severe autism, respectively. Over the course of treatment, the children’s average score dropped from 80.07 to 72.93.

Eleven of the 14 children also completed an emotion recognition exam at the start and end of treatment. In this test, an examiner acted out each of the eight core emotions five times, and the child guessed which emotion the examiner was expressing. Before therapy, kids got an average 28.45 out of 40 questions right; afterward, they averaged 38 correct responses.

While these results are encouraging, the study did not include a control group of children who didn’t receive the treatment. So it’s not entirely clear whether the Google Glass program was the only reason that children showed improved social skills over the course of treatment, says Ned Sahin, a neuroscientist at Brain Power, a company that develops wearable technology to help people with autism, in Boston. A randomized controlled trial, where children are randomly assigned to receive treatment or not, could provide further insight into the therapy’s effects, Sahin says.

Wall and his team are currently working on one such experiment with 74 children ages 6 to 12. If the Google Glass therapy performs well in future clinical trials and is cleared for widespread use, it could be a powerful learning aid for many children with autism — which affects an estimated 1 in 59 children in the United States, according to the U.S. Centers for Disease Control and Prevention.

Already, Cullenbine expects that Alex will have better relationships with people, “and that’s life changing.”

Researchers say CRISPR edits to a human embryo worked. But critics still doubt it

When researchers announced last year that they had edited human embryos to repair a damaged gene that can lead to heart failure, critics called the report into question.

Now new evidence confirms that the gene editing was successful, reproductive and developmental biologist Shoukhrat Mitalipov and colleagues report August 8 in Nature. “All of our conclusions were basically right,” Mitalipov, of Oregon Health & Science University in Portland, said during a news conference on August 6.
But authors of two critiques published in the same issue of Nature say they still aren’t convinced.

At issue is the way that the gene was repaired. Mitalipov and colleagues used the molecular scissors CRISPR/Cas9 to cut a faulty version of a gene called MYBPC3 in sperm (SN: 9/2/17, p. 6). People who inherit this version of the gene often develop heart failure. Cutting the gene allows cells to fix the problem by replacing erroneous instructions in the gene with correct information.

Researchers supplied the correct information in the form of small foreign pieces of DNA, but the embryos ignored that repair template. Instead, Mitalipov and colleagues say, embryos used a healthy version of the gene on the mother’s chromosome to fix the error. That action is called gene conversion.

Gene conversion typically happens when reproductive, or germline, cells swap DNA before making eggs and sperm. So it was completely unexpected to find that type of repair happening in embryos, says geneticist Paul Thomas of the South Australian Health & Medical Research Institute in Acton.
If human embryos do ignore foreign bits of DNA that could be a problem for fixing genetic diseases that result when both parents pass on damaged versions of a gene. In that scenario, there would be no healthy version of the gene to copy and paste.

But Thomas and colleagues propose that Mitalipov’s group may not have detected gene conversion at all. Instead, large chunks may have been cut out of the chromosome containing the faulty version of the gene and not replaced. That wouldn’t fix the defective gene, but could make it look like gene conversion had happened, fooling researchers into thinking they’d made a repair.

Mitalipov’s group used a technique called polymerase chain reaction, or PCR, to confirm that they had repaired the faulty copy of the gene. PCR essentially photocopied stretches of the repaired gene for analysis. The team found that only the mother’s version of the gene was in the edited embryos. That result led the researchers to conclude that gene conversion had copied the maternal version of the gene onto the father’s chromosome.

But because the researchers weren’t able to take a closer look at the gene, they can’t be sure it was gene conversion, Thomas says. Cutting out a portion of the father’s gene would leave only the mother’s version to be copied during PCR. That might give the impression that the father’s gene was converted to the maternal form, when that piece of DNA is missing from the father’s gene.

Such large DNA deletions were common in experiments with mice, Thomas and colleagues say in one critique. About 45 to 57 percent of mouse embryos tested were missing big chunks of genetic material. But Mitalipov and colleagues didn’t report finding any evidence that portions of DNA were deleted from the human embryos.

“I find that surprising,” Thomas says. He is skeptical that the data presented in the new report completely settle the problem.

Rock solid evidence of gene correction was missing from Mitalipov’s original report, agrees Maria Jasin, a developmental biologist at Memorial Sloan Kettering Cancer Center in New York City. The new report presents more convincing data, “but I’m still left with this doubt,” says Jasin, a coauthor on the other critique. “I wouldn’t rule out that gene conversion can happen” in such cases, she says. But in mouse experiments, that type of repair happens infrequently, she says, and there’s no reason to suppose that human embryos do it more frequently.

While there is optimism that scientists will be able to repair broken genes in human embryos, researchers aren’t there yet, Jasin and Thomas say.

Given all the things that might go wrong with gene editing, such as accidentally making mutations, there’s no room for uncertainty about whether the technique works. “You have to be 100 percent confident,” Thomas says, “and we’re a long, long way from being in that position.”

New Horizons may have seen a glow at the solar system’s edge

The New Horizons spacecraft has spotted an ultraviolet glow that seems to emanate from near the edge of the solar system. That glow may come from a long-sought wall of hydrogen that represents where the sun’s influence wanes, the New Horizons team reports online August 7 in Geophysical Research Letters.

“We’re seeing the threshold between being in the solar neighborhood and being in the galaxy,” says team member Leslie Young of the Southwest Research Institute, based in Boulder, Colo.
Even before New Horizons flew past Pluto in 2015 (SN: 8/8/15, p. 6), the spacecraft was scanning the sky with its ultraviolet telescope to look for signs of the hydrogen wall. As the sun moves through the galaxy, it produces a constant stream of charged particles called the solar wind, which inflates a bubble around the solar system called the heliosphere. Just beyond the edge of that bubble, around 100 times farther from the sun than the Earth, uncharged hydrogen atoms in interstellar space should slow when they collide with solar wind particles. That buildup of hydrogen, or wall, should scatter ultraviolet light in a distinctive way.

The two Voyager spacecraft saw signs of such light scattering 30 years ago. One of those craft has since exited the heliosphere and punched into interstellar space (SN: 10/19/13, p. 19).

New Horizons is the first spacecraft in a position to double-check the Voyagers’ observations. It scanned the ultraviolet sky seven times from 2007 to 2017, space scientist Randy Gladstone of the Southwest Research Institute in San Antonio and colleagues report. As the spacecraft traveled, it saw the ultraviolet light change in a way that supports the decades-old observations. All three spacecraft saw more ultraviolet light farther from the sun than expected if there is no wall. But the team cautions that the light could also be from an unknown source farther away in the galaxy.

“It’s really exciting if these data are able to distinguish the hydrogen wall,” says space scientist David McComas of Princeton University, who was not involved in the new work. That could help figure out the shape and variability of the solar system’s boundary (SN: 5/27/17, p. 15).
After New Horizons flies past the outer solar system object Ultima Thule on New Year’s Day 2019 (SN Online: 3/14/18), the spacecraft will continue to look for the wall about twice each year until the mission’s end, hopefully 10 to 15 years from now, Gladstone says.

If the ultraviolet light drops off at some point, then New Horizons may have left the wall in its rear view mirror. But if the light never fades, then its source could be farther ahead — coming from somewhere deeper in space, says team member Wayne Pryor of Central Arizona College in Coolidge.

A galaxy 11.3 billion light-years away appears filled with dark matter

A distant galaxy appears filled with dark matter.

The outermost stars in the Cosmic Seagull, a galaxy 11.3 billion light-years away, race too fast to be propelled by the gravity of the galaxy’s gas and stars alone. Instead, they move as if urged on by an invisible force, indicating the hidden presence of dark matter, astrophysicist Verónica Motta of the University of Valparaíso in Chile and her colleagues report August 8 at arXiv.org.

“In our nearby universe, you see these halos of dark matter around galaxies like ours,” Motta says. “So we should expect that in the past, that halo was there, too.”
Motta and her colleagues used radio telescopes at the Atacama Large Millimeter/submillimeter Array (ALMA) to measure the speed of gas across the Cosmic Seagull’s disk, from the center out to about 9,800 light-years. They found that the galaxy’s stars speed up as they get farther from the galaxy’s center.

That’s a strange setup for most orbiting objects — when planets orbit a star, for instance, the most distant planets move slowest. But it can be explained if the galaxy’s far reaches are dominated by dark matter that speeds things along. Similar measurements of the Milky Way and neighboring galaxies provided one of the first signs that dark matter may exist, although physicists are still trying to detect the proposed particle directly (SN: 2/4/17, p. 15).

Her team’s finding contrasts with a recent claim that such distant galaxies are oddly lacking in dark matter. That idea comes from a 2017 study by astronomer Reinhard Genzel of the Max Planck Institute for Extraterrestrial Physics in Garching, Germany, and his colleagues, who found more than 100 distant galaxies keep their slower stars at the edges and faster stars closer in — little to no dark matter required (SN: 4/15/17, p. 10).
“In the astrophysical community, the [Genzel] result has been viewed with both excitement and skepticism,” says cosmologist Richard Ellis of University College London, who was not involved in either work. “It makes a lot of sense for others to examine galaxies at these [distances] in different ways.”

Motta and her colleagues were able to probe dark matter in the most distant galaxy yet, thanks to a massive galactic train wreck called the Bullet Cluster that acted as a huge cosmic telescope. The Cosmic Seagull lies behind the Bullet Cluster from Earth’s perspective, and the cluster’s mass distorts the Seagull’s light in a phenomenon called gravitational lensing.

That distortion earned the disk-shaped galaxy its name — the first images reminded Motta’s team of the seagull logo of a popular music festival in Viña del Mar, Chile. But it also made the galaxy appear magnified by a factor of 50 — a new record.

“Motta et al have exquisite data,” but their observations are limited, Ellis wrote in an e-mail. The team looked at only one galaxy, and that galaxy is much smaller and less massive than those that seem short on dark matter. Furthermore, the observations don’t cover the entire galactic disk, so the stars may be slower farther out than the team can see.

Motta agrees that a distant slowdown is possible, although her observations cover the same portion of the galaxy’s disk as the study of galaxies that seem light on dark matter.

“We are roughly at the place in which we should see the turning point” from fast to slow stars, if it exists, she says. “But we need to extend the study to get that.” Her team has been granted more time with ALMA next year to keep looking.

Cheese found in an Egyptian tomb is at least 3,200 years old

What may be the oldest known solid cheese has been found in an ancient Egyptian tomb.

Made from a mixture of cow milk and either sheep or goat milk, the cheese filled a broken clay jar unearthed from a 13th century B.C. tomb for Ptahmes, the mayor of the ancient city of Memphis, researchers report online July 25 in Analytical Chemistry.

Chemist Enrico Greco, who did the work while at the University of Catania in Italy, and colleagues used mass spectrometry to analyze the antique cheese — now a white, soapy lump weighing “several hundred grams.” Besides milk and whey proteins, the cheese contained remnants of bacteria that cause an infection called brucellosis, adding to evidence that ancient Egyptians may have grappled with the disease, Greco says.
Cheese making predates the new find by thousands of years, but preserved cheese is hard to come by (SN: 1/26/13, p. 16). Archaeologists found older curds draped around the necks of Bronze Age mummies in China, a different group of researchers reported in 2014 in the Journal of Archaeological Science. “There are other samples of dairy products in the literature, but not solid cheeses in the strict sense,” Greco says.

He says he did not sniff the cheese, but given its degraded state it is unlikely to have an odor, pleasant or not.

How salamanders can regrow nearly complete tails but lizards can’t

Salamanders and lizards can both regrow their tails, but not to equal perfection.

While a regenerated salamander tail closely mimics the original, bone and all, a lizard’s replacement is filled with cartilage and lacks nerve cells. That contrast is due to differences between stem cells in the animals’ spinal cords, researchers report online August 13 in Proceedings of the National Academy of Sciences.

When a salamander loses its tail, neural stem cells in the creature’s spinal cord can develop into any type of nervous system cell, including nerve cells, or neurons. But through evolution, lizard neural stem cells “have lost this ability,” says study coauthor Thomas Lozito, a biologist at the University of Pittsburgh. Lizards, while they can regrow cartilage and skin, cannot regenerate neurons, the researchers found.
Lozito and colleagues studied neural stem cells from the axolotl salamander (Ambystoma mexicanum) and from two lizard species — the green anole (Anolis carolinensis) and the mourning gecko (Lepidodactylus lugubris). The team also wondered if the lizard stem cells themselves weren’t capable of developing into neurons or if there was something about the environment of the lizard tail that prevented their regrowth. So the researchers implanted salamander neural stem cells into five gecko tail stumps. Some of the cells became neurons in the regrown tails, showing that the lizard stem cells were the problem.

The finding suggests that scientists would have to alter only the lizard stem cells instead of other parts of the tail to regrow a more complete appendage.

How lizards lost their ability to regenerate neurons and salamanders didn’t remains a mystery (SN: 11/28/15, p. 12). Scientists know that species’ places on the evolutionary tree have something to do with organisms’ ability to regrow body parts. “The more complex the species are, the less they can regenerate,” says developmental biologist Katharina Lust of the Research Institute of Molecular Pathology in Vienna, who was not involved in the study. Reptiles such as lizards are more complex organisms than amphibians like salamanders.
The researchers plan to use CRISPR/Cas9 gene editing to see if lizard neural stem cells can be modified to regenerate a perfect tail. Ultimately, the team hopes to one day coax stem cells in mammals to regenerate body parts.

“My goal is to make the first mouse that can regenerate its tail,” Lozito says. “We’re kind of using lizards as a stepping-stone.”

An elusive Higgs boson decay has finally been spotted

The Higgs boson has been spotted bottoming out — but that’s a good thing.

Physicists have detected the elementary particle decaying into two bottom quarks, exotic, short-lived particles that often appear in the aftermath of high-energy particle collisions. The elusive process was finally observed six years after the Higgs boson’s initial discovery, by physicists working at the Large Hadron Collider at CERN in Geneva. Researchers from two LHC experiments, ATLAS and CMS, reported their results simultaneously in a seminar held at CERN on August 28.
Scientists don’t detect the Higgs boson directly. Instead, they spot the debris produced when the Higgs disintegrates into less massive particles. The Higgs boson is expected to decay to two bottom quarks more than half of the time. But scientists hadn’t been able to tease out the process until now, because other mechanisms can produce bottom quarks and mimic the Higgs decay (SN: 9/3/16, p. 13). Scientists previously saw the Higgs break down into other types of particles, including particles of light called photons, a process which has fewer issues with Higgs impersonators.

With the Higgs boson’s unveiling in 2012, physicists filled in the last missing piece of the standard model, the theory of the fundamental constituents of matter (SN: 7/28/12, p. 5). But physicists still want to know more about the Higgs’ inner workings.

The standard model makes predictions of how often the Higgs should decay into different types of particles. Bottom quarks are one of six types of quarks in the standard model, each of which has different properties, such as mass and electric charge. While the lightest quarks make up commonplace particles like protons and neutrons, bottom quarks are relatively heavy and rare.

Physicists want to measure the various ways the Higgs boson decays to see if the rates match expectations. If not, that could mean something is wrong with the theory. But the new results upheld the standard model.

The United States and Brazil top the list of nations with the most gun deaths

Gun deaths occur worldwide, but a new survey reveals the hot spots for those that occur outside of war zones.

In 2016, firearm-related homicides, suicides and accidental deaths were highly concentrated. For example, just six countries — the United States, Brazil, Mexico, Colombia, Venezuela and Guatemala — accounted for about half of the estimated number of gun deaths unrelated to armed conflict, even though the nations together contributed less than 10 percent of the world’s population.
That’s just one takeaway from the first look at the global impact of interpersonal and self-inflicted gun violence on public health, published online August 28 in JAMA. Here’s the big picture:

Total global gun deaths rose from 1990 to 2016
Worldwide, an estimated 251,000 people died from guns due to homicide, suicide or unintentional injury in 2016. That’s up from an estimated 209,000 such firearm deaths in 1990, the team found by analyzing data from 195 countries and territories from 1990 to 2016.

In 2016, 64 percent of gun-related deaths were homicides, 27 percent were suicides and 9 percent were accidental deaths.
But the rate of gun deaths dipped a bit
The researchers looked at the global rate of firearm deaths, adjusted for differences in the distribution of ages in a population. The rate decreased slightly, from 4.2 deaths per 100,000 in 1990 to 3.4 deaths per 100,000 in 2016, because the global population grew.

Even so, “we can see the number of deaths due to gun violence — homicide, suicide, unintentional injury — is very high,” says study coauthor and global health researcher Mohsen Naghavi of the University of Washington in Seattle. “Gun violence is a public health problem.”
More gun deaths occur outside of war zones than inside
Globally, for every year studied save one, gun deaths due to homicide, suicide and unintentional injury exceeded those due to conflict and terrorism. The exception: 1994, the year of the Rwandan genocide. That year, the death toll from global conflict reached 551,000, compared with 232,000 deaths from gun homicides, suicides and unintentional injuries.

The United States and Brazil are hot spots of gun violence
These two countries accounted for 32 percent of the total number of estimated deaths in 2016. In Brazil and the other top four Latin America countries, most gun deaths were homicides. The high rate of gun homicide in these countries is associated with drug and weapon trafficking, research has found. One-fourth of all global gun-related homicides in 2016 took place in Brazil.
But in the United States, as in some other wealthy countries, such as France and Germany, suicide accounted for the majority of gun deaths in 2016. Thirty-five percent of all global firearm suicides that year occurred in the United States, the researchers estimate.

Suicide rates have risen across the United States since 1999 (SN: 7/7/18, p. 13). Previous research has shown that having guns in the house is linked to higher use of the weapons to commit suicide and to a larger number of unintentional gun-related deaths.

Rubidium atoms mimic the Eiffel Tower, a Möbius strip and other 3-D shapes

A new experiment gives rubidium atoms a certain je ne sais quoi.

Scientists arranged individual atoms of the element rubidium into a variety of 3-D shapes, including the Eiffel Tower. The team used a laser to trap atoms in the arrangements, performing a hologram-style technique to encode the complex positions. And moveable, laser-based “tweezers” (SN: 5/12/18, p. 24) shifted atoms that were in the wrong position, researchers from the Institut d’Optique Graduate School in Palaiseau, France, report in the Sept. 6 Nature.

In addition to the Parisian landmark, the researchers sculpted a cone, a doughnut and a Möbius strip — a twisted ring with the unusual property of having only one side (SN Online: 7/24/07). The technique may be helpful for creating atomic quantum computers, which could make calculations by manipulating the interactions between individual atoms (SN: 7/8/17, p. 28).