The beard now feared! Visiting NBA superstar James Harden got a taste of Chinese speed with his jaw on the floor, as he sold out 10,000 bottles from his J-HARDEN brand wine within seconds during a live commerce on Tuesday night.
Harden showed up in the Chinese online celebrity CrazyXiaoyangge's livestreaming channel on Tuesday night with his personal brand J-Harden wine. Within seconds, Harden was told that 5,000 orders (436 yuan or $60 for two bottles) had been placed, meaning his 10,000 bottles were sold out at lightning speed. More than 15 million people watched the Harden live stream on Tuesday night.
Finding the China speed unbelievable, Harden shouted with excitement "no way!" Harden had to go to the computer to confirm the sales record.
Harden then added another 3,000 orders and again they were sold out within seconds.
Feeling so pumped, the NBA super star even performed a side cartwheel.
Chinese basketball fans showed much support to Harden during the livestreaming, leaving "MVP" comments all over the live stream .
Harden, in return, learned to say "woaini" - "I love you" in Chinese, to his fans during the livestreaming. And discussion on James Harden being amazed by China speed during the live commercial became trending topic on China's twitter-like Sina Weibo on Wednesday morning.
Diehard Harden fans even suggested that if the NBA star is not happy in the American basketball league, he is welcomed to joint Team China and become an influencer on the Chinese internet.
Harden, although completing a season that failed to meet expectations with Philadelphia 76ers, received broad support from Chinese fans during China summer tour, especially after he lashed out at the team's president Daryl Morey as "a liar" during a commercial event in Beijing on Monday.
"Daryl Morey is a liar and I will never be a part of an organization that he's a part of," "Let me say that again: Daryl Morey is a liar and I will never be a part of an organization that he's a part of," he said.
In October 2019, Morey then the GM for the Houston Rockets posted on Twitter a slogan used by Hong Kong rioters at the time.
He quickly drew the ire of the Chinese people and the team's Chinese fans and also triggered a backlash from business partners, including a more-than-one-year long suspension of NBA games on China Central Television (CCTV).
In a study of pregnant women in Brazil, nearly 30 percent of those infected with Zika virus had babies with fetal abnormalities, researchers report March 4 in the New England Journal of Medicine.
Zika virus is the leading suspect for what’s causing a spike in certain birth defects reported in Brazil. Scientists have previously found traces of Zika in the brains of fetuses with microcephaly (a birth defect that leaves babies with smaller-than-normal heads). And one study has reported that the virus can infect and kill a cell type crucial to developing brains (SN Online: 3/4/16).
The new study enrolled 88 pregnant women from Rio de Janeiro who had developed a rash (a sign of Zika infection). They tracked the women throughout their pregnancies; so far, eight have given birth. Of the 42 women who both tested positive for Zika and received fetal ultrasounds, 12 of the women’s babies had abnormalities (including small heads, damaged brain tissue, and low levels of amniotic fluid).
Despite mild clinical symptoms, Zika infection during pregnancy appears to be linked with grave outcomes, the authors write.
A new, extremely black material can turn water into steam using only sunlight, without the need to bring the water to a boil. Made of gold nanoparticles tens of billionths of a meter wide affixed to a scaffold pocked with tiny channels, or “nanopores,” the material is a deep black color because it reflects very little visible light. It is 99 percent efficient at absorbing light in the visible spectrum and parts of the infrared spectrum, researchers report April 8 in Science Advances.
Thanks to its highly porous structure, the material floats on the surface of water, allowing it to soak up the sun’s rays. When light of a certain wavelength hits a gold nanoparticle inside one of the nanopores, it stirs up the electrons on the surface, sloshing them back in forth in an oscillation known as a plasmon. These plasmons produce localized, intense heating, which vaporizes the water nearby. The wavelength of light that excites a plasmon depends on the size of the nanoparticle. So in order to take advantage of as much of the sun’s output as possible, the group interspersed a variety of sizes of gold nanoparticles in the pores, which could therefore absorb a range of wavelengths. It’s not the first time scientists have produced steam with plasmonic materials, but the new material improves the efficiency of the process, converting up to 90 percent of the light’s energy into steam, says materials scientist Jia Zhu of Nanjing University in China, a leader of the research group.
“They have really come out with a very intriguing solution,” says mechanical engineer Nicholas Fang of MIT, who was not involved in the research. The efficiency isn’t quite as high as scientists have achieved with certain other types of materials, like carbon nanotubes, Fang says. But the new material should be cheaper to manufacture.
Efficient steam generation could be useful for desalination, producing freshwater from salty water, says Zhu. Other potential applications range from sterilization to running steam engines. “Steam can be used for many other things,” he says. “It is a very useful form of energy.”
Just how fantastical a planet can be and still support recognizable life isn’t just a question for science fiction. Astronomers are searching the stars for otherworldly inhabitants, and they need a road map. Which planets are most likely to harbor life? That’s where geoscientists’ imaginations come in. Applying their knowledge of how our world works and what allows life to flourish, they are envisioning what kind of other planetary configurations could sustain thriving biospheres.
You don’t necessarily need an Earth-like planet to support Earth-like life, new research suggests. For decades, thinking about the best way to search for extraterrestrials has centered on a “Goldilocks” zone where temperatures are “just right” for liquid water, a key ingredient for life, to wet the surface of an Earth doppelgänger. But now it’s time to think outside the Goldilocks zone, some scientists say. Unearthly mechanisms could keep greenhouse gas levels in check and warm planets in the coldest outer reaches of a solar system. Life itself could even play a starring role in a planet’s enduring habitability. “It’s an exciting time,” says Harvard planetary scientist Robin Wordsworth. “There’s still a ton for us to learn about the way different planets behave. The Goldilocks zone is just a very rough guide, and we need to keep an open mind.”
Currency of life When it comes to habitable planets, water continues to be the currency of life. Too close to a star and all the water on a planet evaporates; too far and the planet is an icy snowball. The Goldilocks zone marks the region between those two extremes, where water can stay liquid. Every known organism requires liquid water at some point during its life cycle. Extraterrestrial life could be completely unlike anything seen on Earth, of course, but “we’ve got to start looking somewhere,” says Colin Goldblatt, a planetary scientist at the University of Victoria in Canada. “At least we know what Earth life looks like.” With the assumption that water is king, astronomers search for wet planets using powerful telescopes. The search is limited by what the telescopes can see in a planet’s atmosphere, however. Life-supporting liquid water could hide under the surface, for example, inside Jupiter’s icy moon Europa (SN: 10/4/14, p. 10). And any subterranean life, which typically wouldn’t alter the atmosphere, would probably be undetectable. Even with rovers roaming Mars, scientists can’t tell for certain whether Martian groundwater hosts life (SN: 12/26/15, p. 26). For alien life to be observable from afar, liquid water would have to be at the surface, not just concealed belowground.
With liquid surface water as a must-have for hunting extraterrestrials, astronomers estimated the extent of the habitable region more than 50 years ago. Early research confined the Goldilocks zone for our own solar system to a narrow band — one estimate placed it from 0.95 times to 1.01 times Earth’s average distance from the sun. But then scientists realized the surprising influence of Earth’s built-in temperature control system: the carbon cycle, the process by which carbon travels from the atmosphere into the Earth and back out to the atmosphere.
The carbon cycle controls how much heat-trapping carbon dioxide is in the atmosphere. Rainfall weathers exposed rocks, causing a chemical reaction that pulls CO2 from the air and into the oceans and eventually underground via plate tectonics. Volcanoes, meanwhile, spew CO2 into the atmosphere. This cycle keeps the planet’s temperatures from getting too extreme.
If the climate ever gets too cold, the carbon cycle could boost CO2 to compensate. For instance, if temperatures drop and rainfall slows, the lack of weathering will allow CO2 to build up in the atmosphere. And as volcanoes continue belching up additional CO2, temperatures will rise and rainfall will rise. And if things get so hot that glaciers melt and rainfall increases, the planet will cool as weathering accelerates and draws down more CO2 from the atmosphere. Plants and other organisms also play roles in drawing in CO2 or releasing it into the air.
This balancing act could help keep planets within a comfortable range for life, expanding the habitable zone to as wide as 0.5 to 2.0 times Earth’s distance from the sun, though these numbers are hotly contested. Thanks to the carbon cycle, Earth might still be habitable even if pushed out to Mars’ orbit, says Penn State geoscientist James Kasting.
Rocky recycling Not every planet tucked safely inside the habitable zone is necessarily life-friendly. Venus and Mars are within the habitable zone by some definitions, but neither boasts a livable surface climate. More than location is at play. Other factors such as plate tectonics may make a planet right or wrong for life. Plate tectonics is an important piece in the temperature-controlling carbon cycle, as the shifting and sinking plates that cover Earth’s surface carry carbon into Earth’s interior that later erupts from volcanoes. Some scientists propose that planets akin to Venus and Mars that lack the conditions for plate tectonics should be crossed off the “explore list” (SN: 1/23/16, p. 8). Lindy Elkins-Tanton, a planetary scientist at Arizona State University in Tempe, disagrees. On exoplanets, other processes could do the job of plate tectonics, she said last December at an American Geophysical Union meeting in San Francisco. “We’re too Earth-centric in our notion of how you can create a planetary carbon cycle,” she says. “What else can we consider?”
One alternative could be the churning of a planet’s outer layers in a way that doesn’t require giant shifting slabs. The deepest part of a terrestrial planet’s outermost shell becomes denser as pressures increase with depth. Rising molten rock from the planet’s hot interior can also add density and heat to the bottom of the shell, making the rock runnier and denser. Even just a 1 percent density change could produce globs of material dense enough to sink deeper into the planet, carrying carbon along for the ride, Elkins-Tanton proposes.
As the material sinks, it releases some water like a squeezed sponge. This carbon-containing water then seeps back toward the surface. Water loosens the bonds that hold rocks together, which lowers a rock’s melting point. If enough water accumulates, molten magma pools form and fuel volcanic eruptions. Together, these mechanisms could substitute for plate tectonics in the carbon cycle, Elkins-Tanton says. True, the process would be much slower than plate tectonics, but it could keep some planets’ climates livable, her simulations show.
Hot air Of course, the carbon cycle matters only if CO2 is the main driver of the atmospheric blanket that keeps a planet cozy enough for life-sustaining liquid water. Plenty of other greenhouse gases, such as ozone or nitrous oxide, could keep exoplanets temperate. One, however, would be particularly potent: hydrogen.
Earth used to have a lot more hydrogen in its atmosphere. In 2013, Wordsworth and planetary scientist Raymond Pierrehumbert, now at the University of Oxford, proposed that hydrogen could have kept Earth warm back when the sun was cool. They were attempting to resolve the faint young sun paradox (SN: 5/4/13, p. 30).
Early in Earth’s history, about 3.8 billion years ago, the sun shined 20 to 30 percent less brightly than it does now. Keeping the young planet warm posed a problem. Wordsworth and Pierrehumbert proposed that hydrogen, when combined with abundant nitrogen in the atmosphere, could serve as a paradox-resolving greenhouse gas. When hydrogen and nitrogen molecules collide in the air, the hydrogen molecules start wobbling differently. This wobbling increases the range of light wavelengths that hydrogen molecules absorb, amplifying the greenhouse effect. Hydrogen escaped from Earth’s atmosphere over time. But on larger rocky planets with stronger gravitational pulls, that hydrogen would stick around, Wordsworth says. With enough hydrogen and nitrogen, a planet can keep warm far outside of the CO2-based Goldilocks zone, Wordsworth says. Planets as far away from their sun as Pluto is to ours could stay above freezing. Even rogue planets alone in the cosmos with no parent star might keep warm enough to support life (SN: 4/4/15, p. 22).
The problem, however, is that these planets would need something akin to a carbon cycle to fine-tune hydrogen concentrations and prevent temperatures from getting too hot or too cold. Worse yet, at least on Earth, enterprising microbes feast on any available hydrogen for energy. Emerging life-forms could gorge on an exoplanet’s hydrogen, essentially eating the very thing keeping the planet warm enough for life. Those planets therefore might not stay habitable long enough for advanced life to evolve, Wordsworth says. The inhabitance paradox The hungry microbes might actually be good for hydrogen-wrapped planets, planetary scientist Dorian Abbot of the University of Chicago proposed at the AGU meeting in December. Higher temperatures make enzymes work faster and microbes more active. If temperatures rose, the hydrogen-chomping microbes would draw more hydrogen from the atmosphere and cool the planet. And if temperatures fell too far, microbe activity would fall and hydrogen levels would stabilize.
The ability of life, like those microbes, to fundamentally alter the climate and chemistry of its home planet poses a new paradox, Goldblatt said at the same meeting. Whether or not a planet is habitable could sometimes depend on whether life has already made itself at home there. He calls it the inhabitance paradox; the idea is an extension of the Gaia hypothesis, the proposal that organisms alter their surroundings to maintain a habitable environment. In other words, life could be a requirement for life.
The paradox showcases just how complex the hunt for habitable planets has become, Goldblatt says. “There are many other ways to support life — we just don’t know what they are yet,” he says. “Our imagination is limited to our experience. We’re going to observe other planets and see things we never have imagined.”
In a galaxy far, far away, Chewbacca is a 7.5-foot-tall Wookiee. On Earth, he’s a small furry beetle.
Researchers discovered four new species of weevils on an island off the coast of Papua New Guinea, one of which they named after the lofty Star Wars character. Trigonopterus chewbacca is a black, flightless beetle about 3 millimeters long that thrives in the tropical forests of New Britain. Although T. chewbacca doesn’t resemble its namesake in size, the dense hairlike scales covering its head and legs reminded the researchers of Chewbacca’s fur.
Before these finds, Trigonopterus beetles hadn’t been spotted on New Britain. The discovery of T. chewbacca and its three relatives, T. obsidianus, T. puncticollis and T. silaliensis, suggests that the genus colonized the island at least four separate times, the team reports April 21 in ZooKeys.
T. chewbacca joins the ranks of other insects with a Star Wars moniker. Among its peers: a furry moth also named after the heroic Wookiee, a wasp named for Yoda and a Darth Vader slime-mold beetle.
Vultures are the birds everyone loves to hate. Even though you have nothing to fear from them — unless you’re dead — vultures’ steady diet of carrion will gross most people out. That diet may also be responsible for the birds’ quick and steep declines around the globe, a new study shows.
It’s not the dead bodies that are killing vultures, though. It’s the poisons with which humans have laced those meals, both intentionally and inadvertently, Evan Buechley and Çağan Şekercioğlu of the University of Utah in Salt Lake City conclude in the June Biological Conservation.
The team went searching for an explanation to something Şekercioğlu had reported in 2004 and is still true today — that vultures are the most threatened group of birds. Of the 22 species of vultures, nine are now critically endangered, three are endangered and four are near threatened, according to the International Union for Conservation of Nature, which tallies endangered species.
Buechley and Şekercioğlu were looking for an explanation of why these scavenging species (called “obligate scavengers” because they depend almost entirely on carrion for survival) are doing so poorly but “facultative scavengers” — birds such as storks, gulls and crows that can also eat things other than carrion and trash — tend to be doing well and even increasing in numbers in many cases. The researchers collected ecological information and population trend data on the 22 species of vultures and other avian scavengers and then tried to figure out what made the vultures so vulnerable.
Some aspects of biology do contribute to the vulture declines, the team found. These are large animals that live long and don’t produce a lot of offspring. That means that populations can take a long time to recover from bird deaths. But the ultimate cause of those deaths is what is disturbing — dietary toxins, which are the primary cause of declines in 14 of the 16 threatened and near-threatened vulture species, the team found.
Those toxins come in various forms. In India and Southeast Asia, it’s the cattle drug diclofenac, which causes kidney failure in any vulture unlucky enough to come across a cow that didn’t survive its medical treatment. Diclofenac is a problem for vultures in Africa, too, (and now Spain), but there the birds have also fallen victim to the poisons used to kill hyenas, jackals and lions in response to dead livestock. Wildlife poachers have also deliberately poisoned their prey in an effort to get rid of the circling vultures that can alert authorities to their crime. (Buechley and Şekercioğlu discovered a 2007 incident in Namibia in which a poisoned elephant carcass killed as many as 600 birds.) And in Europe and the Americas, carcasses laced with rodenticides, insecticides and lead from ammunition are also killing vulture species.
Without vultures, some of these ecosystems are already having problems. Other scavenging species aren’t quite able to fit into the vulture niche. They can’t eat as much and they don’t have stomachs equipped to kill deadly microbes, like vultures do. That means anything that does eat carrion could potentially spread disease. Populations of scavenging pests, like rats and feral dogs, have already skyrocketed in some places as these animals feast on what vultures would have once dealt with. Perhaps not surprisingly, that has led to problems, such as an increase in dog bites in India that has resulted in thousands of human deaths from rabies.
Much of the vulture declines could be easily solved by banning the chemicals that kill them, the researchers note. Because while vultures may be more inherently vulnerable to extinction than other bird species, due to their biology, their importance to the global ecosystem — and our own health — makes them too valuable to let slip away.
DNA from an ancient woman who lived in what’s now Romania indicates that people in Asia trekked to Africa starting between 45,000 and 40,000 years ago.
Evidence for this back-to-Africa trip comes from the partial remains of a 35,000-year-old Homo sapiens discovered in a Romanian cave more than 60 years ago. A distinctive pattern of alterations to mitochondrial DNA extracted from two of the teeth are similar to alterations seen in mitochondrial DNA of present-day North Africans, signaling an evolutionary connection, the team proposes May 19 in Scientific Reports.
After evolving in Africa around 200,000 years ago, human populations spread out of the continent by 50,000 years ago. The ancient Romanian woman’s DNA came from a maternal line that originated in West Asia after humans initially left Africa but then ended up in North Africa, the scientists propose.
Careening through the bloodstream, a single nanoparticle is dwarfed by red blood cells whizzing by that are 100 times larger. But when specially designed nanoparticles bump into an atherosclerotic plaque — a fatty clog narrowing a blood vessel — the tiny particles can play an outsized role. They can cling to the plaque and begin to break it down, clearing the path for those big blood cells to flow more easily and calming the angry inflammation in the vicinity.
By finding and busting apart plaques in the arteries, nanoparticles may offer a new, non-surgical way to reduce a patient’s risk for heart attack and stroke.
Nanoparticles measure less than 100 nanometers across — a thousandth the thickness of a dollar bill. Despite being tiny, they can be engineered to haul a mix of molecules — such as tags that make them stick to a plaque, drugs that block inflammation or dyes that let scientists track their movements. Over the last two decades, scientists have exploited these strategies to fight cancer, designing nanoparticles that deliver drugs (SN Online: 1/3/14) or dyes for imaging deep into the core of a tumor. The U.S. Food and Drug Administration has approved a few dozen cancer-focused nanomedicines. Now researchers have begun engineering nanoparticles to target cardiovascular disease, which kills even more people each year than cancer. Nanosized compounds have been built that can sweep into clogged arteries to shrink the plaques that threaten to block blood flow. Some nanoparticles home in on the plaques by binding to immune cells in the area, some do so by mimicking natural cholesterol molecules and others search for collagen exposed in damaged vessel walls. Once at the location of a plaque, either the nanoparticles themselves or a piggybacked drug can do the cleanup work.
The aim of all these approaches is to prevent strokes and heart attacks in people with cardiovascular disease, either before surgery becomes necessary or after surgery to prevent a second event. Today, cardiovascular nanoparticles are still far from pharmacy shelves. Most have not reached safety testing in patients. But in mice, rats and pigs, nanodrugs have slowed the growth of the plaques that build up on vessel walls, and in some cases have been able to shrink or clear them.
“I think the effect we can have with these nanoparticles on cardiovascular disease is even more pronounced and direct than what we’ve seen in cancer,” says Prabhas Moghe, a biomedical engineer at Rutgers University in Piscataway, N.J. Every minute, more than a gallon of blood pumps through the human heart, pushing through miles of blood vessels to deliver oxygen and nutrients to organs and extremities. In a healthy person, the trip is as smooth as a drive on a freshly paved highway. But in the more than 10 percent of U.S. adults who have cardiovascular disease, the route might be more like a pothole-filled road squeezed by Jersey barriers.
Waxy globs, or plaques, of fat and cholesterol line the blood vessels, thickening and hardening the walls, impeding blood flow. As fat builds up inside the vessels, it also leaks into the vessel walls, swelling them and signaling the body to send immune cells to the area. The congregation of immune cells aggravates the blockage, the way emergency vehicles surrounding the site of a multi-car pileup further slow traffic on a highway.
“The inflammation and the accumulation of fat in the walls of the blood vessel sort of feed off each other and exacerbate each other,” Moghe says.
If the plaques grow large enough, or pieces chip off and travel to smaller vessels, they can block a vessel. If oxygen-filled blood can’t reach the brain or heart, a stroke or heart attack results.
The drugs most often prescribed to prevent or treat atherosclerosis — plaque buildup on the inner walls of the arteries — are statins (SN: 5/5/12, p. 30). This highly successful and effective class of drugs, available since 1987, slows the growth of the fatty plaques by lowering the amount of cholesterol circulating in the blood. But taking statins is akin to limiting the number of cars on a damaged road rather than repairing potholes, some argue. And the drugs can boost a person’s risk of diabetes and liver damage. In many cases, patients don’t begin taking statins until they already have severe atherosclerosis, and the drugs do little to reverse the buildup of plaques that already exist.
“Heart disease is still the number one killer in the U.S.,” says endocrinologist and biochemist Ira Tabas of Columbia University Medical Center. Drug-carrying nanoparticles that can shrink existing atherosclerotic plaques and eliminate the accompanying inflammation could change that, Tabas and others say. Going places To treat atherosclerotic plaques with nanoparticles, researchers have devised a variety of ways to send circulating particles directly to the fatty clogs. In each approach below, a molecule that’s part of the nanoparticle binds to a molecule in or near the plaques.
Click the black dots in the interactive image below to learn about different types of nanoparticles. Macrophage magnet To make nanoparticles congregate at the dangerous plaques, researchers need to identify something that makes the blockage stand out from the rest of the body. The crowds of immune cells near plaques act as a signpost that a plaque exists.
Many of the immune cells involved in atherosclerosis are macrophages, white blood cells that gulp pathogens, dead cells or debris in the body. At the site of a plaque, macrophages become swollen with fats and transform into what are called “foam cells” because of their foamy appearance. As they digest fats, foam cells send out chemical signals to recruit more inflammation-causing cells and molecules to the area. Because they’re so intimately involved in the formation of plaques, macrophages and foam cells are a prime target for nanoparticles.
Moghe’s group has designed nanoparticles that bind to molecules on the surface of macrophages, preventing them from gobbling fats and becoming foam cells. The researchers made the nanoparticles specifically target a subtype of macrophage that’s involved in atherosclerosis, not the macro-phages that might respond to other injuries in the body. When nanoparticles were injected into mice with narrowed arteries, the blockages decreased by 37 percent, Moghe’s group reported last year in the Proceedings of the National Academy of Sciences.
Others are using cholesterol-like molecules as nanoparticle taxis to carry drugs to plaques and subdue the immune reaction. Statins aim to lower the form of cholesterol called low-density lipoprotein, which earned the name “bad cholesterol” for accumulating in plaques. High-density lipoprotein, or “good cholesterol,” shuttles LDL away from these clogs to the liver, where it can be broken down. HDL also prevents macro-phages from turning into foam cells and producing inflammatory molecules. So Shanta Dhar, a chemist at the University of Georgia in Athens, developed nanoparticles that mimic HDL. She presented the work in March in San Diego at a meeting of the American Chemical Society.
“HDL is our body’s natural cholesterol-removing nanomaterial,” she says. In animal tests, the HDL-based nanoparticle can bind to free-floating macro-phages circulating in the blood, just as HDL does, and follow them to a plaque, she explains. The nanoparticles can also bind to macrophages already glommed on to a plaque, and, mimicking the activities of natural HDL, carry the cells away.
Plaque buster Willem Mulder, a nanomedicine researcher at the University of Amsterdam and the Icahn School of Medicine at Mount Sinai in New York City, has also designed HDL-mimicking nanoparticles. His particles deliver statins that make a beeline for macrophages and plaques, letting him administer the drug at lower-than-usual doses. He was inspired by earlier studies that showed how extremely high doses of statins, given to mice, could lower LDL levels while also packing anti-inflammatory properties. Of course, in humans, such high doses would probably cause liver or kidney damage. Mulder’s solution: tack the statins to a nanoparticle to send them, missile-like, to the plaques. That way, a low dose of the drug could achieve the high concentration needed at the site of the atherosclerosis. “We’re exploiting the inherent targeting properties of HDL,” he says. “And it works well with statins, which are small molecules.”
In 2014 in Nature Communications, Mulder’s group reported that plaque-filled arteries in mice given the nanoparticle were 16 percent more open than arteries in mice with no treatment, and 12 percent more open than in mice given a systemic statin. More work is needed to show whether these modest gains would translate to a reduced risk of heart attacks and strokes.
Others are using plaque-targeting nanoparticles to deliver anti-inflammatory drugs similar to methotrexate, which is used as a treatment for rheumatoid arthritis. The side effects of drugs like this, given systemically, are generally severe: vomiting, hair loss and “brain fog,” to name a few.
“If someone with rheumatoid arthritis comes into your office completely crippled, it’s worth all the side effects to put them on an anti-inflammatory drug,” Tabas says. “But imagine someone with some risk factors for heart disease who feels great. They’re not going to put up with these side effects.”
Tabas thinks that drugs that work distinctly from traditional anti-inflammatory drugs and promote resolution of inflammation and healing, known as pro-resolving drugs, could be perfect candidates to tack on to nanoparticles because they would make possible lower doses with fewer side effects.
He’s awaiting the results of two large clinical trials testing non-nano-versions of the drugs methotrexate and anti-IL1 beta. It remains to be seen whether they’re effective at clearing plaques and how severe the side effect are. If the drugs are effective, even with some side effects, Tabas says, it will give weight to his approach: Activating pro-resolving pathways using targeted nanoparticles.
Tabas and his collaborator Omid Farokhzad at Harvard University encapsulate their nanoparticles with a small section of a protein called annexin A1, which helps resolve inflammation and promote healing. His hope is that delivered only to an atherosclerotic plaque, the drug won’t have the host of side effects that other immune blockers have.
Destination: vessel wall The inflamed vessel wall around an atherosclerotic plaque goes through several changes in addition to the accumulation of belligerent immune molecules. As vessel walls are stretched and inflamed, the structural protein collagen, meant to keep the vessels taut and tubular, becomes exposed the way the threads of a tire begin to appear as it wears down. Scientists are using the exposed collagen to their advantage. Nanoparticles with a tag recognizing the collagen end up at plaques. But it’s not as easy as affixing a GPS destination to the particles, says vascular surgeon Melina Kibbe of Northwestern University Feinberg School of Medicine in Chicago.
“It took us over a year of trying to find the right targeting [molecule] that would work,” Kibbe says. Her nanoparticle combines a collagen-binding protein with nitric oxide, a molecule that stimulates the growth of new cells at wounds. To maximize the surface area of the drug that contacts the vessel wall, Kibbe’s team arranged the molecules in a line, forming a nanofiber, rather than a sphere. As the fiber is swept through the bloodstream, it binds to exposed collagen, anchoring the nitric oxide in place to spur healing of the artery.
Kibbe and colleagues added fluorescent tags to the nanofibers and showed that the fibers congregated at injured spots on mouse arteries within an hour of injection. The tagged particles remained there for three days and the treated vessels ended up 41 percent more open, the researchers reported in the March Antioxidants & Redox Signaling. Tabas also uses a collagen-binding protein, one that is organized in a more spherical shape, to get the piece of annexin A1 to atherosclerotic plaques. In mice, the particles stayed in the plaques up to five days after treatment, shrinking the plaque by more than a third, his team reported in Science Translational Medicine in 2015. By comparison, some circulating statins last less than a day in the blood.
Rather than targeting proteins or immune cells, scientists at Harvard’s Wyss Institute for Biologically Inspired Engineering have designed nanoparticles that are activated by the physical squeeze that comes with being swept through a narrowed artery. When the shear force around them increases, a cue that a plaque is present, the nanoparticles release their payload: a clot-dissolving drug called tissue plasminogen activator. The researchers reported late last year in Stroke that the nanoparticle, coupled with a stentlike device placed in the artery, increased the survival rate to more than 80 percent in mice that normally die of a clot entering their lungs.
Pathway to patients Nanoparticles currently in development for cardio-vascular disease are still in animal testing. While no one has seen major side effects or toxicity in the animal trials so far, it remains a concern with a class of medicines that is so new.
“We sometimes get so wrapped up in exuding only the good stuff about nanomedicine that we forget we also have to look at the side effects,” Dhar says. Another challenge for atherosclerosis drugs is determining who would benefit from treatment. Kibbe imagines her particles being used first in patients with severe atherosclerosis who receive stents or other invasive procedures to clear their plaques. The procedures are intended to help, she says, “but they actually are so traumatic that they cause injury to the vessel wall.” Due in part to this renewed buildup in the arteries, people who have had one heart attack are at higher risk for a second. Even among people who have a permanent stent put in, which is designed to keep part of an artery clear, up to 20 percent become reblocked. Giving these patients nanoparticle-based drugs could keep them healthy, Kibbe says.
Taken to the next level, nanomedicines “certainly might be able to prevent plaques,” she adds. Tabas imagines his nanoparticles given as a once-a-month injection, but that’s speculation.
Moving to test nanoparticles as a preventive — in the huge percentage of the population at risk for athero-sclerosis — is probably a long way off, Mulder says. According to the U.S. Centers for Disease Control and Prevention, around half of all adult Americans have one of the top risk factors for cardiovascular disease.
“I really don’t foresee that you would start preventively treating patients who don’t have symptoms with nanoparticles,” Mulder says. “But to take a person who’s hospitalized after a heart attack and stick a needle in their arm and infuse nanoparticles, that’s not hard.”
Once a few drugs have been validated as working in clinical trials, researchers expect progress to speed up, since the drug cargo on a nanoparticle engineered to target a plaque could easily be switched out for other drugs. Designing the particles, says Moghe, “is almost like building with pieces of Lego.”
This article appears in the June 11, 2016, issue of Science News with the headline, “Nano for the heart.”
Editor’s Note (revised): This article was edited on July 1 and again on July 2, 2016. Due to a misunderstanding by the writer, a quote in the original article mistakenly implied that researcher Ira Tabas of Columbia University was referring to problems with statins. He was, in fact, referring to problems with anti-inflammatories. He is not a critic of statins. Additional changes were made to clarify the activity of annexin A1. It is not a traditional anti-inflammatory agent, as was stated in the article, but what is called a pro-resolving molecule. Tabas did not develop the nanoparticles he works with, as was implied in the original. We now credit the researcher who developed those nanoparticles.
Most people think that autism is a disorder of the brain. But the skin may play a role, too, a new study suggests.
Nerve cells in the skin are abnormal in mice with mutations in autism-related genes, leading to poor touch perception, scientists report June 9 in Cell. This trouble sensing touch may influence the developing brain in a way that leads to social deficits and anxiety later in life.
The results raise the provocative idea that fixing abnormal senses may alleviate some of the behavioral symptoms of autism, says study coauthor David Ginty, a neuroscientist at Harvard Medical School. To explore the role of touch, Ginty and colleagues used mice that carried mutations in genes linked to autism. The genes are active in many places, including the brain. But the researchers used genetic tricks to place the mutated genes only in the peripheral nervous system — the collections of nerves outside the brain and spinal cord.
Adding mutations in a handful of autism-related genes only in peripheral nerves interfered with the mice’s sense of touch. These mice had trouble telling a smooth object from a rough one, and they had outsized reactions to harmless puffs of air. “They’re really touchy when you pick them up,” Ginty says. The sensory breakdown was caused by touch-sensing nerve cells that seemed to have trouble sending messages to the spinal cord, the researchers found.
Some mice also had behavioral deficits. Those with mutations in one of two genes — Mecp2 or Gabrb3 — in the peripheral nervous system, but not the brain, showed more signs of anxiety and interacted with other mice less than mice that didn’t have those mutations. Discovering that changes in the touch-sensing nerve cells could affect behavior was unexpected, Ginty says.
The skin’s influence seems to be important early in life. Social behaviors and anxiety didn’t suffer when the genes were first mutated in touch-sensing nerve cells during adulthood. The effect on behavior showed up only when the genes were abnormal during development, the team found.
That finding is “the most impressive part of the work,” says neuroscientist Kevin Pelphrey of George Washington University in Washington, D.C. The results emphasize how autism is an inherently developmental disorder, he says. Pelphrey and colleagues previously found that the brains of children with autism react differently to light touch, which fits with the idea that problems of touch may be involved in the disorder.
Next, Ginty and colleagues plan to figure out exactly when these genes do their important work in the peripheral nervous system. “We are now really interested in the window of time,” he says. “Presumably that window closes at some point, and we’re trying to figure out when that is.” The researchers will also explore ways to restore normal touch sensation, including drugs or genetic manipulations, that would work before the window closes.
It’s possible that other nerve cells outside the brain are affected in autism, too, says neuroscientist Aaron McGee of the University of Southern California in Los Angeles. “If you have these problems with peripheral nerves that have roles in active sensation, do you also have problems with the nerves that innervate the gut?” If so, that could help explain why people with autism often experience gut trouble.
McGee cautions that it’s difficult to compare behaviors of mice with symptoms of autism in people. But he says that the genetic experiments described in the paper are “awesome, thorough and significant.”
Pig fat has made the leap from kitchen staple to laboratory marvel for its ability to grow bone. Stem cells from the fat tissue of Yucatán minipigs grew into pieces of bone that were then successfully implanted into the pigs’ jaws, researchers report June 15 in Science Translational Medicine.
The team of bioengineers used cow bone scaffolds infused with stem cells from a minipig’s fat tissue to grow bone grafts in a special chamber in the lab. The new bones, which were personally fitted to each minipig’s jaw, fared better after six months than standard bone grafts not seeded with fat cells.
The new research brings scientists a step closer to one day using fat stem cells to repair humans’ broken or worn-out body parts.
