Culture

Salivary gland cells revealed as sites of COVID-19 infection

Scientists have shown that SARS-CoV-2, the virus that causes COVID-19, can infect specific cells in the salivary gland in the mouth. The study by researchers from the Wellcome Sanger Institute, National Institutes of Health and the University of North Carolina at Chapel Hill, and their collaborators within the Human Cell Atlas Oral & Craniofacial Network, also discovered that live cells from the mouth were found in saliva, and that the virus was able to reproduce within these infected cells.

The study revealed that salivary gland cells could play a role in transmission of the SARS-CoV-2 virus to the lungs or digestive system via saliva. Understanding the involvement of mouth cells could inform strategies to reduce viral transmission within and outside the body.

Reported today (25th March) in Nature Medicine, this first publication with the HCA Oral & Craniofacial Network is part of the international Human Cell Atlas (HCA) consortium effort to map every cell type in the human body, transforming our understanding of health, infection and disease. The study could also help explain some of the oral symptoms experienced by COVID-19 patients, including taste loss, dry mouth and blistering.

Previous studies* have shown that cells in the nose and lung contain high levels of RNA for key proteins that allow the SARS-CoV-2 virus to enter cells. However, the role of the mouth in COVID-19 transmission is poorly understood. While it is known that saliva of people with COVID-19 can contain SARS-CoV-2, it has been unclear if mouth cells are involved.

To investigate the role of mouth cells, the researchers first studied mouth tissue samples from healthy volunteers, using cutting-edge single cell RNA sequencing technology and bioinformatics methods. They looked for individual cells that expressed two key entry proteins - ACE2 and the TMPRSS2 protease - which SARS-CoV-2 uses to infect human cells, and discovered that salivary gland ductal cells and some gingival, or gum, cells expressed both proteins. This showed that these cells were vulnerable to infection.

Next, the researchers investigated mouth tissues from COVID-19 patients who had died or who had given biopsy samples. They discovered SARS-CoV-2 RNA in salivary gland cells, indicating these cells had been infected and found evidence that the virus was replicating in some of these cells.

The study also discovered that saliva from people with mild or asymptomatic COVID-19 contained mouth cells carrying SARS-CoV-2 RNA and RNA for the entry proteins. When saliva from eight of the asymptomatic people was added to monkey cells grown in dishes, some of these cells became infected. This raises the possibility that even people without symptoms might transmit infectious SARS-CoV-2 to others through saliva.

Professor Kevin M. Byrd, joint lead author on the study and a coordinator of the HCA Oral & Craniofacial Biological Network, who carried out the work at the Adams School of Dentistry at the University of North Carolina at Chapel Hill, said: "Taken together, the study's findings suggest that the mouth, via infected oral cells, plays a bigger role in SARS-CoV-2 infection than previously thought. When infected saliva is swallowed or tiny particles of it are inhaled, we think it can potentially transmit SARS-CoV-2 further into our throats, our lungs, or even our guts."

Finally, to explore the relationship between oral symptoms and virus in saliva, the team collected saliva from a separate group of 35 NIH volunteers with mild or asymptomatic COVID-19. Of the 27 people who experienced symptoms, those with virus in their saliva were more likely to report loss of taste and smell, suggesting that oral infection might underlie oral symptoms of COVID-19.

Professor Blake M. Warner, assistant clinical investigator and chief of NIDCR's Salivary Disorders Unit, who co-led the study, said: "By revealing a potentially underappreciated role for the oral cavity in SARS-CoV-2 infection, our study could open up new investigative avenues leading to a better understanding of the course of infection and disease. Such information could also inform interventions to combat the virus and alleviate oral symptoms of COVID-19."

The work was carried out as part of the global Human Cell Atlas consortium** which aims to create reference maps of all human cells to understand health and disease. More than 2,000 people across 75 countries are involved in the HCA community, and the data is openly available to scientists worldwide.

The rapid collaboration between researchers on this study led to the creation of the HCA Oral and Craniofacial Biological Network. This is working towards the goal of creating comprehensive maps of oral and craniofacial cells as a basis for understanding oral health and oral diseases.

Dr Sarah Teichmann, a senior author from the Wellcome Sanger Institute and co-chair of the Human Cell Atlas Organising Committee, said: "Human Cell Atlas data is being used to understand COVID-19 and identify which of our cells are critical for initial infection and transmission. This first integrated adult Human Oral Cell Atlas is openly available, to help understand SARS-Cov-2 transmission and inform preventative measures to reduce the spread of this coronavirus. The global Human Cell Atlas community will continue to investigate cells and targets likely to be involved in COVID-19."

Credit: 
Wellcome Trust Sanger Institute

Evidence for reduced antibody protection against SARS-CoV-2 variants

image: The antibodies present in the body after a previous infection or vaccination are less protective against infection with SARS-CoV-2 variants B.1.351 (South Africa) and P.1 (Brazil). The effect of antibodies already approved as drugs for Covid19 therapy also differs among SARS-CoV-2 variants.

Image: 
Figure: Markus Hoffmann

Göttingen, March 25, 2021. Testing and vaccination - these are the pillars on which humanity is trying to get a grip on the Coronavirus pandemic. Although it is taking longer than many had expected, it is believed that it is only a matter of time before we are all vaccinated and thus protected. However, time is also working for the virus, which has now mutated several times, with variants B.1.1.7 from the United Kingdom, B.1.351 from South Africa and P.1 from Brazil spreading rapidly. These viruses have mutations in the so-called spike protein, the structure on the surface of the virus that is responsible for attachment to host cells. At the same time, the spike protein is also the major target of the immune response. Antibodies generated in response to SARS-CoV-2 infection or vaccination bind to the spike protein, thereby blocking the virus. A team led by Markus Hoffmann and Stefan Pöhlmann of the German Primate Center - Leibniz Institute for Primate Research and Jan Münch of the Ulm University Medical Centre has found that the SARS-CoV-2 variants B.1.351 and P.1 are no longer inhibited by an antibody used for COVID-19 therapy. In addition, these variants are less efficiently inhibited by antibodies from recovered patients and vaccinated individuals. Thus, convalescence from COVID-19 as well as vaccination may offer only incomplete protection against these mutant viruses (Cell).

SARS-CoV-2 viruses invade lung cells in order to multiply. For the virus to enter a cell, it must first attach to the cell surface. For this, the virus uses its so-called spike protein, which is located on the viral envelope. The spike protein is also the target for therapies and vaccines aimed at preventing the virus from replicating in the body.

At the beginning of the pandemic, SARS-CoV-2 was relatively stable, but recently several viral variants have been detected and are spreading rapidly. Variants B.1.1.7, B.1.351, and P.1, which first appeared in the United Kingdom, South Africa, and Brazil, respectively, have mutations in the spike protein and some are located in areas targeted by currently used antiviral agents and vaccines. "This is worrisome because the rapid spread of variants that might not be efficiently inhibited by antibodies could undermine our current vaccination strategy," says Stefan Pöhlmann, an infection biologist at the German Primate Center in Göttingen. Therefore, the team led by Pöhlmann and Münch investigated how effectively the mutant viruses are inhibited by drugs and antibodies.

"We found that certain antiviral agents that block host cell entry and are in (pre)clinical development inhibit the mutant viruses just as well as the original virus. Variant B1.1.7, which is currently spreading rapidly in Germany, was also efficiently inhibited by antibodies, including antibodies induced by vaccination. In contrast, an antibody used for COVID-19 therapy did not inhibit variants B.1.351 and P.1. Moreover, these variants were less well inhibited by antibodies from convalescent or vaccinated individuals, they partially bypassed the neutralizing effect of the antibodies," says Jan Münch. The use of the currently available vaccines makes sense and a rapid expansion of the vaccination efforts in Germany is desirable. However, it is possible that vaccination or recovery from COVID-19 may offer reduced protection from SARS-CoV-2 variants B.1.351 and P.1." Clinical studies must now show the extent to which this fear is true. "Our findings show that it is important to limit the spread of the virus as much

Credit: 
Deutsches Primatenzentrum (DPZ)/German Primate Center

Nearly half of poison control calls for supersized alcopops involve underage drinkers

image: Dr. Matthew Rossheim, an expert on supersized alcopop consumption and related health outcomes, led the study published in Drug and Alcohol Dependence.

Image: 
George Mason University

Supersized alcopops are ready-to-drink flavored alcoholic beverages with high alcohol content that are disproportionately consumed by underage drinkers. There can be up to 5.5 standard alcoholic drinks in a single 24 ounce can, so consuming only one can of supersized alcopop is considered binge drinking, and consuming two cans can cause alcohol poisoning. Still, these products remain under-regulated and are available inexpensively at gas stations and convenience stores, where they are more readily accessible by underage youth.

New research led by George Mason University’s College of Health and Human Services found that nearly one-half (46.3 %) of all calls to U.S. poison control centers involving supersized alcopop consumption were made for consumers below the legal drinking age. Additionally, in every year studied, the proportion of calls for supersized alcopops among underage drinkers greatly exceeded the proportion of calls that were for underage drinkers for other types of alcohol.

Dr. Matthew Rossheim, an expert on supersized alcopop consumption and related health outcomes, led the study published in Drug and Alcohol Dependence. This study is the first report of clinical data within the last decade to examine negative effects from supersized alcopop consumption.

“A number of studies we’ve conducted have shown that supersized alcopops are commonly consumed by underage drinkers, which often results in serious negative consequences,” explains Rossheim. “Our latest data show a clear trend of supersized alcopop consumption among underage young people requiring poison center services. In this way, supersized alcopops appear to pose a distinct threat to youth.”

Rossheim and colleagues from the National Capital Poison Center and Emory University analyzed data from the National Poison Data System repository of calls to U.S. poison control centers from 2010 through 2019. This included 1,719 calls for consumption of supersized alcopops, many of whom consumed these products in combination with other substances. Acute care facilities such as emergency departments served as the management site for most calls (67.4 %), with another 14.3% referred to acute care.

While the large majority of consumption (more than 80%) was intentional for most age groups, 91% of the calls for children 0-11 years old who consumed supersized alcopops were for unintentional consumption. This suggests that the packaging and flavoring of these products can be attractive to children who do not understand how much alcohol these products contain or that they contain any alcohol at all.

“Better regulation and policies are urgently needed. Limiting their alcohol content and retail availability are immediate steps regulators must take in order to protect our youth.”

About George Mason University

George Mason University is Virginia's largest and most diverse public research university. Located near Washington, D.C., Mason enrolls 39,000 students from 130 countries and all 50 states. Mason has grown rapidly over the past half-century and is recognized for its innovation and entrepreneurship, remarkable diversity and commitment to accessibility. For more information, visit https://www2.gmu.edu/.

About the College of Health and Human Services

George Mason University's College of Health and Human Services prepares students to become leaders and shape the public's health through academic excellence, research of consequence, community outreach, and interprofessional clinical practice. George Mason is the fastest-growing Research I institution in the country. The College enrolls more than 1,900 undergraduate and 1,370 graduate students in its nationally-recognized offerings, including: 5 undergraduate degrees, 13 graduate degrees, and 7 certificate programs. The college is transitioning to a college of public health in the near future. For more information, visit https://chhs.gmu.edu/.

Journal

Drug and Alcohol Dependence

DOI

10.1016/j.drugalcdep.2021.108657

Credit: 
George Mason University

Warriors' down bedding could ease journey to realm of the dead

video: Valsgärde in Sweden is especially known for its spectacular boat graves from the 600s and 700s CE, an era just before the Viking Age. Two of these spectacular boat graves are at the centre of this story - or more specifically the down bedding that was found in the graves are.

When researchers from the Norwegian University of Science and Technology investigated which birds contributed their feathers to the bedding, they made a surprising discovery that provides new insight into Iron Age society.

Image: 
Norwegian University of Science and Technology, NTNU University Museum

The burial field in Valsgärde outside Uppsala in central Sweden contains more than 90 graves from the Iron Age.

"On a light note, we could say that Valsgärde is Scandinavia's answer to Sutton Hoo in England as portrayed in the film The Dig on Netflix," says Birgitta Berglund, professor emeritus of archaeology at the Norwegian University of Science and Technology's NTNU University Museum.

Valsgärde is especially known for its spectacular boat graves from the 600s and 700s CE. This timeframe is in the middle of what Norway calls the Merovingian period, the era just before the Viking Age.

Two of these spectacular boat graves are at the centre of this story -- or more specifically, the story is really about the down bedding that was found in the graves.

When researchers from NTNU investigated which birds contributed their feathers to the bedding, they made a surprising discovery that provides new insight into Iron Age society.

The boats carrying the two dead men were about 10 metres long, with room for four to five pairs of oars. Both were outfitted for high-ranking warriors, with richly decorated helmets, shields and weapons. Provisions and tools for hunting and cooking were also included for their last voyage.

In one grave, an Eurasian eagle owl (Bubo bubo) had been laid, with its head cut off. We'll return to that. Horses and other animals were arranged close to the boats.

"The buried warriors appear to have been equipped to row to the underworld, but also to be able to get ashore with the help of the horses," says Berglund.

Beauty sleep was also taken care of in death.Two warriors lay atop several layers of down bedding. The contents of the bedding probably had a greater function than simply serving as filler.

You might have thought of down bedding as a modern concept, which admittedly only became available for common folk in recent times. The down bedding in the graves at Valsgärde is the oldest known from Scandinavia and indicate that the two buried men belonged to the top strata of society.

Wealthy Greeks and Romans used down for their bedding a few hundred years earlier, but down probably wasn't used more widely by wealthy people in Europe until the Middle Ages, Berglund says.

Berglund has been studying down harvesting in Helgeland coastal communities in southern Nordland county for many years, where people commercialized down production early on by building houses for the eider ducks that were the source of the down. The theory was that down from this location might have been exported south, so Berglund wanted to investigate whether the bedding at Valsgärde contained eider down.

"It turned out that a lot of kinds of feathers had been used in the bedding at Valsgärde. Only a few feathers from eider ducks were identified, so we have little reason to believe that they were a commodity from Helgeland or other northern areas," says Berglund.

However, she was not disappointed by this discovery. The great variety of species gave the researchers unique insight into the bird fauna in the immediate area in prehistoric times, along with people's relationship to it.

"The feathers provide a source for gaining new perspectives on the relationship between humans and birds in the past. Archaeological excavations rarely find traces of birds other than those that were used for food," the researcher says.

"We also think the choice of feathers in the bedding may hold a deeper, symbolic meaning. It's exciting."

Berglund explains that according to Nordic folklore, the type of feathers contained in the bedding of the dying person was important.

"For example, people believed that using feathers from domestic chickens, owls and other birds of prey, pigeons, crows and squirrels would prolong the death struggle. In some Scandinavian areas, goose feathers were considered best to enable the soul to be released from the body," she said.

These are well-known folk traditions that have been collected from the 18th century onwards. But they may have their roots in prehistoric times.

In the Icelandic Erik the Red saga, a pillow stuffed with feathers from domestic hens was placed on the throne at Heriólfsnes in Greenland, where a visiting female shaman was to sit. The saga is considered to have been written down in the 13th century, but addresses events around the year 1000, says Berglund.

The examples show that that feathers in the bedding from Valsgärde most likely also had a deeper meaning than just serving as a filler. It's also well known that birds could hold special importance for obtaining information in shamanism -- think of Odin's two ravens Hugin and Munin.

Exactly what ritual function the feathers at Valsgärde had is hard to say. But the bedding contained feathers from geese, ducks, grouse, crows, sparrows, waders and -- perhaps most surprisingly --- eagle owls.

Biologist Jørgen Rosvold, now employed at the Norwegian Institute for Natural History (NINA) identified the species from the feather material.

"It was a time consuming and challenging job for several reasons. The material is decomposed, tangled and dirty. This means that a lot of the special features that you can easily observe in fresh material has become indistinct, and you have to spend a lot more time looking for the distinctive features," Rosvold says.

"I'm still surprised at how well the feathers were preserved, despite the fact that they'd been lying in the ground for over 1000 years."

The feathers in the down bedding weren't the only interesting bird find in the graves. One of the graves also contained a headless owl.

From recent graves we know that people took measures to prevent the buried from returning from the dead, and it's easy to imagine that this was also done longer ago as well.

"We believe the beheading had a ritual significance in connection with the burial," says Berglund.

Swords found in tombs from Viking times were sometimes intentionally bent before being laid in the tomb. This was probably done to prevent the deceased from using the weapon if he returned.

"It's conceivable that the owl's head was cut off to prevent it from coming back. Maybe the owl feather in the bedding also had a similar function? In Salme in Estonia, boat graves from the same period have recently been found that are similar to those in Valsgärde. Two birds of prey with a severed head were found there," says Berglund.

Credit: 
Norwegian University of Science and Technology

Where do the gender differences in the human pelvis come from?

image: Photo of a female human pelvis and skull of a newborn baby. (© Barbara Fischer)

Image: 
Photo of a female human pelvis and skull of a newborn baby. (© Barbara Fischer)

Fossil remains of the human pelvis are rare because the pelvic bones do not preserve very well. Therefore, it has remained unclear when human sex differences in the pelvis evolved: jointly with upright walking, or later, together with the large human brains. "We have discovered that the pattern of sex differences in the human pelvis is probably much older than previously thought", says evolutionary biologist Barbara Fischer.

A team of biologists from the University of Vienna, the KLI for Evolution and Cognition Research, and the University of Calgary compared pelvic sex differences in humans with those in chimpanzees, the most closely-related living species to modern humans. Chimpanzees have much easier births than humans, because their fetuses are smaller. "We analyzed 3D data of pelves for these two species and found that they show the same pattern of sex differences, despite large overall species differences," says Fischer. Yet, the magnitude of the differences was only half as large in chimpanzees, compared to humans. The striking similarity of the pattern of pelvic sex differences in humans and chimpanzees strongly suggests that it was already present in the common ancestor of the two species. This implies that all the extinct hominin (human-like) species, including e.g., the Neandertals, probably had the same pattern.

Many mammals give birth to larger fetuses, relative to the birth canal of their mothers, compared to humans, e.g., bats and certain primates. These animals possess adaptations in their pelves to facilitate birth of large babies. At the same time, there are other mammals with tiny neonates, e.g., cats and opossums, which also have subtle sex differences in their pelves that resemble the human pattern. This suggests that these similarities in the pattern of pelvic sex differences reflect an old and evolutionarily conserved mammalian pattern. "We think that modern humans did not evolve this pattern de novo, but that we inherited it from earlier mammals that faced the same problem, namely having to give birth to relatively large fetuses," says Fischer. When our brains became increasingly large over the course of human evolution, the magnitude of pelvic sex differences was therefore able to increase rather rapidly, as the pelvic pattern and the underlying genetic and developmental machinery were already in place and did not have to evolve anew.

Credit: 
University of Vienna

Study introduces 13 new, threatened species of sparkly moths from Hawaii

image: Micromoths are often poorly studied due to their small size, but they can play key roles in their ecosystems. Many Philodoria moths, such as this Philodoria auromagnifica, feature glittering scales and feathery bristles.

Image: 
Chris Johns/Florida Museum of Natural History

Akito Kawahara was snapping pictures at a scenic outlook in Hawaii when he spotted the moth equivalent of a dodo.

An entomologist, Kawahara recognized the squiggly patterns on nearby plants as trails carved by leaf-mining caterpillars and lowered his camera to take a closer look. To his astonishment, he saw a tiny moth most experts assumed was extinct. It belonged to a genus known as Philodoria, a type of moth found only in Hawaii and one that hadn’t been documented in the wild since 1976.

“I thought, ‘Oh my God, there’s a Philodoria right here,’” said Kawahara, associate curator at the Florida Museum of Natural History’s McGuire Center for Lepidoptera and Biodiversity. “That was the beginning. It opened my eyes to the fact that at least one species had not gone extinct. Were there others?”

Kawahara’s chance sighting along a tourist footpath would kick off a hunt for the moths across all major volcanic islands of Hawaii, as well as in museum collections and back through time, resulting in the rediscovery of one of the archipelago’s oldest living lineages of native animals. Over the past eight years, Kawahara and collaborators have labored to fill gaps in our understanding of these poorly-studied insects: what they look like, where they live and what they eat. When the researchers began their work, 30 species of the slender, feathery moths were recorded in the scientific literature. That number has since grown to 51.

Now, the team is capping its project with a nearly 200-page-long study, the first to detail the natural history of all members of Philodoria, including 13 species new to science. The paper also offers a Hawaiian name for the genus, which had no known local epithet: Hunelele ‘elilau (HOO-neh-LEH-leh EH-lee-LAU), which roughly translates as a combination of “tiny flier” and “leaf excavator.”

“This is an amazing opportunity to add another key piece that deepens the Hawaiian story,” said study co-author Chris Johns, who carried out the project’s fieldwork during his doctoral studies in the Kawahara Lab. “Because of its rarity and isolated existence, Philodoria is as unique as it gets. The universe of a Philodoria species could be the size of a room.”

Many of the newly described species are named after native Hawaiian plants, places and people who have contributed to conservation on the islands, Kawahara said. One moth, Philodoria obamaorum, was christened in honor of Barack and Michelle Obama.

Shrinking habitat, disease and invasive species have wiped out much of Hawaii’s native flora and fauna, and more than 530 species on the islands are federally listed as endangered or threatened. Somehow, these micromoths, with a wingspan the length of an eyelash, have persisted.

But their restricted range and the scarcity of their host plants place them in danger of extinction. The researchers were unable to find living representatives of 10 Philodoria species known from museum specimens, and another 12 could be severely threatened, based on how scant their food sources are.

According to research led by Johns, the moths’ lineage likely dates back about 21 million years. Can they survive the next century?

An insect with deep island roots

Though Philodoria is found nowhere except Hawaii, it is related to the common caterpillars that tunnel inside the leaves of tomato plants and other garden staples, creating what look like intricate sketches as they chew through the tissue. The Hawaiian branch of the leaf-mining moth family, however, has a highly specialized diet, the product of millions of years of co-evolution with the islands’ plant life, including relatives of the iconic and endangered silversword plants.

“This tiny, tiny insect has a special relationship to Hawaiian plants,” said study lead author Shigeki Kobayashi, a former postdoctoral researcher in the Kawahara Lab and now a visiting researcher at Japan’s Osaka Prefecture University.

While the diet of the genus as a whole includes 12 families of Hawaiian plants, about 80% of Philodoria species feed exclusively on a single plant genus. More than half of the plant genera they eat contain threatened or endangered species, and three-quarters of the moth species themselves are restricted to one island or volcano. The insects and their host plants are among the many examples of life unique to the Hawaiian archipelago, an incubator for evolution before the arrival of humans.

It’s a delicate system in which the balance can easily be tipped. Invasive species, in particular, can disrupt an island’s native ecosystems with mind-boggling speed, Johns said.

“Within a couple of years, a forest that is fully functioning can be completely erased and replaced with non-native species,” he said. “This can happen in places that researchers just can’t reach. A pig or goat or bird could bring an invasive plant up there. It’s a huge problem.”

Blown or rafted from parts unknown, Philodoria likely first appeared on islands that today are nearly underwater. As new islands rose from the sea, the moths colonized them, and as host plants spread and diversified, the moths followed suit. Over time, they developed intimate links with certain plant species and now depend on them for survival.

Some of their leaf-mining relatives in other parts of the world have become so intertwined with their hosts that neither species can live without the other. In the South Pacific, a local species of plant relies on another leaf-mining moth species for pollination. In turn, the moth deposits its eggs in the plants’ flowers, which will later provide food for its offspring. Whether any members of Philodoria also have this mutually beneficial relationship with their host plants was a question Kawahara hoped to answer.

“The problem is that, in some cases, there’s only one or two of the plants left on the planet,” he said. “They’re often growing off steep cliffs, very hard to find, and you have to be in the right place at the right time to see them flowering. It was hard enough to find the larvae.”

Recruiting a Philodoria whisperer

Kawahara should know. After spotting that first moth as a postdoctoral researcher 10 years ago, he spent months combing the jungle for others with no success.

He had moved halfway across the world for a faculty position at the Florida Museum when Johns knocked on his door. Johns was a recent University of Florida anthropology graduate and a plant guy in search of a moth job. As he described his previous conservation work in Hawaii, an idea began to take shape in Kawahara’s mind. Would Johns be willing to scour the rainforest for an ultra-rare moth that had eluded researchers for nearly half a century?

Johns’ response: Game on.

“Most people think about Hawaii as this vacation spot with Mai-Tais and beaches, but it’s so much more than that,” he said. “It really all revolves around the culture, which revolves around its nature. There are so many things in Hawaii that are small and understated. The fact that Philodoria is this amazing story that no one knew about, just doing its thing – it’s an interesting reflection of what I think true Hawaii is.”

After a month on the islands, Johns appeared in Kawahara’s doorway in Gainesville with a small cooler. Inside were Philodoria.

“I was shocked,” Kawahara said. “I was convinced he was going to come back empty-handed. That was the best plane ticket I ever bought.”

The way to Philodoria is through its stomach

Johns’ strategy was to look not for the moths, but their host plants. He leaned on his ties with local conservation biologists to reach some of the islands’ most remote forests, accessible only by helicopter, four-by-four or a long hike. Once there, he searched for Philodoria’s food sources, using leads from papers published in the early 1900s and an eye already trained to distinguish native plant species from invasive ones.

It wasn’t easy. Some mountainsides were so difficult to get to, he had to be dropped off in the middle of a stream, the helicopter touching a single skid to a rock long enough for him to hop out. He would spot a piece of flagging tied to a faraway tree across a dense forest – that was the trail. Navigating it was “mostly falling,” he recalled.

“You’re on a volcano in the middle of the biggest ocean in the world,” Johns said. “When you get up into these places, you really get a sense of how quiet, still and slow the entire place is. You understand the isolation so much better.”

But due to the islands’ conelike shape, Johns could look out and see the rows of hotels and condominiums packing the distant coastline.

Micromoths often play important but overlooked roles in ecosystems, and Philodoria is no exception. The connections between the moths, their host plants and their habitat are so strong that the team could use traces of leaf mines on century-old herbarium specimens to provide clues to the insects’ current whereabouts.

In one study, Johns, Kawahara and collaborators at the Bishop Museum in Honolulu discovered the dried pupae of an undescribed and possibly extinct Philodoria species on a specimen of Hesperomannia in the Bishop’s herbarium. The plant specimen was collected in 1929 on the island of Lanai where today it no longer grows. In fact, Hesperomannia has become one of the islands’ most critically endangered plants, so rare it must be pollinated by hand – perhaps an example of a host plant that has lost its moth pollinator.

“The only way we could document this particular moth-plant interaction was through museum collections,” Kawahara said. “Whoever collected those leaves may not have even realized there were pupae attached, but that’s the only record we have of that moth.”

The lifecycle of Hawaii

The team also used the moths to revisit a classic evolutionary puzzle: When did plants and animals first appear in Hawaii?

On a map, Hawaii may look like a smattering of islands surrounded by ocean in all directions, but it’s actually the easternmost tip of a vast underwater mountain range that spans more than 3,600 miles, ending off the coast of Russia.

The main Hawaiian Islands – the youngest and largest – sit atop a hotspot, a single magma plume that has been birthing volcanoes for about 85 million years, which are sent on a slow westward journey by the movement of tectonic plates. The farther from the hotspot the islands travel, the more they sink and erode, finally disappearing beneath the ocean surface.

The hotspot has created an estimated 180,000 cubic miles of rock over its history. About 23 million years ago, it formed the Northwest Hawaiian Islands of Lisianski and Laysan. Once enormous landmasses rivalling the size of today’s main islands, they’re now in advanced stages of erosion: Lisianski’s highest point above sea level is a 40-foot sand dune, and Laysan – more than 800 nautical miles west of Honolulu – will likely be submerged this century.

The first of the main Hawaiian Islands to appear, Kauai, surfaced about 4.7 million years ago. Many researchers believe Hawaii’s existing native plants and animals date from this period. But evidence is mounting that some, including certain kinds of insects and spiders, hail from a much earlier era, when Lisianski and Laysan were in their prime.

This is the problem with using the ages of islands to timestamp the origin of species, Kawahara said. Plants and animals can predate the islands they now inhabit.

“Islands can also go extinct,” he said. “There are a lot of gaps in our knowledge, not just in terms of insects and plants, but also in terms of island geology.”

Hawaii’s flora and fauna may have been riding a conveyor belt of islands for millions of years, gradually vanishing from older islands and moving to new ones.

Philodoria is a good example.

Using a combination of DNA evidence, island ages and studies of closely related insect groups, Johns and Kawahara estimated that the moth lineage originated more than 21 million years ago, at least 19 million years before the formation of Kauai. If accurate, this would make the moths the islands’ oldest known living lineage of native arthropods – and possibly their oldest animal lineage alive today.

This timeline and fossil pollen evidence from the moths’ host plants suggest that Lisianski and Laysan were the moths’ first Hawaiian homes.

How did such tiny insects wind up on volcanoes in the middle of the ocean?

“Plants and animals arrived in Hawaii somehow,” Kawahara said. “How they got there, when they got there and how they ended up this way are some of the most fundamentally interesting evolutionary questions.”

Small moth, big dream

The future of Philodoria depends on the conservation of its host plants, Kawahara said. Like other native Hawaiian species, such as land snails, preserving habitat and protecting against invasive species are crucial to ensuring their survival.

While the Philodoria team helped put the shimmering moths back on the map, many questions remain. No one knows exactly how the insects interact with their environment or even the identity of the group’s ancestor. But for Kawahara, publishing a compilation of all known information about the moths carries personal weight.

“This was one of my dreams,” he said. “It’s not necessarily flashy science. It’s natural history. We’re doing it for the moths. We’re doing it for conservation. We’re doing it because it’s important.”

From one Hawaiian’s perspective, the moths are essential to the islands, regardless of whether or not we ever learn their precise roles within the ecosystem.

“Our culture depends on the existence of these moths and other insects and plants,” said collaborator and conservationist Keahi Bustamante in an award-winning video created by Johns. “It’s talked about. It’s put into songs and legends. It’s documented that we respect these things and they respect us in a way that allows us to survive.”

The study was published in Zootaxa.

Funding for the research was provided by the National Science Foundation, the National Geographic Society, the Entomological Society of America, the University of Florida Entomology and Nematology Department, the Florida Museum of Natural History, the UF Tropical Conservation and Development Program, the International Biodiversity Foundation and the Society for Systematic Biologists.

Sources: Akito Kawahara, kawahara@flmnh.ufl.edu, 352-273-2018;
Chris Johns, johns.chris.a@gmail.com;
Shigeki Kobayashi, crossroad1994@hotmail.co.jp

Journal

Zootaxa

DOI

10.11646/zootaxa.4944.1.1

Credit: 
Florida Museum of Natural History

Consumers will dub activist brands as 'woke-washers' if they cannot prove moral competency

New research shows that consumers judge 'activist brands' based on how morally competent they are perceived to be when challenging free speech.

The report, co-authored by experts at the Business School (formerly Cass), Birkbeck, University of London and the University of Sussex Business School explains that stakeholders draw their conclusions on the biggest brands by measuring three moral skills: sensitivity, vision, and integration.

Lacking these traits, a brand raising controversy is judged as transgressing, reproducing and manipulating the boundaries of free speech. Displaying these traits proves the brand is not merely 'woke-washing' -- using customers' social awareness to meet their own ends.

Based on the analysis of 113 controversies involving 18 brand companies such as Nike, Ben & Jerry's, Greenpeace, and Starbucks over the last 38 years, the report authors have created a new method of calculating whether consumers will think of an activist brand as 'real' or 'fake' based on their approach.

Moral sensitivity -- a brand must recognise the moral content of a situation as failure to do so is likely to damage customer satisfaction, customer-brand relations, and brand equity. For example, in 2014 Greenpeace activists in Peru hung a banner on the Nazca lines to appeal for renewable energy, but as this is considered a world heritage site and a Peruvian cultural symbol they were declared morally insensitive.

Moral vision -- a brand must show a clear moral vision when outlining challenges to free speech that help solve problems for markets and society as failure to do so results in brands being dubbed as 'conformists' -- those who reproduce the dominant moral judgments about what is acceptable to say publicly. For example, Mattel's introduction of Barbie Entrepreneur was criticised for promoting 'unhelpful stereotype career images' in 2014, because of the brand's roots in how women are defined by appearance.

Moral integration -- a brand must have the ability to pursue their moral beliefs in all situations as failure to do so results in brands being dubbed as 'opportunists' and 'fame-seekers' -- manipulating the boundaries of free speech to serve personal interest rather than reform morality. For example, cosmetics brand Lush has been praised for its continued stance as ethical, fair, and sustainable, without seeking attention.

The study also introduces new strategies by which brands can implement their activist stance and avoid 'woke-washing'. The three methods managers can use controversies to communicate their brand effectively are;

Creating monstrous hybrids -- breaking down taboos and revitalizing interest around important but displaced causes, such as environmentalism, or bringing to light emerging values in public debates, such as gender non-binaries.

Challenging the moral establishment -- bringing to light the flaws in the moral judgments promoted by powerful social actors.

Demonstrating moral exemplarity -- by pioneering moral precepts, supporting emerging moral leaders whose values align with theirs, or even creating their own social movement.

Dr Laetitia Mimoun, Lecturer in Marketing at the Business School and co-author of the report, said: "This report illuminates new ways of revising free speech boundaries but also the risks and responsibilities for brands that engage in such debates. It is imperative that consumers can trust brands and for that to happen brands must not overstep the mark by falsely labelling themselves as activists to further their own agenda."

Dr Olivier Sibai, Lecturer in Marketing at Birkbeck, University of London, and co-author of the report, said: "Believers in brand activism embrace the trend as a branding revolution, while cynics discount it as a marketing gimmick. We find that brand activism matters because it changes the boundaries of free speech. Yet, marketers must use it responsibly or they will waste an amazing opportunity to turn brands into a force for good."

Dr Achilleas Boukis, Lecturer in Marketing at the University of Sussex and co-author of the report, said: "Our work is a roadmap for activist brands so that they can harmonise their brand comms with their activist profile and stay afloat among the myriads of brands that recklessly jump on the social activism bandwagon."

'Authenticating Brand Activism: Negotiating the Boundaries of Free Speech to Make a Change' by Dr Olivier Sibai, Lecturer in Marketing at Birkbeck, University of London and former visiting scholar at the Business School, Dr Mimoun, Lecturer in Marketing at the Business School, and Dr Achilleas Boukis, Lecturer in Marketing at the University of Sussex, is published in 'Psychology & Marketing'.

Credit: 
City St George’s, University of London

Moffitt researchers use mathematical modeling to analyze dynamics of CAR T-cell therapy

TAMPA, Fla. -- Chimeric antigen receptor T-cell therapy, or CAR T, is a relatively new type of therapy approved to treat several types of aggressive B cell leukemias and lymphomas. Many patients have strong responses to CAR T; however, some have only a short response and develop disease progression quickly. Unfortunately, it is not completely understood why these patients have progression. In an article published in Proceedings of the Royal Society B, Moffitt Cancer Center researchers use mathematical modeling to help explain why CAR T cells work in some patients and not in others.

CAR T is a type of personalized immunotherapy that uses a patient's own T cells to target cancer cells. T cells are harvested from a patient and genetically modified in a laboratory to add a specific receptor that targets cancer cells. The patient then undergoes lymphodepletion with chemotherapy to lower some of their existing normal immune cells to help with expansion of the CAR T cells that are infused back into the patient, where they can get to work and attack the tumor.

Mathematical modeling has been used to help predict how CAR T cells will behave after being infused back into patients; however, no studies have yet considered how interactions between the normal T cells and CAR T cells impact the dynamics of the therapy, in particular how the nonlinear T cell kinetics factor into the chances of therapy success. Moffitt researchers integrated clinical data with mathematical and statistical modeling to address these unknown factors.

The researchers demonstrate that CAR T cells are effective because they rapidly expand after being infused back into the patient; however, the modified T cells are shown to compete with existing normal T cells, which can limit their ability to expand.

"Treatment success critically depends on the ability of the CAR T cells to multiply in the patient, and this is directly dependent upon the effectiveness of lymphodepletion that reduces the normal T cells before CAR T infusion," said Frederick Locke, M.D., co-lead study author and vice chair of the Blood and Marrow Transplant and Cellular Immunotherapy Department at Moffitt.

In their model, the researchers discovered that tumor eradication is a random, yet potentially highly probable event. Despite this randomness of cure, the authors demonstrated that differences in the timing and probability of cures are determined largely by variability among patient and disease factors. The model confirmed that cures tend to happen early, within 20 to 80 days before CAR T cells decline in number, while disease progression tends to happen over a wider time range between 200 to 500 days after treatment.

The researchers' model could also be used to test new treatments or propose refined clinical trial designs. For example, the researchers used their model to demonstrate that another round of CAR T-cell therapy would require a second chemotherapy lymphodepletion to improve patient outcomes.

"Our model confirms the hypothesis that sufficient lymphodepletion is an important factor in determining durable response. Improving the adaptation of CAR T cells to expand more and survive longer in vivo could result in increased likelihood and duration of response," explained Philipp Altrock, Ph.D., lead study author and assistant member of the Integrated Mathematical Oncology Department at Moffitt.

Credit: 
H. Lee Moffitt Cancer Center & Research Institute

A new way to visualize mountains of biological data

image: This is a general example of a type of visual that a graph neural network can create with provided biological data.

Image: 
University of Missouri

Studying genetic material on a cellular level, such as single-cell RNA-sequencing, can provide scientists with a detailed, high-resolution view of biological processes at work. This level of detail helps scientists determine the health of tissues and organs, and better understand the development of diseases such as Alzheimer's that impacts millions of people. However, a lot of data is also generated, and leads to the need for an efficient, easy-to-use way to analyze it.

Now, a team of engineers and scientists from the University of Missouri and the Ohio State University have created a new way to analyze data from single-cell RNA-sequencing by using a computer method called "machine learning." This method uses the power of computers to intelligently analyze large amounts of data and help scientists draw faster conclusions and move to the next stage of the research. Their methodology is detailed in a new paper published by Nature Communications.

"Single cell genetic profiling is on the cutting edge of today's technological advances because it measures how many genes are present and how they are expressed from the level of an individual biological cell," said Dong Xu, a professor in the MU College of Engineering. "At a minimum, there could be tens of thousands of cells being analyzed in this manner, so there ends up being a huge amount of data collected. Currently, determining conclusions from this type of data can be challenging because a lot of data must be filtered through in order to find what researchers are looking for. So, we applied one of the newest machine-learning methods to tackle this problem -- a graph neural network."

After computers intelligently analyze the data through a machine learning process, the graph neural network then takes the results and creates a visual representation of the data to help easily identify patterns. The graph is made up of dots -- each dot representative of a cell -- and similar types of cells are color coded for easy recognition. Xu said precision medicine is a good example of how single-cell RNA-sequencing can be used.

"With this data, scientists can study the interactions between cells within the micro-environment of a cancerous tissue, or watch the T-cells, B-cells and immune cells all try to attack the cancerous cells," Xu said. "Therefore, in cases where a person has a strong immune system, and the cancer hasn't fully developed yet, we can learn how the cancer can possibly be killed at an early stage, and we have our results sooner because of machine learning, which leads us to a viable treatment faster."

Xu believes this is a great example of how engineers and biologists can work together to study problems or issues in biology. He hopes this method can be used by biologists as a new tool to help solve complex biological questions, such as a possible treatment for Alzheimer's disease.

Credit: 
University of Missouri-Columbia

Does selfishness evolve? Ask a cannibal

image: Indian meal moths were raised for successive generations in sealed enclosures where conditions were identical save for the stickiness of their food. In enclosures (top) where food was stickier, caterpillars were more likely to interact with siblings. Meal moths with more local interactions with siblings evolved less selfish behavior - as evidenced by lower rates of cannibalism - within 10 generations.

Image: 
Volker Rudolf/Rice University

HOUSTON – (March 25, 2021) – One of nature’s most prolific cannibals could be hiding in your pantry, and biologists have used it to show how social structure affects the evolution of selfish behavior.

Researchers revealed that less selfish behavior evolved under living conditions that forced individuals to interact more frequently with siblings. While the finding was verified with insect experiments, Rice University biologist Volker Rudolf said the evolutionary principal could be applied to study any species, including humans.

In a study published online this week in Ecology Letters, Rudolf, longtime collaborator Mike Boots of the University of California, Berkeley, and colleagues showed they could drive the evolution of cannibalism in Indian meal moth caterpillars with simple changes to their habitats.

Also known as weevil moths and pantry moths, Indian meal moths are common pantry pests that lay eggs in cereals, flour and other packaged foods. As larvae, they’re vegetarian caterpillars with one exception: They sometimes eat one another, including their own broodmates.

In laboratory tests, researchers showed they could predictably increase or decrease rates of cannibalism in Indian meal moths by decreasing how far individuals could roam from one another, and thus increasing the likelihood of “local” interactions between sibling larvae. In habitats where caterpillars were forced to interact more often with siblings, less selfish behavior evolved within 10 generations.

Rudolf, a professor of biosciences at Rice, said increased local interactions stack the deck against the evolution of selfish behaviors like cannibalism.

To understand why, he suggests imagining behaviors can be sorted from least to most selfish.

“At one end of the continuum are altruistic behaviors, where an individual may be giving up its chance to survive or reproduce to increase reproduction of others,” he said. “Cannibalism is at the other extreme. An individual increases its own survival and reproduction by literally consuming its own kind.”

Rudolf said the study provided a rare experimental test of a key concept in evolutionary theory: As local interactions increase, so does selective pressure against selfish behaviors. That’s the essence of a 2010 theoretical prediction by Rudolf and Boots, the corresponding author of the meal moth study, and Rudolf said the study’s findings upheld the prediction.

“Families that were highly cannibalistic just didn’t do as well in that system,” he said. “Families that were less cannibalistic had much less mortality and produced more offspring.”

In the meal moth experiments, Rudolf said it was fairly easy to ensure that meal moth behavior was influenced by local interactions.

“They live in their food,” he said. “So we varied how sticky it was.”

Fifteen adult females were placed in several enclosures to lay eggs. The moths lay eggs in food, and larval caterpillars eat and live inside the food until they pupate. Food was plentiful in all enclosures, but it varied in stickiness.

“Because they’re laying eggs in clusters, they’re more likely to stay in these little family groups in the stickier foods that limit how fast they can move,” Rudolf said. “It forced more local interactions, which, in our system, meant more interactions with siblings. That’s really what we think was driving this change in cannibalism.”

Rudolf said the same evolutionary principal might also be applied to the study of human behavior.

“In societies or cultures that live in big family groups among close relatives, for example, you might expect to see less selfish behavior, on average, than in societies or cultures where people are more isolated from their families and more likely to be surrounded by strangers because they have to move often for jobs or other reasons,” he said.

Rudolf has studied the ecological and evolutionary impacts of cannibalism for nearly 20 years. He finds it fascinating, partly because it was misunderstood and understudied for decades. Generations of biologists had such a strong aversion to human cannibalism that they wrote off the behavior in all species as a “freak of nature,” he said.

That finally began to change slowly a few decades ago, and cannibalism has now been documented in well over 1,000 species and is believed to occur in many more.

“It’s everywhere. Most animals that eat other animals are cannibalistic to some extent, and even those that don’t normally eat other animals — like the Indian meal moth — are often cannibalistic,” Rudolf said. “There’s no morality attached to it. That’s just a human perspective. In nature, cannibalism is just getting another meal.”

But cannibalism “has important ecological consequences,” Rudolf said. “It determines dynamics of populations and communities, species coexistence and even entire ecosystems. It’s definitely understudied for its importance.”

He said the experimental follow-up to his and Boots’ 2010 theory paper came about almost by chance. Rudolf saw an epidemiological study Boots published a few years later and realized the same experimental setup could be used to test their prediction.

While the moth study showed that “limiting dispersal,” and thus increasing local interactions, can push against the evolution of cannibalism by increasing the cost of extreme selfishness, Rudolf said the evolutionary push can probably go the other way as well. “If food conditions are poor, cannibalism provides additional benefits, which could push for more selfish behavior.”

He said it’s also possible that a third factor, kin recognition, could also provide an evolutionary push.

“If you’re really good at recognizing kin, that limits the cost of cannibalism,” he said. “If you recognize kin and avoid eating them, you can afford to be a lot more cannibalistic in a mixed population, which can have evolutionary benefits.”

Rudolf said he plans to explore the three-way interaction between cannibalism, dispersal and kin recognition in future studies.

“It would be nice to get a better understanding of the driving forces and be able to explain more of the variation that we see,” he said. “Like, why are some species extremely cannibalistic? And even within the same species, why are some populations far more cannibalistic than others. I don’t think it’s going to be one single answer. But are there some basic principles that we can work out and test? Is it super-specific to every system, or are there more general rules?”

Additional co-authors include Dylan Childs and Jessica Crossmore of the University of Sheffield, and Hannah Tidbury of both the University of Sheffield and the Centre for Environment, Fisheries and Aquaculture Science in Weymouth, England.

The research was funded by the National Science Foundation (1256860, 0841686, 2011109) the National Institutes of Health (R01GM122061) and the Natural Environment Research Council (NEJ0097841).

Journal

Ecology Letters

DOI

10.1111/ele.13734

Credit: 
Rice University

Should you take fish oil? Depends on your genotype

Fish oil supplements are a billion-dollar industry built on a foundation of purported, but not proven, health benefits. Now, new research from a team led by a University of Georgia scientist indicates that taking fish oil only provides health benefits if you have the right genetic makeup.

The study, led by Kaixiong Ye and published in PLOS Genetics, focused on fish oil (and the omega-3 fatty acids it contains) and its effect on triglycerides, a type of fat in the blood and a biomarker for cardiovascular disease.

"We've known for a few decades that a higher level of omega-3 fatty acids in the blood is associated with a lower risk of heart disease," said Ye, assistant professor of genetics in the Franklin College of Arts and Sciences. "What we found is that fish oil supplementation is not good for everyone; it depends on your genotype. If you have a specific genetic background, then fish oil supplementation will help lower your triglycerides. But if you do not have that right genotype, taking a fish oil supplement actually increases your triglycerides."

Ye's team, including first author and graduate student Michael Francis, examined four blood lipids (fats)--high-density lipoprotein, low-density lipoprotein, total cholesterol and triglycerides--that are biomarkers for cardiovascular disease. The data for their sample of 70,000 individuals was taken from UK Biobank, a large-scale cohort study collecting genetic and health information from half a million participants.

The team divided the sample into two groups, those taking fish oil supplements (about 11,000) and those not taking fish oil supplements. Then they performed a genome-wide scan for each group, testing for 8 million genetic variants to compare. After running over 64 million tests, their results revealed a significant genetic variant at gene GJB2. Individuals with the AG genotype who took fish oil decreased their triglycerides. Individuals with the AA genotype who took fish oil slightly increased their triglycerides. (A third possible genotype, GG, was not evident in enough study volunteers to draw conclusions.)

Determining your genotype is not as far-fetched as it sounds, thanks to direct-to-consumer genetic testing companies. Companies may not report that specific genetic variant yet, but a tech-savvy consumer should be able to download the raw data and look at the specific position to discover the genotype, according to Ye. The ID for the variant is rs112803755 (A>G).

Looking at earlier fish oil studies

The study's findings may also shed light on previous trials, most of which found that fish oil provides no benefit in preventing cardiovascular disease.

"One possible explanation is that those clinical trials didn't consider the genotypes of the participants," Ye said. "Some participants may benefit, and some may not, so if you mix them together and do the analysis, you do not see the impact."

Now that Ye has identified a specific gene that can modify an individual's response to fish oil supplementation, his next step will be directly testing the effects of fish oil on cardiovascular disease.

"Personalizing and optimizing fish oil supplementation recommendations based on a person's unique genetic composition can improve our understanding of nutrition," he said, "and lead to significant improvements in human health and well-being."

Credit: 
University of Georgia

Will COVID-19 vaccines need to be adapted regularly?

image: Just like the phylogenetic tree of the influenza virus subtype H3N2 (right), the phylogenetic tree of the 'common cold' coronavirus 229E (left) shows an asymmetrical shape, indicating a shift towards evasion of the immune system (antigenic drift). Scale: Mutations per nucleotide (genetic building block).

Image: 
Image: Jó/Charité

Influenza vaccines need to be evaluated every year to ensure they remain effective against new influenza viruses. Will the same apply to COVID-19 vaccines? In order to gauge whether and to what extent this may be necessary, a team of researchers from Charité - Universitätsmedizin Berlin compared the evolution of endemic 'common cold' coronaviruses with that of influenza viruses. The researchers predict that, while the pandemic is ongoing, vaccines will need to undergo regular updates. A few years into the post-pandemic period, however, vaccines are likely to remain effective for longer. This study has been published in Virus Evolution*.

Influenza viruses are masters at evading the human immune system. They undergo such rapid changes that antibodies produced by the immune system in response to a previous infection or vaccination become unable to neutralize them. This is why the complex task of evaluating and updating the seasonal influenza vaccine has to be repeated every year. Mutations within SARS-CoV-2 have already produced a number of variants, some of which (such as the South African variant) partially evade the body's immune response. As a result, some vaccine manufacturers have already started to develop new versions of their vaccines. What does this mean for the future? Will COVID-19 vaccines mirror influenza vaccines in requiring regular updates?

In order to gauge whether, over the long term, SARS-CoV-2 is likely to demonstrate an immune evasion capability on par with that of influenza viruses, Charité virologists have studied the genetic evolution of the four currently known 'common cold' coronaviruses. These relatively harmless coronaviruses are known to be responsible for approximately 10 percent of common colds in the world and have been in circulation in humans significantly longer than SARS-CoV-2. Just like SARS-CoV-2, they enter human cells using the 'spike protein', a surface protein which gives the virus its characteristic crown-like appearance (and name). The spike protein also forms the target of all current COVID-19 vaccines.

For their study, the researchers focused on the two longest-known coronaviruses (termed 229E and OC43), tracing changes in the spike gene approximately 40 years into the past. The researchers started by comparing sequences from a range of old samples which had been deposited in a genetic sequence data bank. Based on the mutations which had emerged over time, they then produced phylogenetic trees for both coronaviruses. The researchers compared their findings with the phylogenetic tree of H3N2, an influenza subtype which is particularly effective at evading the human immune response.

The researchers' calculations revealed one feature which was common to the phylogenetic reconstructions of both the coronaviruses and the influenza virus: all three had a pronounced ladder-like shape. "An asymmetrical tree of this kind likely results from the repeated replacement of one circulating virus variant by another which carried a fitness advantage," explains the study's first author, Dr. Wendy K. Jó from Charité's Institute of Virology. "This is evidence of 'antigenic drift', a continuous process involving changes to surface structures which enable viruses to evade the human immune response. It means that these endemic coronaviruses also evade the immune system, just like the influenza virus. However, one also has to look at the speed with which this evolutionary adaptation happens."

For this step, the researchers determined the three viruses' evolutionary rates. While the influenza virus accumulated 25 mutations per 10,000 nucleotides (genetic building blocks) per year, the coronaviruses accumulated approximately 6 such mutations in the same timeframe. The rate of change of the endemic coronaviruses was therefore four times slower than that of the influenza virus. "As far as SARS-CoV-2 is concerned, this is good news," summarizes Prof. Dr. Christian Drosten, Director of the Institute of Virology and a researcher at the German Center for Infection Research (DZIF).

SARS-CoV-2 is currently estimated to change at a rate of approximately 10 mutations per 10,000 nucleotides per year, meaning the speed at which it evolves is substantially higher than that of the endemic coronaviruses. "This rapid genetic change in SARS-CoV-2 is reflected in the emergence of numerous virus variants across the globe," explains study lead Prof. Dr. Jan Felix Drexler, a researcher at both the Institute of Virology and the DZIF. "This, however, is likely due to the high rates of infection seen during the pandemic. When infection numbers are so high, a virus is able to evolve more rapidly. Based on the rates of evolution seen in the endemic common cold coronaviruses, we expect that SARS-CoV-2 will start to change more slowly once infections start to die down - meaning once a large proportion of the global population has developed immunity either as a result of infection or through vaccination. We expect therefore that COVID-19 vaccines will need to be monitored regularly throughout the pandemic and updated where necessary. Once the situation has stabilized, vaccines are likely to remain effective for longer."

*Jo WK et al. The evolutionary dynamics of endemic human coronaviruses. Vir Evol 2021. doi: 10.1093/ve/veab020

Credit: 
Charité - Universitätsmedizin Berlin

Women accumulate Alzheimer's-related protein faster

Alzheimer's disease seems to progress faster in women than in men. The protein tau accumulates at a higher rate in women, according to research from Lund University in Sweden. The study was recently published in Brain.

Over 30 million people suffer from Alzheimer's disease worldwide, making it the most common form of dementia. Tau and beta-amyloid are two proteins known to aggregate and accumulate in the brain in patients with Alzheimer's.

The first protein to aggregate in Alzheimer's is beta-amyloid. Men and women are equally affected by the first disease stages, and the analysis did not show any differences in the accumulation of beta-amyloid. Memory dysfunction arises later, when tau starts to accumulate. More women than men are affected by memory problems due to Alzheimer's, and it was for tau that the researchers found a higher rate of accumulation in women.

"Tau accumulation rates vary greatly between individuals of the same sex, but in the temporal lobe, which is affected in Alzheimer's disease, we found a 75% higher accumulation rate in women as a group compared to men," explains Ruben Smith, first author of the study.

The accumulation of tau is faster in patients who already have a pathological accumulation of beta-amyloid, and are in the early phase of the disease. The discovery that the accumulation rate of tau is higher in women remained even after adjusting for age and the levels of tau they had at the beginning. Together with data from three similar cohorts in the USA, the project contains 209 women and 210 men.

"The next step would be to examine why this accumulation is faster in women," says Sebastian Palmqvist, the researcher responsible for the cognitive assessment of the patients.

The study did not investigate the reasons for the higher rate of tau accumulation in women.

"Our study strongly indicates that the faster spread of tau makes women more prone to develop dementia because of Alzheimer's pathology compared to men. Future experimental studies will be important to understand the reasons behind this," concludes Professor Oskar Hansson.

Credit: 
Lund University

Massive study reveals few differences between men and women's brains

How different are men and women's brains? The question has been explored for decades, but a new study led by Rosalind Franklin University neuroscientist Lise Eliot is the first to coalesce this wide-ranging research into a single mega-synthesis. And the answer is: hardly at all.

"Men and women's brains do differ slightly, but the key finding is that these distinctions are due to brain size, not sex or gender," Dr. Eliot said. "Sex differences in the brain are tiny and inconsistent, once individuals' head size is accounted for."

The unusually large study of studies, "Dump the 'dimorphism': Comprehensive synthesis of human brain studies reveals few male-female differences beyond size," published in Neuroscience and Biobehavioral Reviews, finds that size is the only clear-cut difference between male and female brains. Women's brains are about 11% smaller than men's, in proportion to their body size. Smaller brains allow certain features, such as a slightly higher ratio of gray matter to white matter, and a higher ratio of connections between, versus within, cerebral hemispheres.

"This means that the brain differences between large- and small-headed men are as great as the brain differences between the average man and woman," Dr. Eliot said. "And importantly, none of these size-related differences can account for familiar behavioral differences between men and women, such as empathy or spatial skills."

This is not the story typically publicized about sex differences in the human brain.

"Since the dawn of MRI, studies finding statistically significant sex differences have received outsized attention by scientists and the media," said Dr. Eliot, whose books include "Pink Brain, Blue Brain: How Small Differences Grow Into Troublesome Gaps."

"Researchers have been quietly accumulating massive amounts of data comparing male and female brains, but it's only the differences that get hyped," Dr. Eliot continued. "Unlike other areas of health research, women have been equally included in brain imaging from the outset."

Dr. Eliot and her collaborators -- fourth-year Chicago Medical School students Adnan Ahmed, Hiba Khan and Julie Patel -- conducted a meta-synthesis of three decades of research, assimilating hundreds of the largest and most highly-cited brain imaging studies addressing 13 distinct measures of alleged sex difference. For nearly every measure, they found almost no differences that were widely reproduced across studies, even those involving thousands of participants. For example, the volume or thickness of specific regions in the cerebral cortex is often reported to differ between men and women. However, the meta-synthesis shows that the regions identified differ enormously between studies.

Male-female brain differences are also poorly replicated between diverse populations, such as Chinese versus American, meaning there is no universal marker that distinguishes men and women's brains across the human species.

"The handful of features that do differ most reliably are quite small in magnitude," Dr. Eliot said. "The volume of the amygdala, an olive-sized part of the temporal lobe that is important for social-emotional behaviors, is a mere 1% larger in men across studies."

The study also rebuts a longstanding view that men's brains are more lateralized, meaning each hemisphere acts independently, whereas women's two hemispheres are said to be better connected and to operate more in sync with each other. Such a difference could make males more vulnerable to disability following brain injury such as stroke. Here again, the consensus of many studies shows that the difference is extremely small, accounting for even less than 1% of the range of left-right connectivity across the population. This finding does agree with large datasets that have found no gender difference in aphasia, or the loss of language, following a stroke in the left hemisphere, contrary to long belief.

A last focus of the new study is on functional MRI. This method allows neuroscientists to see areas that "light up" during particular mental tasks and has been widely used to look for male-female differences during language, spatial and emotional tasks.

Across hundreds of such studies, Dr. Eliot's team found extremely poor reliability in sex difference findings -- nearly all specific brain areas that differed in activity between men and women were not repeated across studies. Such poor reproducibility agrees with recent research out of Stanford University demonstrating "false discovery," or the over-publication of false-positive findings in the scientific literature on functional MRI sex difference.

"Sex comparisons are super easy for researchers to conduct after an experiment is already done. If they find something, it gets another publication. If not, it gets ignored," Dr. Eliot said. Publication bias is common in sex-difference research, she added, because the topic garners high interest.

"Sex differences are sexy, but this false impression that there is such a thing as a 'male brain' and a 'female brain' has had wide impact on how we treat boys and girls, men and women," Dr. Eliot said.

"The truth is that there are no universal, species-wide brain features that differ between the sexes. Rather, the brain is like other organs, such as the heart and kidneys, which are similar enough to be transplanted between women and men quite successfully."

Credit: 
Rosalind Franklin University of Medicine and Science

In certain circumstances, outsourcing poses risks to vendors

video: New research from the Lally School of Management at Rensselaer Polytechnic Institute found that not all client-vendor relationships are beneficial for the vendors.

Image: 
Rensselaer Polytechnic Institute

TROY, N.Y. -- Outsourcing routine tasks, like payroll, customer service, and accounting, offers well-known benefits to businesses and contributes to an economy in which entrepreneurial vendors can support industry and expand employment. However, new research from the Lally School of Management at Rensselaer Polytechnic Institute discovered that not all client-vendor relationships are beneficial for the vendors.

"It's important to observe and study both sides of a business relationship," said T. Ravichandran, a chaired professor of information systems in Lally and an author of a new study published in Information Systems Frontiers. "For businesses to thrive, they need a vibrant vendor community that will support growth. But it's equally important for vendors to be informed on risks involved with the undertaking."

Ravichandran and his co-author, Sukruth Suresh from St. John Fisher College, examined 231 business process outsourcing announcements spanning 13 years and found that the least beneficial proposition for a vendor tasks them with developing specific capabilities for the client, leading to significant uncertainties. Combined with the complexities associated with managing the client's expectations, such an arrangement amplifies the vendor's risks.

For more information, watch this video.

"A contract may appear to be lucrative but if it involves significant client-specific investment of vendor resources, our findings show that it is a risky proposition for the vendors," Ravichandran said. "When vendors fail, it means reduced options for businesses, which directly disrupts the lives of many people through unemployment and strains the economy in general."

The authors found that the value gains for vendors were substantial when the task being outsourced was well-defined, and required specifically trained workers. Knowledge-intensive processes in areas like supply chain management, finance and accounting services, and research and development are particularly promising. Additionally, the researchers found that contracts of longer duration are generally more beneficial for vendors, no matter the task.

Credit: 
Rensselaer Polytechnic Institute