Tech

New phase for synthetic aperture microscopy

image: Observation of subcellular structures in unlabeled living cells, from doi: 10.1117/1.AP.2.6.065002

Image: 
SPIE

Microscopy is an essential tool in multiple research fields and industries, such as biology, medicine, materials science, and quality control, to name a few. Although many microscopy techniques exist, each has pros and cons, mostly in terms of spatial resolution, speed (images per second), and applicability. For example, scanning electron microscopy can capture images with nanometric resolution, but it offers lower speed and is impractical for certain samples. Other simpler light-based microscopy techniques, such as fluorescence microscopy, are not suitable for visualizing living cells or other small structures because these are generally transparent and thin, which results in low light absorption.

Scientists have developed a technique called synthetic aperture microscopy (SAM), which makes use of an intrinsic property of light, called phase. This property refers to the relative delay between two electromagnetic waves. When light waves pass through a target sample, their relative phases change differently according to the optical properties at each point in the sample and the incident angle of the light. In SAM, multiple phase images can be taken in quick succession with different incident angles. These images are then processed and combined to form a crisper picture.

Although SAM is undoubtedly a promising approach, current implementations lack in both spatial resolution and frame rate to be useful for emerging applications. To address these issues, a team of researchers led by Renjie Zhou from The Chinese University of Hong Kong recently developed a novel SAM method. In their study, published in Advanced Photonics, the team presents an innovative setup for SAM imaging based on digital micromirror devices (DMDs).

DMDs are electronic components widely used in commercial digital projectors. They have a matrix of micromirrors whose orientation can be individually and electronically controlled at high speeds. Using two DMDs and appropriate lenses, the researchers devised a scheme in which the angle of a laser beam reaching the sample can be changed thousands of times per second. Once the light has gone through the sample, it is combined with a portion of the original laser to produce a light pattern known as an interferogram, which carries the phase information. To create the final phase image, multiple interferograms for different incident angles are combined using specially designed algorithms.

The researchers tested their novel method using various types of samples, such as nanometric gratings, red blood cells, and cancer cells. The results were very promising across the board, as Zhou remarks, "Using our DMD-based approach, we could accurately image material structures with features as small as 132 nm, quantify millisecond fluctuations in the membranes of red blood cells, and observe dynamic changes in cellular structure in response to exposure to chemicals." This technique is also label-free, which means that one can observe living cells without harming them with fluorescent chemicals.

Another notable advantage of this new method is the cancellation of laser speckle, a type of unwanted interference that occurs when illuminating a sample with a laser. The use of multiple interferograms to compute one image irons out the random contributions of speckle in each interferogram, making the final composite image crisper. Moreover, one can increase the imaging frame rate as needed by using a lower number of interferograms, as long as the desired image quality is reached.

Zhou believes their SAM method could be a game changer in various fields where microscopy is essential, "We envision that our high-speed imaging technique will find applications in biology and materials research, such as studying the motions and interactions of live cells and monitoring material manufacturing processes in real time for quality control purposes." He also notes that there is room for improvement in terms of speed by using even faster cameras, and that the underlying principles of their approach could be adapted with different algorithms to build a 3D imaging system.

Credit: 
SPIE--International Society for Optics and Photonics

New population of blue whales discovered in the western Indian ocean

image: A Northwest Indian Ocean blue whale flukes up for a dive off the Arabian Sea coast of Oman.

Image: 
Robert Baldwin/Environment Society of Oman

An international team of researchers has discovered what it believes to be a new population of blue whales in the western Indian Ocean.

Blue whales are the largest animals that have ever lived on our planet, and they are found around the globe in all oceans. All blue whales sing very low-pitched and recognizable songs, and conveniently for researchers, every population has its own unique song. In a recently published paper in the journal Endangered Species Research, the researchers describe a new blue whale song that is heard from the Arabian Sea coast of Oman across to the Chagos Archipelago in the central Indian Ocean and as far south as Madagascar in the southwest Indian Ocean.

Dr. Salvatore Cerchio, Director of the African Aquatic Conservation Fund's Cetacean Program and Visiting Scientist at the New England Aquarium, led the analysis of recordings of the whale from three locations in the western Indian Ocean. Dr. Cerchio first recorded the novel song in 2017, during research focused on Omura's whales in the Mozambique Channel off Madagascar, and he recognized it as a blue whale song that had never been described. Cerchio was also working with a team of scientists collecting acoustic recordings off the coast of Oman in the Arabian Sea. This is part of a research effort focused on the highly endangered Arabian Sea humpback whale, an ongoing collaboration between the Environment Society of Oman, Five Oceans Environmental Services LLC, Oman's Environment Authority and Oman's Ministry of Agriculture, Fisheries and Water Resources.

While analyzing the Oman acoustic data, the team recognized the same unusual song. This novel blue whale song was recorded even more prevalently off Oman than Madagascar, and it became clear to the researchers that they had found what was likely a previously unrecognized population of blue whales in the western Indian Ocean.

"It was quite remarkable," said Cerchio, "to find a whale song in your data that was completely unique, never before reported, and recognize it as a blue whale." Blue whale song has been extensively studied globally, and several blue whale populations have been identified based on their distinct songs throughout the Indian Ocean.

"With all that work on blue whale songs, to think there was a population out there that no one knew about until 2017, well, it kind of blows your mind," Cerchio said.

In 2018, the team reported their findings to the Scientific Committee of the International Whaling Commission (IWC), which was in the process of evaluating the status of blue whale populations in the Indian Ocean. The finding created quite a bit of excitement at the meeting, and raised many new questions about blue whale population movements and structure in the Indian Ocean. Emmanuelle Leroy and Tracey Rogers of the University of New South Wales, in Sydney, Australia, were also conducting acoustic research on blue whales in the Indian Ocean. Upon reading the IWC report on the new song, Leroy recognized that they also had recorded the same song off the Chagos Archipelago in the central Indian Ocean.

"Shortly after we made the first report at IWC," said Cerchio, "I received an email from Emmanuelle saying, 'Hey Sal, I think we have that Oman song off the Chagos!'"

The collaborative team grew, and analysis of data from all three sites suggested that the population may spend most of its time in the northwestern Indian Ocean, in the Arabian Sea and to the west of the Chagos. It has long been recognized that a unique population of blue whales resides in the Northern Indian Ocean, but it was assumed that whales in the Arabian Sea belonged to the same population that has been studied off Sri Lanka and ranges into the southcentral Indian Ocean. However, the songs tell a different story.

"Before our recording effort off Oman, there were no acoustic data from the Arabian Sea, and so the identity of that population of blue whales was initially just a guess," said Andrew Willson from Five Oceans Environmental Services LLC, who led the deployment of the recording units. "Our work shows that there is a lot more to learn about these animals, and this is an urgent requirement in light of the wide range of threats to large whales related to expanding maritime industries in the region."

Blue whales were hunted to near extinction around the globe during the 20th century, and populations have only started to recover very slowly over the past several decades following the global moratorium on commercial whaling. The Arabian Sea was targeted by illegal Soviet whaling in the 1960's, an activity that nearly eradicated what were already likely to be small populations of humpback whales, blue whales, sperm whales, and Bryde's whales.

Some researchers consider both the northern Indian Ocean blue whales and Arabian Sea humpback whales to comprise unique subspecies, not simply populations, making them particularly special and important to biodiversity.

"These populations appear to be unique among baleen whales, in the case of the Arabian Sea humpback whales because of their year-round residency in the region without the same long-range migration of other populations," Willson points out.

"For 20 years we have focused work on the highly endangered Arabian Sea humpback whale, for which we believe only about 100 animals remain off the coast of Oman," says Suaad Al Harthi, Executive Director of the Environment Society of Oman. "Now, we are just beginning to learn more about another equally special, and likely equally endangered, population of blue whale."

Credit: 
New England Aquarium

Using wearable activity trackers to distinguish COVID-19 from flu

By analyzing Fitbit data and self-reported symptoms, researchers from Evidation Health and collaborators analyzed trends in heart rate, step count, and symptom duration between patients with flu and those with COVID-19. While both showed similar-looking spikes in resting heart rate and decreases in average step count, COVID-19 symptoms lasted longer and peaked later. Contrasting and comparing flu and COVID-19 is important for COVID-19 screening, as current practices often only check for more general symptoms like fever. The study was conducted using Evidation's app and network, Achievement--a connected cohort comprised of over 4 million individuals nationwide. The results appear December 12 in the journal Patterns.

"It's surprising to see that many screening tests at building entrances are all temperature-based, since a lot of people don't develop a fever right away and there are so many things that cause fever other than COVID-19." says senior author Luca Foschini, co-founder of Evidation Health, based in the United States. "A huge spike in resting heart rate is a more sensitive indicator of COVID. And for people with activity trackers, you could ask them permission to share that information for screening purposes, just like taking a temperature reading."

The findings confirmed that certain other symptoms are characteristic of COVID but not flu, like shortness of breath and coughing. They also examined the impact of each illness on decreasing daily step count, finding that the impacts lasted much longer for COVID than for flu.

"We used step count to measure change in mobility, because you don't move as much when you're sick," says Foschini, "Compared to their baseline, the number of steps didn't go back to normal for people with COVID, even after three or four weeks."

This result, as well as reports of long-term fatigue, also hinted at the existence of chronic COVID cases, which had not yet been studied closely at the beginning of the pandemic when this data was gathered.

"What was most interesting and surprising to us was looking at the progression of symptoms over time, particularly fatigue," says Foschini. "We didn't know about long-haulers back then, but now we know that Long COVID exists and that the hallmark is persistent fatigue."

While data from wearables such as Fitbit can reveal a lot about these respiratory illnesses, the researchers maintain that it should be used as a general screening method, not a complete diagnostic tool.

"There's potential to use wearable sensors and smartphones as high frequency/low-sensitive tests to shorten the time of detection and awareness of a possible ongoing infection.," says Foschini. "It's not a magic bullet, but if you can isolate yourself one or two days earlier than current standard testing procedures allow , that's the most important thing because infectivity is highest around when symptoms first appear in symptomatic cases."

The researchers however warn that to develop these solutions, it is important to consider flu and other Influenza-like illness as a potential source of false positives. "Whoever designs these systems of detection needs to be wary of other conditions and focus not just on distinguishing COVID from healthy, but distinguishing COVID from anything else going on in the world, including flu," says Foschini. "Only 1 in 5 American have a wearable, and that 20% is not equally distributed. We must focus research toward solutions that can benefit everyone equally."

Credit: 
Cell Press

Silkworm's brain determines diapause by thermal information

image: Thionin staining of embryos 8 days after oviposition in DW-injected silkworms and 60 days after oviposition in DH-injected and PTX-injected silkworms in wt of N4 strain. (Scale bar: 200μm)

Image: 
Copyright 2020, PNAS, Licensed under CC BY 4.0

Diapause is a seasonal adaptation strategy of insects and animals where biological functions are put on hold, such as insect eggs that remain dormant until conditions are more favorable to hatch. This is not a passive response of dormancy to adverse situations but an actively induced state that takes place well in advance in anticipation of natural conditions. Although it has been hypothesized that the neuroendocrine systems are associated with seasonal reproductive plasticity, the morphological, physiological, behavioral, reproductive responses of diapause remain unclear.

In this study, silkworms (Bombyx mori) were found to lay diapause eggs at 25°C and non-diapause eggs at 15°C. Females were observed to determine whether to lay diapause eggs or not according to thermal information received by the embryonic Bombyx TRPA1 ortholog (BmTRPA1). Scientists have previously known that there is a chemical released from the brain to signal diapause. In this study scientists at Shinshu University et al. have elucidated that the neuropeptide corazonin regulates the release of the diapause hormone.

Associate Professor Shiomi of Shinshu University states, "we have revealed for the first time that corazonin is a key player in the production of dormant eggs due to temperature. Currently, we are investigating the higher-level mechanism of why the hormone secretion mechanism differs depending on the temperature. We have also begun research on the evolutionary process of that pathway. A series of studies revealed a part of the mechanism of the seasonal response of the brain in a wide range of insects and other animals. In the future, this novel information may be used in the control of insect reproduction and effective pest control."

Corazonin (Crz) is a neuropeptide that is in the same family of neuropeptides as the mammalian gonadotropin-releasing hormone (GnRH) known to control seasonal reproduction. The researchers found that Crz release is controlled by GABA neurotransmission and that temperatures during the egg period affect the GABA neurotransmission during the pupal period, which determines diapause. This predictive adaptive response or PARs is even observed in mammals including humans.

Silkworms are dimorphic insects, meaning they repeat a life cycle of two generations in one year. They are known to lay dormant eggs that stop normal development in the early stages of embryogenesis. This is determined by the maternal effect of thermal information which is memorized and stored. Crz is also known to slow the silk spinning rate of worms, suggesting it has multiple physiological functions. Shinshu University is home to the only Faculty of Textile Science and Technology in Japan. They celebrate its 110th year anniversary this year, of which research into silk and silkworms has the longest history. Please read Maternal GABAergic and GnRH/corazonin pathway modulates egg diapause phenotype of the silkworm Bombyx mori to find out more.

Credit: 
Shinshu University

Deep, slow-slip action may direct largest earthquakes and their tsunamis

image: Map of the Cascadia subduction zone.

Image: 
Public Domain

Megathrust earthquakes and subsequent tsunamis that originate in subduction zones like Cascadia -- Vancouver Island, Canada, to northern California -- are some of the most severe natural disasters in the world. Now a team of geoscientists thinks the key to understanding some of these destructive events may lie in the deep, gradual slow-slip behaviors beneath the subduction zones. This information might help in planning for future earthquakes in the area.

"What we found was pretty unexpected," said Kirsty A. McKenzie, doctoral candidate in geoscience, Penn State.

Unlike the bigger, shallower megathrust earthquakes that move and put out energy in the same direction as the plates move, the slow-slip earthquakes' energy may move in other directions, primarily down.

Subduction zones occur when two of the Earth's plates meet and one moves beneath the other. This typically creates a fault line and some distance away, a line of volcanoes. Cascadia is typical in that the tectonic plates meet near the Pacific coast and the Cascade Mountains, a volcanic range containing Mount St. Helens, Mount Hood and Mount Rainier, forms to the east.

According to the researchers, a megathrust earthquake of magnitude 9 occurred in Cascadia in 1700 and there has not been a large earthquake there since then. Rather, slow-slip earthquakes, events that happen deeper and move very short distances at a very slow rate, happen continuously.

"Usually, when an earthquake occurs we find that the motion is in the direction opposite to how the plates have moved, accumulating that slip deficit," said Kevin P. Furlong, professor of geosciences, Penn State. "For these slow-slip earthquakes, the direction of movement is directly downward in the direction of gravity instead of in the plate motion directions."

The researchers have found that areas in New Zealand, identified by other geologists, slow slip the same way Cascadia does.

"But there are subduction zones that don't have these slow-slip events, so we don't have direct measurements of how the deeper part of the subducting plate is moving," said Furlong. "In Sumatra, the shallower seismic zone, as expected, moves in the plate-motion direction, but even though there are no slow-slip events, the deeper plate movement still appears to be primarily controlled by gravity."

Slow-slip earthquakes occur at a deeper depth than the earthquakes that cause major damage and earth-shaking events, and the researchers have analyzed how this deep slip may affect the timing and behavior of the larger, damaging megathrust earthquakes.

"Slow-slip earthquakes rupture over several weeks, so they are not just one event," said McKenzie. "It's like a swarm of events."

According to the researchers, in southern Cascadia, the overall plate motion is about an inch of movement per year and in the north by Vancouver Island, it is about 1.5 inches.

"We don't know how much of that 30 millimeters (1 inch) per year is accumulating to be released in the next big earthquake or if some movement is taken up by some non-observable process," said McKenzie. "These slow-slip events put out signals we can see. We can observe the slow-slip events going east to west and not in the plate motion direction."

Slow-slip events in Cascadia occur every one to two years, but geologists wonder if one of them will be the one that will trigger the next megathrust earthquake.

The researchers measure surface movement using permanent, high-resolution GPS stations on the surface. The result is a stair step pattern of loading and slipping during slow-slip events. The events are visible on the surface even though geologists know they are about 22 miles beneath the surface. They report their results in Geochemistry, Geophysics, Geosystems.

"The reason we don't know all that much about slow-slip earthquakes is they were only discovered about 20 years ago," said Furlong. "It took five years to figure out what they were and then we needed precise enough GPS to actually measure the motion on the Earth's surface. Then we had to use modeling to convert the slip on the surface to the slip beneath the surface on the plate boundary itself, which is bigger."

The researchers believe that understanding the effects of slow-slip earthquakes in the region at these deeper depths will allow them to understand what might trigger the next megathrust earthquake in the area. Engineers want to know how strong shaking in an earthquake will be, but they also want to know the direction the forces will be in. If the difference in direction of slow-slip events indicates a potential change in behavior in a large event, that information would be helpful in planning.

"More fundamentally, we don't know what triggers the big earthquake in this situation," said McKenzie. "Every time we add new data about the physics of the problem, it becomes an important component. In the past, everyone thought that the events were unidirectional, but they can be different by 40 or 50 degrees."

While the slow-events in Cascadia are shedding light on potential megathrust earthquakes in the area and the tsunamis they can trigger, Furlong thinks that other subduction zones may also have similar patterns.

"I would argue that it (differences in direction of motion) is happening in Alaska, Chile, Sumatra," said Furlong. "It is only in a few that we see the evidence of it, but it may be a universal process that has been missed. Cascadia exhibits it because of the slow-slip events, but it may be fundamental to subduction zones."

Credit: 
Penn State

Researchers invent method to 'sketch' quantum devices with focused electrons

image: Illustration of an electron-beam "sketching" a quantum dot at the LaAlO3/SrTiO3 interface

Image: 
Muqing Yu

PITTSBURGH--It has long been a dream to invent new materials from the "top down" choosing which atoms go where to engineer properties of interest. A technique created by researchers out of the Department of Physics and Astronomy enables them to "sketch" patterns of electrons into a programmable quantum material--lanthanum aluminate/strontium titanate or "LAO/STO". Using this approach, they can create quantum devices and with feature sizes comparable to the spacing between electrons, and even "sketch" artificial lattices for electrons to traverse, with extremely high precision.

To develop this capability, the researchers repurposed an electron beam lithography instrument, which is ordinarily used to create nanostructures by exposing a resist that hardens into a mask, enabling layers of material to be subsequently added or removed. Instead of operating the instrument at its usual value of 20,000 Volts, the researchers dialed it down to only a few hundred volts, where the electrons could not penetrate the surface of their oxide material, and instead--without any resist--catalyze a surface reaction that renders the LAO surface positively charged, and the LAO/STO interface locally conductive. The electron beam is 10,000 times faster at writing compared with atomic-force microscope-based lithography, without losing spatial resolution or ability to be reprogrammed. In addition, the authors showed that this technique can program the LAO/STO interface when integrated with other 2D layers such as graphene.

The team is led by Jeremy Levy, a Distinguished Professor of Condensed Matter Physics and director of the Pittsburgh Quantum Institute, describe the method in the paper, "Nanoscale control of LaAIO3/SrTiO3 metal-insulator transition using ultra-low-voltage electron-beam lithography." The paper was published in Applied Physics Letter on Dec. 21.

Dengyu Yang, a graduate student who developed the technique and is lead author on the paper, compared it to "imaging a sketch on a canvas with a pen."

"In this case, the canvas is LAO/STO and the "pen" is a beam of electrons. This powerful ability allows us to participate with more complex structures and expend the device from one dimension to two dimensions," she said.

Yang and Levy said the discovery could have implications in the fields of quantum transport and quantum simulation.

"We are very interested in using this technique to programmatically create new families of two-dimensional electronic materials based on arrays of artificial atoms written using this technique. Our group recently published a paper in Science Advances demonstrating the idea of quantum simulation in one-dimensional devices, using the AFM method. This new EBL-based technique will enable us to perform quantum simulation in two dimensions," said Levy.

In addition to Yang and Levy, Pitt collaborators on the paper include research professor Patrick Irvin and graduate students Shan Hao, Qing Guo, Muqing Yu, Yang Hu, Assistant Professor Jun Chen from the Swanson School of Engineering. Additional affiliations include the Department of Materials Science and Engineering at University of Wisconsin-Madison and Pittsburgh Quantum Institute.

Credit: 
University of Pittsburgh

Regulating off-centering distortion maximizes photoluminescence in halide perovskites

image: Pressure-regulated off-centering distortion maximizes photoluminescence in halide perovskites

Image: 
Xujie Lü

In work published in the National Science Review (nwaa288), a team at HPSTAR led by Dr. Xujie Lü applied high pressure to tune the remarkable photoluminescence (PL) properties in halide perovskites. For the first time, they reveal a universal relationship whereby regulating the level of off-centering distortion (towards 0.2) can achieve optimal PL performance.

The extraordinary electronic and optical properties that halide perovskites possess have revolutionized next-generation photovoltaics and optoelectronics' prospects. However, the underlying mechanisms responsible for their unique functionalities are still not fully understood. Developing our fundamental understanding of how structural configurations affect their properties is crucial. As a thermodynamic variable, pressure can effectively tune the lattice and electronic configurations, resulting in concomitant changes in materials' properties.

Using advanced in situ/operando high-pressure techniques in combination with theoretical calculations yielded fascinating results. "By carefully selecting and regulating the highly-distorted halide perovskites, we reached an otherwise unreachable structural region for probing properties that affords a great opportunity to understand the structure-property relationship," said Dr. Lü.

The team applied their obtained principle as a guideline to achieve bright PL in (CH3NH3)1-xCsxGeI3 by chemically substituting CH3NH3+ with smaller sized Cs+. The chemical substitution tunes the distortion, much like external pressure. The compression of CsGeI3 further regulates the distortion to the optimal value at 0.7 GPa, which maximizes the emission with a ten-fold enhancement. These findings open new paths to high-performance optoelectronic materials by leveraging the distortion and strain degrees of freedom.

"This work not only demonstrates the quantitative relationship between structural distortion and the PL property of halide perovskites," said Dr. Lü. "But also illustrates the use of the extracted knowledge for the virtuous cycle of materials design and optimization."

This direct use of knowledge gained from high-pressure research to purposefully design and synthesize materials with desired properties at ambient conditions is rarely reported.

Credit: 
Center for High Pressure Science & Technology Advanced Research

Screen time, emotional health among parents' top concerns for children during pandemic

image: A new national poll gives a glimpse into parents' greatest concerns about their kids in the pandemic-era.

Image: 
C.S. Mott Children's Hospital National Poll on Children's Health at Michigan Medicine.

ANN ARBOR, Mich. -- Parenting in a pandemic is not for the faint of heart.

Many children are in virtual school, less physically connected to friends and activities like sports and may have experienced major lifestyle changes from spending more time at home during quarantine.

Now, a new national poll gives a glimpse into parents' greatest concerns about their kids in the pandemic-era. High on the top 10 list: overuse of social media and screen time, internet safety, unhealthy eating, depression and suicide and lack of physical activity.

Almost half of parents also describe COVID-19, the disease itself, as a "big problem" impacting kids, coming in at No.10, according to the C.S. Mott Children's Hospital National Poll on Children's Health at Michigan Medicine.

"This is an especially challenging time for families, with many children experiencing significant changes in routine that may negatively impact their health and wellbeing," says Mott Poll co-director and Mott pediatrician Gary Freed, M.D., M.P.H.

"Parents' biggest concerns for young people seem to be associated with changes in lifestyle as a result of the pandemic. COVID-19 has turned the world of our children and teens upside down in many ways and this is reflected in how parents rate health issues in 2020."

But there are key racial and ethnic differences among families when it comes to worries about children's health, according to the report.

Black parents rate racism as their No.1 health concern for children and teens, with COVID-19 coming in at No.2. Racism ranks sixth among Hispanic parents, with COVID-19 at No.8. Racism does not make the top 10 health issues for U.S. children among white parents and COVID-19 much lower on among their concerns.

These differences are likely due to African-American and Hispanic communities being disproportionately impacted by COVID-19 in the U.S., Freed says. People from minority groups have been more likely to contract COVID-19, gotten sicker and died of the virus at significantly higher rates than white individuals.

Systemic racism has also been a national focus, as massive demonstrations protesting racial injustice swept the country over recent months.

Black parents are also the only group that rates gun injuries and unequal access to health care as a top 10 concern. Meanwhile, white parents are the only group to rate lack of physical activity in the top 10.

"Families' backgrounds and experiences likely shape what health concerns they prioritize as most pressing for American children today," Freed says.

The nationally-representative report is based on responses from 2,027 parents with children ages 18 and under.

A closer look at top health concerns highlighted in the report:

Screen time

Freed says it's not surprising that the top three issues on parents' list of concerns are related to screen use. Children are spending more time online because of virtual school or not being able to spend time with friends in person.

But he says parents should worry less about the amount of time children are using devices and more on how they are using the technology.

"It's important for children and teens to maintain social and family connections that we know are critical for their emotional well-being, especially during a time when they are feeling stressed or isolated," Freed says. "Technology may be an important vehicle for those connections."

Still, parents should set clear ground rules and boundaries about how and when children can use devices to ensure it's not disrupting sleep habits, replacing healthy habits like physical activity and that children's privacy is protected. They should also watch for any signs of cyberbullying and other types of online abuse, which also made the top 10 list.

"Parents need to have ongoing conversations with their children and teens to guide them on safe internet practices," Freed says.

Emotional and physical health

Some parents reported great concern about kids experiencing increased negative emotions such as stress, anxiety, or depression, which may be related to or exacerbated by lifesyle changes caused by COVID-19.

"Parents may notice changes, such as increased behavioral issues in younger kids or more moodiness or lethargy from older kids and teenagers," Freed says.

In these situations, parents should encourage children and teens to talk about their feelings, and find healthy outlets to help them cope.

Changes in routine and social isolation from COVID-19 may also affect a child's physical health. Inconsistent sleep habits may particularly increase the potential for unhealthy eating and reducing outside physical activity---all issues parents identified as top health concerns.

Families should try to maintain routines, especially keeping regular sleep schedules and helping teens resist the temptation to go to bed much later than usual and sleeping in later, Freed says.

Mott experts also recommend intentional "unplugged" times to spend together as a family and getting outside daily, even for a brisk walk, as much as possible.

But parents should also look for red flags that kids need more help to manage feelings, such as comments about how they might hurt themselves or experiencing dramatic shifts in usual mood, appetite or sleep. In these cases, families should reach out to pediatricians and consider enlisting the help of therapists or other health professionals.

Children who have lost family members to COVID-19 may also need special attention and mental health services to help in how to understand and cope with their loss, Freed says.

Racism

Families should recognize the emotional toll of racism on children and teens.

The impact of racism may be reflected in physical problems, such as disparities in the rates of diseases among different populations, and also in children's mental health. Children targeted by racism have higher rates of depression, anxiety, and behavior problems, research shows.

"Although racism directly affects specific populations, its impact on children's health is a societal concern," Freed says. "It's important for parents to recognize the detrimental consequences of racism for children in our communities."

Finding ways for young people to get involved either through safely participating in protests or supporting groups or causes that aim to fight racism can be valuable, Freed says.

"Racism can instill a sense of helplessness in both children and teens," he says. "When young people are empowered to stand up to racism, it can make a big difference by showing them they can be part of a solution."

Credit: 
Michigan Medicine - University of Michigan

Exposure to metals can impact pregnancy

Exposure to metals such as nickel, arsenic, cobalt and lead may disrupt a woman's hormones during pregnancy, according to a Rutgers study.

The study appears in the journal Environment International.

Exposure to metals has been associated with problems at birth such as preterm birth and low birth weight in babies, and preeclampsia in women. However, little is known about how metals exposure can lead to such problems.

This new research shows that some metals may disrupt the endocrine system, which is responsible for regulating our body's hormones. These disruptions may contribute to children's later health and disease risk.

"A delicate hormonal balance orchestrates pregnancy from conception to delivery and perturbations of this balance may negatively impact both mother and fetus," said lead author Zorimar Rivera-Núnez, an assistant professor in the Department of Biostatistics and Epidemiology at the Rutgers School of Public Health.

The researchers analyzed blood and urine samples from 815 women enrolled in the Puerto Rico Test site for Exploring Contamination Threats (PROTECT) study.

Initiated in 2010, PROTECT is an ongoing prospective birth cohort studying environmental exposures in pregnant women and their children around the northern karst zone, which include urban and mountainous rural areas of Puerto Rico.

They found that metals can act as endocrine disruptors by altering prenatal hormone concentrations during pregnancy. This disruption may depend on when in the pregnancy the mother was exposed.

Prenatal exposure to metals can have enormous consequences even beyond health at birth. Alterations in sex-steroid hormones during pregnancy have been associated with inadequate fetal growth, which leads to low birthweight. Birth size is strongly associated with a child's growth and risk of chronic diseases, including obesity and breast cancer.

"Puerto Rico has one of the highest rates of Superfund sites of any of the U.S. jurisdictions with 18 active sites, which can contribute to the higher rates of exposure to toxic metals," said Rivera-Núnez.

Among pregnant women, metal exposure is higher in those living in Puerto Rico than in those in the continental United States.

"This is important because, compared to the U.S. overall, women in Puerto Rico have significantly higher rates of preterm birth [nearly 12 percent] and other adverse birth outcomes. Additionally, exposure to environmental pollution is exacerbated by extreme weather events, such as hurricanes, droughts and flooding, which may result in elevated exposures to Superfund sites," she added.

According to the study authors, future research should investigate how changes in markers of endocrine function affect birth and other health outcomes. Future studies also should look at essential metals in relation to maternal and fetal health, and metals as mixtures in relation to markers of endocrine function.

Credit: 
Rutgers University

Wa­ter and genes flow between the two largest Baltic sal­mon rivers

image: Juvenile salmon from the Tornio River.

Image: 
Ville Vähä

Salmon from upstream reaches of the two northernmost Baltic rivers are different from downstream salmon. A recent study found that upstream salmon from the large Tornio and Kalix Rivers in Finland and Sweden are genetically distinct and migrate at different times and ages than their downstream counterparts. However, there seems to be no such distinction between salmon from these two neighbouring rivers.

Traffic is busy below the surface of the Baltic Sea and rivers flowing into it. Starting in early summer, mature salmon migrate from the sea into their home rivers to spawn. The study by the University of Helsinki, Natural Resources Institute Finland (Luke) and Swedish University of Agricultural Sciences (SLU) found that salmon destined to spawn far upstream entered the Tornio (Torne in Swedish) River at an earlier date during their spawning migration.

Morever, salmon heading to the upper parts of the river system had almost always spent more than one year at the sea. This is relevant for fisheries, as salmon grow larger the more time they spend at sea. Old and large salmon are particularly prized catches, and essential for the stocks' wellbeing: large salmon produce the most offspring. How to preserve this kind of diversity is an important consideration in the management and conservation of the largest wild Baltic salmon stocks.

"Salmon that entered the Tornio River earliest in the summer appeared to be mostly on their way to the upper reaches. This suggests that there is good reason to study and closely follow how fishing early in the season may affect the upstream populations," says lead author of the article Antti Miettinen, from the Faculty of Biological and Environmental Sciences, University of Helsinki.

Sal­mon don't fol­low bor­ders

The Tornio River acts as the border between Finland and Sweden, whereas the neighbouring Kalix River is located entirely in Sweden. These rivers host by far the largest remaining wild Baltic salmon stocks.

Surprisingly, the study found no clear genetic differences separating salmon from the two rivers. This may partly be explained by the rivers being connected to each other by one of the largest bifurcations in the world. About half of the water from the Swedish Torne River flows into the Kalix River through the bifurcation. From the salmon's perspective, it makes the rivers one vast system to navigate in. In practice, salmon and their genes have a way of reaching the other river.

"The bifurcation and intriguing genetic similarity between salmon from these rivers highlight the significance of cross-border collaboration in conserving and managing this important salmon stock," Miettinen says.

Credit: 
University of Helsinki

Targeting the deadly coils of Ebola

video: Molecular surface representation of the Ebola virus nucleocapsid with bound RNA.

Image: 
Juan R. Perilla, University of Delaware.

In the midst of a global pandemic with COVID-19, it's hard to appreciate how lucky those outside of Africa have been to avoid the deadly Ebola virus disease. It incapacitates its victims soon after infection with massive vomiting or diarrhea, leading to death from fluid loss in about 50 percent of the afflicted. The Ebola virus transmits only through bodily fluids, marking a key difference from the COVID-19 virus and one that has helped contain Ebola's spread.

Ebola outbreaks continue to flare up in West Africa, although a vaccine developed in December 2019 and improvements in care and containment have helped keep Ebola in check. Supercomputer simulations by a University of Delaware team that included an undergraduate supported by the XSEDE EMPOWER program are adding to the mix and helping to crack the defenses of Ebola's coiled genetic material. This new research could help lead to breakthroughs in treatment and improved vaccines for Ebola and other deadly viral diseases such as COVID-19.

"Our main findings are related to the stability of the Ebola nucleocapsid," said Juan R. Perilla, an assistant professor in the Department of Chemistry and Biochemistry at the University of Delaware. Perilla co-authored a study published in October 2020 in the AIP Journal of Chemistry Physics. It focused on the nucleocapsid, a protein shell that protects against the body's defenses the genetic material Ebola uses to replicate itself.

"What we've found is that the Ebola virus has evolved to regulate the stability of the nucleocapsid by forming electrostatic interactions with its RNA, its genetic material," Perilla said. "There is an interplay between the RNA and the nucleocapsid that keeps it together."

Like coronaviruses, the Ebola virus depends on a rod-like and helically-shaped nucleocapsid to complete its life cycle. In particular, structural proteins called nucleoproteins assemble in a helical arrangement to encapsulate the single-stranded viral RNA genome (ssRNA) that forms the nucleocapsid.

The study by Perilla and his science team sought the molecular determinants of the nucleocapsid stability, such as how the ssRNA genetic material is packaged, the electrostatic potential of the system, and the residue arrangement in the helical assembly. This knowledge is essential for developing new therapeutics against Ebola. Yet these insights remain out of reach even by the world's best experimental labs. Computer simulations, however, can and did fill that gap.

"You can think of simulation work as a theoretical extension of experimental work," said study co-author Tanya Nesterova, an undergraduate researcher in the Perilla Lab. "We found that RNA is highly negatively charged and helps stabilize the nucleocapsid through electrostatic interaction with the mostly positively charged nucleoproteins," she said.

Nesterova was awarded funding through an XSEDE Expert Mentoring Producing Opportunities for Work, Education, and Research (EMPOWER) scholarship in 2019, which supports undergrads participate in the actual work of XSEDE.

"It was an effective program," she said. "We used computational resources such as Bridges this summer. We also had regular communication with the coordinator to keep our progress on track."

The team developed a molecular dynamics simulation of the Ebola nucleocapsid, a system that contains 4.8 million atoms. They used the cryo-electron microscopy structure of the Ebola virus published in Nature in October of 2018 for their data in building the model.

"We built two systems," said study co-author Chaoyi Xu, a PhD student in the Perilla Lab. "One system is the Ebola nucleocapsid with the RNA. And the other one is just the nucleocapsid as a control."

"After we built the whole tube, we put each nucleocapsid in an environment that is similar to the cell," Xu explained. They basically added sodium chloride ions, and then adjusted the concentration to match that found in the cytoplasm. They also put a water box inside around the nucleocapsid. "And then we ran a very powerful simulation," Xu added.

The NSF-funded Extreme Science and Engineering Discovery Environment (XSEDE) awarded the team supercomputing allocations on the Stampede2 system at the Texas Advanced Computing Center and the Bridges system of the Pittsburgh Supercomputing Center.

"We are very thankful for the supercomputer resources provided by XSEDE that allowed this work to be possible. XSEDE also provided training through online courses that was helpful," Xu said.

"On Stampede2, we have access to run simulations on hundreds or even thousands of nodes," Xu continued. "This makes it possible for us to run simulations of larger systems, for example, the Ebola nucleocapsid. This simulation is impossible to finish locally. That's very important," he said.

"I like how with Bridges, when you run a simulation, you can be up to date on when it completes and when it started," Nesterova added. She said that was helpful for creating Slurm scripts, which help manage and schedule jobs on compute clusters.

"We just started using Frontera for the Ebola project," Xu added. Frontera is the NSF flagship Tier 1 system at TACC, ranked #9 in the world by Top500. "It's more powerful because it has the latest CPU architecture. And it's very fast," he said.

"Frontera is part of the TACC infrastructure," Perilla said. "We knew what developmental tools were going to be there, and also the queueing system and other intricacies of these machines. That helped a lot. In terms of architecture, we're familiar with Stampede2, although this is a different machine. Our experience with Stampede2 allowed us to move quickly to start using Frontera," he said.

The science team simulated the interaction of the atoms in the Ebola virus nucleocapsid and measured how they change in time, yielding useful information about the atomic interactions. One of the things they found was that without the RNA, the Ebola virus nucleocapsid kept its tube-like shape. But the packing of the nucleoprotein monomers became disordered, and its helical symmetry was lost. With the RNA, it kept its helix. Their results showed that the RNA binding stabilized the helix and preserved the structure of the Ebola virus nucleocapsid.

The team also found important interactions between the nucleoprotein residues and the ssRNA, and also interactions between two nucleoproteins.

"There's two kinds of interfaces between the pairs of nucleoproteins that form the helical arrangement. We figured out which of these interfaces plays a more important role. We can either target that interface to destabilize the helical arrangement or stabilize the helical arrangement to a large extent such that the virus nucleocapsid is unable to disassemble," said study co-author Nidhi Katyal, a postdoctoral researcher in the Perilla Lab.

The Ebola virus is one tough organism because it tightly regulates its macromolecular assembly. Perilla suggested that instead of trying to devise drugs that destroy the nucleocapsid, a good strategy might be to do the opposite.

"If you make it too stable, that's enough to kill the virus," he said. Borrowing a strategy from his background in HIV research, he wants to find targets for drugs to over-stabilize the Ebola virus and keep it from releasing its genetic material, a key step in its replication.

Perilla suggested a similar strategy for other pathogens that are tightly regulated, such as coronaviruses and hepatitis B viruses. "They're a sweet spot, so to speak. We know what confers stability. Other teams can look to see if maybe this is a good druggable site for making it hypostable or making it hyperstable," Perilla said.

Looking ahead, Perilla indicated his lab will be looking more closely at the specifics of ssRNA sequence and whether it confers stability to the Ebola virus nucleocapsid tube. If it does, then some regions might be exposed and might be transcribed first, similar to what happens in the nucleus of the cell. Perilla said it would be "unheard of in a virus," and extremely advanced behavior in terms of the RNA regulating transcription.

Said Perilla: "We know that there will be more pathogens that just keep coming, particularly with coronaviruses now, and they can stop the world. It's beneficial to society having the ability to study not only one virus, but taking these techniques to study a new virus, something like coronaviruses. In addition, the ability to train new students, like Tanya, provides the taxpayers their money's worth in terms of training the next generation, transferring knowledge from other viruses, and fighting the current problems."

Credit: 
University of Texas at Austin, Texas Advanced Computing Center

Three flavors are better than one -- in ice cream and supernova research

Any Neapolitan ice cream lover knows three flavors are better than one. New research from Northwestern University has found that by studying all three "flavors" involved in a supernova, they've unlocked more clues as to how and why stars die.

Scientists look at neutrinos (subatomic particles) for critical information about supernova explosions. While previous research identified three "flavors" of neutrinos, many researchers continued to simplify studies on the topic by studying "vanilla" while ignoring "chocolate" and "strawberry."

By including all three flavors in the study, Northwestern researchers have developed a deeper knowledge of dying stars and begun to unravel existing hypotheses.

The study was published Wednesday, Dec. 16, in the journal Physical Review Letters.

In a supernova explosion, 99% of the dead star's energy is emitted through neutrinos. Traveling almost at the speed of light and interacting extremely weakly with matter, neutrinos are the first messengers to reach the earth and indicate a star has died.

Since their initial discovery in the 1950s, particle physicists and astrophysicists have made important strides in understanding, detecting and creating neutrinos. But to limit the complexity of models, many people studying subatomic particles make assumptions to simplify the research - for example, that non-electron neutrinos behave identically when they are propelled from a supernova.

Part of what makes studying neutrinos so complicated is they come from compact objects (the inside of a star) and then interact with one another, said senior author Manibrata Sen, a postdoctoral researcher currently based at Northwestern under the Network for Neutrinos, Nuclear Astrophysics and Symmetries program at University of California - Berkeley. That means when one flavor is impacted, much like a melting tub of Neapolitan ice cream, its evolution is affected by all others in the system.

"You can't create conditions to have neutrinos interacting with each other on Earth," Sen said. "But in compact objects, you have a very high density of neutrinos. So now each neutrino is interacting with each other because there are so many around."

As a result, when an enormous number of neutrinos are sent careening during the massive explosion of a core-collapse supernova, they begin to oscillate. Interactions between neutrinos change the properties and behaviors of the whole system, creating a coupled relationship.

Therefore, when neutrino density is high, a fraction of neutrinos interchange flavors. When different flavors are emitted in different directions deep within a star, conversions occur rapidly and are called "fast conversions." Interestingly, the research found that as the number of neutrinos grows, so do their conversion rates, regardless of mass.

In the study, the scientist created a non-linear simulation of a "fast conversion" when three neutrino flavors are present, where a fast conversion is marked by neutrinos interacting and changing flavors. The researchers removed the assumption that the three flavors of neutrinos -- muon, electron and tau neutrinos -- have the same angular distribution, giving them each a different distribution.

A two-flavor setup of the same concept looks at electron neutrinos and "x" neutrinos, in which x can be either muon or tau neutrinos and where differences between the two are insignificant.

"We've shown that they actually are all relevant, and ignoring the presence of muons is not a good strategy," Sen said. "By including them we show past results are incomplete, and results change drastically when you perform a three-flavor study."

While the research could have major implications in both particle and astrophysics, even models used in this research included simplifications. The team hopes to make their results more generic by including spatial dimensions in addition to components of momentum and time.

In the meantime, Sen said he hopes his team's research will help the community embrace more complexity in their studies.

"We are trying to convince the community that when you take these fast conversions into account, you have to use all three flavors to understand it," he said. "A proper understanding of fast oscillations can actually hold the key to why some stars explode from supernovas."

Credit: 
Northwestern University

Goldilocks and the three quantum dots: Just right for peak solar panel performance

image: Quantum dots, represented here, that are the right size will capture more sunlight, making it available to solar cells.

Image: 
Laszlo Frazer

Scientists in Australia have developed a process for calculating the perfect size and density of quantum dots needed to achieve record efficiency in solar panels.

Quantum dots, man-made nanocrystals 100,000 times thinner than a sheet of paper, can be used as light sensitisers, absorbing infrared and visible light and transferring it to other molecules.

This could enable new types of solar panels to capture more of the light spectrum and generate more electrical current, through a process of 'light fusion' known as photochemical upconversion.

The researchers, from the ARC Centre of Excellence in Exciton Science, used lead sulfide quantum dots in their example. The algorithm is free to access and their results have been published in the journal Nanoscale.

Significantly, existing upconversion results achieved by test devices used organic sensitisers that do not work with silicon solar cells - currently the most commonly available type of photovoltaics technology - due to their inability to absorb much of the infrared part of the light spectrum.

Using the right size and density of lead sulfide quantum dots as sensitisers would not only lead to efficiency increases but also be compatible with nearly all existing and planned solar cell technology.

These findings indicate that when it comes to the quantum dot size, it isn't as simple as bigger meaning better.

Using a basic theory, a larger quantum dot might appear to be able to capture more of the colours of sunlight, or more light of a certain wavelength, and be able to help create a device with higher efficiency.

The researchers, though, have taken into account several practical constraints on quantum dot size.

Most importantly, the near infrared part of sunlight at the Earth's surface has a complicated structure, influenced by water in the atmosphere and the sun's heat.

This means the colour of the quantum dot must be tuned to match the peaks of sunlight, like adjusting a musical instrument to a certain pitch.

According to corresponding author Dr Laszlo Frazer, the work demonstrates that a complete picture of the conditions influencing solar cell performance, from the star at the centre of our solar system to nanoscale particles, is necessary to achieve peak efficiency.

"This whole thing requires understanding of the sun, the atmosphere, the solar cell and the quantum dot," he said.

While the projected efficiency increases demonstrated by these results remain modest, the potential benefits are considerable, as they can be used in nearly all solar devices, including those made from silicon.

The next step for researchers is to design and create emitters that will transfer energy from the optimised quantum dot sensitisers most effectively.

"This work tells us a lot about the capturing of light," Laszlo said.

"Releasing it again is something that needs a lot of improvement. There's definitely a need for multidisciplinary contributions here."

Author Benedicta Sherrie of Monash University said: "More work needs to be done on building the solar cell prototypes with these sensitizers (and hopefully with the suitable emitters), and to test them.

"I hope this research will eventually allow society to rely more on photovoltaic solar energy that is not only efficient, but also affordable."

Credit: 
ARC Centre of Excellence in Exciton Science

Modeling rainfall drop by drop

Using a network of a newly introduced type of rain gauge that can measure rainfall with drop-by-drop precision, KAUST researchers have developed a high-frequency rainfall model to improve understanding of rainfall/runoff dynamics, such as flash flooding and hydrodynamics in small watersheds.

Rainfall modeling is one of the core aspects of weather forecasting and is often used to predict other weather parameters, such as wind and solar irradiance. Yet the power and insight of such models are limited by the data used to construct them. When it comes to precipitation, this means that modelers have to rely on sparse recordings of rainfall at 6-15-minute intervals at best, but more often hourly intervals. This leads to a "smoothing" of rainfall over time and a loss of information about how much rain falls during each rainfall event, which is a problem, according to Ph.D. student Yuxiao Li.

"This assumption is not appropriate for modeling precipitation at high frequency because large quantities of rainfall in the past can result in an unrealistically high probability of rainfall occurrence in such models," explains Li. "In this study, we used the high-frequency rainfall data collected by new instruments called Pluvimate rain gauges to better reproduce the statistical properties of precipitation occurrence, intensity and dry-spell duration."

The new acoustic rain gauges, which record each drop of rain caught in a receptacle, can provide precise high-frequency rainfall data, which are impossible to acquire using classical measurement devices such as tipping-bucket rain gauges and radar. These new datasets provide unprecedented insight into the minute-to-minute dynamics of rainfall, which requires a change in the statistical modeling approach.

"High-frequency precipitation data include more zeros and have longer 'tails' to high rainfall intensities than common precipitation data," says Li. "We developed a model that can capture this 'skewness' and the heavy tail of the high-frequency precipitation data, allowing us to generate synthetic precipitation data that provides valuable information for water management, especially at unobserved times and locations."

The model developed by Li and his supervisor Ying Sun also includes meteorological representations of ground and atmospheric layers, which allows direct physical interpretation of the statistical characteristics.

"Precipitation modeling is one of the main research topics in our Environmental Statistics Group," says Li. "Our model is the first stochastic precipitation generator for high-frequency precipitation and will be valuable for analyzing many short-term phenomena, as well as forming the basis for a 'digital twin' model to reproduce physical processes using a virtual replica, which is a hot topic for smart cities and industry 4.0."

Credit: 
King Abdullah University of Science & Technology (KAUST)

How cancers hurt themselves to hurt immune cells more

image: Ribosomes (large, dark circles) working their way down a strand of mRNA. Proteins are forming to the top and bottom. Amino acid scarcity results in ribosome logjams

Image: 
the Weizmann Institute of Science

Cancers like melanoma are hard to treat, not least because they have a varied bag of tricks for defeating or evading treatments. A combined research effort by scientists at the Weizmann Institute of Science and researchers in the Netherlands Cancer Institute in Amsterdam and the University of Oslo, Norway, shows exactly how tumors, in their battles to survive, will go so far as to starve themselves in order to keep the immune cells that would eradicate them from functioning.

The immunotherapies currently administered for melanomas work by removing obstacles that keep immune cells called T cells from identifying and killing tumor cells. Recent research suggested that in melanoma, another blocker could assist the T cells - this one to stop an enzyme called IDO1 that is overproduced by the cancer cells. IDO1 breaks down an essential amino acid, tryptophan, which is needed to make proteins, in the process leaving behind tryptophan breakdown byproducts that suppress the immune response. But IDO1 blockers did not fare well in clinical trials, suggesting more knowledge was needed - including how the cancer cells, which also require tryptophan, can function after they have destroyed this resource.

The research team, including the group of Prof. Yardena Samuels of Weizmann's Molecular Cell Biology Department, members of the lab of Prof. Reuven Agami of the Netherlands Cancer Institute; Dr. Noam Stern-Ginossar of the Weizmann Institute's Molecular Genetics Department; Dr. Yishai Levin and his group at the Nancy and Stephen Grand Israel National Center for Personalized Medicine on the Institute campus; and the group of Prof. Johanna Olweus of the University of Oslo, investigated the mystery of the missing tryptophan in melanoma cells.

Agami and his team had, in previous research shown that in normal cells, when an amino acid like tryptophan is missing, this causes a sort of logjam in the protein production process. The ribosomes - protein production units - make their way down a strand of messenger RNA (mRNA), translating three-letter "words" known as codons into amino acids, which they grab and add to the expanding protein chain. When an amino acid is missing, the ribosomes stop working until one can be found, causing a pile-up in the ribosomes coming up the mRNA strand from behind.

But that is not what happens in melanoma cells. The group found that some ribosomes manage to keep going, past the codons encoding the missing tryptophan. What was going on?

It turned out that the melanoma ribosomes were engaging in a ruse known as "frameshifting." That is, they simply moved up or down one letter in the RNA strand. In the economical gene code - based on just four letters - the next three spelled the name of a different amino acid and the ribosomes continued down the mRNA strand, assembling protein chains. Of course, the frames of subsequent codon triplets shifted as well, so that the resultant proteins were quite abnormal. The cancer cells then displayed them on their outer membranes, where immune cells could pick up on the aberrant protein structures.

Such frameshifting had been seen before in viruses and bacteria, but not in human cells. Previous studies have missed these proteins because they do not arise from genetic mutations (of which there are hundreds in melanoma), but from a sort of calculated blip in the production process. Agami, whose lab is now investigating exactly how this frameshifting is initiated and whether it occurs in other cancers, says: "This flexibility in mRNA translation might stimulate tumor growth and aggressive behavior by using an emergency program for scarcity."

Dr. Osnat Bartok, in Samuels's group: "When things get stressful in the tumor's microenvironment, it can affect protein production, harming immune cells but also adding to the immune cells' clues for identifying cancer." Samuels adds: "These findings add to our knowledge of immune system interactions with cancer as well as the landscape immune cells encounter in a tumor. They suggest exciting ways we might regulate and therapeutically target the presentation of defective immune-reactive peptides on the cell surface."

Credit: 
Weizmann Institute of Science