Tech

Hearing acrobatics

The sense of hearing is, quite literally, a molecular tightrope act. Turns out, it involves acrobatics as well.

In a paper published in Nature Communications on Feb 8, researchers at Harvard Medical School and Boston Children's Hospital show that a dynamic and delicate connection between two pairs of diminutive protein filaments plays a central role in in hearing.

The tension held by these filaments, together called a tip link, is essential for the activation of sensory cells in the inner ear. The team's analyses reveal that the filaments, which are joined end-to-end, work together like trapeze artists holding hands. Their grasp on each other can be disrupted, by a loud noise, for example. But with a two-handed grip, they can quickly reconnect when one hand slips.

The findings present a new understanding of the molecular underpinnings of hearing, as well as the sense of balance, which arises from similar processes in the inner ear. Disorders of deafness and balance have been linked to mutations in tip links, and the study results could lead to new therapeutic strategies for such disorders, according to the authors.

"This tiny apparatus, made of less than a dozen proteins, is what helps change sound from a mechanical stimulus into an electrical signal that the brain can decipher," said co-corresponding author David Corey, the Bertarelli Professor of Translational Medical Science at HMS. "Understanding how these proteins work provides insights into the secrets of the sensation of sound."

The dynamic connection between the filaments may also function as a circuit breaker that protects other cellular components, according to the researchers.

"I think our study gives us a sense of awe for how perfectly engineered this system in the ear is," said co-corresponding author Wesley Wong, HMS associate professor of biological chemistry and molecular pharmacology at Boston Children's. "It maintains a delicate balance between being just strong enough to carry out its function but weak enough to break to potentially preserve the function of other elements that can't be as easily reformed."

Decoding the handshake

For hearing to occur, cells must detect and translate pressure waves in the air into bioelectrical signals. This task falls upon hair cells, the sensory cells of the inner ear. Protruding from these cells are bundles of hair-like structures, which bend back and forth as pressure waves move through the inner ear.

Tip link filaments physically connect each hair to another and are anchored onto specialized ion channels. As the bundle moves, the tension of the tip links changes, opening and closing the channels like a gate to allow electric current to enter the cell. In this way, tip links initiate the bioelectrical signals that the brain ultimately processes as sound.

In previous studies, Corey and colleagues explored the composition of tip links and identified the precise atomic structure of the bond between the two protein filaments. Intriguingly, this bond was evocative of a molecular handshake, according to the authors.

In the current study, Corey, Wong and the team set out to understand the nature of this handshake. To do so, they applied single-molecule force spectroscopy, a technique that often uses optical tweezers--highly focused laser beams that can hold extremely small objects and move them by distances as short as a billionth of a meter.

The researchers, led by study first authors Eric Mulhall and Andrew Ward, both research fellows in neurobiology in the Blavatnik Institute at HMS, coated microscopic glass beads with strands of either protocadherin-15 or cadherin-23, the two proteins that make up the tip link. Using optical tweezers, they moved beads close to each other until the protein strands stuck together end to end and then measured the forces needed to pull the bonds apart.

Stronger than the sum

Each tip link is made up of two strands of both proteins. The team found that the strength of this double-stranded bond far surpassed the strength of the bond between individual strands of either protein. Under low tension, a double-stranded bond lasted ten times longer than a single-stranded bond before breaking.

This increased strength appears to be due to the dynamic nature of the connection, according to the authors. Rather than acting as a simple static rope, the filaments detach and reattach to each other within tenths of a second. A force may break one pair of strands apart, but the other pair can remain connected long enough for the broken pair to rejoin.

At extremely high forces, however, the double-stranded bond breaks rapidly. This feature may help to prevent catastrophic damage to other components of the hair cell, the authors said.

"If the tip link were super strong, then when exposed to a very loud sound it might rip the whole complex out of the cell membrane, which would be hard to recover from," said Wong, who is also an associate faculty member at the Wyss Institute for Biologically Inspired Engineering at Harvard.

"The ability to break with loud sounds is analogous to a mechanical circuit breaker," he added. "This use of multiple weak bonds to form a tunable biological circuit breaker could potentially be very interesting for synthetically engineered systems."

Surprisingly, the team found that under resting tension, each tip link lasts only around eight seconds before it breaks. Their analyses, coupled with evidence from other studies, suggest that new tip links can form rapidly from other strands of protein nearby. Together, the results support a new paradigm of highly dynamic tip link formation and rupture that both enables and protects hearing.

The team also looked at mutations to protocadherin-15 that are linked to Usher syndrome, a rare hereditary disorder of deafness and blindness. Their experiments suggest that some of these mutations can greatly weaken the bond between the tip link filaments. This may be why the disorder leads to deafness, and further mechanistic understanding of this process could lead to new therapeutic approaches, the authors said.

"It's hard to fix something if you don't really know what's broken, and we are optimistic that a better understanding can help lead to new solutions," Corey said.

In addition, the new findings may help inform study in other areas of the body.

"We have many different mechanical senses besides hearing, such as touch, the sensation of blood pressure, and certain types of pain," Corey added. "We understand hearing in more molecular detail than any of the others--knowledge that can help us probe the workings of other mechanical senses."

Credit: 
Harvard Medical School

Half of global wastewater treated, rates in developing countries still lagging

image: Wastewater treatment plant

Image: 
CC0 Public Domain

A new study by scientists at Utrecht University and the United Nations University concludes that about half of global wastewater is treated, rather than the previous estimate of 20%. Despite this promising finding, the authors warn that treatment rates in developing countries are still very low. The study and its dataset were published Open Access in the journal Earth System Science Data.

Humans and factories produce vast quantities of wastewater per day. If not properly collected and treated, wastewater may severely threaten human health and pollute the environment.

144 million swimming pools

The authors use national statistics to estimate volumes of wastewater production, collection, treatment and reuse. "Globally, about 359 billion cubic metres of wastewater is produced each year, equivalent to 144 million Olympic-sized swimming pools," says Edward Jones, PhD researcher at Utrecht University and lead author of the study. "About 48 percent of that water is currently released untreated. This is much lower than the frequently cited figure of 80 percent."

While the results show a more optimistic outlook compared to previous work, the authors stress that many challenges still exist. "We see that particularly in the developing world, where most of the future population growth will likely occur, treatment rates are lagging behind," Jones explains. "In these countries in particular, wastewater production is likely to rise at a faster pace than the current development of collection infrastructure and treatment facilities. This poses serious threats to both human health and the environment. There is still a long way to go!"

Creative reuse

The main problem, especially in the developing world, is the lack of financial resources to build infrastructure to collect and treat wastewater. This is particularly the case for advanced treatment technologies, which can be prohibitively expensive. However, the authors highlight potential opportunities for creative reuse of wastewater streams that could help to finance improved wastewater treatment practices.

"The most obvious reuse of treated wastewater is to augment freshwater water supplies," Jones states. Treated wastewater reuse is already an important source of irrigation water in many dry countries, particularly in the Middle East and North Africa. However, only 11% of the wastewater produced globally is currently being reused, which shows large opportunities for expansion.

From 'waste' to resource

"But freshwater augmentation is not the only opportunity," says Jones. "Wastewater also has large potential as a source of nutrients and energy. Recognition of wastewater as a resource, opposed to as 'waste', will be key to driving improved treatment going forward."

However, the authors stress the importance of proper monitoring of wastewater treatment plants, accompanied by strong legislation and regulations, to ensure that the reuse of wastewater is safe. The authors also acknowledge public acceptance as another key barrier towards increasing wastewater reuse.

Credit: 
Utrecht University

Coal and COVID-19: How the pandemic is accelerating the end of fossil power generation

COVID-19 has not only caused a temporary drop in global CO2 emissions, it has also reduced the share of power generated by burning coal - a trend that could in fact outlast the pandemic. This is the key result of a new study by a team of economists based in Potsdam and Berlin that looked at COVID-19's impact on the energy system and demand for electricity. Their findings show that the pandemic, while putting a terrible toll on people's lives and the economy, has also opened a window of opportunity to make this current trend of decreasing coal use irreversible: Supported by the right climate policy measures, power sector emissions could decline more rapidly than previously thought.

"Coal has been hit harder by the Corona crisis than other power sources - and the reason is simple," explains lead author Christoph Bertram from the Potsdam Institute for Climate Impact Research (PIK). "If demand for electricity drops, coal plants are usually switched off first. This is because the process of burning fuels constantly runs up costs. The plant operators have to pay for each single ton of coal. In contrast, renewable power sources such as wind and solar plants, once built, have significantly lower running costs - and keep on operating even if the demand is reduced."

This way, fossil fuels were partly squeezed out of the electricity generation mix in 2020 and global CO2 emissions from the power sector decreased around 7%. By looking at India, the USA, and European countries alone a more dramatic picture emerges: In these key markets, where monthly electricity demand declined by up to 20% compared to 2019, the monthly CO2 emissions decreased by up to 50%.

The researchers estimate that it's likely that emissions will not reach the all-time high of 2018 anymore. "Due to the ongoing crisis, we expect that 2021 electricity demand will be at about 2019's levels, which, given ongoing investments into low-carbon generation means lower fossil generation than in that year," says co-author Gunnar Luderer from PIK. "As long as this clean electricity generation growth exceeds increases in electricity demand, CO2 emissions from the power sector will decline. Only if we saw unusually high demand for electricity along with surprisingly few additions of renewable power plants from 2022-2024 and beyond, fossil fuel generation would rebound to pre-pandemic levels."

While the power sector has seen a dynamic transformation process even before the advent of COVID-19, the pandemic has weakened the market position of coal-fired power generation and illustrated its vulnerability.

"Our research shows that investing in fossil-fueled power is not only environmentally irresponsible - it is economically very risky," says co-author Ottmar Edenhofer, Director of both PIK and the Mercator Research Institute on Global Commons and Climate Change. "In the end, it will certainly take carbon pricing to cut emissions at the required pace and stabilize our Climate. Yet the impacts of the Corona crisis on the power generation sector have put political leaders in a unique position: Along with additional policies such as eliminating subsidies for fossil fuels and increasing investments in wind and solar power, it is now easier than ever before to put an end to high-carbon electricity."

Credit: 
Potsdam Institute for Climate Impact Research (PIK)

Researchers find peptide that treats, prevents killer citrus disease

image: Images depict citrus plants, one treated with the peptide and one that was not.

Image: 
Hailing Jin/UCR

New research affirms a unique peptide found in an Australian plant can destroy the No. 1 killer of citrus trees worldwide and help prevent infection.

Huanglongbing, HLB, or citrus greening has multiple names, but one ultimate result: bitter and worthless citrus fruits. It has wiped out citrus orchards across the globe, causing billions in annual production losses.

All commercially important citrus varieties are susceptible to it, and there is no effective tool to treat HLB-positive trees, or to prevent new infections.

However, new UC Riverside research shows that a naturally occurring peptide found in HLB-tolerant citrus relatives, such as Australian finger lime, can not only kill the bacteria that causes the disease, it can also activate the plant's own immune system to inhibit new HLB infection. Few treatments can do both.

Research demonstrating the effectiveness of the peptide in greenhouse experiments has just been published in the Proceedings of the National Academy of Sciences.

The disease is caused by a bacterium called CLas that is transmitted to trees by a flying insect. One of the most effective ways to treat it may be through the use of this antimicrobial peptide found in Australian finger lime, a fruit that is a close relative of citrus plants.

"The peptide's corkscrew-like helix structure can quickly puncture the bacterium, causing it to leak fluid and die within half an hour, much faster than antibiotics," explained Hailing Jin, the UCR geneticist who led the research.

When the research team injected the peptide into plants already sick with HLB, the plants survived and grew healthy new shoots. Infected plants that went untreated became sicker and some eventually died.

"The treated trees had very low bacteria counts, and one had no detectable bacteria anymore," Jin said. "This shows the peptide can rescue infected plants, which is important as so many trees are already positive."

The team also tested applying the peptide by spraying it. For this experiment, researchers took healthy sweet orange trees and infected them with HLB-positive citrus psyllids -- the insect that transmits CLas.

After spraying at regular intervals, only three of 10 treated trees tested positive for the disease, and none of them died. By comparison, nine of 10 untreated trees became positive, and four of them died.

In addition to its efficacy against the bacterium, the stable anti-microbial peptide, or SAMP, offers a number of benefits over current control methods. For one, as the name implies, it remains stable and active even when used in 130-degree heat, unlike most antibiotic sprays that are heat sensitive -- an important attribute for citrus orchards in hot climates like Florida and parts of California.

In addition, the peptide is much safer for the environment than other synthetic treatments. "Because it's in the finger lime fruit, people have eaten this peptide for hundreds of years," Jin said.

Researchers also identified that one half of the peptide's helix structure is responsible for most of its antimicrobial activity. Since it is only necessary to synthesize half the peptide, this is likely to reduce the cost of large-scale manufacturing.

The SAMP technology has already been licensed by Invaio Sciences, whose proprietary injection technology will further enhance the treatment.

Following the successful greenhouse experiments, the researchers have started field tests of the peptides in Florida. They are also studying whether the peptide can inhibit diseases caused by the same family of bacteria that affect other crops, such as potato and tomato.

"The potential for this discovery to solve such devastating problems with our food supply is extremely exciting," Jin said.

Credit: 
University of California - Riverside

Front-of-package product names and ingredient lists of infant and toddler food can be hard to navigate

audio: Disconnects between the front labels and ingredient lists of packaging containing fruits and vegetables make it more difficult for parents to understand what kind of food they are buying for their children.

Image: 
Journal of Nutrition Education and Behavior

Philadelphia, February 8, 2021 - Early exposure to nutritious foods may help children develop more healthful eating habits, but package labels can make it difficult for parents to understand what they are feeding their young children, according to a new study in the Journal of Nutrition Education and Behavior, published by Elsevier.

Researchers compared products for infants and toddlers, examining aspects of vegetable and fruits contributing to the ingredient lists. They reviewed, for example, whether the vegetable or the fruit in the product was a puree or a powder, and where it was listed among the ingredients and product name.

The goal of the research is to help parents understand how the front-of-package labels indicate the contents of infant and toddler foods. By better understanding packaging and labels, parents can make more informed decisions regarding food purchases for their children.

"Our hope is that nutrition educators will note differences between the ingredients list and the front label of the package. Many parents use the front of the package to decide on their purchases. So, it's important for nutrition educators who are well-informed to help parents navigate this occasionally challenging infant and toddler food product market," explained Mackenzie J. Ferrante, PhD, RDN, Department of Food Science and Human Nutrition, Colorado State University, Fort Collins, CO, USA.

This study's findings demonstrate that inconsistent information exists on some commercial infant and toddler food packages. Food preferences develop early for children by exposures to flavors. Thus, it is important that nutrition educators and healthcare professionals help parents navigate the marketplace. Their work can help parents improve their children's lifelong health through better nutrition as infants and toddlers.

"We want the front of the packages - where those vegetables might be listed - to accurately represent the primary ingredients, and even the flavor, of the product. We want to promote more transparency so parents and caregivers can buy the food they want their children to learn to eat at the family table. Let's make it easier for them to do that," said Susan L. Johnson, PhD, Department of Pediatrics, Section of Nutrition, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.

Credit: 
Elsevier

High CO2 to slow tropical fish move to cooler waters

image: Moorish idol - a coral reef species extending its ranges into temperate Australia under climate change.

Image: 
Image Ericka Coni

Under increasing global warming, tropical fish are escaping warmer seas by extending their habitat ranges towards more temperate waters.

But a new study from the University of Adelaide, published in Nature Climate Change, shows that the ocean acidification predicted under continuing high CO2 emissions may make cooler, temperate waters less welcoming.

"Every summer hundreds of tropical fish species extend their range to cooler and temperate regions as the waters of their natural habitat become a little too warm for comfort," says lead author Ericka Coni, PhD student in the University's School of Biological Sciences. "For at least two decades, Australian temperate reefs have been receiving new guests from the tropics.

"As a result of warming, we also see warm-temperate long-spined sea urchins increasing in numbers in southeast Australia, where they overgraze kelp forests and turn them into deserts known as 'urchin barrens'. Coral reef fishes that are expanding their ranges to temperate Australia prefer these barrens over the natural kelp habitats.

"But what we don't know is how expected ocean acidification, in combination with this warming, will change the temperate habitat composition and consequently the rate of tropical species range-extension into cooler water ecosystems."

The researchers hypothesised that these two divergent global change forces - warming and acidification - play opposing effects on the rate of tropicalisation of temperate waters.

"We know that as oceans warm they also acidify, because they absorb about a third of the CO2 emissions from fossil-fuel burning," says Ericka's PhD supervisor and project leader Professor Ivan Nagelkerken from the University's Environment Institute and Southern Seas Ecology Laboratories.

"We also know that calcifying species like sea urchins are typically challenged by seawater with reduced pH levels resulting from elevated CO2."

The research team, which also included Camilo Ferreira and Professor Sean Connell from the University of Adelaide, and Professor David Booth from the University of Technology Sydney, used two 'natural laboratories' to study ocean warming (tropicalisation hotspots on the south-eastern Australian coast) and ocean acidification predicted for the end of this century (natural CO2 vents off the coast of New Zealand) as an "early warning" system to assess the combined consequences of ocean acidification and ocean warming.

They found that sea urchin numbers were reduced by 87% under elevated CO2, leading to a reduction in number and size of urchin barrens. In their place turf algal cover increased which is less preferred by tropical species.

"Our study highlights that it is critical to study climate stressors together - we show that ocean acidification can mitigate some of the ecological effects of ocean warming," says Professor Nagelkerken.

"For south-eastern Australia, and likely other temperate waters, this means that ocean acidification could slow down the tropicalisation of temperate ecosystems by coral reef fishes.

"But in the meantime, if left unabated, these tropical species could increase competition with local temperate species under climate change and reduce their populations.

"In the short-term we need to take steps to preserve kelp forests to help maintain the biodiversity and populations of temperate species and reduce the invasion of tropical species."

Credit: 
University of Adelaide

Food waste researcher: We must learn that brown fruit isn't bad fruit

Which bananas end up in your shopping basket-- the uniformly yellow ones or those with brown spots?

If you are like most people, you skip the spotted ones and select those that are perfectly yellow. This is because emotions play an an oversized role in our shopping decisions, according to a new study by Danish and Swedish researchers.

"We choose food based upon an expectation of what it will taste like that is bound to our feelings. So, if we expect a brown banana to not match the taste of a yellow one, we opt for the latter," explains Karin Wendin, an associate professor at University of Copenhagen's Department of Food Science, and one of the researchers behind the study.

Approximately 716,000 tonnes of food are tossed out in Denmark every year--the majority of which are fruits and vegetables. Wendin laments this waste because brown fruit are not bad fruit:

"Bruised or oddly shaped fruit can easily be used. They usually taste just as good as nicely looking specimens. And in cases when an apple is bruised or a bit floury in texture, one can still use it for juice or pie. When an "ugly" piece of fruit gets tossed, it becomes food waste, which is a big problem-- including financially. This is why we need to work on reevaluating our feelings about brown and oddly-shaped fruit," she says.

The stickiness of a bad first impression
In the study, 130 participants were asked to rate a series of images of apples with varying appearances. Unsurprisingly, apples with deformities and imperfections ranked lowest in terms of how many participants wanted to eat them.

The participants then had to taste a different apple. This is when it became apparent that the bad first impression became sticky.

"When participants saw a photo of an ugly apple, and then tasted one that was green and perfect, they stuck by their belief that it tasted awful. This speaks to the extent to which our emotions and psychology factor in with taste sensations," says Karin Wendin.

"We remember negative feelings and expectations more than positive ones," she elaborates.

Better communication about browning food can help limit food waste

This is why it is imperative that we discover strategies to disrupt the negative emotions associated with brown fruit. Karin Wendin explains in greater detail:

"As things stand, communication about our foods--and what is good or bad--does not work optimally. People don't know where to seek advice and guidance. Few go online to investigate Nordic dietary recommendations on the Danish government's website. Did you know, for example, that imperfect fruit is often cheaper than its more perfect neighbors, even though both products probably taste the same?" asks the food waste researcher.

This is why we need to help supermarkets communicate clearly about how to avoid food waste by grabbing an imperfect fruit, and also explore which platforms are most effective in getting messages about diet and food waste out to consumers, Karin Wendin believes.

"Or, should we instead communicate on social media, where people are and spend time on lifestyle issues? It would be interesting to dive into," she concludes.

Credit: 
University of Copenhagen - Faculty of Science

NTUsg researchers develop flexible piezoelectric crystal

image: NTU Prof Fan Hong Jin (left) with PhD student Mr Hu Yuzhong, both holding the new piezoelectric crystal which can flex up to 40 times more than conventional ferroelectric crystals when electricity is applied.

Image: 
NTU Singapore

A team of researchers led by Nanyang Technological University, Singapore (NTU Singapore) has developed a new material, that when electricity is applied to it, can flex and bend forty times more than its competitors, opening the way to better micro machines.

Conversely, when it is bent, it generates electricity very effectively and could be used for better "energy harvesting" - potentially recharging batteries in gadgets just from everyday movements.

The novel material is both electrostrictive and piezoelectric. Its electrostrictive properties means it can change shape when an electric current is applied, while piezoelectric means the material can convert pressure into electric charges.

When an electric field is applied, the atoms that make up electrostrictive materials shift, causing the material to deform and flex. When piezoelectrics are compressed, the pressure is converted to electric charges which accumulate in the material.

The scientists found that when an electric field is applied, the new hybrid material could be strained up to 22 per cent, the highest strain reported in a piezoelectric material so far. This far surpasses conventional piezoelectric materials that only deform up to 0.5 per cent when a current is passed through it. The new material is also more energy-efficient than other piezoelectric and electrostrictive materials.

Piezoelectric materials are commonly used in guitars, loudspeakers, sensors and electric motors. For instance, a piezoelectric pick-up is a device used in an electric guitar to convert the vibrations from the strings into an electric signal, which is then processed for music recording or to be amplified through loudspeakers.

Ferroelectric crystals were first discovered in 1920 and have been used to make piezoelectrics for over 70 years, as they are easily integrated into electrical devices.

However, they are brittle and inflexible, bending only 0.5 per cent, which largely limits their application in electronic devices such as actuators (parts that convert an electric control signal into mechanical motion, for example, a valve that opens and closes).

Some ferroelectrics also contain lead, which is toxic, and its presence in piezoelectric devices is one of the reasons why electronic waste is challenging to recycle. Traditional ferroelectrics such as perovskite oxides are also unsuitable for flexible electrical devices that are in contact with the skin, such as wearable biomedical devices that track heart rate.

Published in the scientific journal Nature Materials last month, the new material was created at NTU by Professor Fan Hong Jin from the School of Physical & Mathematical Sciences and his team, including his PhD student Mr Hu Yuzhong who is the first author of this paper. Also part of the team is Professor Junling Wang from the Southern University of Science and Technology, China, a former NTU professor at the School of Materials Science and Engineering.

Prof Fan said, "Being more than 40 times more flexible than similar electrostrictive materials, the new ferroelectric material may be used in highly efficient devices such as actuators and sensors that flex when an electric field is applied. With its superior piezoelectric properties, the material can also be used in mechanical devices that harvest energy when bent, which will be useful to recharge wearable devices.

"We think we can substantially improve on this performance in future by further optimising the chemical composition, and we believe this type of material could play a key role in the development of wearable devices for the Internet of Things (IOT), one of the key technologies enabling the 4th Industrial Revolution."

Developing a flexible ferroelectric material

To develop a flexible ferroelectric material, the researchers modified the chemical structure of a hybrid ferroelectric compound C6H5N(CH3)3CdCl3, or PCCF in short, which can potentially bend up to a hundred times more than traditional ferroelectrics.

To increase the material's range of movement further, the scientists modified the chemical makeup of the compound by substituting some of its chlorine (Cl) atoms for bromine (Br), which has a similar size to chlorine, to weaken the chemical bonds at specific points in the structure. This made the material more flexible without affecting its piezoelectric qualities.

The new material is easy to manufacture, requiring only solution-based processing in which the crystal forms as the liquid evaporates, unlike typical ferroelectric crystals that require the use of high-powered lasers and energy to form.

When an electric field was applied to the new PCCF compound, the atoms in it shifted substantially more than the atoms in most conventional ferroelectrics, straining up to 22 per cent far more than conventional piezoelectric materials.

Credit: 
Nanyang Technological University

Identification of three genes that determine the stemness of gastric tissue stem cells

image: A. Outline of GeCKO screening using organoids. Gastric organoids are established from mice that allow visualization of tissue stem cells; genes are randomly rendered loss-of-function by introducing a mouse CRISPR gRNA library for gene knockout. Thereafter, organoids that proliferate in a Wnt signaling-independent manner are collected and responsible genes are identified by using a next generation sequencer.

B. The important point revealed in this study. The genes Alk, Bclaf3 and Prkra are expressed in differentiated cells of gastric glands. Alk destabilizes Gsk3β by phosphorylation, thus suppressing Wnt signaling. On the other hand, Bclaf3 and Prkra negatively regulate Reg gene expressions that are essential for proliferation of gastric epithelial cells through suppressing the expression of interleukins 11 (IL-11) and 23 (IL-23). It is thought that the stemness of gastric tissue stem cells is determined by cooperation of Alk, Bclaf3 and Prkra.

Image: 
Kanazawa University

[Background]

The human body consists of about 60 trillion cells that are renewed day by day to maintain homeostasis of body tissues. In particular, cells of the digestive tract are renewed completely within several weeks thanks to vigorous proliferation where tissue stem cells of every tissue play critical roles in supplying those cells. Tissue stem cells play essential roles in various phenomena such as histogenesis and recovery from damage by producing differentiated cells while dividing. They do this by producing identical cells (self-renewal) or by differentiating into other types of cells. The research team led by Profs. Murakami and Barker of the Cancer Research Institute, Kanazawa University revealed the presence of gastric tissue stem cells expressing the Lgr5 gene*1), a tissue stem cell marker at the gastric gland base in the gastric tissue, the stemness*2) of which could be suppressed by Wnt signaling*3) (Leushacke M. et al., Nat. Cell Biol., 2017). However, due to the technical difficulty of further detailed in vivo verification, most of the molecular mechanisms related to tissue stem cells regulated by Wnt signaling remained a mystery.

[Results]

The research team investigated the intracellular molecular mechanisms for Wnt signaling-dependent regulation of proliferation and self-renewal of gastric tissue stem cells by using organoids*4) established from mice. These enabled visualization of Lgr5+ gastric tissue stem cells. Further, screening using Genome-Scale CRISPR Knock-Out (GeCKO)*5), which can arbitrarily produce loss-of-function of various genes, allowed the elucidation of molecular mechanisms regulating the Wnt signaling-dependence of gastric tissue stem cells. The team revealed that loss-of-function of Alk, Bclaf3 and Prkra genes induced Wnt signaling-independent proliferation of the organoids. Because these genes are expressed in differentiated cells of mouse gastric tissues but not in stem cells, the team postulated that these genes might negatively regulate the stemness of tissue cells. Further analyses have revealed that Alk suppresses Wnt signaling by phosphorylating Gsk3β, one of the regulatory factors of Wnt signaling. Further, Bclaf3 and Prkra regulate the expression of Reg family genes, which are essential for proliferation of gastric tissue stem cells, by inhibiting expression of epithelial interleukins 11 and 23*6). From these results, Alk, Bclaf3 and Prkra have been identified as the genes that determine the stemness of gastric tissue stem cells.

[Future Prospects]

The present study has elucidated previously unknown molecular mechanisms regulating the self-renewal and differentiation of tissue stem cells, which play roles in tissue homeostasis and recovery from damage. Similar molecular mechanisms may exist and function in other tissue stem cells, since Wnt signaling is widely activated in various stem cells regardless of their developmental stages. It is expected that treatments for tissue damage, not only of the digestive tract but also in liver, kidney and pancreas, should become possible if regulation of the self-renewal and differentiation of stem cells via the regulatory mechanisms described above could be verified in other tissues. The results of the present study provide new insights and technical approaches in stem cell research and are expected to stimulate innovation in the field of regenerative medicine and cancer treatment in the future.

Credit: 
Kanazawa University

Scientists create armour for fragile quantum technology

image: FLEET PhD student Matthias Wurdack

Image: 
Phil Dooley ANU

An international team of scientists has invented the equivalent of body armour for extremely fragile quantum systems, which will make them robust enough to be used as the basis for a new generation of low-energy electronics.

The scientists applied the armour by gently squashing droplets of liquid metal gallium onto the materials, coating them with gallium oxide.

Protection is crucial for thin materials such as graphene, which are only a single atom thick - essentially two-dimensional (2D) - and so are easily damaged by conventional layering technology, said Matthias Wurdack, who is the lead author of the group's publication in Advanced Materials.

"The protective coating basically works like a body armour for the atomically-thin material, it shields against high-energy particles, which would cause a large degree of harm to it, while fully maintaining its optoelectronic properties and its functionality," said Mr Wurdack, a PhD student in the Nonlinear Physics Centre (NLPC) of the Research School of Physics, and the FLEET ARC Centre of Excellence.

The new technique opens the way for an industry based on ultra-thin electronics to expand, said leader of the research team, Professor Elena Ostrovskaya, also from NLPC and FLEET.

"Two-dimensional materials have extraordinary properties such as extremely low resistance or highly efficient interactions with light."

"Because of these properties they could have big role in the fight against climate change."

Eight percent of global electricity consumption in 2020, was due to information technologies, including computers, smartphones and large data centres of tech giants such as Google and Amazon. That figure is projected to double every decade as demand for AI services and smart devices skyrockets.

However, this work promises lower-energy alternatives for electronics and optoelectronics, by harnessing the superior performance of 2D semiconducting materials, such as tungsten disulphide, which was used in this study.

Using 2D materials to make more efficient devices will have advantages beyond reduced carbon emissions, says Mr Wurdack.

"2D technology could also enable super-efficient sensors on space craft, or processors in Internet of Things devices that are less limited by battery life."

The team created their protective layer by exposing to air a droplet of liquid gallium, which immediately formed a perfectly even layer of gallium oxide on its surface a mere three nanometers thick.

By squashing the droplet on top of the 2D material with a glass slide, the gallium oxide layer can be transferred from the liquid gallium onto the material's entire surface, up to centimetres in scale.

Because this ultrathin gallium oxide is an insulating amorphous glass, it conserves the optoelectronic properties of the underlying 2D semiconductor. The gallium oxide glass can also enhance these properties at cryogenic temperatures and protects well against other materials deposited on top. This allows the fabrication of sophisticated, layered nanoscale electronic and optical devices, such as light emitting diodes, lasers and transistors.

"We've generated a nice alternative to existing technology that can be scaled for industry applications," Mr Wurdack said.

"We hope to find industry partners to work with us to develop a protective layer printer based on this technology, that can go into any lab, like a lithography machine."

"It would be exciting to see fundamental research like this find its way into industry!"

Credit: 
ARC Centre of Excellence in Future Low-Energy Electronics Technologies

Meet the Smurfs: A bone metabolism family

image: BMP-induced ectopic bone formation in wild type and Smurf2-deficient mice.
In the Smurf2-deficient mice, ectopic bone induced by bone morphogenetic protein (BMP) was large and composed of abundant trabecular bone.

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<i>Bone Research</i> (Springer Nature) ISSN 2095-6231 (online)

Osaka, Japan - Bone morphogenetic protein (BMP) has a strong osteogenic (bone forming) ability. BMP has already been clinically applied to spinal fusion and non-union fractures. However, dose-dependent side effects related to BMP use, such as inflammatory reactions at the administration site, prevent widespread use.

For safe use, it was necessary to clarify how the BMP signaling pathway is controlled. In a report published in Bone Research, a group of researchers from Osaka University and Ehime University has recently identified a novel role for the protein Smurf2 in regulating bone formation by BMP.

When BMP transmits its message within cells, it can induce rapid bone formation. Previous studies have shown that Smurf2 can control another similar signaling pathway known as TGF-β (also involved in bone formation). Smurf2 prevents TGF-β signaling from going out of control by degrading the messenger proteins. However, the research team became interested in whether Smurf2 would have any effect on BMP signaling.

"Proper regulation of the BMP pathway is crucial for healthy bone metabolism and formation in humans," says lead author of the study Junichi Kushioka. "Learning more about the role of Smurf2 in these processes will ultimately provide a deeper understanding of bone regeneration treatment."

To address their questions, the researchers induced bone formation with BMP in both wild type (normal) mice and mice genetically altered to have the Smurf2 gene knocked out. They looked for differences between the two groups in aspects such as bone mass and bone formation rates. The group also examined the number of osteoblasts, which are cells involved in bone formation.

"We saw that the BMP-induced bone in mice without the Smurf2 protein had significantly greater mass, formation rates, and number of osteoblasts than the wild type mice," explains Takashi Kaito, the corresponding author. "The outer shell was also much thicker in the BMP-induced bone in Smurf2 knockout mice."

Further experiments also suggested that Smurf2 uses a process called ubiquitination to mark the BMP pathway messenger proteins for destruction, just like it does in the TGF-β pathway.

"Our results show that Smurf2 can regulate several different mechanisms that affect bone formation," says Kushioka. "This work will pave the way for bone regeneration treatment for bone non-union, spinal fusion, or bone tumors with massive bone defects."

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Osaka University

Insights into lithium metal battery failure open doors to doubling battery life

image: The temperature sensitive equilibrium governing the formation and decomposition process of LiH at Li anode

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XU Gaojie

Lithium metal batteries could double the amount of energy held by lithium-ion batteries, if only their anodes didn't break down into small pieces when they were used.

Now, researchers led by Prof. CUI Guanglei from the Qingdao Institute of Bioenergy and Bioprocess Technology (QIBEBT) of the Chinese Academy of Sciences (CAS) have identified what causes lithium metal batteries (LMBs) to "self-destruct" and proposed a way to prevent it. The findings were published in Angewandte Chemie on Jan. 19.

This offers hope of radically enhancing the energy held in batteries without any increase in their size, and at reduced cost.

In fact, LMBs were the original concept for long-lasting batteries, but their anodes break down into small pieces - a microstructure known as "pulverization". The LMBs thus quickly stop working when being cycled through. Lithium-ion batteries were actually a compromise: tweaking the LMB concept prevented the anode failure by using graphite anode, but at a cost of much lower energy storage levels.

One of the problems facing LMB development has been a lack of understanding, and even controversy over, why the anode fails. Conventionally, it is argued that tiny tree-branchlike structures of lithium called dendrites form during cycling of the battery. In addition, the pulverization structure always appears in any failed LMB.

What has been contentious though is whether lithium hydride (LiH) is present in the pulverization structure. LiH has poor electrical conductivity, but it is also very brittle, which would explain the pulverization. In the past, one group of researchers had identified LiH as a distinct type of dendrite, but another group found nothing along these lines.

However, both research groups had only used simplified versions of an LMB. To properly investigate what is going on, the QIBEBT research team ran a practical LMB under typical operating conditions.

Using a type of mass spectrometry (an analytical tool that allows identification of unknown compounds), the researchers were able to confirm that LiH did indeed become the dominant compound on the anode as the battery was being used.

But more importantly, they found that this chemical reaction is temperature sensitive: it only happens at room temperature, and the process can be reversed if the temperature rises above this level.

This suggests ways that the production of LiH can be prevented, either via heat treatment or a pressure treatment producing the same effect, or a combination of the two. Additional options include suppressing the production of hydrogen ions, or the placement of interface materials that can protect the lithium from the hydrogen.

"Coming out of this study, the next step is to produce some form of really good lithium protection," said CUI Guanglei, lead author and a scientist with QIBEBT, "which should then deliver on the long-held promise of practical applications of the 'holy grail' of lithium metal batteries."

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Chinese Academy of Sciences Headquarters

Efficiency limits of next-generation hybrid photovoltaic-thermal solar technology

image: The solar spectrum is separated by an optical filter, and only part of the spectrum is sent to the PV cells for electricity generation. The rest of the spectrum, which cannot be utilized by the solar cells, is directed to a thermal absorber to generate thermal energy.

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by Gan Huang, Kai Wang and Christos N. Markides.

Solar energy is one of the most abundant renewable energy sources, and effective solar technologies have great potential to alleviate the grand challenges of rising global energy demands, while reducing associated emissions. Solar energy is capable of satisfying the electrical and thermal-energy needs of diverse end-users by means of photovoltaic (PV) and solar thermal (ST) technologies, respectively. Recently, hybrid photovoltaic-thermal (PVT) concepts have been proposed that synergistically combine the benefits of PV and ST technologies, and are capable of generating both electricity and useful heat simultaneously from the same area and component.

Spectral splitting is an emerging approach for designing high-performance PVT solar collectors, which employ advanced designs with optical filters that direct different parts of the solar spectrum either to the PV cells for electricity generation or to a thermal absorber for heat generation. Nevertheless, the ultimate efficiency limits of spectral-splitting PVT (SSPVT) collectors depending on the application and end-user demands, along with the optimal collector designs, PV cell and optical filter materials that can enable us to approach these limits have remained unclear, with a lack of consensus in the field, motivating a closer examination of these aspects of SSPVT technology.

In a new paper published in Light Science & Application, Christos N. Markides and Gan Huang from Imperial College London in the UK, in collaboration with Kai Wang from Zhejiang University in China, report a comprehensive framework for predicting the performance of such collectors, which is then used to identify their efficiency limits, and to provide detailed guidance for selecting optimal PV materials and optimal spectral-splitting filters capable of delivering a combined thermal and electrical performance that approaches the efficiency limits of this technology.

"We found that the relative value of thermal energy to that of electricity has a significant influence on the total effective efficiency limits, the optimal PV cell material and the optimal spectral-splitting filter of SSPVT collectors."

"CIGS solar cells are considered particularly promising for SSPVT collector applications owing to their adjustable bandgap energy. The optimal lower- and upper-bounds of the spectral-splitting filter depend strongly on the PV material" they added.

"Detailed maps in our research can assist designers in selecting appropriate solar-cell materials and spectral-splitting optical filters, depending on the conditions and application, in order to achieve optimal overall performance accounting for both energy vectors (electricity and heat) generated by these systems." the scientists stated.

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Light Publishing Center, Changchun Institute of Optics, Fine Mechanics And Physics, CAS

Silicon waveguides move us closer to faster, light-based logic circuits

image: Illustration of a pair of silicon high contrast gratings that can be used to guide visible light on a chip with low losses despite large absorption by the silicon material.

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by Urbonas, D., Mahrt, R.F. and St&ouml;ferle

For decades, the speed of our computers has been growing at a steady pace. The processor of the first IBM PC released 40 years ago, operated at a rate of roughly 5 million clock cycles per second (4.77 MHz). Today, the processors in our personal computers run around 1000 times faster.

However, with current technology, they're not likely to get any faster than that.

For the last 15 years, the clock rate of single processor cores has stalled at a few Gigahertz (1 Gigahertz = 1 billion clock cycles per second). And the old and tested approach of cramming ever more transistors on a chip will no longer help in pushing that boundary. At least not without breaking the bank in terms of power consumption.

A way out of the stagnation could come in the form of optical circuits in which the information is encoded in light rather than electronics. In 2019, an IBM Research team together with partners from academia built the world's first ultrafast all-optical transistor capable of operating at room temperature. The team now follows up with another piece of the puzzle, a silicon waveguide that links up such transistors, carrying light between them with minimal losses.

Wiring up the transistors of an optical circuit with silicon waveguides is an important requirement to make compact, highly integrated chips. That's because it's easier to place other needed components such as electrodes in its close vicinity if the waveguide is made of silicon. The techniques used for that purpose have been refined for decades in the semiconductor industry.

However, silicon being a notoriously strong absorber of visible light makes it great for capturing sunlight in a photovoltaics panels but a poor choice for a waveguide where light absorption means signal loss.

Making a fence to confine light

So, the IBM researchers thought of ways to use the mature silicon technology while circumventing the absorption issue. Their solution involves nanostructures called high contrast gratings with a striking behavior that some of the team members had already discovered over 10 years ago, albeit for another application.

A high contrast grating consists of nanometer sized "posts" lined up to form a sort of fence that prevents light from escaping. The posts are 150 nanometers in diameter and are spaced in such a way that light passing through the posts interferes destructively with light passing between posts. Destructive interference is a well-known phenomenon by which waves oscillating out of sync cancel each other out at a point in space. It affects light, which is an electromagnetic wave, just as it does sound and other types of wave. In this case, the destructive interference makes sure that no light can "leak" through the grating. Instead, most of the light gets reflected back inside the waveguide. The IBM researchers also showed that absorption of light inside the posts themselves is minimal. All this together translates in losses of only 13 percent along a light travel path of 1 millimeter inside the waveguide. For comparison: Along already only one hundredth of that distance (10 micrometers) in a pure silicon waveguide without the gratings, the losses would amount to 99.7 percent.

Simulations for precise grating design

On its face, the basic idea behind the high contrast gratings looks simple. However, it was indeed surprising when the researchers found out for the first time that they could keep light from being absorbed by a "dark" material like silicon.

Back in 2010, when they first observed the grating effect, it occurred in a laser microcavity which helped because the light amplification by the laser would compensate for the losses. Also, they had the light hitting the gratings at almost 90 degrees which is a sweet spot for the grating effect to kick in. But keeping the losses low in a waveguide without the benefit of the laser gain and at almost grazing light incidence was much more challenging.

To make sure their grating design would be up to the task, the team ran simulations showing how light propagation inside the waveguide would change with varying grating dimensions. They found out that the grating would provide efficient guiding of light over a broad band of wavelengths. All they needed to do was choose the right spacing between the grating posts and make the posts themselves to the right thickness within a precision margin of 15 nanometers. Using a standard silicon photonics fabrication process, those requirements proved manageable. In fact, the experiments confirmed what the simulations had predicted in terms of low loss for visible light in the range between 550 and 650 nanometers.

Potential benefits for optical circuits and beyond

The team found some evidence through simulations that this design can be used to make not only straight waveguides but also guide the light around corners. But they haven't yet run the experiments to confirm this idea. Even if it proves feasible, some further optimization will be needed to keep the additional losses low in that case. Looking ahead, a next step will be to engineer the efficient coupling of the light out of the waveguides into other components. That will be a crucial step in the team's multi-year exploratory research project with the goal of integrating the all-optical transistors they demonstrated in 2019 into integrated circuits capable of performing simple logic operations.

The team believes that their low-loss silicon waveguide could enable new photonic chip designs for use in biosensing and other applications that rely on visible light. It could also benefit the engineering of more efficient optical components such as lasers and modulators widely used in telecommunications.

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Light Publishing Center, Changchun Institute of Optics, Fine Mechanics And Physics, CAS

Two-phase material with surprising properties

image: Jonas Hafner, Ulrich Schmid and Michael Schneider in the lab at TU Wien

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TU Wien

In certain materials, electrical and mechanical effects are closely linked: for example, the material may change its shape when an electrical field is applied or, conversely, an electrical field may be created when the material is deformed. Such electromechanically active materials are very important for many technical applications.

Usually, such materials are special, inorganic crystals, which are hard and brittle. For this reason, so-called ferroelectric polymers are now being used. They are characterised by the fact that their polymer chains exist simultaneously in two different microstructures: some areas are strongly ordered (crystalline), while disordered (amorphous) areas form in between. These semicrystalline composites are electromechanically active and therefore combine electrical and mechanical effects, but at the same time they are also flexible and soft. At TU Wien, such materials have now been studied in detail - with surprising results: above a certain temperature, the properties change dramatically. A research team from TU Wien in cooperation with research groups from Madrid and London has now been able to explain why this happens.

From micro-sensors to smart textiles

"If you can control the mechanical behaviour of a material with the help of electric fields, you can use it to build tiny sensors, for example," says Prof. Ulrich Schmid from the Institute of Sensor and Actuator Systems at TU Wien. "This is also interesting for atomic force microscopes, where you set a tiny tip in vibration to scan a surface and generate an image."

The field of application of such materials can be expanded dramatically if it is possible to induce such electromechanical properties not only in rigid materials, but also in flexible, soft materials. On the one hand, flexible materials have a completely different vibration behaviour, which can be exploited in the construction of tiny sensors. On the other hand, such materials also open up completely new possibilities - such as smart textiles, flexible energy storage or for integrated energy harvesting.

"Solids can be crystalline, in which case the atoms are arranged in a regular lattice, or they can be amorphous, in which case the individual atoms are randomly distributed," explains Jonas Hafner, who is working on this research project as part of his dissertation. "The special thing about the material we studied is that it can be both at the same time: It forms crystalline regions, and in between the material is amorphous."

The crystals are responsible for the electromechanical properties of the material, the amorphous matrix holds the tiny crystals together, overall creating a very soft, flexible material.

Too much heat

In order to be able to further develop and improve such materials, the research team first investigated their basic physical properties. During their investigations, they came across a surprising phenomenon: the ferroelectric polymers, which consist of a combination of crystalline and amorphous areas, change their microscopic composition at a certain temperature - which has surprising effects on the macroscopic electromechanical behaviour.

Normally, the electromechanical properties of a material only disappear when a very high temperature causes such large oscillations at the atomic level, that the electrical order in the material disappears completely. This critical temperature is called the "Curie temperature". But in the case of the material now being studied, things are more complicated: "In our case, the electromechanical properties of the tiny crystals remain. Microscopically, the crystals are still electroactive, but on the macroscopic level, this electroactive behaviour disappears," says Jonas Hafner.

Lost contact between the crystal grains

The team was able to explain how this effect occurs: As the temperature rises, the proportion of amorphous areas of the polymer increases, and at a certain point the tiny crystals lose direct contact among each other. This means that mechanical forces can no longer be transferred from one of the tiny crystals to the next, because they are all completely embedded in a damping amorphous matrix. This dramatically changes the mechanical and electromechanical behaviour of the material.

"Only if we understand these fundamental effects we can explain how microscopic and macroscopic properties correlate in such materials," says Ulrich Schmid. "We are working with numerous project partners who then use such materials - in atomic force microscopes, in sensors, in chips. There are numerous potential applications for this exciting material phase."

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Vienna University of Technology