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Physicists at MIT have designed a quantum "light squeezer" that reduces quantum noise in an incoming laser beam by 15 percent. It is the first system of its kind to work at room temperature, making it amenable to a compact, portable setup that may be added to high-precision experiments to improve laser measurements where quantum noise is a limiting factor.

The heart of the new squeezer is a marble-sized optical cavity, housed in a vacuum chamber and containing two mirrors, one of which is smaller than the diameter of a human hair. The larger mirror stands stationary while the other is movable, suspended by a spring-like cantilever.

The shape and makeup of this second "nanomechanical" mirror is the key to the system's ability to work at room temperature. When a laser beam enters the cavity, it bounces between the two mirrors. The force imparted by the light makes the nanomechanical mirror swing back and forth in a way that allows the researchers to engineer the light exiting the cavity to have special quantum properties.

The laser light can exit the system in a squeezed state, which can be used to make more precise measurements, for instance, in quantum computation and cryptology, and in the detection of gravitational waves.

"The importance of the result is that you can engineer these mechanical systems so that at room temperature, they still can have quantum mechanical properties," says Nergis Mavalvala, the Marble Professor and associate head of physics at MIT. "That changes the game completely in terms of being able to use these systems, not just in our own labs, housed in large cryogenic refrigerators, but out in the world."

The team has published its results in the journal Nature Physics. The paper's lead author is Nancy Aggarwal, a former physics graduate student in the MIT LIGO Laboratory, now a postdoc at Northwestern University. Other co-authors on the paper along with Mavalvala are Robert Lanza and Adam Libson at MIT; Torrey Cullen, Jonathan Cripe, and Thomas Corbitt of Louisiana State University; and Garrett Cole, David Follman, and Paula Heu of Crystalline Mirror Solutions in Santa Barbara, California.

A cold "showstopper"

A laser contains multitudes of photons that stream out in synchronized waves to produce a bright, focused beam of light. Within this ordered configuration, however, there is a bit of randomness among a laser's individual photons, in the form of quantum fluctuations, also known in physics as "shot noise."

For instance, the number of photons in a laser that arrive at a detector at any given time can fluctuate around an average number, in a quantum way that is difficult to predict. Likewise, the time at which a photon arrives at a detector, related to its phase, can also fluctuate around an average value.

Both of these values -- the number and timing of a laser's photons -- determine how precisely researchers can interpret laser measurements. But according to the Heisenberg uncertainty principle, one of the foundational tenets of quantum mechanics, it is impossible to simultaneously measure both the position (or timing) and the momentum (or number) of particles at the same time with absolute certainty.

Scientists work around this physical constraint through quantum squeezing -- the idea that the uncertainty in a laser's quantum properties, in this case the number and timing of photons, can be represented as a theoretical circle. A perfectly round circle symbolizes equal uncertainty in both properties. An ellipse -- a squeezed circle -- represents a smaller uncertainty for one property and a larger uncertainty for the other, depending on how the circle, and the ratio of uncertainty in a laser's quantum properties, is manipulated.

One way researchers have carried out quantum squeezing is through optomechanical systems, designed with parts, such as mirrors, that can be moved to a tiny degree by incoming laser light. A mirror can move due to the force applied on it by photons that make up the light, and that force is proportional to the number of photons that hit the mirror at a given time. The distance the mirror moved at that time is connected to the timing of photons arriving at the mirror.

Of course, scientists cannot know the precise values for both the number and timing of photons at a given time, but through this kind of system they can establish a correlation between the two quantum properties, and thereby squeeze down the uncertainty and the laser's overall quantum noise.

Until now, optomechanical squeezing has been realized in large setups that need to be housed in cryogenic freezers. That's because, even at room temperature, the surrounding thermal energy is enough to have an effect on the system's movable parts, causing a "jitter" that overwhelms any contribution from quantum noise. To shield against thermal noise, researchers have had to cool systems down to about 10 Kelvin, or -440 degrees Fahrenheit.

"The minute you need cryogenic cooling, you can't have a portable, compact squeezer," Mavalvala says. "That can be a showstopper, because you can't have a squeezer that lives in a big refrigerator, and then use it in an experiment or some device that operates in the field."

Giving light a squeeze

The team, led by Aggarwal, looked to design an optomechanical system with a movable mirror made from materials that intrinsically absorb very little thermal energy, so that they would not need to cool the system externally. They ultimately designed a very small, 70-micron-wide mirror from alternating layers of gallium arsenide and aluminum gallium arsenide. Both materials are crystals with a very ordered atomic structure that prevents any incoming heat from escaping.

"Very disordered materials can easily lose energy because there are lots of places electrons can bang and collide and generate thermal motion," Aggarwal says. "The more ordered and pure a material, the less places it has to lose or dissipate energy."

The team suspended this multilayer mirror with a small, 55-micron-long cantilever. The cantilever and multilayer mirror have also been shaped to absorb minimal thermal energy. Both the movable mirror and the cantilever were fabricated by Cole and his colleagues at Crystalline Mirror Solutions, and placed in a cavity with a stationary mirror.

The system was then installed in a laser experiment built by Corbitt's group at Louisiana State University, where the researchers made the measurements. With the new squeezer, the researchers were able to characterize the quantum fluctuations in the number of photons versus their timing, as the laser bounced and reflected off both mirrors. This characterization allowed the team to identify and thereby reduce the quantum noise from the laser by 15 percent, producing a more precise "squeezed" light.

Aggarwal has drawn up a blueprint for researchers to adopt the system to any wavelength of incoming laser light.

"As optomechanical squeezers become more practical, this is the work that started it," Mavalvala says. "It shows that we know how to make these room temperature, wavelength-agnostic squeezers. As we improve the experiment and materials, we'll make better squeezers."

TROY, N.Y. -- An over-abundance of the protein PRC1, which is essential to cell division, is a telltale sign in many cancer types, including prostate, ovarian, and breast cancer. New research, published online today in Developmental Cell, shows that PRC1 acts as a "viscous glue" during cell division, precisely controlling the speed at which two sets of DNA are separated as a single cell divides. The finding could explain why too much or too little PRC1 disrupts that process and causes genome errors linked to cancer.

"PRC1 produces a viscous frictional force, a drag that increases with speed," said Scott Forth, an assistant professor of biological sciences and member of the Center for Biotechnology and Interdisciplinary Studies at Rensselaer Polytechnic Institute. "The friction it produces is similar to that of water - if you try to move your hand through water slowly, you move easily, but if you push your hand fast, the water pushes back hard."

At the nitty-gritty level of DNA, motor proteins, and microtubules, biology takes its cue from physics. During the mitotic stage of cell division, a single cell must copy its DNA into two identical sets, and then rapidly and efficiently pull that DNA apart into two new daughter cells. It's a physical act, and the cellular structure that does it, the mitotic spindle, is a machine that uses mechanical forces - push, pull, and resistance - to complete the task.

"We think the force PRC1 produces is integrating and dampening out cellular motions as the DNA is separated so that ultimately, you get the correct rate of chromosome segregation," Forth said. But if the process goes awry, the cells end up working with the wrong instruction manual, which can lead to the uncontrollable growth of cancer.

The Forth lab examines the physical forces exerted by components of cellular structures like the mitotic spindle. The spindle is formed when two centrosomes, take a position on opposite sides of the two newly created, and hopefully identical, sets of chromosomes massed near the center of the cell. A dense network of microtubules extends from the centrosomes, forming a cage that surrounds and connects the chromosomes. Then the microtubules - aided by millions of proteins and motor proteins - begin to shorten and slide, pulling the chromosomes toward the centrosomes, until the two sets have been separated.

PRC1 is a "cross-linker," a long, springy molecule with a head at either end that links two microtubules along their length. Near the center of the mitotic spindle, large quantities of PRC1 link groups of microtubules into bundles.

Forth's team created a controlled version of the microtubule sliding mechanism in the lab and used an optical trapping technique to measure the frictional force PRC1 exerts between the sliding microtubules. Optical trapping relies on a tightly focused laser beam which attracts an object - in this case, a miniscule polystyrene bead - attached to the microtubule. The researchers use the laser beam to pull on the bead - similar to the "tractor beam" of science fiction - and convert the shift in refracted light as the bead resists the pull of the trap into a direct measure of force.

The team also tagged PRC1 with a fluorescent molecule, allowing them to observe its shifting movement and distribution as the microtubules were pulled apart. They used total internal reflection fluorescence microscopy to collect images of the experiment while simultaneously recording the forces.

Forth and his colleagues found that, as more of the protein is added into the system, the microtubules meet more resistance as they move faster. Essentially, PRC1 behaves like a glue holding the cell together.

"Like a lot of biological processes, it's a bit of a Goldilocks problem," Forth said. "If you don't have this protein, you're in trouble, because the cell fails at division. If you have too much, we think that it gums up the works and holds everything together too much, which may be how this protein is linked to cancer. There's a sort of sweet spot in healthy cell division, where there's just the right amount controlling the rates carefully and precisely."

"This research reveals the inner workings of a fundamental mechanism of biology, providing knowledge that better positions us to defeat cancer," said Curt Breneman, dean of the School of Science. "It's a carefully and beautifully designed study, the results of which have created a foundation on which future anti-cancer strategies can be built."

"The mitotic crosslinking protein PRC1 acts like a mechanical dashpost to resist microtubule sliding" was published in Developmental Cell. Forth was joined in the research by RPI graduate students Ignas Gaska, April Alfieri, and RPI undergraduate student Mason Armstrong.

PHILADELPHA-- A new study from Penn Medicine lends further evidence that the social behaviors tied to autism spectrum disorders (ASD) emerge from abnormal function of sensory neurons outside the brain. It's an important finding, published today in the journal Cell Reports, because peripheral sensory systems--which determine how we perceive the environment around us --makes for more accessible therapeutic targets to treat ASD-related symptoms, rather than the central brain itself.

In the fruit fly Drosophila-- a powerful model for studying neurobiology-- the researchers showed that loss of a protein known as neurofibromin 1 caused adult male flies to have social impairments. Those deficits, the researchers also showed, traced back to a primary disruption in a small group of peripheral neurons controlling external stimuli, like smell and touch, that communicate to the brain.

"These data raise the exciting possibility that the root of the problem doesn't begin with errors in the brain itself. It's the disrupted flow of information from the periphery to the brain we should be taking a closer look at," said senior author Matthew Kayser, MD, PhD, an assistant professor in the department of Psychiatry in the Perelman School of Medicine at the University of Pennsylvania. "The findings should help guide the field toward sensory processing therapeutic targets that, if effective, could be transformative for patients suffering from these disorders."

In humans, a loss of neurofibromin 1 is associated with neurofibromatosis type 1 (NF1), a neurodevelopmental disorder with high rates of ASD, but how that loss leads to social deficits is unknown. Past studies have also shown a link between the peripheral sensory system and social deficits; however, this is the first study to implicate neurofibromin's function.

Up to 50 percent of children with NF1 fall on the autism spectrum, and are 13 times more likely to exhibit highly elevated ASD symptoms, including social and communicative disabilities, increased isolation and bullying, difficulties on social tasks, and sensitivities to sound or light. Those symptoms are all tied to difficulties with processing sensory information. Face and gaze processing, for example, makes a social gesture like eye contact exceedingly difficult.

The team, led by Penn postdoctoral scientist Emilia Moscato, PhD, used genetically manipulated flies to show that a loss of neurofibromin led to diminished social courtship behavior and errors in gustatory sensory neurons called ppk23, which are known to coordinate such behaviors. These behavioral deficits stem from an ongoing role for neurofibromin in coordinating social functions in adults, as opposed to guiding development of social behavioral neural circuits.

More specifically, in vivo monitoring of neural activity in the mutant flies showed decreased sensory neuron activation in response to specific pheromonal cues, which then disrupted proper function of downstream brain neurons that direct social decisions. The disruption also led to persistent changes in behavior of the flies beyond the social interaction itself, suggesting a brief sensory error can have long-lasting consequences on behavior.

Next, the researchers aim to better understand how this mutation translates to disruption in brain activity and ultimately behaviors associated with ASD and NF1. They also hope to test different drugs in animal models to identify novel compounds that can restore social behaviors.

"Sensory processing is a readily testable entry-point into social behavioral dysfunction," Kayser said, "so findings from these experiments have potential to rapidly impact the clinical setting."

LA JOLLA--(July 7, 2020) The human immune system is a finely-tuned machine, balancing when to release a cellular army to deal with pathogens, with when to rein in that army, stopping an onslaught from attacking the body itself. Now, Salk researchers have discovered a way to control regulatory T cells, immune cells that act as a cease-fire signal, telling the immune system when to stand down.

"Our ultimate goal is to be able to use these genes that modulate regulatory T cells to interfere with autoimmune diseases and cancers," says Ye Zheng, an associate professor in Salk's NOMIS Center for Immunobiology and Microbial Pathogenesis.

"The idea of manipulating this cell type for therapeutic purposes is very exciting," says Assistant Professor Diana Hargreaves, holder of the Richard Heyman and Anne Daigle Endowed Developmental Chair and the co-corresponding author of the new paper with Zheng. Their study appeared in the journal Immunity on July 7, 2020.

Regulatory T cells are responsible for reining in the activity of other cells in the immune system. They prevent the immune system from attacking the body's own tissues, and tell the immune response to fade when it is no longer needed, acting like an all-clear signal. Underactive regulatory T cells are associated with autoimmune diseases where the immune system attacks the body, including rheumatoid arthritis, multiple sclerosis, inflammatory bowel disease and lupus. Some cancers, on the other hand, have higher-than-usual regulatory T cell activity, preventing the immune system from attacking a tumor and allowing its growth.

Researchers already knew that the gene called Foxp3 is a key player in the development and function of regulatory T cells. If regulatory T cells are like the lead peacekeepers, Foxp3 is like the UN, encouraging the peacekeeping force to organize. Without Foxp3, the body doesn't form regulatory T cells. So Zheng's group set out to find other genes that impacted levels of Foxp3. They used CRISPR gene-editing technology to test which genes throughout the genome affected Foxp3. This screen turned up hundreds of genes, including a handful that encoded different subunits of the SWI/SNF complex, a group of proteins that plays a role in turning many other genes on and off by physically making DNA accessible to cellular machinery.

Hargreaves and her group were already studying a number of genes in the SWI/SNF complex, including a new variant that the lab identified in 2018 called the ncBAF complex, so the two labs teamed up to uncover the role of the complex in regulatory T cells.

"There was already data to show how the SWI/SNF complex is important for the development of cells, but not much data in regulatory T cells specifically," says Salk postdoctoral researcher Jovylyn Gatchalian, co-first author of the new work.

The researchers used CRISPR to selectively remove the SWI/SNF complex genes from regulatory T cells. They found that the deletion of one gene in the ncBAF complex, called Brd9, had a particularly strong effect on the immune cells; regulatory T cells without Brd9 had lower levels of Foxp3 and weakened function.

"Until now, it's been very hard to fine-tune regulatory T cell activity in the body," says Eric Chin-San Loo, a graduate student and co-first author of the new paper. "This complex allows us to do just that--turn up or down the activity of the immune cells but not enough to cause other forms of disease."

In mice with cancer, treatment with the weakened immune cells without Brd9 enabled other immune cells--the fighters and soldiers of the immune system--normally blocked by the regulatory T cells to infiltrate the tumors and shrink them. In mice with inflammatory bowel disease, however, the weakened regulatory T cells left the immune system attacking the digestive tract unchecked. These results suggest that controlling the strength of regulatory T cells has potential for treating both cancer and autoimmune diseases.

In the future, the researchers say they'd like to dive deeper into the molecular mechanisms by which Brd9 is controlling Foxp3 expression and how the ncBAF complex might change the tumor environment in other ways.

Hargreaves adds that future studies could look at whether small molecules can control the activity of the ncBAF complex; these would be more relevant for human therapeutics than genetic methods of altering the proteins. Such molecules might one day be able to turn down the activity of regulatory T cells to treat cancer, or turn up their activity to treat autoimmune disease.

A team of engineers may be one step closer to cleaning up heavily contaminated industrial wastewater streams.

Researchers from the School of Chemical and Biomolecular Engineering developed an electrochemical oxidation process with the aim of cleaning up complex wastewater that contained a toxic cocktail of chemical pollutants.

"Our study, published in Algal Research, involved industrial wastewater that had been heavily contaminated with a cocktail of organic and inorganic species during a biofuel production process", said Julia Ciarlini Jungers Soares, who is completing a PhD in Chemical and Biomolecular Engineering under the supervision of Dr Alejandro Montoya.

The wastewater, which contained carbon, nitrogen and phosphorus, was generated in a pilot plant, designed by the team for the production of biofuels using naturally abundant microalgae.

The process involved treating wastewater with electricity using specialised electrodes. They discharged electricity, then drove oxidation reactions near the electrode surfaces, transforming the organic contaminants into harmless gasses, ions or minerals.

The water before, during and after treatment. Photo credit: Julia Ciarlini Jungers Soares, University of Sydney

"We have employed an incredibly powerful process that eliminates even the most persistent non-biodegradable pollutants, such as pharmaceuticals and pesticides, as well as various classes of organic compounds that can be found in many industrial effluents," she said.

"The process is relatively simple, does not require the addition of chemicals or severe operation conditions, and does not produce additional waste streams."

"Wastewater is a significant issue for our environment, as well as for many industries who use substantial volumes of water in their processes, such as in reactions, transport, and washing and cooling. Finding suitable solutions for reuse or disposal is often very challenging and costly.

"The electrochemical method that we used can be readily applied to industries that must comply with strict regulations for wastewater disposal, such as pulp and paper processing, wineries, as well as pharmaceutical production facilities.

"Worldwide, researchers are investigating methods for the development of biofuels from algae. Developing alternatives for the treatment and reuse of this industrial effluent is a hot research topic and can bring opportunities for energy and resource recovery within a circular bio-economy framework."

The team will soon carry out research focused on specific contaminants to better understand the chemical transformations that take place during electrochemical oxidation and will upscale the process.

A 2017 UNESCO report found that the opportunities from exploiting wastewater as a resource were vast, and that safely managed wastewater is an affordable and sustainable source of water, energy, nutrients and other recoverable materials.

In experiments in rats and mice, two Johns Hopkins scientists -- an engineer and an ophthalmologist -- report the successful use of nanoparticles to deliver gene therapy for blinding eye disease. A uniquely engineered large molecule allows researchers to compact large bundles of therapeutic DNA to be delivered into the cells of the eye.

The research, described July 3 in Science Advances, provides evidence of the potential value of nanoparticle-delivered gene therapy to treat wet age-related macular degeneration -- an eye disease characterized by abnormal blood vessel growth that damages the light-sensitive tissue in the back of the eye -- as well as more rare, inherited blinding diseases of the retina.

Many gene therapy approaches depend on viral vectors, which use a virus's natural ability to carry genetic material into cells. However, viruses create an immune response, which prevents repeat dosing, and the most commonly used one for ocular gene therapy cannot carry large genes.

"Some of the most prevalent inherited retinal degenerations are due to mutations in large genes that simply cannot fit into the most commonly used viral vector," says Peter Campochiaro, M.D., the Eccles Professor of Ophthalmology at the Johns Hopkins University School of Medicine, and a member of the Johns Hopkins Medicine Wilmer Eye Institute.

To overcome such limitations, Campochiaro and Jordan Green, Ph.D., developed a new approach involving a biodegradable polymer that surrounds and compacts long stretches of DNA, creating nanoparticles that can enter the cells. This technology allows the researchers to convert the cells of the eye into minifactories for a therapeutic protein.

To first test whether the nanoparticles could reach their target cells, the researchers loaded the nanoparticles with a gene for a florescent protein that causes cells to light up like a glow stick.

This glowing molecule allowed the researchers to determine the location, amount and duration of gene expression achievable with the nanoparticles.

They found that even eight months after treatment, the majority of the light-sensitive cells in the rats' eyes glowed, showing that the nanoparticles effectively deposited the florescent gene into the cells.

Next, the researchers set up a similar experiment, this time using the nanoparticles to shuttle a biologically relevant gene into the eye. They loaded the nanoparticles with a gene for vascular endothelial growth factor (VEGF), which is responsible for the growth of abnormal blood vessels in people with wet macular degeneration.

The researchers injected the eyes of 30 rats with the nanoparticles carrying the VEGF gene and determined the effects in the retina one, two and five months after injection. One month after injection, each rat tested had developed abnormal blood vessels under and within the retina, like those seen in patients with wet macular degeneration. The abnormal blood vessels were more extensive at two and five months after injection, and there was associated scarring under the retina similar to that seen in chronic untreated wet macular degeneration.

"These results show that the genes delivered by nanoparticles stayed active within the cells for several months," says Campochiaro.

Finally, to test a nanoparticle's ability to deliver a therapeutic gene for the disease, the researchers used mice genetically engineered to develop a form of wet macular degeneration similar to that in humans. The researchers loaded nanoparticles with a gene that produces a protein that neutralizes VEGF.

Currently, physicians inject such proteins that block VEGF proteins into the eyes of people with macular degeneration, a treatment that helps control the overgrowth of abnormal, leaky blood vessels. But this procedure must be repeated frequently and is burdensome for patients and their caretakers.

Three weeks after injecting nanoparticles containing the gene for the anti-VEGF protein, the mice had a 60% reduction in abnormal blood vessels when compared to control mice. The same effect was seen 35 days later.

"These results are extremely promising," says Jordan Green, Ph.D., professor of biomedical engineering at the Johns Hopkins University School of Medicine. "We have the ability to reach the cells most significantly affected by degenerative eye disease with nonviral treatments that can allow the eye to create its own sustained therapies."

An estimated 1.6 million people in the U.S. with macular degeneration receive injected drugs to the eye every four to six weeks. A gene therapy treatment could provide a way for the eye's tissue to prevent further vision deterioration with as little as a few initial treatments. Genetic diseases that cause blindness could be treated in a similar way, by introducing functional versions of genes that inherited mutations have disabled.

Discrimination against people thought to be infected with coronavirus was experienced by a rising number of United States residents, particularly racial minorities, in the early stages of the COVID-19 pandemic, according to a new study from the USC Dornsife College of Letters, Arts and Sciences.

From March to April 2020, the overall percentage of U.S. residents who experienced COVID-related discrimination more than doubled from 4% to 10%, according to researchers. The sharpest increase was among Asians and African Americans, who were most likely to report experiences of discrimination based on the perception they were infected with COVID-19.

In March, during the early stage of the pandemic in the U.S., 11% of Asians and 9% of African Americans had experienced discrimination by someone who perceived them as having the coronavirus, compared to 4% of whites. In April, this increased to 16% of Asians and 15% of African Americans, compared to 9% of whites, according to the study, which was published in the American Journal of Preventive Medicine.

Researchers analyzed responses from the Understanding Coronavirus in America tracking survey conducted by the USC Dornsife Center for Economic and Social Research (CESR) to evaluate the contribution of various risk factors for discrimination--including race/ethnicity and wearing a face mask--during in-person and social media encounters when discriminatory acts might occur. They also looked at how such discrimination was related to mental distress among U.S. adults in the early stage of the COVID-19 pandemic in March and April 2020.

Mask-wearing was a risk factor for discrimination

Survey participants consisted of a probability-based, nationally representative sample of 3,665 U.S. residents aged 18 years or older who completed COVID-19-related surveys online in March and April. To measure incidents of discrimination, respondents were asked if "people thinking they might have the coronavirus" acted as if they were afraid of them, threatened or harassed them, treated them with less courtesy and respect, or gave them poorer service at restaurants or stores.

"The early spike in the percentage of people who experienced COVID-related discrimination was attributable - in part - to discriminatory reactions to the growing number of people wearing masks or face coverings at the early stage of the pandemic," said Ying Liu, a research scientist with CESR.

The researchers found Asian Americans were the first racial/ethnic group to experience substantial discrimination, followed by African Americans, and that the higher degree of discrimination experienced by Asians in March was partially explained by their immigration status and mask-wearing.

African Americans' risk of experiencing discrimination was higher than other non-Asian groups and also increased faster between March and April than other groups, according to the study.

"This increase may in part be attributable to the spike in media coverage we saw during this time regarding African Americans' disproportionate vulnerability to COVID-19," said Kyla Thomas, a sociologist at CESR.

Mask-wearing was a persistent risk factor for discrimination associated with COVID-19, although it varied from March to April. The study found other groups, including frontline workers who didn't wear masks, people who worked partially or fully from home, and those who did not work experienced less discrimination.

"In March, before widespread stay-at-home orders and when mask-wearing was rare, people wearing masks were more likely to experience discrimination," said Brian Karl Finch, research professor of sociology and spatial sciences with CESR. "In April, only the frontline workers who wore masks had higher risks of experiencing discrimination."

The research team found that in some earlier weeks of the pandemic, people who were heavy users of social media were more likely to report an experience of discrimination. They also found that experiences of discrimination were associated with increased anxiety and depression, consistent with literature associating general discrimination with poorer mental health especially among racial/ethnic minorities.

"The relationship between COVID-related discrimination and worsening anxiety and depression is particularly pertinent during this pandemic, as it compounds mental health distress attributable to concerns of disease spread, social restrictions, and financial stress," said PhuongThao Le, a postdoctoral researcher at Johns Hopkins Bloomberg School of Public Health.

Stigma can undermine public health efforts

Discrimination toward people who share social or behavioral characteristics with COVID-19 patients, but may not carry the novel virus, was first seen in heightened anti-Chinese rhetoric online. Social media analyses showed a nearly 10-fold increase in the use of offensive language, and reports on in-person racist acts against Asians increased during the early stages of the pandemic.

"In mid-March, President Donald Trump referred to a 'China virus' or 'Chinese virus,' which coincided with an increase of online and in-person crimes including robbery and harassment of Asian Americans," said Savannah Brenneke, a pre-doctoral researcher at Johns Hopkins Bloomberg School of Public Health.

Researchers say this disease-associated stigma toward people, regardless of infection status, has been observed in previous outbreaks of novel viruses. For example, Mexicans and other Latinos were shunned during the 2009 H1N1 pandemic owing to the virus' link to hog farms where migrants worked.

The United Nations and the U.S. Centers for Disease Control and Prevention have called for increased attention to preventing stigma associated with COVID-19, which could undermine disease control efforts, worsen mental health outcomes and exacerbate disparities.

On a gram for gram basis, animal proteins are more effective than plant proteins in supporting the maintenance of skeletal muscle mass with advancing age, shows research presented this week at The Physiological Society's virtual early career conference Future Physiology 2020.

The number of vegans in the UK has quadrupled since 2006, meaning that there are around 600,000 vegans in Great Britain (1). While we know plant-based diets are beneficial for the environment, we don't actually know how healthy these diets are for keeping muscles strong in elderly people.

Scientists generally agree that the primary driver of muscle loss with age -- at least in healthy individuals -- is a reduction of muscle proteins being built from amino acids. These amino acids come from protein that we eat and are also formed when we exercise.

Oliver Witard of King's College London is presenting research at The Physiological Society's Future Physiology 2020 conference about soy and wheat proteins showing that a larger dose of these plant proteins is required to achieve a comparable response of building muscles.

Simply transitioning from an animal-based protein diet to a plant-based diet, without adjusting total protein intake, will likely to be detrimental to muscle health during ageing. A more balanced and less extreme approach to changing dietary behaviour, meaning eating both animal and plant-based proteins, is best.

Witard and his colleagues conducted carefully controlled laboratory studies in human volunteers that involve the ingestion of plant compared with animal-based protein sources. To test changes in participants' muscles, they use several techniques including stable isotope methodology, blood sampling, and skeletal muscle biopsies to see how quickly the muscles were building up from amino acids.

It's important to note that this research to date has only compared two plant-based protein sources, namely soy and wheat. The researchers in this field will be conducting further research on other promising plant proteins such as oat, quinoa and maize.

Commenting on the research, Oliver Witard said:
"This research challenges the broad viewpoint that plant proteins don't help build muscles as much as animal protein by highlighting the potential of alternative plant-based protein sources to maintain the size and quality of ageing muscles."

The novel coronavirus disease (COVID-19) spreads rapidly around the world, and has limited people's outdoor activities substantially. Air quality is therefore expected to be improved due to reduced anthropogenic emissions. However, in some megacities it has not been improved as expected and severe haze episodes still occurred during the COVID-19 lockdown.

A research team led by Prof. Yele Sun from the Institute of Atmospheric Physics of the Chinese Academy of Sciences analyzed six-year aerosol particle composition measurements to investigate responses of air quality to the changes in anthropogenic emissions during the COVID-19 outbreak in Beijing, China, as well as the Chinese New Year holiday effects on air pollution.

They found that air pollution during the COVID-19 lockdown was mainly due to different chemical responses of primary and secondary aerosols to changes in anthropogenic emissions.

"Primary gaseous and aerosol species responded directly to emission changes and decreased substantially by 30-50%", said Sun. "However, secondary aerosol species that are formed from oxidation of gaseous precursors and accounted for more than 70% of particulate matter remained small changes of less than 12%. Therefore, fine particle pollution hasn't been improved as expected."

The air quality in Beijing has been improved during the last decade, and the mass concentrations of both primary and secondary pollutants decreased considerably.

However, according to this new study published in Sci. Total Environ, the increased sulfur and nitrogen oxidation capacity have suppressed the effects of emission reductions due to enhanced secondary formation.

These findings highlight a great challenge for mitigating secondary air pollution in regions with a cocktail of high concentrations of gaseous precursors.

"There's an urgent need for a better understanding of the chemical interactions between precursors and secondary aerosol under complex meteorological environments," said Sun.

Agricultural activity is responsible for about 12% of the total emissions of greenhouse gases in Spain. Nevertheless, adopting good agricultural practices can help reverse this situation, by increasing the sequestration of organic carbon in soil. With the goal of compensating for CO2 emissions produced by agricultural activity by means of fixing organic carbon in soil, the 4perMille initiative came about, in the framework of the Paris Climate Agreement (adopted at the COP21 in 2015).

Conservation Agriculture uses practices such as no-till farming (sowing without having previously tilled the soil), making use of the organic soil cover and rotating crops, which are beneficial in decreasing greenhouse gas emissions. In this vein, Rural Engineering Department Professor, at the School of Agricultural and Forestry Engineering, University of Cordoba, Emilio J. González, in the GI AGR 126 Mechanization and Rural Technology group, participated in the project working with Dr. Rafaela Ordóñez's team, from the Agriculture and the Environment Area at the Institute of Agricultural Research and Training. They analyzed the potential of Conservation Agriculture to reach the aim of increasing organic carbon in soil by 0.4% yearly, which is the main goal of the 4perMille initiative. Applying the Carbon Benefit Project model, designed by the UN Environment Programme, they concluded that by using no-till farming for extensive crops, carbon sequestration levels could reach up to three times the goal amount in the agreement.

After comparing the situation of conventional agriculture based on heavy tilling to data from the model based on a no-till farming situation with extensive crops (grains, sunflower, legumes, forage crops), regions appeared where carbon sequestration could triple the amount fixed by the 4permille initiative, places such as the Guadalquivir valley, Navarre, Aragon and Catalonia. With this study, Conservation Agriculture's capacity to mitigate climate change has been scientifically contrasted, and in doing so, tools are offered up for agricultural management policies such as the European Union's Common Agricultural Policy (CAP), which is currently undergoing debate on green aims focused on mitigation and adaptation to climate change. This study is found within the European project called LIFE Agromitiga, whose objective is to contribute to shifting towards a low-carbon farming system.

Soil conservation

In addition to increasing organic carbon sequestration, using no-till farming and other Conservation Agriculture practices means reducing soil erosion by up to 95%. In this way, the main environmental problem in this country is also being dealt with. Soil loss is especially marked in the basins of the Guadalquivir and Ebro rivers.

Large communities devoted to agriculture, therefore, will benefit greatly from applying Conservation Agriculture, which has over 700,000 ha of extensive crops in Spain, making it the European country with the greatest amount of application of these techniques.

If we continue down this path, we will not only increase the environmental advantages for the surrounding area and society, but also increase the financial feasibility of farms, farms that will keep their key production asset, soil, and will also save on work and fuel costs.

Global water consumption has increased almost fourfold in the past 100 years, and many regions can only meet their water demand thanks to essential contributions from mountain regions. In 30 years, almost a quarter of the world's lowland population will strongly depend on runoff from the mountains. Only sustainable development can ensure the important function of mountain areas as Earth's "water towers".

Water is a key resource for the 21st century, and many lowland regions all over the world depend on water resources originating in mountain regions, not least when it comes to irrigating agricultural land. A study led by the University of Zurich has now quantified this dependence for the first time by comparing water supply and consumption in the world's lowland areas with runoff contributions from the mountains. Based on a high-resolution global model, the study provides detailed information on the dependence on mountain water resources around the globe. The comprehensive analyses were carried out using a regular grid and then compared for every river catchment area of at least 10,000 km2. This allowed for highly differentiated insights into regional characteristics and differences.

Increasing dependence despite declining per-capita consumption

"Until now, research has focused mainly on river basins that originate in High Mountain Asia," says Daniel Viviroli from the Department of Geography at the University of Zurich, first author of the study. "But in many other regions, irrigated agriculture is heavily dependent on water from mountainous areas, such as in the Middle East and North Africa, as well as parts of North America, South America and Australia."

This dependence has increased strongly since the 1960s - despite more efficient water use and thus declining per-capita water consumption. Whereas only 7 percent of the lowland population used to be strongly dependent on contributions from mountain areas at that time, this figure is projected to rise to 24 percent by mid-21st century. This corresponds to about 1.5 billion people in lowland areas. Particular focus is on catchment areas such as those of the Ganges-Brahmaputra-Meghna, Yangtze and Indus rivers in Asia, the Nile and Niger in Africa, the Euphrates and Tigris in the Middle East as well as the Colorado River in North America. For their analyses, the researchers assumed a middle-of-the-road scenario in terms of population growth as well as technological, economic and social development.

Functioning ecosystems and climate protection

"Ensuring the function of mountains as 'water towers' should be a major concern of the world's lowland populations," says Viviroli. Sustainable development of mountain regions is therefore essential, for example by preventing agricultural overuse and ensuring the functioning of ecosystems, the researchers say. In addition, climate action is of paramount importance: Due to the rising temperatures, meltwater peaks from snow-covered mountain regions sometimes already occur several weeks earlier and are thus not as useful for summer agriculture. Adjustments in water management will be necessary, and possibly also new infrastructure such as dams and water transfers.

"However, technical solutions go hand in hand with major ecological damage, and some rivers, such as the Indus, have little potential for expansion," says Viviroli. For the future, it will be crucial that lowland and mountain regions work closely together despite political, cultural, social and economic differences.

Tsukuba, Japan - In Indiana Jones and the Last Crusade, Indiana must choose his grail "wisely", as a poor choice spells instant death. According to a new study by Professor Masayuki Matsumoto at the University of Tsukuba, making these kinds of choices involves dopamine neurons in the brain. Specifically, the study shows that dopamine neurons represent different parts of the decision-making process as it unfolds.

Although the choices we make are rarely as dramatic as Indiana's, the ability to evaluate options and choose the one that leads to the best outcome is critical--even if the choice is simply from a lunch menu. Researchers like Professor Matsumoto who study decision-making in the brain often focus on what is called the "reward network". Two important parts of this network are dopamine neurons deep in the midbrain and a region called the orbito-frontal cortex in the front of the brain. "We know that dopamine neurons encode reward prediction error," explains Professor Matsumoto. "They become very active after an animal receives an unexpected reward and become less active as expectations are learned." In their new study, the team wanted to find out what these neurons are doing as decisions are being made, rather than afterwards.

When making economic choices, typically, items are first evaluated, then compared, a decision is made, and action is taken. This process was replicated in a game for monkeys. The monkeys learned to associate six pictures with different amounts of reward. They were shown one of the images and could choose it and get the reward, or they could pass and get the reward associated with a second image. With this setup, when the first image gave a mid-level reward, the monkeys sometimes chose to take the reward and sometimes risked passing to get a bigger reward. This allowed the researchers to separate the evaluation and decision processes.

The team found that dopamine neurons represented both parts of the decision-making process. Some indicated the amount of reward represented by the picture, and others indicated the final yes/no choice. Many neurons displayed both types of information, transitioning from value to choice over time. You can imagine Indiana's dopamine neurons firing like crazy as he eyes a jewel-encrusted grail, but then dying down as he decides to choose the plain one. "These neurons especially reflect the entire integrated decision-making process," says Professor Matsumoto, "and we suspect that they send this decision out to other parts of the brain such as the orbito-frontal cortex, and finally to the muscles for an action to take place."

The field of neuroeconomics is relatively new and understanding the role of dopamine neurons in decision-making and risk-taking is critical. "The dopamine neurons we study are actually the same dopamine neurons that die in Parkinson's disease and are over-sensitized in addition," says Professor Matsumoto. "Our research may thus provide insight into decision-making deficits that might be present in these illnesses."

The three known human trefoil factor family peptides TFF1, TFF2 and TFF3 are mainly produced by the gastrointestinal mucosa. Named after their trefoil-like folded structure, the molecules provide clinically intriguing properties. Studies demonstrated that these peptides are locally produced to combat inflammation and injuries of the gastrointestinal tract by accelerating wound healing. Therefore, they have a considerable therapeutic potential for gastrointestinal and other mucosal disorders such as the dry eye disease and asthma as the researchers state in an additional review article published in ACS Pharmacology & Translational Science.

Local effects

"To date, there are two oral peptide therapeutics against diseases such as irritable bowel syndrome on the market," says the medicinal chemist Muttenthaler. "Due to the relatively large size of the molecules, they are not being absorbed through the gastrointestinal wall into the bloodstream, and therefore can only act locally in the gastrointestinal tract without major side effects."

The trefoil factor family is "an essential starting point for new therapeutic strategies to treat chronic diseases that remain incurable", explains Muttenthaler, who leads research groups at the Department of Biological Chemistry at the University of Vienna and at the University of Queensland in Brisbane. The studies are being conducted in the context of Muttenthaler's ERC Starting Grant project, which aims at disclosing the mechanisms of wound healing in the gastrointestinal tract. "Based on the chemical synthesis of the TFF peptides, we can now find answers to fundamental questions that we were not able to tackle before."

TFF1 acts as homodimer

In their study, the researchers present the chemical synthesis of TFF1 and its homodimer, a molecule that comprises two TFF1 subunits. Only in its homodimeric form was TFF1 able to interact with mucins, main structural constituents of the gastrointestinal tract, which accelerates the closure of the mucosal barrier and its healing process.

With a length of 60 amino acids, conventional approaches were not applicable for the synthesis of TFF1. The scientists developed a new method to synthesise the peptide in two fragments and assemble them subsequently. The second challenge that the scientists had to overcome was to fold TFF1 correctly by selecting from a multitude of possibilities. Correct folding was then confirmed through structural analysis and the TFF1 homodimer was shown to interact with the gastric mucosa. Muttenthaler and his team now work on the chemical synthesis of the other two members of the trefoil factor family, TFF3 and the more challenging TFF2, which is longer and more complex with its 106 amino acids and 7 disulfide bonds.

New possibilities for molecular design

The chemical synthesis of TFF1 is a milestone for the field since it provides more options to modify this peptide class. To date, recombinant expression was the only way to produce these molecules. "Therefore, their design was limited to the 20 natural amino acids. Chemical synthesis now enables us to design advanced TFF1 probes to study their mechanisms of action or to optimise TFF1 towards its therapeutic applications", Muttenthaler explains.

Molecular probes are essential for a better understanding of TFF1 and its mode of action. Certain attachments such as fluorescent molecules or other reporter tags can help to study TFF1 interactions with its target proteins or receptors. Other modifications could be used to further improve the stability of the peptides and their drug-like properties for a more efficient therapeutic application.

BINGHAMTON, NY -- Students tend to be more engaged in activism if the school that they attend emphasizes social and political issues, according to new research featuring faculty at Binghamton University, State University of New York.

A research team including Binghamton University Assistant Professor of Student Affairs Administration John Zilvinskis examined survey responses to an experimental itemset of the National Survey of Student Engagement measuring behaviors related to student activism. The sample included 3,257 seniors from 22 four-year institutions.

The survey items had respondents measure, "How much does your institution emphasize the following?"

- Discussing social or political issues, causes, campaigns or organizations

- Participating in activities focused on social or political issues, causes, campaigns or organizations

- Organizing activities focused on social or political issues, causes, campaigns or organizations

- Being an informed and active citizen focused on social or political issues, causes, campaigns or organizations

For administrators and educators in higher education, the researchers found that institutions with higher averages of emphasized activism had students who were more likely to participate in these behaviors.

"The higher institutional averages could indicate that a culture of emphasizing activism leads to more student engagement in activism; however, there also may be a self-selection effect in that activists choose to attend institutions that hold these values," said Zilvinskis.

The researchers also found that Black students and queer students were significantly more likely than other respondents to participate in activism.

"Our country has a history of marginalizing people from these groups, so I suspect they are more motivated to engage in activism behaviors to create more equitable experiences," said Zilvinskis. "The disappointing counter-finding is that their straight and White peers are not as engaged in activism."

Zilvinskis is now researching student participation in high-impact practices at community colleges and the engagement of students with disabilities at these institutions.

Scientists have engineered natural killer immune cells that not only kill head and neck tumour cells in mice but also reduce the immune-suppressing myeloid cells that allow tumours to evade the immune response, according to a new study in eLife.

The engineered cell therapy could be used as an alternative approach for treating cancer in patients for whom previous immunotherapy based on the activation of T cells has failed. These findings are reported by researchers at the U.S. National Institutes of Health (NIH) in Bethesda, Maryland.

In recent years, treatments called T-cell therapy or CAR-T cell therapy have been approved to treat blood cancers, and many others are now in development for other forms of cancer. However, these T-cell therapies rely on the ability to reprogram a patient's own T cells to express a chimeric antigen receptor (CAR) that targets tumour cells. This process of reprogramming a patient's own T cells is expensive and laborious.

High affinity natural killer cells (haNKs) represent potential 'off-the-shelf' cell therapies that do not rely on reprogramming a patient's own immune cells. The same cells could be produced in mass and potentially given to anyone. But the presence of immune-suppressing myeloid cells in the tumour microenvironment remains a barrier to effective immunotherapy, including haNK cell-based treatment.

To address this barrier, researchers from the NIH's National Institute on Deafness and Other Communication Disorders (NIDCD) and National Cancer Institute have utilised haNKs expressing a CAR that targets a molecule called programmed death ligand 1 (PD-L1). PD-L1 is a well-known culprit that cancer and immunosuppressive myeloid cells produce in high amounts to dampen down the immune system.

Led by senior author Clint Allen, Principal Investigator, Section on Translational Tumor Immunology, NIDCD, the team tested the engineered PD-L1 haNKs versus ordinary haNKs against human and mouse head and neck cancer cells. They found that the haNKs expressing the PD-L1 CAR kill mouse and human tumour cells to a greater degree than haNKs without the CAR, and that this ability was retained even if they had already been exposed to cells carrying PD-L1 before. This is important because natural killer cells are known to become 'exhausted' after killing target cells.

In mice with head and neck tumours, the haNK cell-based therapy cured the mice in 30% of cases and slowed the growth of tumours in the rest of the mice, without causing toxicity. Treatment with haNKs also reduced the numbers of immunosuppressive myeloid cells that carry PD-L1 within the tumour, while having no effect on other immune-boosting white blood cells.

To investigate whether this effect on the immune cells also occurred in patients, the team incubated white blood cells from people with advanced head and neck cancer with the PD-L1 haNK cells. As they saw in the mice, the immunosuppressive myeloid cells that carry PD-L1 were significantly reduced after treatment with the PD-L1 haNK cells. This suggests that this treatment can both directly kill tumour cells and remove the immunosuppressive myeloid cells that prevent conventional immunotherapies from working.

These findings suggest that haNK cells expressing a PD-L1 CAR may overcome some of the limitations of conventional immunotherapy that relies on T-cell activation, and could be used in patients who are predicted to be insensitive to or have failed existing immunotherapy treatments. The researchers say the next steps would be to take this treatment into the clinic to explore the safety of PD-L1 haNKs in people with advanced or recurring cancer, and to see whether combining haNK cell therapy with other immunotherapies that activate T cells can enhance treatment response.