Culture

Engineers use electricity to clean up toxic water

image: Water before and after electrochemical treatment.

Image: 
Julia Ciarlini Jungers Soares, University of Sydney

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.

Credit: 
University of Sydney

Scientists use nanoparticle-delivered gene therapy to inhibit blinding eye disease in rodents

image: 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.

Image: 
Johns Hopkins Medicine

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.

Credit: 
Johns Hopkins Medicine

COVID-related discrimination disproportionately impacts racial minorities, study shows

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.

Credit: 
University of Southern California

Soy and wheat proteins helpful for building aging muscles, but not as potent as animal protein

image: These meals are examples of vegetarian meals that help build muscle proteins because they consist of a complementary and complete profile of all essential amino acids.

Image: 
Photo Anita Bean

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."

Credit: 
The Physiological Society

A chemical cocktail of air pollution in Beijing, China during COVID-19 outbreak

image: Changes in primary aerosols, gaseous precursors, and secondary aerosols during the COVID-19 outbreak and Chinese New Year holiday.

Image: 
Hao Li

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.

Credit: 
Institute of Atmospheric Physics, Chinese Academy of Sciences

Conservation agriculture increases carbon sequestration in extensive crops

image: Crops sown under no till farming.

Image: 
University of Cordoba

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.

Credit: 
University of Córdoba

1.5 billion people will depend on water from mountains

image: The Rosegbach River in the Upper Engadine, Switzerland, is part of the Danube River basin where roughly one third of the 46 million people living downstream strongly depend on water resources from mountain areas.

Image: 
D. Viviroli

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.

Credit: 
University of Zurich

Dopamine neurons mull over your options

image: Researchers at the University of Tsukuba have found that dopamine neurons in the brain can represent the decision-making process when making economic choices. As monkeys contemplated whether or not to choose an item, a subset of dopamine neurons transitioned from indicating the item's value to indicating the monkey's ultimate decision. Encoding of the decision into these dopamine neurons happened earlier than it did in other parts of the brain related to economic decision-making.

Image: 
University of Tsukuba

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."

Credit: 
University of Tsukuba

Towards improved wound healing -- Chemical synthesis of a trefoil factor peptide

image: Studies demonstrated that trefoil factor peptides are locally produced to combat inflammation and injuries of the gastrointestinal tract by accelerating wound healing.

Image: 
© Universität Wien

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.

Credit: 
University of Vienna

Colleges that emphasize activism have more civically engaged students

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.

Credit: 
Binghamton University

Engineered killer immune cells target tumours and their immunosuppressive allies

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.

Credit: 
eLife

Childhood obesity linked to poor heart health signs at 11-12 years

image: Toddlers who were obese or overweight show concerning signs of cardiovascular disease at 11-12 years of age, according to a new study.

Image: 
Kai Keisuke

Toddlers who were obese or overweight show concerning signs of cardiovascular disease at 11-12 years of age, according to a new study led by the Murdoch Children's Research Institute (MCRI).

The study, published in Pediatrics, found Australian children who were obese or overweight very early in life already show evidence by age 11-12 years of stiffer arteries, thickened arterial lining and are a high risk of later developing metabolic syndrome. This worsened the longer these young children were overweight or obese.

MCRI Professor Melissa Wake said the study highlighted the silent effects of obesity in childhood and the need to intervene early.

"Public health efforts are needed in the very early years to prevent problems with obesity and being overweight, to avoid the risk of adolescent and adult cardiovascular disease," she said.

"Our findings are in line with the World Health Organization's calls for urgent collaborative action to address the matter through systems-based approaches and policy implementation.

"Such policies include increasing taxes on processed foods high in fat and sugar, safer and improved public transport and walking to school pathways and making community-based sporting activities more affordable and accessible."

MCRI Dr Kate Lycett said until now little was known about when and how early life BMI impacted heart health in childhood and most studies have previously just looked at standard risk factors such as blood pressure alone.

"Previous studies have tended to rely on a single BMI measurement in childhood and then examined subsequent heart health outcomes in adulthood," she said.

"This overlooks the considerable BMI changes as part of normal childhood growth."

The study involved 1811 children from the Longitudinal Study of Australian Children whose weight and height were measured every two years (age 0-1 to 9-10 years) to determine cardiovascular disease risk scores. At age 11-12, the participants underwent further health checks looking at blood pressure, blood vessel health, cholesterol and glucose levels.

Dr Lycett said the obesity epidemic was a major threat to public health.

"This public health crisis threatens the modest decline in cardiovascular deaths in developed countries, which has largely been achieved through preventive efforts focused on cardiovascular risk factors," she said.

"Policy changes to reign in this epidemic require strong support from the clinical community if they are to be realised."

Credit: 
Murdoch Childrens Research Institute

Flu in early life determines our susceptibility to future infections

Early infections of influenza A can help predict how the virus will affect people across different ages in the future and could impact the effectiveness of flu vaccines, says a new study published today in eLife.

The findings may help improve estimates of both the age-specific risk of acquiring seasonal influenza infections and vaccine effectiveness in similarly vaccinated populations.

Seasonal influenza is an acute respiratory infection caused by influenza viruses that occur across the world. It causes approximately 100,000-600,000 hospitalisations and 5,000-27,000 deaths per year in the US alone. There are three types of seasonal influenza viruses in humans: A, B and C, although C is much less common. Influenza A viruses are further classified into subtypes, with the A(H1N1) and A(H3N2) subtypes currently circulating in humans. A(H1N1) is also written as A(H1N1)pdm09 as it caused the 2009 pandemic and replaced the A(H1N1) virus which had circulated before that year.*

The rapid evolution of seasonal influenza that allows it to escape preexisting immunity adds to the relatively high incidence of infections, including in previously infected older children and adults. But how susceptibility arises and changes over time in human populations has been difficult to quantify.

"Since the risk of influenza infection in a given age group changes over time, factors other than age may affect our susceptibility to infection," says first author Philip Arevalo, a postdoctoral researcher in senior author Sarah Cobey's lab, Department of Ecology and Evolution, University of Chicago, US. "We wanted to see whether these differences can be explained in part by the protection gained from childhood flu infection, which has lasting impacts on the immune response to future infections and the protection against new influenza A subtypes."

To measure the effect of early exposures to seasonal influenza on risk and vaccine effectiveness, Arevalo and his team applied statistical models to flu cases identified through seasonal studies of vaccine effectiveness from the 2007-2008 to 2017-2018 seasons in the Marshfield Epidemiologic Study Area (MESA) in Marshfield, Wisconsin, US. Each flu season, individuals in a defined community group were recruited and tested for flu when seeking outpatient care for acute respiratory infection. Those eligible for the study were individuals older than six months of age living in MESA and who received routine care from the Marshfield Clinic.

Despite the extensive evolution in influenza A subtypes H1N1 and H3N2 over the study period, the team's model showed that early infection reduces the risk of people needing to seek medical attention for infections with the same subtype later in life. This effect is stronger for H1N1 compared to H3N2. The model also revealed that the effectiveness of flu vaccines varies with both age and birth year, suggesting that this effectiveness also depends on early exposure.

"We hope the findings from our study will improve our understanding of influenza epidemiology and the low and variable effectiveness of the seasonal flu vaccine," concludes senior author Sarah Cobey, Principal Investigator at the Department of Ecology and Evolution, University of Chicago. "This would lead to better forecasting and vaccination strategies to help combat future flu seasons."

Credit: 
eLife

Study: Interplay of impact, moral goals influences charitable giving to different causes

image: With the rise of globalization, geographic borders are becoming less relevant for making charitable donations, which means nonprofits and charities can make more effective pitches to donors by emphasizing higher-level concepts such as morality and idealistic values, said Carlos Torelli, a professor of business administration and the James F. Towey Faculty Fellow at Illinois.

Image: 
Photo by Gies College of Business

CHAMPAIGN, Ill. -- Charitable giving is a nearly half-trillion-dollar sector of the U.S. economy, but what accounts for why some individuals, foundations and corporations give locally while others give to charities on the other side of the globe? According to a new paper co-written by a University of Illinois at Urbana-Champaign expert in consumer behavior and global marketing, the dynamic interplay between the accessibility of local impact versus more global goals can influence charitable behaviors between donors and recipients.

An appeal to morality can persuade people to make donations that benefit recipients halfway around the world - even though those same resources could be allocated to helping those with similar needs who live closer, said Carlos Torelli, a professor of business administration and the James F. Towey Faculty Fellow at Illinois.

"Although past research suggests that people are more likely to donate money to nearby causes to maximize the positive impact on their local community, donations to foreign causes are growing rapidly," he said. "With the rise of globalization, geographic borders are becoming less relevant for making charitable donations, which means nonprofits and charities can make more effective pitches to donors by emphasizing higher-level concepts such as morality and idealistic values."

Torelli and his co-authors conducted five studies to identify the conditions under which donors pledge higher amounts of money to recipients who are located spatially far away versus nearby recipients, and to rule out the possibility that the effect of spatial distance is driven by unequal economic conditions and, thus, differences in need between the two recipients.

"What we found is that people who donate money to causes that aren't local do so to feel more fulfilled, because it's something that's more aligned with their moral identity, which is the extent to which moral traits, goals and behaviors are important to one's self-concept or self-identity," said Torelli, also the executive director of Executive and Professional Education at the Gies College of Business. "We also found that this positive effect was more prevalent among people high in moral self-concept and was attenuated or even reversed among people low in moral self-concept."

The appeal to morality in requesting donations for distant recipients is "an entirely different framework" than for requesting donations to a local cause, which should emphasize the concrete, actionable impact of a monetary donation, Torelli said.

"For local or nearby causes, you really have to push the immediate impact aspect of it - how many people you can help, how much and how quickly your dollar can be put to work for individuals who are members of the community," he said. "The morality appeal, on the other hand, really has to tap into higher-level idealistic goals - clean water for everyone the alleviation of hunger, for example."

The paper's findings can help organizations increase the efficacy of marketing initiatives, Torelli said.

"The same cause can use different appeals depending on who they're targeting and where they are," he said. "If they're far away, then an appeal to morality is going to be more effective than an appeal to sheer numbers and impact."

The research also has implications for for-profit organizations engaging in corporate social-responsibility initiatives.

"Many large organizations are global and choose international charitable organizations to partner with, to align their social impact with their practices and beliefs," Torelli said. "Not only does this type of initiative have a social impact, it can also have a positive impact on employees of the organization. Our findings suggest that companies with corporate social-responsibility initiatives that help recipients in distant locations could benefit by focusing their communications on the higher-level goals that such initiatives are accomplishing instead of just touting their impact.

"Doing so might result in higher employee involvement with the charitable cause and higher employee satisfaction, particularly for employees who place a lot of importance on moral identity."

Credit: 
University of Illinois at Urbana-Champaign, News Bureau

Restructuring a general surgery residency program in epicenter of COVID-19 pandemic

What The Article Says: A New York hospital's restructuring of general surgery resident teams and educational infrastructure in response to the COVID-19 pandemic is detailed in this article.

Authors: Heather L. Yeo, M.D., M.H.S., M.B.A., M.S., of NewYork-Presbyterian Hospital/Weill Cornell Medicine in New York, is the corresponding author.

To access the embargoed study: Visit our For The Media website at this link https://media.jamanetwork.com/

(doi:10.1001/jamasurg.2020.3107)

Editor's Note: The article includes conflicts of interest disclosures. Please see the article for additional information, including other authors, author contributions and affiliations, conflicts of interest and financial disclosures, and funding and support.

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JAMA Network