Culture

Laboratory cell experiments and computer simulations have revealed molecular mechanisms regulating a protein channel responsible for transporting chloride and other charged molecules across cell membranes. The findings were published in the Proceedings of the National Academy of Sciences (PNAS).

"Our findings could help provide clues for developing treatments for diseases associated with this channel's malfunction, including some cancers, cystic fibrosis, and neurological pain," says molecular neurophysiologist Byung-Chang Suh of Daegu Gyeongbuk Institute of Science and Technology (DGIST), who led the study.

Transmembrane 16A (TMEM16A) is a chloride channel found in cell membranes. It is involved in diverse physiological roles, including small muscle contraction, regulating nerve excitability and cell volume, and detecting 'bad' heat by sensory nerve fibres. Scientists already know quite a lot about this protein. Now, Suh and his colleagues in Korea and the US have revealed some of the molecular underpinnings of its interaction with a cellular signalling phospholipid called PIP2.

PIP2 is found in the inner leaflet of the cell's membrane. PIP2 binding to TMEM16A regulates the amount of chloride, and thus the electric current, that passes through it.

The team found that PIP2 acts differently on two variations of the TMEM16A channel. Human cell experiments showed that PIP2 depletion reduced the current passing through the version called TMEM16A(ac) but not through TMEM16A(a). They also found that the energy-carrying molecule called ATP was needed for current to run through both types of the channel.

Structural analyses and computer simulations showed that phosphorylation - or adding a phosphate group¬ - of a specific amino acid on TMEM16A changed how PIP2 bound to that part of the chloride channel, with different effects on TMEM16A(ac) and TMEM16A(a).

"Our investigations provide an important foundation for mechanistic understanding of TMEM16A activity, suggesting its function depends on the channel variant, and is regulated by PIP2 binding and channel phosphorylation," says Suh. The scientists hope their investigations will assist other studies of similar cell membrane proteins, in addition to supporting drug development research.

They recommend further studies to understand how the structures of TMEM16A variants impact its physiological functions in various tissues.

After analysing the data from 226 large manufacturing companies from the European Union, a team of researchers from Lithuania, Poland and Sweden have drawn a conclusion that organisations almost do not mention circular economy principles in their environmental reporting. In their reports, the organisations mostly refer to the effective use of primary flows and minimising waste. However, the other principles related to product lifecycle extending and useful application of materials are not sufficiently disclosed, according to a recent study lead by researchers of Kaunas University of Technology (KTU), Lithuania.

Although the idea of a circular economy model, as opposed to the current, linear economy, has emerged as early as the 1970s, it gained wider exposure only decades later. In 2015, The European Commission launched the first EU Circular Economy Action Plan.

"Indeed, the circularity concept has deep historical roots, the manufacturing organisations have been investing in recycling technologies, were employing an environmentally conscious attitude for years. However, only the relatively recent EU strategy made the public and industry more aware of the concept", says Dr Lina Dagiliene, Head of the Circular Economy Research Team, Professor at KTU School of Economics Business.

In 2020, the EU Circular Economy Action Plan already includes enhancing disclosure of environmental data by companies in the upcoming review of the non-financial reporting directive and supporting a business-led initiative to develop environmental accounting principles that complement financial data with circular economy performance data.

Hence, the KTU research team set out to explore how the circular economy principles (in a popular language they are communicated through 4R's - reduce, reuse, recycle and recover) are reflected in the environmental reports of the manufacturing companies across Europe. Employing qualitative content analysis and statistical methods (ANOVA and PCA), researchers collected original empirical evidence from 226 large manufacturing companies whose environmental impact reports were published on GRI (Global Reporting Initiative) Sustainability Disclosure Database. GRI is an independent, international organisation that provides the world's most widely used standards for sustainability reporting. While selecting the companies, the research team drew on the EU definition of a large company, i.e. having more than 250 staff, a turnover of more than EUR 50 million or a balance sheet total of more than EUR 43 million. Although there were 1001 large EU organisations in the Database, the study focused only on manufacturing companies due to their obvious impact on the environment.

"Reporting the company's environmental impact is a formal way for the organisations to tell about their other activities than those related to financial matters. As manufacturing organisations are often criticised for their impact on the environment, these reports provide them with the possibility of explaining to the public how they are changing, in what initiatives they are participating, how they are involved in the lives of communities and society", says Prof Dagiliene.

According to her, there is a substantial body of research proving that investors are paying great attention to this kind of reporting - sometimes called social responsibility, sustainability or environmental impact report - while making their decisions.

However, the research lead by the KTU team revealed that the companies tend to focus on reporting on their ecoefficiency, i.e. using less raw resources and reducing their greenhouse gas emissions than on any other aspects of the circular economy. The text analysis, where Reduce, Reuse, Recycle, Recover and Circular Economy were the keywords used to indicate the amount of textual CE information in the reports, revealed that mainly reduce (of emissions, energy) is reported and the disclosures of reuse, recycle and recover information in the reports are not sufficient from the CE point of view. The resource efficiency approach implemented through the minimization of raw (critical) materials, creation of shorter loops and closed loops by the use of secondary raw materials is weakly reflected. It means that environmental reporting will have to change to reflect circularity.

"We are talking about large companies here, about the industry leaders, the trendsetters. Therefore, it is somewhat surprising to find out that these companies are not inclined to report about the innovative business models, which would increase the longevity of their products or about the recycling technologies implemented in their production cycle. These activities were mentioned in some of the reports, but only fleetingly, not as a common practice", says Prof Dagiliene.

According to her, there might be a couple of reasons for this. Firstly, the study is based on the external information, i.e. publicly available GRI reports, not on interviews with the organisations or their internal documents. Secondly, the organisations are following the GRI guidelines for preparing their environmental impact reports, and the guidelines for 2020 have no clear indication on how the circular economy principles should be reflected upon in the environmental impact reports. Hence, the implications of this research for the professional organisations, the facilitators of the non-financial information disclosure procedure could be: to include CE into the official guidelines on how to report circular economy environmental impact.

"While conducting this research, we were fully aware that circular economy is a relatively new term and we might not be able to find direct references to it. Therefore, through the content analysis and the analysis of the companies' key performance indicators, we were looking at the circular economy principles - how they are reflected in the organisations' activities. For example, some of the researched companies were from the food and beverage sector, where the recycle principle for diminishing food waste and recovery of raw materials might be applied. However, there was no much communication on these activities in the reports", says Prof Dagiliene.

Researchers are not inclined to say that any of the 4 R's is more important than the others. Using less raw resources and reducing emissions is crucial in order to optimise the manufacturing process. However, as much as 80 per cent of the environmental impact takes effect in the product design stage: before releasing the product into the market the manufacturer needs to be aware of its full life cycle - how long the product will be usable, what parts can be recycled, how the disposed products can be collected and reused again.

"Interestingly enough, those industries, which are considered the most controversial, such as alcohol, tobacco and those, which are considered the most polluting, such as mining or textile industries are more prone to communicate about their steps toward sustainable production. For example, Tom Hilfiger brand has already announced that they are switching to entirely circular production by 2030", says Prof Dagiliene from KTU School of Economics and Business.

According to her, all the industries would benefit from wider communication about the implementation of circular economy principles in their activities as consumers all over the world are becoming more aware of the environmental issues.

England's proposed mandatory Biodiversity Net Gain requirement for new developments might not deliver on promises to increase biodiversity, according to research being presented at British Ecological Society's Festival of Ecology.

A research team at the Durrell Institute of Conservation and Ecology, University of Kent, analysed ecological changes occurring under Biodiversity Net Gain (BNG)-type policies in four early-adopter councils in England. They found that although a net gain in biodiversity was being promised across the BNG assessments, these translated into considerable losses of habitat area. Habitat losses were compensated for by commitments to deliver higher quality habitats years later in the development project cycle.

In the sample of BNG assessments analysed by the authors, large areas of low-ecological value habitats such as modified grasslands and cropland were being lost, coupled with promises from developers to increase the condition of habitats that the government's Metric values more highly such as deciduous woodlands and mixed scrub habitats.

"Whether these promises of future condition increases materialise in reality is a question of governance." said Sophus zu Ermgassen, a PhD student who will be presenting the research at the Festival of Ecology. "Unfortunately, our analysis also shows that the governance might not be there to ensure these promises are kept for habitats delivered within the footprints of proposed developments."

Dr Joseph Bull, another researcher on the study, said: "Biodiversity Net Gain has the potential to deliver the improvement to biodiversity in England that many hope, but not unless governance mechanisms are designed that let local councils hold developers accountable for the quality of the nature within their developments."

The mandatory BNG requirement for new developments regulated under the Town and Country Planning Act, which will be introduced in the Environment Bill, means that for new building projects, developers must go beyond merely not harming nature and instead demonstrate their actions will increase biodiversity by 10%.

To calculate these biodiversity losses and gains, planning applications will need to use DEFRA's Biodiversity Metric 2.0. This metric takes into account factors like habitat distinctiveness and condition to give an overall indicative score - known as 'biodiversity units' - for the biodiversity quality of the site being built on. If developers cannot demonstrate they can meet the 10% requirement on land they manage, they will then need to fund the generation of equivalent biodiversity units elsewhere to make up the shortfall.

"This metric used to 'value' the biodiversity at different sites allows developers to lose some areas of semi-natural habitats, as long as they promise to increase the condition of other, non-impacted habitats so the total number of biodiversity units delivered actually goes up." explained Sophus zu Ermgassen.

"However, our preliminary results warn that the market for biodiversity units, which many people optimistically believe will be a major funding stream for investments in nature in England, may well be smaller than many hope, unless there are further changes to the policy design."

In the study, the researchers collected the Biodiversity Net Gain assessments associated with planning applications from four local councils who have already adopted Net Gain-type policies in advance of its national rollout: Tunbridge Wells Borough Council, Leeds City Council, Vale of White Horse District Council and South Oxfordshire District Council.

"We aggregated all of the assessments to get a picture of what the impacts of the policy as a whole are likely to be." said Sophus zu Ermgassen. "Next we read all of the public documentation about the policy, to understand what governance mechanisms are being proposed in order to deliver the policy and whether they are likely to be sufficient to achieve the policy's ambitions."

Because the vast majority of councils are yet to implement BNG-type policies, the researchers were limited in the number of assessments they could analyse, with their overall dataset accounting for around 1% of England's annual housebuilding.

The researchers are planning to keep constructing the database over the coming year. This will help them to see if their results continue to hold even as the policy develops and the regional biodiversity unit markets grow more mature.

Sophus zu Ermgassen will present the work in at the Festival of Ecology. This work is unpublished and is currently going through the peer-review process. This online conference will bring together 1,400 ecologists from than 50 countries to discuss the most recent breakthroughs in ecology.

In 2017, the World Health Organization published a list of pathogens for which new drugs are urgently needed. Acinetobacter baumannii was ranked in the critical priority group along with other Gram-negative bacteria such as Pseudomonas aeruginosa and carbapenemase-producing Enterobacteria. Specifically, A. baumannii is responsible for more than 10% of hospital infections, often severe, such as pneumonia linked to mechanical ventilation, and bacteremias, especially in intensive care units.

The 'Bacterial and Antimicrobial Resistance' group at the Institute of Biomedicine of Seville, led by Dr. José Miguel Cisneros, has published the results of a collaborative preclinical study focused on this specific pathogen. The study was conducted together with the 'Emerging Antibiotic Resistances' group, headed by Prof. Patrice Nordmann from the University of Fribourg, Switzerland.

As part of a line of research looking for effective new antimicrobial treatments against infections by carbapenemase-producing bacteria, and based on the results published in 2019 on the in vitro activity of combinations of two carbapenems against clinical strains of carbapenemase-producing A. baumannii, not clonally related, the group launched a study to evaluate in vivo the efficacy of imipenem plus meropenem in an experimental murine model of sepsis caused by clinical isolates of carbapenemase-producing A. baumannii. The results of this study show that the combination of imipenem plus meropenem could be effective in the treatment of infections caused by strains of carbapenemase-producing A. baumannii (OXA-23 and OXA-58).

Chemists at Martin Luther University Halle-Wittenberg (MLU) have developed a way to integrate liquids directly into materials during the 3D printing process. This allows, for example, active medical agents to be incorporated into pharmaceutical products or luminous liquids to be integrated into materials, which allow monitoring of damage. The study was published in "Advanced Materials Technologies".

3D printing is now widely used for a range of applications. Generally, however, the method is limited to materials which are liquefied through heat and become solid after printing. If the finished product is to contain liquid components, these are usually added afterwards. This is time-consuming and costly. "The future lies in more complex methods that combine several production steps," says Professor Wolfgang Binder from the Institute of Chemistry at MLU. "That is why we were looking for a way to integrate liquids directly into the material during the printing process."

To this endeavour, Binder and his colleague Harald Rupp combined common 3D printing processes with traditional printing methods such as those used in inkjet or laser printers. Liquids are added drop by drop at the desired location during the extrusion of the basic material. This allows them to be integrated directly and into the material in a targeted manner.

The chemists have been able to show that their method works through two examples. First, they integrated an active liquid substance into a biodegradable material. "We were able to prove that the active ingredient was not affected by the printing process and remained active," explains Binder. In the pharmaceutical industry, such materials are used as drug depots which can be slowly broken down by the body. They can be used after operations, for example, to prevent inflammation. This new process could facilitate their production.

Secondly, the scientists integrated a luminous liquid into a plastic material. When the material becomes damaged, the liquid leaks out and indicates where the damage has occurred. "You could imprint something like this into a small part of a product that is exposed to particularly high levels of stress," says Binder. For example, in parts of cars or aircraft that are under a lot of strain. According to Binder, damage to plastic materials has so far been difficult to detect - unlike damage to metals, where X-rays can expose micro-cracks. The new approach could therefore increase safety.

The combined process is also conceivable for many other areas of application, says the chemist. The team soon plans to use the method to print parts of batteries. "Larger quantities cannot be produced in the laboratory with our setup," Binder explains. In order to produce industrial quantities, the process must be further developed outside the university.

Like all viruses, the novel coronavirus is dependent on help from the human host cell. Proteins are the functional units of the cell and enable the virus to enter the host cell or help the virus to replicate. Scientists from Charité - Universitätsmedizin Berlin and from the Berlin Institute of Health (BIH), along with colleagues from the United Kingdom, Germany and the United States, have examined the corresponding genes of the helper proteins in a large study. They discovered numerous variants that influence the amount or function of the proteins as well as their ability to support the virus. The gene variants reveal potential target structures for new drugs. The researchers have now published their results in the journal Nature Communications*.

An infection of the novel coronavirus SARS-CoV-2, just like any other viral infection, follows a specific pattern: The viruses first bind to receptor proteins on the surface of the human host cells in the throat, nose or lungs before entering the cell, where they replicate with the help of the host cell machinery. The newly formed virus particles cause the infected cell to burst and infect other cells. As soon as the immune system notices what is happening, a defense mechanism is activated with the goal of destroying and removing both the viruses and virus-infected cells. Under normal circumstances, the infection is over within two weeks at the most. For all these processes, however, the virus is dependent on human or host proteins.

"In severe courses of COVID-19, this regulated process gets out of control and the immune system causes an excessive inflammatory response that attacks not only virus-infected cells but also healthy tissue," says Prof. Dr. Claudia Langenberg, BIH Professor of Computational Medicine and head of the study now being published. "Naturally occurring variations in the genes that make up the blueprint for these human proteins can alter their concentration or function and may thus be responsible for the different course of the disease." The team is well versed in the discovery of genetic variants that not only affect specific proteins but also common complex diseases. "As molecular epidemiologists, we study the diversity of genes - that is, the building instructions for proteins - of entire population groups in order to uncover susceptibilities to diseases whose cause lies in the interaction of many small deviations," explains the epidemiologist, who joined the BIH from the Medical Research Council Epidemiology Unit at the University of Cambridge in September. "We wanted to use these experiences and data sets for the COVID-19 epidemic and make them available to the scientific community."

"We examined 179 proteins known to be involved in SARS-CoV-2 infection for their naturally occurring variants," reports Dr. Maik Pietzner, the study's lead author and a scientist in Prof. Langenberg's lab. "We were able to draw on findings which were based on samples of the first COVID-19 patients at Charité. " This was possible due to close collaboration with the research group led by Professor Dr. Markus Ralser, Director of the Institute of Biochemistry at Charité, which had previously reported these findings. The team of Prof. Langenberg was able to use data from the MRC Fenland Cohort, a large population study that contains information from more than 10,000 individuals. They discovered 38 targets for existing drugs as well as evidence that certain proteins that interact with the virus influence the immune system. "Our findings also help to better understand risk factors for severe courses of COVID-19. We were able to show that blood coagulation proteins are influenced by the same genetic variant that increases the risk of contracting COVID-19 and that determines blood group 0," reports Dr. Pietzner.

The team immediately made the results publicly available via an interactive webserver, which was developed with colleagues from Helmholtz Zentrum München (https://omicscience.org/apps/covidpgwas/). Scientists from around the world have since been using the data to identify new drug targets or to better understand the course of COVID-19. "Journal articles that used our findings appeared even before our work was officially published," says a delighted Prof. Langenberg. "This is exactly what we had hoped for."

Washington, DC-- Developing nations have an opportunity to avoid long-term dependence on fossil fuel-burning infrastructure as they move toward economic stability, even if they are slow to cut carbon emissions, say the authors of a new paper in Environmental Research Letters.

Countries with low per capita incomes can keep their contributions to global warming to 0.3 degrees Celsius with careful foresight and planning, urge Carnegie's Lei Duan and Ken Caldeira with Juan Moreno-Cruz of the University of Waterloo. However, fueling economic development with coal, oil, or gas risks locking societies into a fossil-fuel burning infrastructure in the long-term, the authors caution.

"People in less wealthy countries are often motivated to use fossil fuels to drive their economic development and meet basic human needs," said lead author, Carnegie's Lei Duan. He continued, "While the direct climate effects from emissions from poor people will be minor, the world will care what kinds of energy systems they have as they increase their wealth."

More than half of the world's population resides in countries that have a per capita gross domestic product of less than $10,000 per year. But these nations produce less than 7 percent of global carbon dioxide emissions.

So Duan, Caldeira, and Juan Moreno-Cruz of the University of Waterloo set out to determine the consequences to the climate if only richer countries focused on decarbonization and developing countries delayed emissions cuts until they achieved economic stability.

They tested several future scenarios in which carbon emissions were cut only when countries reached specified levels of economic growth.

If every country in the world started to cut emissions by 2 percent annually in 2020, the world would warm to the climate-stabilizing Paris Agreement goal of 2 degrees Celsius over the pre-industrial era. However, Duan explained, "we determined that if decarbonization began only when a country reached a $10,000 per capita GDP, it would cause less than 0.3 degrees Celsius additional warming. This demonstrates that the onus of fighting climate change really falls on the shoulders of more developed nations."

This is, in part, because developing nations tend to prioritize low-cost and easy to operate energy sources. In fact, the authors said that the biggest risk to allowing these countries to delay emissions cuts would be the possibility of their constructing more-permanent fossil-fuel-burning infrastructure that would be too costly to eliminate.

In fact, last year, a study on which Caldeira was a coauthor determined that the world's power plants, boilers, furnaces, vehicles, and other fossil fuel technology must be retired early to meet the Paris Agreement goal.

"My professional career has been focused on addressing the climate problem, but I could do that because I had access to food, and shelter, and education, and energy and a thousand other things," Caldeira said. "If I didn't have those things, I would be focused on getting those things. We in the rich world can't fault anybody for trying to meet basic needs. We need to be thinking about ways to help people meet their basic needs today, while we help them and ourselves to transition to an energy system that does not use the sky as a waste dump."

Pasadena, CA-- New work from an international team of astronomers including Carnegie's Gregory Walth improves our understanding of the most-distant known astrophysical object-- GN-z11, a galaxy 13.4 billion light-years from Earth.

Formed 400 million years after the Big Bang, GN-z11 was previously determined by space telescope data to be the most-distant object yet discovered. In two newly published Nature Astronomy papers, a team led by Linhua Jiang at the Kavli Institute for Astronomy and Astrophysics at Peking University took near-infrared spectra using ground-based telescopes that confirmed the galaxy's distance. They also caught an ultraviolet flash associated with a gamma-ray burst from the galaxy.

Their findings will improve our understanding the formation of stars and galaxies in the very early universe.

The Big Bang started the universe as a hot, murky soup of extremely energetic particles that was rapidly expanding. After about 400,000 years, these particles cooled and coalesced into neutral hydrogen gas initiating a cosmic dark age.

Some patches of gas were denser than others and, eventually, their material collapsed inward, forming the first clumps of structure in the cosmos. The energy released by these ancient stars and galaxies caused the neutral hydrogen strewn throughout the universe to get excited and lose an electron--a process called ionization. Because photons could travel freely through this ionized gas, the universe became luminous again.

This period of cosmic reionization lasted several hundred million years and represents one of the most important phase transitions of the history of the universe. One of the primary scientific goals of the next generation telescopes, including the Giant Magellan Telescope under construction at Carnegie's Las Campanas Observatory, is to understand this epoch and to detect light from these first objects. However, it is very difficult for existing telescopes to detect spectra from such distant galaxies, which is what makes this discovery so exciting.

By taking deep spectroscopic observations of GN-z11 using the Keck I telescope on Mauna Kea in Hawaii, the team was able to confirm its distance of 13.4 billion light-years. However, analysis of the light coming from GN-z11 indicated an abundance of elements heavier than hydrogen and helium in the galaxy's composition. This indicates that it is not one of the original galaxies, which were formed in a cold, pristine universe and lacked the cornucopia of elements synthesized by previous generations of stars and seeded into the surrounding raw material when they exploded as supernovae.

The Keck observations also revealed a bright burst of light that lasted less than three minutes. Detailed analysis of this flash was produced by a gamma-ray burst in GN-z11. It was not previously known that these phenomena existed only a few hundred million years after the Big Bang.

"The more we learn about the universe's earliest objects, the better we can understand how the structure of our cosmos was shaped," Walth said.

Patients who have had weight loss surgery may not be receiving follow up care from their GPs as recommended in clinical guidelines - according to new research from the University of East Anglia and the University of Birmingham.

Clinical guidelines recommend that patients receive nutritional and weight monitoring annually for life following procedures such as having a gastric bypass.

But a new study published today shows that this does not appear to be happening in most cases - which can lead to patients putting weight back on or developing low levels of vitamins and other nutrients, which can have serious health consequences.

The study was funded by the National Institute for Health Research (NIHR) Clinical Research Network West Midlands.

It is the first study to investigate whether patients receive sufficient long-term routine care and monitoring in primary care following weight loss surgery.

Lead researcher Dr Helen Parretti, from UEA's Norwich Medical School, said: "Obesity is a healthcare priority and weight loss surgery, also known as bariatric surgery is an effective treatment.

"It can lead to significant weight loss and improve many obesity-related conditions such as type 2 diabetes or high blood pressure. It is the most cost-effective treatment for severe obesity and it can achieve dramatic weight loss. But it's not a cure for obesity on its own.

"Patients are supported to make changes to their eating before surgery and these changes need to continue after surgery to help avoid putting weight back on and to keep well. In addition, it is important that patients take lifelong nutritional supplements after their surgery.

"But patients need support to achieve this after their operations and current guidance recommends this is offered by GPs. Without this, weight loss surgery has long-term risks such as nutritional deficiencies and weight regain can occur.

"There is international clinical consensus that long-term follow-up care following bariatric surgery is important to optimise patient outcomes and reduce the risk of preventable harms.

"We wanted to find out whether the nutritional care and weight monitoring delivered by GPs following bariatric surgery meets current clinical guidance."

The team studied data from 3,137 patients in the UK who had received bariatric surgery between 2000 and 2015.

Types of surgery included gastric bands (where a silicone band is placed around the stomach), gastric bypass (where the top part of the stomach is joined to the small intestine) and sleeve gastrectomy (where some of the stomach is removed).

They looked to see whether patients had received the recommended advice and monitoring after their operations - particularly weight measurement, blood tests to check for nutritional deficiencies, and the prescription of nutritional supplements.

Dr Parretti said: "We found that in most cases, patients were not receiving the recommended long-term monitoring after they are discharged from bariatric services.

"We found that only around half of the participants were having their weight measured annually. In addition, only around half were having blood tests for nutritional deficiencies commonly seen in general practice, such as anaemia. The percentage of participants having blood tests more specific to bariatric surgery was very low - around five percent or less each year.

"The most common deficiency we found was anaemia - around 40-50 per cent of those patients who had had a blood test.

"We also found that the proportion of patients with prescriptions for recommended nutritional supplements was low.

"This shows that there is an urgent need to support GPs and patients to engage with post-bariatric surgery nutritional reviews and monitoring, for example through education and commissioning of services to provide this long-term care."

Maresin and resolvin, produced by the body from omega-3 fatty acids, can help repair tissue damaged by periodontal disease. A recent study shows that even in the presence of inflammation they stimulate periodontal ligament stem cells. The periodontal ligament is one of the structures lost in severe cases of the disease.

The study was part of the PhD research of Emmanuel Albuquerque de Souza at the University of São Paulo's Dental School (FO-USP) in Brazil and was conducted at the Forsyth Institute, an affiliate of the Harvard School of Dental Medicine in the United States, with a scholarship from FAPESP (São Paulo Research Foundation ).

Local inflammation is one of the most challenging aspects of the treatment of periodontal disease. "It destroys the tissues that maintain and secure the teeth in the mouth, and although treatment with stem cells stimulates regeneration of these structures in studies performed in vitro and in experimental animals, it doesn't work so well in humans because of inflammation," Souza said.

Forsyth and FO-USP have long studied the mechanisms that lead to a resolution of inflammation in the periodontium. One of the focuses for the partnership is what is called pro-resolving lipid mediators, such as maresin and resolvin. "These molecules come into play in the second stage of the inflammatory process, referred to nowadays as the resolution stage, but some people apparently don't produce enough of them, while in other cases their functions appear to be altered in some way," Souza said.

Stimulating the release of these mediators could be a way to improve the success rate of so-called regenerative therapy. "The study shows for the first time that these two mediators enhance stem cell regenerative capacity even in the presence of inflammation," said Marinella Holzhausen Caldeira, a professor in FO-USP's Department of Periodontics and Souza's thesis advisor in Brazil.

Pro-inflammatory versus pro-resolving environments

Based on previous research demonstrating the action of maresin and resolvin in periodontal regeneration, the group created two in vitro environments for stem cells, one representing inflamed tissue full of pro-inflammatory cytokines, and the other simulating the inflammation resolution stage.

"We found that pro-inflammation reduced stem cell activity, while the presence of maresin and resolvin increased their capacity to proliferate, migrate and rapidly acquire the functions of cells in the lost tissue," Souza said.

"When these stem cells are stimulated, they can acquire properties similar to those of periodontal cementoblasts, fibroblasts, and osteoblasts," Caldeira said.

The finding shows the importance of creating a favorable environment for stem cells to function properly. The next step is understanding how to use maresin and resolvin therapeutically. "We don't know how much we can alter the organism's capacity to synthesize these mediators," Souza said.

One possibility could be to use their precursor, omega-3, via supplementation. "Recent clinical studies have shown that supplementation can have a highly positive effect when combined with basic periodontal therapy, which involves removal of the biofilm that accumulates in the tissue," Caldeira said. The benefits are seen mainly in patients with diabetes or metabolic syndrome, which point to an altered inflammatory profile (read more at: agencia.fapesp.br/34357).

Another possibility could be to treat stem cells with maresin and resolvin before using them in regenerative therapy in order to make the treatment more effective.

The future of the fight against inflammation
Although the discovery comes from dentistry, it may pave the way to advances in the treatment of other conditions. "Explaining how these mediators act on the regeneration process means explaining how the organism recovers from an inflammatory disease," Souza said. This is resolution pharmacology, a new line of research that aims to revolutionize the current approach to anti-inflammatory medication.

Recent research has shown that inflammation occurs in two stages. The first involves the release of pro-inflammatory substances as part of the organism's defenses against attack. Next, enzymes are activated to produce a change in various cell phenotypes and the resolution stage begins.

For example, macrophages (one type of immune system cell) that produce many inflammatory cytokines, such as tumor necrosis factor, begin to secrete pro-resolving mediators that clear up the mess made by the inflammation. "The phagocytosis performed by macrophages is important to defend us against bacteria and other microorganisms, but leaves behind a kind of inflammatory refuse that has harmful effects on the organism," Souza said.

The changes driven by pro-resolving mediators lead macrophages and other immune cells to perform this cleansing process and secrete fewer toxins. Similar benefits also appear to come from stem cells, which restore what was lost to inflammation. This is a different view from the use of classic anti-inflammatory drugs to interrupt or block the inflammatory response. "In resolution pharmacology, you don't prescribe a drug to block inflammation. What you want is to stimulate the beneficial inflammatory stage, which is the resolution stage," Souza said.

The approach appears to offer advantages. "Currently we don't have specifically pro-resolving drugs, but this research will lead to the development of alternatives that will overlap with existing anti-inflammatory medications, which have various limitations and adverse side-effects," Caldeira said.

BOSTON - What does SARS-CoV-2, the virus that causes COVID-19, do once it enters a person's airways, and how does infection in lung cells affect patients' immune responses? New research led by investigators at Massachusetts General Hospital (MGH) and published in Nature Communications provides insights that could help improve treatment strategies for infected patients.

To analyze SARS-CoV-2 at the tissue level, the scientists examined autopsied material from 24 patients who succumbed to COVID-19. "We used a method called RNA in situ hybridization to visualize the actual SARS-CoV-2 virus in human lung specimens. This assay is now a clinical test being used at MGH to understand what tissues can be infected by the virus," explains co-author David T. Ting, MD, associate clinical director for Innovation at the Mass General Cancer Center and an assistant professor of Medicine at Harvard Medical School.

The analyses revealed two phases of infection in patients with severe COVID-19 pneumonia. The early phase is defined by high levels of virus in the lungs that trigger patients' cells to express genes involved with the interferon pathway, a critical part of the immune response. In the later phase, virus is no longer present, but the damage to the lungs is too severe for recovery.

"The interferon response to SARS-CoV-2 indicates that people's immune systems are able to attack SARS-CoV-2, but the response is variable between patients and even in different parts of the lung of the same patient, making a 'one drug fits all' therapy approach difficult," says Ting. Also, treatments that target viral replication, such as remdesivir, may only be effective in the early phase of infection.

The team also found that there is surprisingly very little viral replication in the lungs, which suggests that the virus is mostly replicating in the nasal passages and then dropping into the lungs, where it can cause pneumonia and other complications.

It will be important to conduct additional autopsy analyses to better understand the extent and timing of SARS-CoV-2 infection in the lungs and other tissues, which could lead to improved treatment strategies for patients with COVID-19.

High levels of cadmium, a chemical found in cigarettes and in contaminated vegetables, are associated with higher death rates in patients with influenza or pneumonia--and may increase the severity of COVID-19 and other respiratory viruses, according to a new study.

"Our study suggests the public in general, both smokers and nonsmokers, could benefit from reduced exposure to cadmium," said lead author Sung Kyun Park, associate professor of epidemiology and environmental health sciences at the University of Michigan School of Public Health.

Long-term exposure to cadmium, even at low levels, may undermine our defense system in the lungs, and people with high levels of the chemical may not be able to cope with influenza virus attacks, Park said.

The study by researchers at U-M, the University of Southern California and the University of Washington is published in the December issue of Environmental Health Perspectives.

"The associations we found need to be verified in other populations and also studied with respect to cadmium's potential impact on COVID-19 related morbidity and mortality," said senior author Howard Hu, professor and chair of USC's Department of Preventive Medicine and an occupational/environmental physician.

"Unfortunately, the human body finds it much more difficult to excrete cadmium than other toxic metals, and its presence in many nutritious foods means it is critical to continue reducing sources of environmental pollution that contribute to its presence in air, soil and water."

Early in the pandemic, as data was starting to come out of Wuhan, China, a large percentage of people dying from the coronavirus shared a few characteristics--they were male, smokers and older.

That prompted Finnish researcher Matti Sirén, a co-author of the study, to reach out to Park and Hu, who a decade ago had conducted a comprehensive study on the impact of cadmium on chronic diseases, including lung and cardiovascular diseases.

Interested in looking into the association between cadmium and COVID-19, but understanding that little data would be available to look at this link, the researchers instead focused on studying the potential association of cadmium to other viral infections: influenza and pneumonia.

The researchers utilized data from the U.S. National Health and Nutrition Examination Survey from 1988-1994 and 1999-2006. NHANES is conducted by the National Center for Health Statistics and provides nationally representative survey data on the health and nutritional status of the noninstitutionalized U.S. population.

Nearly 16,000 participants in the two separate cohorts were used for the analysis. Cadmium was measured in urine in the first survey and blood in the second. And because tobacco has more than 3,000 chemical components, researchers also looked at cadmium levels in nonsmokers.

After adjusting for age, sex, race/ethnicity, education, body mass index, serum cholesterol and hypertension, researchers found that patients with cadmium levels in the 80th percentile were 15% more likely to die of influenza or pneumonia compared to those in the 20th percentile.

Among those who never smoked, the difference was even greater with a 27% higher risk of mortality among those in the 80th percentile compared to the 20th percentile.

"We couldn't directly look at cadmium body burden among COVID-19 patients in the early pandemic," Park said. "Our motivation was to find a modifiable risk factor that can predispose people with COVID-19 infection to develop a severe complication and die of COVID-19.

"COVID-19 may not be a one-time event. Our findings suggest that the public can benefit from reduced cadmium exposure when the next pandemic occurs. This cannot be done suddenly and takes time through policy changes."

In the meantime, Park said smokers should stop smoking. And everyone should be aware of the major sources of cadmium in their diets: cereal, rice, animal organs such as the liver and kidneys, soybeans and some types of leafy vegetables.

There are many other sources of vitamins, he said. Cruciferous vegetables, such as cabbage and broccoli, contain high levels of antioxidants but relatively low levels of cadmium.

"This isn't a recommendation for a draconian change in lifestyle, since many of these foods are typical staples of a balanced, nutritious diet, and their overall contribution to cadmium burden is likely modest," Hu said. "Rather, the suggestion is to consider some shifts in choices.

"Meanwhile, epidemiologists need to focus on the issue we raised. Increased scrutiny is needed of sources of cadmium exposure and surveillance of cadmium levels in the general population, and policymakers need to work on continuing to reduce environmental cadmium pollution."

From a half-hidden corner in a crowded scene, a thief emerges to snatch a purse. Three days later, can you remember what he looks like?

That may depend upon how long after the incident you are asked about it and what you remember about the details surrounding the event, according to research published this August in the Journal of Cognitive Psychology.

The first author of the article, "Effects on memory of early testing and accuracy assessment for central and contextual content," is Jessica S. Wasserman; she and third author Crystal Casado were Binghamton University undergraduate students working with Distinguished Professor of Psychology Ralph Miller. Both have since graduated, along with doctoral student Cody W. Polack. The first author, Wasserman, is now pursuing a doctorate in clinical psychology at Yeshiva University.

The team also included Professor Mohamed El Haj at the Université de Nantes in France and Maïte Brunel, a French psychologist at the Université de Lille who trains the French police how to interrogate witnesses without biasing their accounts.

The researchers gathered data from an experiment conducted with Binghamton undergraduates. Participants were shown a video depicting a purse-snatching and then asked to recall details of the event in a series of forced-choice questions. One group of students was asked the questions immediately after watching the video and again 48 hours later; the second group was tested only after the 48-hour delay.

The researchers found that early testing not only resulted in more accurate memory than when initial testing was delayed two days, but also reduced forgetting over the two-day period. Memory about the context of the event -- the time and place -- also correlated positively with the central memory of the thief.

Because of this, they recommended that investigators interview witnesses as early as possible after the event to minimize subsequent forgetting, and ask questions about multiple aspects of the context surrounding the event in addition to questions about the perpetrator.

Eyewitness testimony certainly can be fallible, which is well known in memory research, Miller acknowledged. The paper explored ways to increase the accuracy of eyewitness testimony --with the understanding that you cannot ever completely eliminate the potential for error.

"All evidence, without exception, is potentially imperfect. Realistically, there's no such thing in a court of law as evidence beyond a shadow of a doubt. What we are concerned with is the degree of doubt," Miller said.

The testing effect

Memory is a complex process, whether you're finding your car keys or giving a statement to police as a witness to a crime.

The ability to retrieve information fluctuates in the first day after the event. But by the 48-hour mark, no further major fluctuations occur, which is why that time frame is often used in memory research, explained Miller, who has studied the workings of memory for 55 years. After that point, the relationship between different memories will decay at roughly an equal rate proportional to their strengths.

If you're quizzed about an event soon after it happens, you're more likely to remember details during later interviews, a phenomenon known as the "testing effect." The testing effect itself isn't new; in fact, Miller published research concerning the testing effect in rodents 40 years ago. This new research, however, is the first to directly link the testing effect to an eyewitness situation.

"If the first recall is accurate, it's going to contribute to the second recall being more accurate, which is one of the important points of the paper," Miller said.

During trials, juries often assess the potential accuracy of eyewitnesses by asking them known contextual details about the event, such as the place and time. Although a correlation between the contextual details and central information concerning the thief is often assumed, the connection hadn't previously been explored experimentally, Miller said.

In addition to providing data that support the connection between remembering the peripheral and central details of an event, the research also shows a higher correlation between remembering details about bystanders and the perpetrator, something that hadn't been previously explored in the literature, he said.

Individuals who are more attuned to other people -- those who are more apt to remember faces, for example -- may be more likely to retain personal details, Miller explained.

"The memory of all of the details was positively correlated with memory for the perpetrator, but memory of the other people who were present had the highest correlation with accurate recall of the perpetrator," he said.

Incineration of solid waste produces millions of tonnes of waste fly ash in Europe each year, that most commonly ends up in landfill. But this ash often contains significant amounts of precious metals, such as zinc. A unique method developed by researchers at Chalmers University of Technology, Sweden, can now help extract these precious metals, potentially leading to reductions in environmental pollution, landfill and transport.

During waste incineration, the released flue gases are purified and the small particles present are separated, leading to the formation of fly ash. This fly ash contains toxic substances, such as dioxins, and so is normally classified as hazardous waste and landfilled. But it also contains valuable metals, such as zinc, which are thereby lost.

But a new method from Chalmers University of Technology, tested at pilot scale and detailed over several years of research, involves treating this waste with an acid wash, also separated from the flue gases, to separate the zinc from the fly ash. The zinc can then be extracted, washed and processed into raw material.

"In our pilot study, we found that 70 percent of the zinc present in fly ash can be recycled. The zinc is not extracted as a pure metal, which would be a much more intensive process, but instead as a zinc-rich product, which can be sold to the metal industry and processed further in currently existing industry production lines," says Karin Karlfeldt Fedje, Associate Professor at Chalmers University of Technology, and researcher at the recycling and waste management company Renova AB.

Ash turned into useful material

In further refinement to the method, the researchers have been able to significantly reduce the level of toxicity.

"After extraction, we incinerate the residual ash again to break down the dioxins. Ninety percent of this is then turned into bottom ash, which can be used as a construction material, for example," explains Karin Karlfeldt Fedje.

Internationally, the prevalence of waste incineration is varied, but the need to handle large amounts of ash after the process is widespread. In Sweden, incineration of household waste in waste-to-energy plants is common, and results in around 250,000 tonnes of fly ash every year that could potentially be treated in this way. The rest of Europe accounts for around ten times that amount.

Although it is hard to estimate how many tonnes of zinc are currently lost through landfill in Sweden and beyond, the method developed by the Chalmers researchers can be of great interest to all waste management actors. It offers great potential for recovering these metals in a relatively simple way and could have a significant impact on the profitability of waste incineration, as well as its role in the circular economy.

"The technology for extracting zinc from fly ash could have several positive effects, such as reducing the need for mining virgin zinc raw material, lower levels of toxicity in the ash, and greatly reduced landfill contributions. It can be a vital contribution to society's efforts towards a more circular economy," says Sven Andersson, Adjunct Professor at Chalmers and R&D Manager at flue gas cleaning supplier Babcock & Wilcox Vølund AB.

Applied at full scale in Sweden

Dividing her time between Chalmers and Renova, Karin Karlfeldt Fedje has spent many years developing the methodology, in collaboration with several external actors. Together with

Sven Andersson, they have been able to design a full-scale process. Their research has led to Renova AB and B&W Vølund now building an ash washing facility with zinc recycling in Gothenburg Sweden, an investment that is estimated to save hundreds of thousands of euro every year for the municipally owned waste management company.

An international research team involving Professor Federico Rosei of the Institut national de la recherche scientifique (INRS) has demonstrated a novel process to modify the structure and properties of graphene, a one atom thick carbon. This chemical reaction, known as photocycloaddition, modifies the bonds between atoms using ultraviolet (UV) light. The results of the study were recently published in the prestigious journal Nature Chemistry.

Graphene has outstanding physical, optical and mechanical properties. For instance, it is commonly used in the manufacture of transparent touch screens, in aerospace, and in biomedicine. This material, however, has limited use in electronics.

"No other material has properties similar to graphene, yet unlike semiconductors used in electronics, it lacks a band gap. In electronics, this gap is a space in which there are no energy levels that can be occupied by electrons. Yet it is essential for interacting with light," explains Professor Federico Rosei of INRS's Énergie Matériaux Télécommunications Research Centre.

"The multidisciplinary group of researchers from Canada, China, Denmark, France and the United Kingdom succeeded in modifying graphene so as to create a band gap. Current research is rather fundamental but could have repercussions over the next few years in optoelectronics, such as in the fabrication of photodetectors or in the field of solar energy. These include the manufacture of high-performance photovoltaic cells for converting solar energy into electricity, or the field of nanoelectronics, for the extreme miniaturisation of devices," emphasizes Professor Rosei.

This breakthrough is complementary to the results published in Nature Materials, in May 2020, by an Italian-Canadian team of researchers under the supervision of Professor Rosei.

Professor Rosei's research has been recognized numerous times by national and international awards and distinctions. These include the recent Brimacombe Medal from the Minerals, Metals & Materials Society (TMS), the Royal Society of Chemistry, which identified him as one of the 5% most cited authors for its journals in 2019, and the Stanford list of the 2% most cited researchers in the world.