Culture

Today, phenols are used to produce medicines, paints, and inexpensive furniture made of chipboard or MDF panels and also to process food. Some of them are capable of imparting a pleasant smoky aroma to food, so they are often added to sausage or fish. But if we eat something that is high in phenols, it can have a deleterious effect on our health, so at factories they pay close attention to their concentrations in food. During tests, more often than not meat samples are dissolved in alkalis (in which phenols are very soluble), but the resulting emulsions require additional purification from the fats contained in sausage.

'Our method is based on application deep eutectic solvents - very promising compounds that have been studied extensively over the last fifteen years,' said Andrei Shishov, the project leader, who has a PhD in Chemistry and is an associate professor in the Department of Analytical Chemistry at St Petersburg University. 'Usually, such solvents formed from two substances, which are then used to extract a third. But we got to thinking about it and wondered if it wouldn't be a good idea to try deriving this substance not through a solvent but by means of the way it is formed. After all, phenols themselves produce such compounds when they bond with choline chloride - it's the commonly known vitamin B4.'

This innovative approach involves only a few steps. First of all, a meat sample is minced and then mixed with organic solvent. After that, a piece of paper with a layer of choline chloride crystals, on which phenol is excreted, is immersed in the solution. The composition on the surface of the paper is washed off with water, and the concentration of phenols in it is determined by using, for example, a chromatograph - a special device for analysing a mixture of substances.

The paper membrane is impregnated in a special substance, choline chloride, which is used to discharge phenols. The meat sample is put in the solvent, in which the membrane has been placed on a needle. Phenols are excreted on its surface. After that, the phenols are washed off the surface of the membrane with water, and the resulting solution is analysed with the use of a special device.

Best of all, as the chemists in Professor Bulatov's research team note, this technique is perfect for solid products, which are easy to grind up. Among its advantages are safety - after all, vitamin B4 is nontoxic - and speed - if all of the instruments are properly adjusted, an analysis takes no more than half an hour. What is more, this new approach makes it possible to determine whether a sausage has really been smoke-cured or liquid smoke has simply been added to it.

'Besides, using this method, it is also possible to identify polyphenol compounds in edible oils, for example olive oil, and this is exactly what we are looking at now,' said Mr Shishov. 'It is known that these are the compounds that account for the antioxidant activity of edible oils, and they are beneficial for our health.'

As social insects, ants are particularly dependent on optimizing their communication in order to ward off enemies and to recognize individuals from their own colony. They must also protect themselves against desiccation. Their bodies are covered with wax-like substances known as cuticular hydrocarbons (CHCs) that serve both purposes - communication and protection against desiccation. However, while recognition of other ants requires the CHC layer to be not too solid, making it easier for other ants to sense the chemical signals in the layer, desiccation protection requires it to be as solid as possible. To resolve this conflict between the needs of communication and waterproofing, this layer is composed of CHCs with special physical properties, as biologists have now discovered. "We were surprised to find that the layer does not melt at a specific temperature or a narrow temperature range, but rather has a huge melting range: It starts melting at around minus 45 degrees Celsius and is only fully liquid above 30 to 40 degrees Celsius," explained Dr. Florian Menzel of Johannes Gutenberg University Mainz (JGU). "We found that the layer is, in fact, composed of a mixture of liquid and solid components, similar to ice cubes in a glass of water or liquid honey containing sugar crystals."

Conflicting functions: communication versus waterproofing

The CHC layer covering the bodies of almost all insects like an external skin has already been studied in detail. For instance, scientists already know that CHCs form a mixture of several dozens to over a hundred different compounds and that each species of ant has its own distinctive hydrocarbon blend. The chemical composition of the hydrocarbons determines not only their information content, but it also influences how well the layer prevents desiccation. "In other words, the substances have to serve different purposes simultaneously, which can, of course, be a problem," said Menzel.

Along with chemist Dr. Svenja Morsbach of the Max Planck Institute for Polymer Research in Mainz and physicist Dr. Bérengère Abou of the Centre national de la recherche scientifique (CNRS) in Paris, Menzel has now studied the physical properties of this wax-like layer, in particular the melting ranges of the hydrocarbons and their flow characteristics. To date, neither has been an issue in research.

Viscosity similar to that of motor oil

Finding suitable methods for investigating such tiny quantities of material was particularly challenging. Based on a formula developed by Albert Einstein, Abou had developed a novel microrheological technique to measure viscosity in this case, which allows to measure liquid drops as tiny as 100 pikoliters. The viscosity of the CHC layer was found to be similar to that of motor oil. Although the investigated hydrocarbon mixtures were completely different from each other - the CHCs of eleven different ant species were included in the study -, the viscosity was very similar for all species. The research team attributes this similarity to the fact that the exchange of communication signals may require a specific degree of viscosity or fluidity.

The chemical composition of the wax layer alone does not predict its waterproofing ability

Scientists at the Max Planck Institute for Polymer Research employed differential scanning calorimetry (DSC) to determine the melting behavior of the hydrocarbons. "We were astonished by the results. To date, this aspect has been largely neglected, while numerous studies implicitly assumed that the CHC layer is completely solid at ambient temperatures," said Menzel. Over the entire melting range, between minus 45 degrees Celsius and plus 40 degrees Celsius, the hydrocarbons take the form of a blend of liquid and solid components. According to Menzel, this liquid-solid mixture is essential to allow the CHC layer to fulfill both purposes. "There might be a fundamental conflict between the two functions of waterproofing and communication, which makes the evolution of CHCs particularly intriguing," the biologist added. If this is the case, the melting behavior of the CHCs, which directly depends on their chemical composition, would be one of the most important functional characteristics of the waxy CHC layer. It determines how effectively the CHC layer inhibits desiccation at different temperatures, while at the same time influencing how signals are exchanged. This not only applies to ants but most likely also to nearly all other insects.

Menzel and his team now plan to investigate how the viscosity and melting behavior of hydrocarbons change when ants can acclimate to different temperatures over several weeks. Insects may rely on such acclimation strategies to survive temperature fluctuations that are associated with a higher risk of desiccation.

Hamilton, ON (February 26, 2020) - McMaster University researchers have identified an antibacterial compound made by cannabis plants that may serve as a lead for new drug development.

An interdisciplinary team of McMaster researchers found that the chemical compound, or cannabinoid, called cannabigerol (CBG) is not only antibacterial but also effective in mice against a resilient family of bacteria known as methicillin-resistant Staphylococcus aureus (MRSA).

The findings were published in the journal American Chemical Society Infectious Diseases.

"In this study, we investigated 18 commercially available cannabinoids and they all showed antibiotic activity, some much more than others," said study lead Eric Brown, professor of biochemistry and biomedical sciences at McMaster.

"The one we focused on was a non-psychoactive cannabinoid called CBG, as it had the most promising activity. We synthesized that cannabinoid in mass quantity which gave us sufficient compound to go deep into the research."

The research team found that CBG had antibacterial activity against drug-resistant MRSA. It prevented the ability of that bacteria to form biofilms, which are communities of microorganisms that attach to each other and to surfaces; and it destroyed preformed biofilms and cells resistant to antibiotics. CBG achieved this by targeting the cell membrane of the bacteria.

These findings in the laboratory were supported when mice with an MRSA infection were given CBG.

"CBG proved to be marvellous at tackling pathogenic bacteria," Brown said. "The findings suggest real therapeutic potential for cannabinoids as antibiotics."

One caveat noted by the research team is the toxicity of CBG on the host cells which makes the study's findings an important lead rather than a likely final product, Brown said.

"It opens a therapeutic window, but a narrow one, to develop this into a drug," he said. "The next steps are to try to make the compound better in that it is more specific to the bacteria and has a lower chance of toxicity."

The Brown lab has been studying the antibiotic potential of cannabis for the past two years since the legalization of marijuana in Canada.

"This research became top of mind for us, in part, because we are in Canada," Brown said. "There has been some stigma of investing in this kind of research, but there's increasing anecdotal evidence of the medicinal use of cannabis. The stigma seems to be waning."

Brown said the study was reliant on his collaborator, Jakob Magolan, a McMaster associate professor of biochemistry and biomedical sciences who specializes in drug development using organic synthetic chemistry.

"The labs of Jake and I are just steps away from each other and our teams are talking to each other all the time," Brown said. "This is just one of many exciting projects we're involved with that combine scientists with very different but complementary expertise."

As metropolises balloon with growth and sprawl widens the footprint of cities around the world, access to nature for people living in urban areas is becoming harder to find.

If you're lucky, a pocket park might be installed next to a new condominium complex on your block, or perhaps a green roof tops the building where you work downtown. But it's unusual to find places in a city that are relatively wild -- even though our evolutionary history suggests we need interactions with wild nature to thrive.

A new study led by the University of Washington has found that not all forms of nature are created equal when considering benefits to people's well-being. Experiencing wildness, specifically, is particularly important for physical and mental health, according to the study published Jan. 29 in the journal Frontiers in Sustainable Cities.

Past research has found health and wellness benefits of nature for humans, but this is the first study to show that wildness in urban areas is profoundly important for human well-being.

"It was clear from our results that different kinds of nature can have different effects on people," said lead author Elizabeth Lev, a graduate student in the UW School of Environmental and Forest Sciences. "The wilder areas in an urban park seem to be affording more benefits to people -- and their most meaningful interactions depended on those relatively wild features."

While these findings likely hold true in most major cities, the research team focused on Discovery Park in Seattle, the city's most expansive urban park, which encompasses about 500 acres. The park, less than a 20-minute drive from the downtown core, has faced development pressures common for parks in cities with burgeoning populations.

The park's advisory board asked the UW researchers to look at what elements were most important to people who visit, with the goal of gaining usable information for decision-makers.

"We looked at Discovery Park, but this is about the entire planet," said senior author Peter Kahn, a UW professor of environmental and forest sciences and psychology. "Everywhere, development is chipping away at wild areas. Humanity has caused so much destruction and there's no stopping it -- unless we stop. We're trying to show that if you're going to develop an area, you at least need to understand the human costs."

The research team surveyed several hundred park-goers, asking them to submit a written summary online of a meaningful interaction they had with nature in Discovery Park. The researchers then pored over these submissions, coding experiences into different categories. For example, one participant's experience of "We sat and listened to the waves at the beach for a while" was assigned the categories "sitting at beach" and "listening to waves."

Across the 320 participant submissions, a pattern of categories the researchers call a "nature language" began to emerge. After coding all of the submissions, half a dozen categories -- what the researchers call "interaction patterns" -- were noted most often as important to visitors. These include encountering wildlife, walking along the edge of water, gazing out at a view and following an established trail.

Additionally, the researchers looked at whether the park's relative wildness was important in each visitor's most meaningful experiences in the park. They defined "relatively wild" as including Discovery Park's varied and relatively unmanaged land, its high levels of biodiversity, its "big nature" like old growth trees, large open spaces, expansive vistas, and people's experience of the park's solitude and removal from civilization.

These wild features were important to people's experiences, in nearly every case. For example, "spotting bald eagle" references a relatively wild bird, and "watching birds perched on an old growth tree," denotes a wild habitat where that tree can thrive.

Naming each nature experience creates a usable language, which is important for people to be able to recognize and take part in the activities that are most fulfilling and meaningful to them. For example, the experience of walking along the edge of water might be fulfilling for a young professional on a weekend hike in the park. Back downtown during a workday, they can enjoy a more domestic form of this interaction by walking along a fountain or water feature on their lunch break.

"We're losing the language of interaction with nature and as we do, we also lose the cultural practice of these deep forms of interaction with nature, the wellsprings of human existence," Kahn said. "We're trying to generate a nature language that helps bring these human-nature interactions back into our daily lives. And for that to happen, we also need to protect nature so that we can interact with it."

The researchers hope this study -- and future ones conducted in other cities -- can be used as part of the decision-making process for development proposals in parks and urban natural areas. They compiled their analysis methods into a handbook that can be used to undertake similar studies in other cities around the world.

When it comes to encouraging manufacturers to reduce their carbon dioxide (CO2) emissions, a carrot might be more effective than a stick. That's the approach taken by a recent U.S. tax code rule that offers credits to companies that capture and then store or use CO2. The rule will likely spur innovations in carbon capture technology, according to an article in Chemical & Engineering News (C&EN), the weekly newsmagazine of the American Chemical Society. 

The rule, enacted in February 2018, expands a tax credit, called 45Q. Under the rule, industrial manufacturers can earn a tax credit of $50 per metric ton of CO2 captured and stored permanently in geologic formations, or $35 per metric ton of CO2 captured and used, such as for enhanced oil recovery (EOR). A previous version capped the credit at 75 million metric tons of captured CO2, and paid only $20 per metric ton of the captured gas. Companies with emission-intensive operations, such as those in the cement, steel and power industries, are busy modeling whether their facilities can take advantage of the credit, Senior Business Editor Melody Bomgardner writes. 

The corn ethanol industry, which produces as much as 40 million metric tons per year of CO2, already captures about 20% of the gas to sell to soda bottlers or for dry ice. The tax credit could spur investment in pipelines to transport CO2 from ethanol plants to use for EOR and other purposes. The cement maker LafargeHolcim has partnered with Svante, a provider of CO2 capture technology, to study whether the credit makes it profitable to capture and permanently store underground CO2 emissions from a cement plant in Colorado. And Net Power, with partner Toshiba Energy Systems & Solutions, have demonstrated a gas-fired power plant that uses captured CO2 to power a turbine before recycling or reuse. Because 45Q mandates that companies start constructing carbon-capture facilities within seven years, most companies benefiting from the rule will rely on mature carbon-capture technologies, but these projects will drive demand for next-generation technologies, experts say. 

The article, "45Q, the tax credit that's luring US companies to capture CO2," is freely available here.

Forget what you know about bile because that's about to change, thanks to a new discovery made by Michigan State University and published in the current issue of Nature.

Much of our knowledge about bile hasn't changed in many decades. It's produced in the liver, stored in our gall bladder and injected into our intestine when we eat, where it breaks down fats in our gut. In fact, the first bile acid was discovered in 1848, and the scientists who revealed the structure of bile acids in 1928 won the Nobel Prize. That's a long time ago.

"Since then, our understanding of the chemistry of bile production in the liver was that the cholesterol backbone of the bile acid structure is linked to the amino acids glycine or taurine to produce our primary bile acids," said Robert Quinn, assistant professor of biochemistry and molecular biology and Global Impact researcher, and lead author of the study. "It begs the question of how the new bile acids we've discovered have remained hidden during the last 170 years of bile acid chemical research."

These new bile acids are not produced by our enzymes; they're made by microbes in our gut. This discovery will change how medical textbooks address digestion, and it contributes to an ever-growing body of knowledge supporting the importance of the microbiome, the collective community of bacteria and other microorganisms living in our guts.

Quinn's team, comprised of scientists from MSU, the University of California San Diego and a number of collaborating institutions, showed that microbes in the gut, members of the microbiome, produce unique bile acids by conjugating the cholesterol backbone with myriad other amino acids.

This represents a fifth mechanism of bile acid metabolism by the microbiome that greatly expands our understanding of mammalian bile.

While much of the study was conducted in mice, these novel bile acids were also found in humans. And here's the kicker that will guide future research: They're particularly abundant in the guts of people suffering with gastrointestinal diseases, such as Crohn's disease and cystic fibrosis.

"These molecules can alter signaling pathways in the human gut that result in a reduction of overall bile acid production, representing a new mechanism where our gut bacteria can manipulate our own physiology," Quinn said.

While the disease connection is an intriguing line of research, this is merely one aspect being pursued by Quinn's lab.

"Clearly, our understanding of these compounds is in its infancy," Quinn said. "This exciting new discovery opens more questions than answers about these compounds and their role in our health."

Oncotarget Volume 11 Issue 8 features Figure 8, "MLN4924 treatment induces DNA damage by stabilizing CDT1 and accumulates the cells in S phase which are enhanced by MLN4924/cisplatin co-treatment," by Misra, et al.

Moreover, adding MLN4924 to the standard TNBC chemotherapeutic agent cisplatin increased the DNA damage level, further enhancing the sensitivity.

In vivo, MLN4924 reduced tumor growth in a NOD-SCID mouse xenograft model by inducing DNA damage which was further augmented with the MLN4924 and cisplatin cotreatment.

Taken together, we demonstrated the mechanism of TNBC sensitization by the MLN4924 and MLN4924/cisplatin treatments irrespective of BRCA1 status, provided a strong justification for using MLN4924 alone or in combination with cisplatin, and identified a genetic background in which this combination will be particularly effective.

Dr. Alo Ray from the Department of Pathology and the Comprehensive Cancer Center at the Ohio State University in Columbus Ohio said, "Triple-negative breast cancer (TNBC) comprises 15–20% of breast cancer."

"Triple-negative breast cancer (TNBC) comprises 15–20% of breast cancer."

- Dr. Alo Ray, Center for Radiological Research, Department of Pathology and the Comprehensive Cancer Center at the Ohio State University

However, whether MLN4924 sensitizes breast tumors in vivo, is cytotoxic to BRCA1-mutated TNBC, and sensitizes TNBC to standard TNBC chemotherapeutics have not been investigated.

Here, we evaluated the efficacy of MLN4924 as a therapeutic agent in BRCA1-wild type and -mutant cells and examined if MLN4924 in combination with cisplatin, a standard platinum-based TNBC chemotherapeutic, enhances cytotoxicity.

Our results demonstrated that TNBC cell lines show a higher sensitivity to MLN4924 compared to cell lines representing other breast cancer subtypes due to the overexpression of NAE1 in TNBC compared to non-TNBC subtypes.

MLN4924 treatment resulted in >4N DNA content due to the re-replication of DNA leading to the accumulation of DNA damage, apoptosis, and senescence.

In vivo, MLN4924 significantly inhibited the growth of a TNBC xenograft model by inducing DNA damage, and MLN4924/cisplatin combination further reduced tumor growth by enhancing DNA damage.

The Ray Research Team concluded in their Oncotarget Research Paper that Additionally, the presence of p53 mutation in TNBC cells may promote re-replication upon MLN4924 treatment since activation of p53 by ATM/ATR/Chk2 regulates the re-replication through the induction of p21 supporting that p53 status is prognostic of outcome and MLN4924 treatment response of TNBC. Collectively, our results established the molecular mechanism by which MLN4924 induces TNBC cell death and enhances cisplatin sensitivity, provided the rationale of combining MLN4924 with cisplatin in both BRCA1-wild type and mutant TNBCs, and identified a cancer genetic background where this combination will be more effective.

A new special issue of the journal The Gerontologist from The Gerontological Society of America explores how contemporary trends in immigration, migration, and refugee movement affect how people age and how societies care for aging people.

Under the issue title “Immigration and Aging,” the 16 included papers come from seven countries: Australia, Canada, Germany, the Netherlands, Switzerland, the U.K, and the U.S. Im/migrant groups studied come from across the globe and from within different communities.

“The papers … address the needs and perspectives of older adults who have experienced im/migration,” wrote Suzanne Meeks, PhD, FGSA, the editor-in-chief of The Gerontologist, in her opening editorial. “They illustrate the rich variety of communities in which im/migrants live and the cultural and social ties that support and protect the well-being of older im/migrants despite disruptions inherent in relocating across national borders.” Three U.S. studies focused on Chinese immigrants; two used data from a large sample of Chinese immigrants in Chicago, Illinois, while one studied Chinese immigrants in Hawaii, which has its own cultural distinctness from other U.S. states. Two others focused on im/migrants from Mexico living in California, and a multistate study of Korean-Americans, respectively.

Elsewhere, in the Netherlands, researchers worked with im/migrants from Turkey, Morocco, Surinam, the Antilles, and Indonesia. Authors from the U.K. and Australia studied South Asian im/migrants in their countries. South Asians were also part of a Canadian study, which also included Muslim participants from East and North Africa and the Middle East. The papers also included studies of European migrants from Italy, Spain, and Portugal to Switzerland, and, within Germany, historical “migrants” from East Germany to contemporary, unified Germany.

“Trends in migration, immigration, and refugee movement and resettlement are dramatically changing cultural, ethnic, and age dynamics across the globe,” Meeks stated.

She also highlighted common themes woven through the papers in the special issue.

“Strongest of these was the importance of social ties for promoting health and well-being, social ties that come from family and from living in cohesive neighborhoods or ethnically homogeneous communities,” Meeks said. “Filial obligation was a common value across many cultures of origin, and while this obligation may lead to dedicated family caregivers, it also creates barriers to seeking and receiving formalcare.”

She added that “lack of culturally accessible services, and language barriers were common impediments to receiving care. Discrimination arose as a barrier to care from the perspective of care recipients, and also from the perspective of care providers who also are im/migrants.”

Meeks also said the articles suggest that addressing cultural competence in care delivery, and respecting and bolstering community and family ties are important for supporting diverse im/migrant communities.

“As our global population ever moves and shifts, there is a need to move from seeing im/migration history as deficit or risk to recognizing ways in which cultural factors contribute to individual and community resilience,” she wrote.

CHAMPAIGN, Ill. -- With a new CRISPR gene-editing methodology, scientists from the University of Illinois at Urbana-Champaign inactivated one of the genes responsible for an inherited form of amyotrophic lateral sclerosis - a debilitating and fatal neurological disease for which there is no cure. The novel treatment slowed disease progression, improved muscle function and extended lifespan in mice with an aggressive form of ALS.

"ALS unfortunately has few treatment options. This is an important first step in showing that this new form of gene editing could be used to potentially treat the disease," said bioengineering professor Thomas Gaj, who co-led the study with bioengineering professor Pablo Perez-Pinera.

The method relied on an emerging gene-editing technology known as CRISPR base editors.

Traditional CRISPR gene-editing technologies cut both strands of a DNA molecule, which can introduce a variety of errors in the DNA sequence, limiting its efficiency and potentially leading to a number of unintended mutations in the genome. The Illinois group instead used base editing "to change one letter of the DNA sequence to another without cutting through both DNA strands," Perez-Pinera said.

"Base editors are too large to be delivered into cells with one of the most promising and successful gene therapy vectors, known as adeno-associated virus," Gaj said. However, in 2019, Perez-Pinera's group developed a method of splitting the base editor proteins into halves that can be delivered by two separate AAV particles. Once inside the cell, the halves reassemble into the full-length base editor protein.

By combining the power of AAV gene delivery and split-base editors, Gaj and Perez-Pinera targeted and permanently disabled a mutant SOD1 gene, which is responsible for roughly 20% of inherited forms of ALS. They published their results in the journal Molecular Therapy.

"Many ALS studies are focused on preventing or delaying the onset of the disease. However, in the real world, most patients are not diagnosed until symptoms are advanced," said graduate student Colin Lim. "Slowing progression, rather than preventing it, may have a greater impact on patients." Lim is the co-first author of the study along with graduate students Michael Gapinske and Alexandra Brooks.

The researchers first tested the SOD1 base editor in human cells to verify reassembly of the split CRISPR base editor and inactivation of the SOD1 gene. Then they injected AAV particles encoding the base editors into the spinal columns of mice carrying a mutant SOD1 gene that causes a particularly severe form of ALS that paralyzes the mice within a few months after birth.

The disease progressed more slowly in treated mice, which had improved motor function, greater muscle strength and less weight loss. The researchers observed an 85% increase in time between the onset of the late stage of the disease and the end stage, as well as increased overall survival.

"We were excited to find that many of the improvements happened well after the onset of the disease. This told us that we were slowing the progression of the disorder," Gapinske said.

The base editor introduces a stop signal near the start of the SOD1 gene, so it has the advantage of stopping the cell from making the malfunctioning protein no matter which genetic mutation a patient has. However, it potentially disrupts the healthy version of the gene, so the researchers are exploring ways to target the gene's mutant copy.

"Moving forward, we are thinking about how we can bring this and other gene-editing technologies to the clinic so that we can someday treat ALS in patients," Gaj said. "For that, we have to develop new strategies capable of targeting all of the cells involved in the disease. We also have to further evaluate the efficiency and safety of this approach in other clinically relevant models."

The split base editor approach has potential for treating other diseases with a genetic basis as well, Perez-Pinera said. Though ALS was the first demonstration of the tool, his group has studies underway applying it to Duchenne muscular dystrophy and spinal muscular atrophy.

The aggravating skin condition eczema is most commonly treated by suppressing the immune system, but not all patients get relief. Now, a drug strategy aimed at revving up the immune system and boosting a type of immune cell known as natural killer cells appears, at least in mice, to effectively treat eczema.

The innovative approach, from researchers at Washington University School of Medicine in St. Louis, may point to a potential treatment for the skin condition, as well as other health problems linked to it, including asthma.

The findings are published online Feb. 26 in the journal Science Translational Medicine.

Natural killer (NK) cells -- a type of immune cell -- also are being evaluated as a cancer therapy. These cells play a particular role in attacking cells the immune system recognizes as foreign, including some tumor cells. In the new study, the researchers were surprised to learn that natural killer cells also effectively treated eczema in mice.

"If you look at the skin of the mice we studied, their eczema resolves in a way we haven't seen before with other therapies," said principal investigator Brian S. Kim, MD, a dermatologist and an associate professor of medicine. "And so far, our mouse model of eczema has accurately predicted what we will see in patients."

At least 10% of the U.S. population has eczema, an itchy, splotchy rash that leaves many patients discouraged due to a lack of many effective treatments. Therapies for eczema include topical steroids, drugs called calcineurin inhibitors, and the monoclonal antibody drug dupilumab (Dupixent), all of which treat the rash by blocking part of the body's immune response.

"Eczema is a chronic disease, and using steroids day in and day out is not advisable because it can contribute to thinning of the skin, which can contribute to other side effects," Kim said. "Long-term use can lead to easy bruising and even stretch marks on the skin. We need more reliable treatments to bring relief, and we think boosting natural killer cells may be one way to do that."

Kim, who also is co-director of Washington University's Center for the Study of Itch & Sensory Disorders, said he has noticed over time that his patients tend to have very low levels of NK cells in their blood.

"We were perplexed as to why that might be, but the numbers were low enough, consistently enough, that eventually we started using them almost like a diagnostic tool," he explained. "If we had any doubt about whether a person had eczema, we'd take a blood sample and look at their NK cell levels."

With the study's first author, Madison Mack, PhD, a graduate student in immunology at the time of the study, Kim took that clinical observation to the laboratory and a mouse model of the skin disease. After removing the animals' ability to make NK cells, Mack noticed that markers of inflammation in the animals worsened. Later, when they used an investigational drug prototype to increase the number of NK cells in the animals, inflammation lessened, and the mice got better.

Kim said he believes that in addition to improving skin rash associated with eczema, boosting the numbers of NK cells could help restore immunity to viruses in eczema patients. People who have very low numbers of NK cells turn out to be more susceptible to the herpes virus, pox viruses and HPV viruses, among others.

Rather than revving up part of the immune system, the drug dupilumab, on the other hand, blocks part of the body's immune response. The drug was approved for clinical use in 2017, and is safe, very effective and has helped many eczema patients improve, Kim said. Patients typically receive injections of the drug twice a month. However, about 60% of those treated with the drug in clinical trials did not respond as well as their doctors would have liked. In addition, some patients see improvement on most of the body but experience flare-ups on the face. There also are side effects in some patients, such as conjunctivitis.

Kim is eager to see if the strategy of revving up part of the immune system might help eczema patients. Investigational drugs that increase NK cell populations are being tested as treatments for some types of cancer in clinical trials at Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine. Kim said those studies suggest the drugs selectively boost NK cells, so he is now working with researchers from Siteman to test them in a clinical trial targeting eczema.

"We have a patent pending for this strategy, and we're planning to move toward trials," he said. "And we won't limit our studies to eczema. This strategy could help patients who have asthma or food allergies, conditions that often appear along with eczema."

Seawater is more than just saltwater. The ocean is a veritable soup of chemicals.

Part of that broth comes from dissolved carbon compounds, which account for a significant store of global carbon, on par with the amount held in the atmosphere. Researchers are actively working to classify what forms carbon takes in the world's oceans, as well as the biological processes that recycle it in the ocean's water.

Some molecules, like proteins and sugars, readily break down, while others are more resistant to degradation. A new study, led by UC Santa Barbara postdoctoral researcher Shuting Liu, investigated some of these more recalcitrant compounds and the microbes that can digest them. The results, which appear in the journal Limnology and Oceanography, illuminate basic aspects of the ocean carbon cycle and may help scientists predict the role microbes play in its regulation.

Liu and Professor Craig Carlson, in the Department of Ecology, Evolution and Marine Biology, are part of a group conducting research at the Bermuda Atlantic Time-series Study site. The site is a long-term research project in the Sargasso Sea, itself a region of the Atlantic in the vicinity of Bermuda. Over the course of many years, the scientists noticed dissolved organic matter building up in surface water during the calmer summer months. Rougher conditions in the winter mixed these compounds into deeper water, a layer scientists call the mesopelagic zone -- or, the twilight zone, because spans the lowest depths that light can reach. Once that happened, some of the organic matter would break down, and the cycle would begin again. The team was eager to understand why.

To do so, Liu and her colleagues focused on carboxyl-rich alicyclic molecules, or CRAMs, a particularly tough and diverse array of organic compounds with similar chemical properties, some of which comprise the more tenacious organic molecules in the ocean.

One class of compounds that fits the CRAM description are lignins, the group of molecules that give wood its rigidity. In fact, Liu used lignin as one of four model CRAM-like compounds in her experiment.

The team's goal was simple. "We're trying to see what types of microbes are responding to these CRAM-like compounds in the mesopelagic," said Liu.

The scientists introduced their four model CRAM compounds into samples of seawater from the mesopelagic and observed the results. At various time intervals, they analyzed the concentrations of dissolved organic carbon and counted the total number of bacterial cells using a microscope. The group also used molecular probes that targeted six specific microbe lineages to determine how much each lineage was growing relative to total cell growth in the sample. This told them which of these groups were most active.

The researchers used these compounds in concentrations orders of magnitude larger than the microbes would ever see in nature. "We were taking an experimental enrichment approach," Carlson said. "If we give it to them at elevated concentrations, will they use it? And if they do use it, who's using it?"

They found that, despite the compounds' shared characteristics, their availability to the microbes differed between the various lineages. "Some of the compounds were very easily utilized," said Carlson, "while others were more resistant to degradation, like the lignin and humic acid."

The experiment also confirmed the team's hypothesis that microbes that are relatively more common in the mesopelagic, rather than the ocean's surface, were capable of breaking down and using these tough compounds. This finding had previously been implied from genomic studies by their co-authors and collaborators Stephen Giovannoni and Jimmy Saw at Oregon State University.

Liu and Carlson, among other researchers, hypothesize that the mesopelagic zone hosts a distinct community of microbes with the ability to take advantage of material untouched by the microbes living above. Surface bacteria must spend more energy sequestering nutrients like nitrogen and phosphorus, which are scarce in the upper ocean. By contrast, the photosynthetic plankton living in the sunlit surface provide easily digestible carbon. As a result, surface microbes likely use the most accessible forms of carbon instead of sinking energy into more resistant organic compounds.

Meanwhile, nitrogen and phosphorus are abundant deeper in the mesopelagic zone, according to the researchers. As a result, microbes living there may have the resources and energy to invest in breaking down and absorbing more recalcitrant forms of carbon, like CRAMs.

Right now, the relationship between the degradation of CRAMs and the presence of certain microbes in the mesopelagic zone is just a correlation, Liu explained. She hopes to establish a causal link by tracking the carbon from CRAM compounds as they degrade and seeing if it's taken up by the microbes she studies.

Liu and Carlson plan to use compounds and concentrations more similar to actual seawater in upcoming experiments. One of their colleagues is employing mass spectrometry to characterize dissolved organic compounds in seawater, including some CRAMs. Once more characteristics of these compounds are identified, Liu can use similar methods to extract organic components from the environment and conduct a similar experiment.

"Microbes are the organisms that are driving these big biogeochemical cycles," said Carlson. "There's so many of them, they grow so fast, and they turn over so quickly. They can transform the chemical distributions of entire ecosystems. Studying what controls the growth of the ocean's smallest organisms has big implications to how chemical cycles are governed in the ocean."

More than eight million to 14 million tonnes of unreported fish catches are traded illicitly every year, costing the legitimate market between $9 billion and $17 billion in trade each year, according to new UBC research.

In a paper published in Science Advances, researchers from the Fisheries Economics Research Unit and the Sea Around Us initiative, both based at UBC's Institute for the Oceans and Fisheries, as well as the Sea Around Us - Indian Ocean at the University of Western Australia, looked at catch losses for 143 countries and found that significant amounts of seafood are being illicitly taken out of the food supply system of many countries, impacting the nutritional food security and livelihoods of millions.

"The overall economic impact related to the diversion of fish from the legitimate trade system is costing us $26 billion to 50 billion globally," said Rashid Sumaila, lead author and professor in the Institute for the Oceans and Fisheries and the School of Public Policy and Global Affairs. "Further, the substantial economic effects of the illicit trade in marine fish catch is affecting countries in Asia, Africa and South America who can hardly afford this loss. Those three geographic regions combined account for around 85 per cent of total catch losses to illicit trade globally."

"Many species of fish are targeted by industrial fishing fleets including illegal, unreported and unregulated vessels," said co-author Daniel Pauly, professor and the Sea Around Us principal investigator. "Illicit trade in fish and seafood products contributes to the depletion of a region's fish stocks. The Sea Around Us research has shown that fish catches are already vastly underreported, and if the catches that enter illicit trade are not also accounted for, we are moving closer and closer to wholesale depletion of this resource."

The potential loss to the legitimate trade system of global marine fisheries catches due to likely diversion into the illicit trade network is equivalent to losing 12 million to 22 million mature cows in weight annually.

"Not only is this a huge amount of animal protein that may be traded illicitly, such catches are often processed aboard large foreign industrial transshipment vessels, and directly shipped overseas without unloading and processing in host countries, thereby depriving local economies of revenue, income, jobs, and economic impacts," Sumaila said.

Increased transparency, including whole-of-industry supply chain accountability are urgently needed. Ratifying and enforcing of various existing international agreements, addressing fish 'laundering' via transshipment operations, granting fishing access permission only to vessels that are insured by marine insurance companies with the ability to exclude blacklisted vessels through transparent due diligence, and stepping up collaborative enforcement activities across all on-the water activities between countries are some of the solutions that the researchers propose.

"Only through full accountability and public transparency can we ensure that fish resources are not only sustainably and legally caught and traded, but that the benefits of this economic activity accrue to the people and governments of each country where fisheries occur," said Dirk Zeller, professor and director of the Sea Around Us - Indian Ocean at the University of Western Australia and co-author of the study.

Doctors who use drugs that target antibiotic-resistant bacteria as a first-line defense against pneumonia should probably reconsider this approach, according to a new study of more than 88,000 veterans hospitalized with the disease. The study, conducted by University of Utah Health and VA Salt Lake City Health Care System researchers, found that pneumonia patients given these medications in the first few days after hospitalization fared no better than those receiving standard medical care for the condition.

"Sometimes in our eagerness to improve outcomes, particularly among critically ill patients, we, as doctors, may be overly broad in our initial treatments. This appears to be true with pneumonia, where we found no benefit associated with use of the so-called 'big gun' antibiotics as an initial treatment to cover resistant organisms, even among those patients who are at high risk for these types of infections." says Matthew Samore, M.D., the study's senior author, a U of U Health professor of medicine, and Director of the Informatics Decision Enhancement and Analytic Sciences Center at the VA Salt Lake City Health Care System.

The study, one of the largest ever to examine trends of antibiotic use in the treatment of pneumonia, appears in the JAMA Internal Medicine.

Pneumonia is the eighth leading cause of death in the United States, accounting for more than 1 million hospitalizations and about 50,000 deaths each year. It can be caused by viruses, fungi, and bacteria, including Methicillin-resistant Staphylococcus aureus (MRSA), which can cause a rare but hard-to-treat form of pneumonia.

Unfortunately, determining whether MRSA or other pathogens are responsible for any particular case of pneumonia is difficult. That's because testing sputum (mucus) samples for the cause of pneumonia is often inaccurate, and collecting lung tissue samples can be invasive and risky, especially in patients who are extremely ill.

So, doctors often have to rely on their best judgment to deduce what treatment might work until if and when definitive test results are available, says Barbara Jones, M.D., the study's lead author, a U of U Health assistant professor of internal medicine, and career development awardee of VA Health Research & Development Service.

To determine how this decision-making process affects patient care, Samore, Jones, and colleagues retrospectively examined the medical records of 88,605 pneumonia patients, ages 62 to 81, who were admitted to VA Medical Centers nationwide between 2008 and 2013. The researchers tracked whether these patients were initially treated with standard antibiotic therapy for pneumonia--such as cerftriaxone and azithromycin--or two types of anti-MRSA care:

standard therapy plus vancomycin (an antibiotic,)

vancomycin without standard therapy.

The researchers observed that as doctors became more aware of and concerned about MRSA infection in the lungs, they became more likely to use anti-MRSA therapies¬ as an initial treatment, despite the fact that MRSA only accounts for about 2% of pneumonia cases. In fact, use rose from about 20% of patients in 2008 to nearly half of them in 2013. As a result, many of the patients who were treated with anti-MRSA antibiotics probably didn't need them.

The researchers found no discernable benefit of anti-MRSA treatment in addition to standard treatment. In fact, anti-MRSA treatment was associated with a 40 % higher risk of dying within 30 days of discharge, perhaps due to the potentially severe side effects of vancomycin including increased incidence of kidney failure and secondary infections. However, further study is needed to fully determine the underlying causes of this increased risk, according to the researchers.

"Our study calls into question the strategy of broad empiric antibiotic coverage that has previously been promoted by pneumonia practice guidelines," Jones says. "We're not saying that it's never appropriate to use anti-MRSA therapy for treating pneumonia. But in the absence of better tests to identify MRSA as a potential pathogen causing the disease, using anti-MRSA therapies does not seem to offer any advantage over standard treatment therapy.

"Under these circumstances," she adds, "it may be safer for patients if physicians to stick to standard antibiotic treatments for a couple of days to see how patients are doing rather than leaping into anti-MRSA therapy right off the bat."

When it comes to the smallest of creatures, the hydrogen bonds that hold water molecules together to form "surface tension" lend enough strength to support their mass: think of insects that skip across the surface of water. But what happens to small creatures that dwell below the surface of the water?

UConn researchers have taken a close look, and in research published recently in The Proceedings of the Royal Society B, have documented how tiny tadpoles are able to access air above the water's surface, breathing without having to break through the surface tension.

Tadpoles often live in water with low oxygen levels where fewer predators lurk, but this also means the tadpoles need a way to get to air to breathe. Tadpoles have gills, but they don't usually provide enough oxygen for them to survive, so most tadpoles also have lungs and breathe air as a back-up. But during the earliest period of their lives, tadpoles are too small to break through the water's surface to breathe. Luckily for the tadpoles, they have a way to work around this problem, says ecology and evolutionary biology professor Kurt Schwenk.

Tadpoles will often charge upward toward the surface of the water, yet due to their small size and the surface tension of the water, they bounce back down. While watching this during an unrelated study on aquatic salamanders feeding on tadpoles, Schwenk noticed a bubble left behind after one tadpole's visit to the underside of the water's surface.

"Many researchers have observed tadpoles breathing at the surface before, but unless you look very closely and slow the action down, you can't see what is actually happening," says Schwenk.

Using high-speed macro-videography, Schwenk and graduate researcher Jackson Phillips captured hundreds of breathing events on film shooting at the super slow motion rate of 500-1000 frames per second. The tadpoles were seen to use a never-before-described breathing mechanism they call "bubble-sucking," a novel breathing mechanism for vertebrates captured with novel technology.

"This research would have been much more difficult to do before high-speed video cameras were developed, and that is probably why the behavior has not been described before," says Schwenk.

The researchers studied tadpoles from five species of frogs -- four of which can be found in Connecticut. What they found was that tadpoles of all species were able to inflate their lungs within a few days of hatching, despite being too small to access air.

Instead of breaching the water's surface, the tadpoles were seen to bubble-suck. To bubble-suck, the tadpoles first attach their mouths to the undersurface of the water. They then open their jaws wide and draw a bubble of air into the mouth. What happens next was visible through the skin of some of the tadpoles. The tadpoles empty their lungs into their mouths, where the air mixes with the fresh air of the newly sucked bubble. After the mouth closes, the air bubble is forced down into the lungs, but since the bubble is larger than their lung capacity, a portion of the air remains in the mouth, which is then expelled as a small bubble that floats to the surface. The entire process takes about three tenths of a second.

Bubble-sucking appears to be an adaptation the tadpoles use while they are still small. When they grow large enough and charge the water's surface, they are able to break the surface tension and "breach-breathe." The researchers observed bubble-sucking in other species, as well -- larval salamanders and even snails. They note that it is likely limited to organisms that can create the suction necessary, therefore arthropods, like insects, cannot bubble-suck.

"As a result of an accidental observation, my research has taken a turn--I never expected to work on these organisms," Schwenk says. "Before, I thought that tadpoles were uninteresting. But now I find them deeply fascinating."

Schwenk says this accidental discovery conveys an important point about research in general.

"These frog species are incredibly well-studied and very common," he says. "Yet, one can learn new things even about the most common animals, which is a good lesson for students, because when getting into research, one can be left with the sense that it has all been done. The fact is, it hasn't been--we just have to be observant and keep asking questions."

Cats who suffered burns and smoke inhalation in recent California wildfires also had a high incidence of heart problems, according to a new study from researchers at the University of California, Davis, Veterinary Medical Teaching Hospital. The study represents the first published research to come from the UC Davis School of Veterinary Medicine on feline victims of California wildfires and was recently published in the journal Scientific Reports.

Researchers studied 51 cats referred for treatment after the 2017 Tubbs Fire in Santa Rosa and the 2018 Camp Fire in Paradise. Echocardiograms, or heart ultrasounds, found the cats had significant cardiovascular effects, including a much higher incidence of heart muscle thickening and blood clot formation.

"What was most surprising to us was the vast number of cats that were affected and the severity of their condition," said lead author Catherine Gunther-Harrington, assistant professor of clinical cardiology at UC Davis VMTH.

The study found more than half of the cats had heart muscle thickening and close to 30 percent had blood clots or were found to be at high risk of developing blood clots.

If cats develop blood clots, they are also at high risk of sudden death. Six of the cats in the study died or were euthanized due to cardiac issues during the course of their care, but 82 percent survived and were discharged.

TRANSLATING RESEARCH TO HUMANS

People also experience cardiovascular changes after burn injuries. Gunther-Harrington said with humans, the more severe and extensive the burn, the higher the risk of cardiovascular changes. In the cats studied, the incidence of cardiac changes was higher than that reported in humans and occurred in cats with moderate and severe burns.

"Many of these cats had moderate burns but had really severe heart changes," said Gunther-Harrington.

Further research may help scientists understand if the severity of the problem is specific to cats or if this translates to people as well. Understanding the changes observed in cats could lead to a better understanding of the most effective treatment and prevention for both human and feline patients.

"We also know that these cats inhaled smoke in a very urban environment, exposing them to toxicants," said Gunther-Harrington. "These cats could be the canary in the coal mine, letting us know what might happen if more people are exposed to these types of wildfires."

FUTURE WITH FIRES

The research points to the need for veterinarians to screen for cardiovascular changes in cats as part of their treatment after a wildfire to help reduce cats' risk of death.

"Most of these cats were able to survive and recover, despite the severity of their condition," said Gunther-Harrington. "That gives us hope because we know there will likely be more cats in the future injured in wildfires. The more we learn, the better care we can provide for them."

Co-author Ronald Li, an assistant professor of emergency and critical care medicine, has continued to study the mechanism responsible for the generation of blood clots in these feline fire victims. As a result of this study, the Li laboratory hopes to document a pathway that points to the most effective drug therapy to treat and prevent blood clots in future feline fire victims.