Culture

"Fit for 55": under this heading, the EU Commission will specify the implementation of the European Green Deal on 14 July. This refers to the more ambitious climate policy announced, with 55 instead of 40 percent emission reduction by 2030 (relative to 1990), and net-zero emissions in 2050. Coordination between the 27 EU states is expected to be difficult since unanimity is usually required here for sweeping changes. An economic model study by the Berlin-based climate research institute MCC (Mercator Research Institute on Global Commons and Climate Change) and the Potsdam Institute for Climate Impact Research (PIK) examines how to achieve good results under such conditions. The study has just been published in the renowned Journal of Environmental Economics and Management.

In a model based on so-called game theory, the researchers mathematically depict the main features of such negotiations. This includes a coexistence of climate policy at the federal and state levels, the need for coordination between rich and poor as well as large and small countries and, as an anchor point, the assumption that there is zero idealism involved in the tug-of-war over climate protection. Focusing on maximising national welfare, governments veto any action they perceive as excessive at the federal level, generating more costs than benefits.

"We expand the economic theory on fiscal federalism to include climate policy and consensus-building," explains Christina Roolfs, researcher in the joint MCC-PIK Future Lab on Public Economics and Climate Finance and lead author of the study. "We were interested in how we could achieve as much climate protection as possible under such circumstances. It is about smart policy design that should set the right incentives, so that common plus national policy together render climate emissions as costly as appropriately, and accordingly cause them to decline."

The decisive factor is how the revenues from joint emissions pricing are being distributed within the states. Up to a certain point, rich countries accept the role of net donor, making transfers to poorer countries to support climate policy. Given their prosperity, the effect of climate damage on their economy is likely to be large, and countermeasures are therefore particularly worthwhile. Only when the transfers become too high will they switch from being the driver to putting on the brakes. The researchers model the behaviour of individual governments under different forms of revenue distribution, and for different decision processes: if the countries anticipate that they will benefit from the revenues generated from federal emissions pricing, they will agree to a higher common price. The key finding of the study is that the revenues from emissions pricing should be distributed between countries not according to population, and not according to current emissions, but according to historical emissions before the start of the pricing system. This principal will provide the greatest leeway for a consensual ambitious climate policy.

"This is of practical importance for the European Green Deal," emphasises Ottmar Edenhofer, Director of MCC and PIK and one of the study's co-authors." Money from the EU Emissions Trading System in the energy and industry sectors is already distributed primarily according to historical emissions. But the revenue base is currently riddled with holes because about half of the emission rights are allocated for free. There is a need for a harmonised and consistent design. This also applies to the intended expansion of pricing to the transport and heat sectors." According to Edenhofer, the study is relevant to international cooperation in general: "The theoretical analysis shows that large differences in size and wealth are obstacles. That is why, for example, linking carbon pricing systems might initially be a sensible thing to undertake between similarly strong partners, for example between the EU and the USA."

LA JOLLA, CA--Researchers at La Jolla Institute for Immunology (LJI) have shed light on a process in immune cells that may explain why some people develop cardiovascular diseases.

Their research, published recently in Genome Biology, shows the key role that TET enzymes play in keeping immune cells on a healthy track as they mature. The scientists found that other enzymes do play a role in this process--but TET enzymes do the heavy lifting.

"If we can figure out what's going on with these enzymes, that could be important for controlling cardiovascular disease," says Atsushi Onodera, Ph.D., a postdoctoral researcher at LJI and first author of the new Genome Biology study.

LJI Professor Anjana Rao, Ph.D., co-discovered TET enzymes while working at Harvard University alongside Mamta Tahiliani, Ph.D., and L. Aravind, Ph.D. Their work showed that this family of three enzymes alters how our genes are expressed.

TET enzymes control gene expression by triggering a process called demethylation, where a molecule called a methyl group is removed from where it sits in the genetic code. Demethylation is important because it alters how a cell "reads" DNA.

Over the last decade, Rao has shown the importance of TET activity in cancer development. Her work has revealed that TET enzymes are key to proper gene expression in immune cells--and they can actually protect against cancerous mutations.

For the new study, Rao and Onodera investigated how immune cell DNA can be altered by either TET enzymes (a process called passive demethylation) or by a DNA repair enzyme called TDG (active demethylation).

The researchers aimed to uncover which demethylation pathway has a bigger role in determining the gene expression--the very fate--of immune cells.

The researchers started with two immune cell models: CD4 "helper" T cells and monocytes. Both cell types must proliferate and mature into more specific cell types to help fight off pathogens. However, once monocytes are differentiated into macrophages and stimulated with a molecule called LPS, they stop proliferating. By taking a close look at these CD4 helper T cells and macrophages the researchers could better understand proliferating and non-proliferating models.

The proliferation process is very quick, making it a prime time to witness how demethylation occurs and how it affects gene expression. Onodera used CD4 helper T cells to analyze the demethylation process using a cutting-edge computational analysis program developed for this study. This tool gives scientists an unprecedented look at which regions of DNA within a cell are methylated.

"We found that in immune cells, most demethylation happens through the passive pathway," explains Onodera.

Using a new technique called pyridine borane sequencing, the researchers showed that "active" demethylation--through TDG--is working in immune cells. Onodera says TDG's role is minor: it does the job of removing two molecules generated by TET enzyme activity.

This discovery is important because TET mutations can be life-threatening. Previous studies have shown that mutations in the TET2 enzyme disable (or interfere with) some of the normal restraints on healthy monocytes. The monocytes go rogue and mature into inflammatory macrophages. People bearing TET2 mutations in macrophages have a 40 percent increase in their risk of developing cardiovascular disease.

A deeper understanding of how TET enzymes work could help researchers know where to intervene and help patients with this kind of mutation.

Onodera's new analysis program for identifying changes in DNA modification may also prove useful for understanding how TET mutations in immune cells can lead to blood cancers. He explains that researchers could potentially use the program to identify patients who may have different treatment outcomes based on where their DNA has been demethylated.

"Hopefully we can apply this technique to disease diagnoses," says Onodera.

In fact, Onodera says the new sequencing and analysis program from this study can be applied to many immune cell types and many disease models.

"At this point, we can make significant progress in understanding the molecular mechanisms behind DNA demethylation," Onodera says.

A study from UCLA neurologists challenges the idea that the brain recruits existing neurons to take over for those that are lost from stroke. It shows that in mice, undamaged neurons do not change their function after a stroke to compensate for damaged ones.

A stroke occurs when the blood supply to a certain part of the brain is interrupted, such as by a blood clot. Brain cells in that area become damaged and can no longer function.

A person who is having a stroke may temporarily lose the ability to speak, walk, or move their arms. Few patients recover fully and most are left with some disability, but the majority exhibit some degree of spontaneous recovery during the first few weeks after the stroke.

Doctors and scientists don't fully understand how this happens, because the brain does not grow new cells to replace the ones damaged by the stroke. Neurologists have generally assumed that the brain instead recruits existing neurons to take over for those that are lost.

Now, new results from neurologists William Zeiger and Carlos Portera-Cailliau from the David Geffen School of Medicine at UCLA challenge that idea. In their paper, published June 25 in the journal Nature Communications, they show that in mice, undamaged neurons do not change their function after a stroke to compensate for damaged ones.

Neurologists have been "mapping" the brain since the mid-1800s, when the French physician Paul Broca realized that patients who sustained damage to a certain part of the frontal lobe lost the ability to speak. Over the years, scientists have created increasingly detailed maps of which brain regions control various functions. Still, the resolution of the map has been limited by the precision of the tools available to study the living brain.

Studies in animals and humans that recorded activity across different brain regions have found that activity patterns change after a stroke, suggesting that the damaged brain can "re-map" functions from one area to another. In the last few years, innovative new tools have enabled researchers to start looking at individual neuron activation in real-time. By using a technique called two-photon fluorescence microscopy that causes neurons to light up when they are activated, researchers can observe which neurons in the animal brain are called upon during certain activities and determine if neurons that survived a stroke can assume the function of those that were lost.

"We thought, now that we have this tool where we can record the activity of neurons in the brain, we could directly test this question," says Zeiger. By learning the functions of individual neurons, then causing a targeted stroke, the researchers could use the new technique to observe how the neighboring neurons responded.

Mice gather information about their environment primarily through their whiskers, and each whisker transmits sensory signals to a specific group of neurons. By destroying the neurons coded to a specific whisker, the researchers could look at whether neurons for a different whisker took over for their lost neighbors.

Think of a departmental office, says Portera-Cailliau. "Imagine that several admin staff in human resources for the Department of Neurology suddenly quit their jobs one day. Instantly, the department would suffer their absence, but would try to make up for it." The department might do this by asking HR employees from other departments to do some of the missing employees' work on top of their own.

That's what the re-mapping hypothesis predicts would happen in the brain. "If the hypothesis were true, we would see cells that survived the stroke start to respond to that whisker that had the stroke," Zeiger says. "What we found was that that didn't happen."

Adjacent to the main column of neurons that respond to a given whisker are neurons called "surround-responsive" cells. These are located in the column for one whisker, but they react to the stimulation of a neighboring whisker. Using the office analogy, these neurons would be like employees that work on HR but happen to have their desks in a different physical office.

Logically, then, the team thought that the surround-responsive neurons would be good candidates to take over when the primary responding neurons were destroyed by the stroke. "If the HR office suddenly shut down, you might think more people in these other offices would start doing human resource jobs," Portera-Cailliau says. Yet not only did these other neurons fail to step up, the activity of the surround-responsive neurons themselves decreased after the stroke.

"That was pretty strong evidence against this remapping hypothesis," Zeiger says. "It did not seem like there was bulk recruitment to take over the function which had been lost to stroke."

More studies will be needed to gain a full understanding of what happens in the human brain after a stroke, including why spontaneous recovery happens. Zeiger says that future studies could also explore various ways to induce the surviving cells to compensate for the lost neurons.

"I think it gives the field more of a direction," Zeiger says. "Rather than assuming the brain can remap on its own, now we know that to achieve full recovery, we're going to need a way to get cells to do things they are not already doing."

A new study by UC Davis researchers confirms the low likelihood that SARS-CoV-2 contamination on hospital surfaces is infectious. The study, published June 24 in PLOS ONE, is the original report on recovering near-complete SARS-CoV-2 genome sequences directly from surface swabs.

"Our team was the first to demonstrate that SARS-CoV-2 virus sequences could be identified from environmental swabs collected from hospital surfaces," said Angela Haczku, a respiratory immunologist and senior author on the study.

Changing cleaning and ICU protocols linked to lower SARS-CoV-2 contamination

In April 2020, a COVID-19 outbreak among hospital staff led an interdisciplinary team of UC Davis researchers to investigate if there was virus contamination of frequently used surfaces in patient serving ICU and staff meeting areas at the UC Davis Medical Center. At that time the role of fomites (surfaces) in spreading the disease was highly debated. They collected multiple samples during the first (April 2020) and the second (August 2020) waves of COVID-19 from surfaces and HVAC filters in the hospital.

The researchers analyzed the surface swabs for SARS-CoV-2 RNA and infectivity and assessed the suitability of the RNA for sequencing.

Despite a significant increase in the number of hospital patients with COVID-19 during the second surge, the team found that only 2% of swabs tested positive in August, compared to 11% of samples collected in April.

"The reduction in the virus contamination was likely due to improved ICU patient management and cleaning protocols," Haczku said. Haczku is a professor of medicine, director at the UC Davis Lung Center and associate dean for translational research at the UC Davis School of Medicine.

Genome sequence of coronavirus found on surfaces

The study demonstrated that by genome sequencing, SARS-CoV-2 could be detected even from samples that otherwise tested negative (undetectable) by commonly used PCR tests. The results also confirmed that the SARS-CoV-2 RNA picked up from a surface, although containing near- intact genomic sequence, was not infectious. This finding supports the hypothesis that contaminated surfaces may not be a major way for spreading COVID-19 disease.

"For the first time, to our knowledge, we were able to determine the viral genome sequence from surface swab samples obtained in a hospital environment," said David Coil, project scientist at the UC Davis Genome Center and the first author on the study. "We found SARS-CoV-2 in samples that were tested negative by RT-PCR, suggesting that the sequencing technology is superior for virus detection in environmental samples."

According to Coil, the genome sequencing performed on the hospital surface swab samples is very important. By getting accurate viral genomic sequences, the researchers could track the source and figure out how an infection moves.

"Our data indicated that the sequences determined for the viral RNA from surfaces were identical to the ones derived from the patients hospitalized in the ICU at the time of sample collection. The ability to identify viral genome sequences from environmental samples may have high public health significance in outbreak surveillance and monitoring the spread of new viral variants," Haczku said.

BOSTON - At the recent 2021 Annual Scientific Sessions of the American Diabetes Association, researchers from Massachusetts General Hospital (MGH) presented positive updates on their trials of the bacillus Calmette-Guérin (BCG) vaccine to safely and significantly lower blood sugars.

In type 1 diabetes, an autoimmune disease which currently has no cure, T cells attack the pancreas and destroy its ability to create insulin, a hormone vital in allowing glucose to enter cells to produce energy. In prior work, Denise Faustman, MD, PhD, director of the MGH Immunobiology Laboratory, and colleagues have found that BCG boosts a substance called TNF, which eliminates the harmful T cells and aids development of beneficial ones called regulatory T cells, or Tregs.

Key findings include new understanding in how response to BCG vaccination differs depending on a patient's age of onset and additional support for the role of BCG vaccination to alter glucose transport and change Tregs. Currently 143 type 1 diabetics have received at least two doses of BCG, including 25 patients enrolled in a recently launched trial of adults who had pediatric onset. Pending FDA approval, MGH aims to launch a multi-center pediatric trial later this year.

"More data from randomized double-blinded clinical trials will be reported as we move towards additional readout of the Phase II trial," says Faustman, principal investigator of BCG clinical trials at MGH. "We have continued evidence of BCG's ability to reset and restore the immune system."

In 2018 MGH published results of the follow-up of Phase I trial of BCG-treated long-term diabetic participants, showing lasting clinically and statistically significant drops in HbA1c values that persisted with eight years of follow-up. The new data presented at the ADA include:

Type 1 diabetics with age of onset younger than 21 years have a faster response time and greater change in HbA1c than adult onset type 1 diabetics.

Over a period of three years BCG returns gene expression in Tregs in type 1 diabetics to a pattern consistent with non-type 1 control subjects.

The HbA1c response at two years in juvenile onset subjects is consistent with the three-year response seen in the Phase 1 study.

"BCG is an old vaccine, but it seems to be presenting new gifts," says Nigel Curtis, MD, PhD, of the Murdoch Children's Research Institute in Melbourne, Australia. He directs global clinical trials on the beneficial and off-targets effects of the BCG vaccine but was not involved in the current study. "This new data from MGH adds the growing understanding of how BCG changes the way the body responds to autoimmune and infectious disease."

After suffering a stroke, patients often are unable to use the arm on their affected side. Sometimes, they end up holding it close to their body, with the elbow flexed.

In a new study, Northwestern University and Shirley Ryan AbilityLab researchers have discovered that, in an attempt to adapt to this impairment, muscles actually lose sarcomeres -- their smallest, most basic building blocks.

Stacked end to end (in series) and side to side (in parallel), sarcomeres make up the length and width of muscle fibers. By imaging biceps muscles with three noninvasive methods, the researchers found that stroke patients had fewer sarcomeres along the length of the muscle fiber, resulting in a shorter overall muscle structure.

The research was published today (June 25) in the Proceedings of the National Academy of Arts and Sciences.

This finding is consistent with the common patient experience of abnormally tight, stiff muscles that resist stretching, and it suggests that changes in the muscle potentially amplify existing issues caused by stroke, which is a brain injury. The team hopes this discovery can help improve rehabilitation techniques to rebuild sarcomeres, ultimately helping to ease muscle tightening and shortening.

"This is the most direct evidence yet that chronic impairments, which place a muscle in a shortened position, are associated with the loss of serial sarcomeres in humans," said Wendy Murray, the study's senior author. "Understanding how muscles adapt following impairments is critical to designing more effective clinical interventions to mitigate such adaptations and to improve function following motor impairments."

Murray is a professor of biomedical engineering at Northwestern's McCormick School of Engineering, a professor of physical medicine and rehabilitation at the Northwestern University Feinberg School of Medicine and research scientist at the Shirley Ryan AbilityLab. The research was completed in collaboration with Julius Dewald, professor of physical therapy and human movement sciences and of physical medicine and rehabilitation at Feinberg, professor of biomedical engineering at McCormick, and research scientist at Shirley Ryan AbilityLab.

First demonstration in humans

Measuring just 1.5 to 4.0 microns in length, sarcomeres comprise two main proteins: actin and myosin. When these proteins work together, they enable a muscle to contract and produce force. Although previous animal studies have found that muscles lose serial sarcomeres after a limb is immobilized in a cast, the phenomenon had never before been demonstrated in humans. In the animal studies, muscles that were shorter because they lost serial sarcomeres also became stiffer.

"There is a classic relationship between force and length," said Amy Adkins, a Ph.D. student in Murray's laboratory and the study's first author. "Given that the whole muscle is composed of these building blocks, losing some of them affects how much force the muscle can generate."

To conduct the study in humans, the researchers combined three non-invasive medical imaging techniques: MRI to measure muscle volume, ultrasound to measure bundles of muscle fibers and two-photon microendoscopy to measure the microscopic sarcomeres.

Imaging opens new possibilities

Combining these technologies at Northwestern and Shirley Ryan AbilityLab, the researchers imaged biceps from seven stroke patients and four healthy participants. Because stroke patients are more affected on one side of their body, the researchers compared imaging from the patients' affected side to their unaffected side as well as to images from the healthy participants.

The researchers found that the stroke patients' affected biceps had less volume, shorter muscle fibers and comparable sarcomere lengths. After combining data across scales, they found that affected biceps had fewer sarcomeres in series compared to the unaffected biceps. The differences between stroke patients' arms were greater than in in healthy participants' arms, indicating that the differences were associated with stroke.

By combining medical imaging to better view muscle structure, the study also establishes that it is possible to study muscle adaptations in sarcomere number in humans. Before two-photon microendoscopy, human studies were limited either to examining dissected tissues in anatomy labs, which give imperfect insight into how muscles adapt to injury and impairment, measuring sarcomere lengths during surgery or from a muscle biopsy, which restricts who can participate in the study.

"In almost every facet of our world, there is an important relationship between how something is put together (its structure) and how it works (its function)," the researchers said. "Part of the reason medical imaging is such a valuable resource and clinical tool is that this is also true for the human body, and imaging gives us an opportunity to measure structure."

Three years ago, Arthur Ashkin won the Nobel Prize for inventing optical tweezers, which use light in the form of a high-powered laser beam to capture and manipulate particles. Despite being created decades ago, optical tweezers still lead to major breakthroughs and are widely used today to study biological systems.

However, optical tweezers do have flaws. The prolonged interaction with the laser beam can alter molecules and particles or damage them with excessive heat.

Researchers at The University of Texas at Austin have created a new version of optical tweezer technology that fixes this problem, a development that could open the already highly regarded tools to new types of research and simplify processes for using them today.

The breakthrough that avoids this problem of overheating comes out of a combination of two concepts: the use of a substrate composed of materials that are cooled when a light is shined on them (in this case, a laser); and a concept called thermophoresis, a phenomenon in which mobile particles will commonly gravitate toward a cooler environment.

The cooler materials attract particles, making them easier to isolate, while also protecting them from overheating. By solving the heat problem, optical tweezers could become more widely used to study biomolecules, DNA, diseases and more.

"Optical tweezers have many advantages, but they are limited because whenever the light captures objects, they heat up," said Yuebing Zheng, the corresponding author of a new paper published in Science Advances and an associate professor in the Walker Department of Mechanical Engineering. "Our tool addresses this critical challenge; instead of heating the trapped objects, we have them controlled at a lower temperature."

Optical tweezers do the same thing as regular tweezers -- pick up small objects and manipulate them. However, optical tweezers work at a much smaller scale and use light to capture and move objects.

Analyzing DNA is a common use of optical tweezers. But doing so requires attaching nano-sized glass beads to the particles. Then to move the particles, the laser is shined on the beads, not the particles themselves, because the DNA would be damaged by the heating effect of the light.

"When you are forced to add more steps to the process, you increase uncertainty because now you have introduced something else into the biological system that may impact it," Zheng said.

This new and improved version of optical tweezers eliminates these extra steps.

The team's next steps include developing autonomous control systems, making them easier for people without specialized training to use and extending the tweezers' capabilities to handle biological fluids such as blood and urine. And they are working to commercialize the discovery.

Zheng and his team have much variety in their research, but it all centers on light and how it interacts with materials. Because of this focus on light, he has closely followed, and used, optical tweezers in his research. The researchers were familiar with thermophoresis and hoped they could trigger it with cooler materials, which would actually draw particles to the laser to simplify analysis.

Tsukuba, Japan - The COVID-19 pandemic has changed the way people eat, work, shop and go to school. Now, researchers from Japan have found surprising differences in the way people use healthcare services--including house calls from doctors.

In a study published this month in BMC Emergency Medicine, researchers from the University of Tsukuba have revealed that patterns in illness type and severity did change during the pandemic--with unexpected trends that may tell us about how people use health care services when personal contact carries inherent risk.

In Tokyo, private after-hours house call services (AHHC) provide in-home medical service outside of regular hospital hours. But as the COVID-19 pandemic developed in Japan, filling hospital rooms and straining healthcare services, this service began to take on a new dimension. Would people with cold and flu-like symptoms use AHHC services more than before?

The largest AHHC service in Japan (Fast Doctor Ltd.) had large amounts of anonymized scientific data available to compare in a retrospective cohort study. By comparing data from before the pandemic (December 2018 through April 2019) against that from the pandemic exposure period (December 2019 through April 2020), the University of Tsukuba researchers were able to draw statistically significant conclusions about the changes in numbers and types of cases and calls. While the proportion of patients with moderate or severe illness increased during the pandemic, the proportion of calls owing to cold and fever symptoms went down.

"We initially thought that people with cold and fever symptoms might be hesitant to visit hospitals during the pandemic, driving up the number of calls to house call services," says lead author of the study Ryota Inokuchi. "This would also serve to alleviate some of the burden on emergency departments."

Of the more than 16,000 patients who contacted the AHHC service in the two study periods, 82.6% in the pre-pandemic control group had fever or cold symptoms, versus 74.2% in the pandemic period. However, the proportion of patients with symptoms categorized as "severe" increased from 0.2% to 0.9% in the pandemic, while the proportion of patients with "moderate" symptoms nearly doubled in the pandemic, from 28.7% to 56.7%.

"The decrease in calls owing to fever and colds was clear and significant, possibly because of lower seasonal flu activity due to school closings and lockdowns," explains Professor Nanako Tamiya, senior author. "But an important question is to what degree reluctancy to use medical services during the pandemic played a part, and whether this contributed to the observed increase in case severity."

Early detection is critical for treating COVID-19, and many other diseases as well. When this study was conducted, however, Tokyo's hospitals were dangerously strained, operating at 80% capacity. Given the risk of delays in seeking medical care, AHHC services may play a critical role in helping national healthcare systems handle these emergencies if health authorities and governments can develop policies and encourage social behaviors promoting their use.

The contemporary materials industry raises the problem of creating a microscopic theory that allows to describe the observed physicochemical properties of a wide class of substances which are in demand in modern industry, medicine, and agriculture. A general and consistent theory will help to obtain reliable information from experimental data on the structure of matter, existing interactions and dynamic processes occurring in it, which can help in the synthesis and quality control of prospective materials.

The study of the molecular structure of a substance and its intermolecular interactions is one of the most important and interesting tasks facing modern science. Of particular interest is the study of molecular interactions in media with a disordered structure. Molecular interactions in disordered materials are studied by a variety of methods, but the most universal is the method of dielectric spectroscopy, which makes it possible to study processes occurring in perioids to 10^(-9) sec.

In disordered media, the main peak of the dielectric loss spectrum, as a rule, has a non-Debye shape: at low and high frequencies, it is determined by fractional power-law frequency dependences. Power exponents characterize the shape of the peak and are associated with the parameters of microscopic structural and dynamic processes in the studied environment. The non-Debye dielectric loss spectra can be divided into two groups according to the shape of the main peak: typical and atypical. Typical spectra, for which the high-frequency power-law exponent is higher than the low-frequency one, are well described by the so-called Havriliak-Negami function, account for 70% of the total number of non-Debye spectra and are well studied theoretically. Atypical spectra, for which, on the contrary, the low-frequency power exponent is higher than the high-frequency one, cannot be described by this function and have been studied much less. An atypical dielectric response is usually observed in disordered media with limited geometry.

This article, co-authored by Airat Khamzin (Kazan Federal University) and Alexander Nikitin (Kazan State Power Engineering Unviersity), proposes a new dielectric relaxation model that takes into account the spatial and energy disorder in the system. Spatial disorder is modeled using a space-dependent diffusion coefficient for charge carriers. Energy disorder is determined by widely distributed energy traps (localized states). The model leads to a new expression for the frequency dependence of the complex dielectric constant. The advantage of the new model is the possibility of obtaining relationships between the parameters of the dielectric function and the parameters of the microscopic structure of the medium under study.

The developed model is of great practical importance, since the application of the dielectric function obtained within the framework of the model to describe atypical peaks of dielectric losses will allow experimenters to extract the maximum of useful information about the structural and dynamic processes in the medium under study. In particular, the article shows that one of the indicators of the peak shape is directly related to the porosity of the medium. For porous glass, the porosity was estimated, which coincided with the value found in it by direct measurement.

The theoretical approach proposed in this article for describing dielectric behavior in media with a disordered structure is planned to be further developed to describe complex spectra, which, depending on temperature, exhibit features of atypical or typical relaxation behavior.

This study was made available online in March 2021 ahead of final publication in issue on July 1, 2021

A recent study finds states that exhibit higher levels of systemic racism also have pronounced racial disparities regarding access to health care. In short, the more racist a state was, the better access white people had - and the worse access Black people had.

"This study highlights the extent to which health care inequities are intertwined with other social inequities, such as employment and education," says Vanessa Volpe, corresponding author of the study and an assistant professor of psychology at North Carolina State University. "This helps explain why health inequities are so intractable. Tackling health care inequities will require us to address broader social systems that significantly benefit white people - and that makes them difficult to change."

Previous research has examined how people's individual experiences with racism affect the quality of their health care. There is also research that examines relationships between structural racism and health outcomes. The recent study from Volpe and her collaborators looks at structural racism at the state level, people's individual experiences with racism, the extent to which those things affected the ability of Black people to access health care, and the quality of that health care. The researchers also examined the ability of white people to access health care and the quality of their health care.

For their study, the researchers drew on the Association of American Medical Colleges' Consumer Survey of Health Care Access for the years 2014 to 2019. The survey, of adults who needed care within the previous year, included measures of self-reported health care access, quality, and provider racial discrimination. The survey included 2,110 Black adults and 18,920 white adults. The researchers also used publicly available state-level data from the Census Bureau and the U.S. Department of Justice to create an index of state-level racial disparities that serve as a proxy for structural racism. The researchers used the index to determine racism scores for all 50 states and the District of Columbia.

The researchers found that the higher the level of racism in a given state, the less access Black people in that state had to health care. There was no statistically significant relationship between a state's racism index score and quality of health care. However, Black people who reported experiencing racism with their health care providers also reported lower quality of care.

Meanwhile, the higher the level of racism in a given state, the more access white people had to health care. In addition, the worse the state's racism score, the higher the quality of care white people reported receiving.

"These state-level inequities are symptoms of racism baked into laws, policies and practices that ensure there is not a level playing field," Volpe says. "It underscores the need to address inequities in a meaningful, structural way, not just assume that racism is solely an interpersonal phenomenon. And it's important to use data-driven approaches like the ones we used here, so laws or regulations can be developed by policymakers to more effectively even the playing field."

With age, a diet lacking in the essential amino acid tryptophan -- which has a key role in our mood, energy level and immune response -- makes the gut microbiome less protective and increases inflammation body-wide, investigators report.

In a normally reciprocal relationship that appears to go awry with age, sufficient tryptophan, which we consume in foods like milk, turkey, chicken and oats, helps keep our microbiota healthy.

A healthy microbiota in turn helps ensure that tryptophan mainly results in good things for us like producing the neurotransmitter serotonin, which reduces depression risk, and melatonin, which aids a good night's sleep, says Dr. Sadanand Fulzele, an aging researcher in the Medical College of Georgia Department of Medicine.

But in aged mice, just eight weeks on a low-tryptophan diet results in some unhealthy changes in the trillions of bacteria that comprise the gut microbiota and higher levels of systemic inflammation, they report in the International Journal of Molecular Sciences.

Diet has been directly linked to microbiota composition in humans and rodents, they write, and they were able to document impactful shifts.

For example, when tryptophan levels are low, the MCG investigators found lower levels of Clostridium sp., the bacterium that metabolizes the essential amino acid enabling production of good products like serotonin in the gut, and a threefold increase in the bacterium Acetatifactor, which is associated with intestinal inflammation.

"We think the microbiome plays an important role in the aging process and we think one of those players in the aging is tryptophan, which produces metabolites that affect every organ function," says Dr. Carlos M. Isales, co-director of the MCG Center for Healthy Aging and chief of the MCG Division of Endocrinology, Diabetes and Metabolism. "We also have evidence that the composition of the bacteria that utilize tryptophan changes so even if you eat more tryptophan, you may not use it correctly," he says.

Fulzele and Isales are co-corresponding authors of the new study further exploring the relationship between tryptophan, the gut microbiome and the inflammatory response, in which they fed the aged mice three different diets for eight weeks -- diets that were deficient, had recommended levels and high levels of tryptophan.

In the face of low tryptophan, they saw both a direct and indirect impact on the microbiota. These included changes like reduced levels of the bacterium Mucispirillum and Blautia, which play a big role in maintaining microbiota health in humans and animals. Some of these bacteria also have been found to be significantly decreased in patients with Crohn's and colitis, where inflammation can be rampant. Mucispirillum, for example, resists oxidative "bursts" associated with inflammation and produces numerous factors associated with reducing reactive oxygen species and consequently inflammation.

It was the unhealthy changes they saw in the microbiota that made Fulzele, Isales and their colleagues also suspect increased release of inflammation-promoting signaling molecules called cytokines, hypothesizing that microbiota changes might induce release of the molecules body-wide. They looked specifically at the largely inflammation-promoting IL-17 and IL-1a as well as IL-6 and IL-27, which can both promote and suppress inflammation, in the blood of mice on a low tryptophan diet. They found significant increases of IL-6, IL-17A and IL-1a and a significant decrease in IL-27, a cytokine which prevents transcription of inflammation-invoking IL-17 and helps do things like increase regulatory T cells in the gut, which suppress inflammation. Conversely, mice on a tryptophan-rich diet had higher levels of the calming IL-27.

Generally the low-tryptophan diet set the stage for inflammation body-wide, the investigators say.

When the aged mice resumed a healthy tryptophan intake, some of the unhealthy changes resolved in just a few days, Fulzele notes. But the reality that just increasing tryptophan did not always correct problems, and that some tryptophan metabolites are actually harmful, provides more evidence that a better option is giving select metabolites early on to help keep the microbiota functioning optimally, rather than attempting a tryptophan rescue, the investigators say.

Their current work is further exploring what a good metabolite mix would look like. "We want to define what products that the gut generates that are good versus bad," Isales says.

Each human has a unique microbiota that results from our birth mothers, and can change based on what we consume, breathe in or are otherwise exposed to over time. It is generally considered an organ system that enables us to digest food and has a key role in the immune response and our overall health. The microbiota also should help protect us from the ill effects of environmental exposures at all ages, and from the ravages of aging itself, Isales says.

Those ravages can include a reduced sense of smell, taste and appetite, and related dietary changes like inadequate or poor nutrition. Also, stem cells throughout the body, which are designed to keep us functioning at a premium by repairing or replacing dysfunctional cells, become less functional because of the cumulative effect of toxins we are exposed to. In a bit of a vicious cycle, our body systems become less efficient, most of us lose lean muscle mass and gain fat, which produces inflammatory molecules, and our weight shifts around so we store more of that fat in and around our abdominal area where it tends to be the most inflammatory and lethal. Fat is also less efficient than lean muscle at burning calories so our metabolism slows, which should in theory slow aging, but in the face of other changes mostly cannot.

"Basically your immune system has been dysregulated, you have continued inflammation from damaged tissue by the processes that normally keep you healthy," Isales says as chronic inflammation can replace the classic episodic immune response that fights infection and enables healing.

What Isales calls this "unnatural" process of aging, is associated with chronic disease conditions like impaired digestive health, declining cognitive function and a compromised immune system, and he and Fulzele agree that the gut microbiota is a significant modulator of these.

"We accept as normal that your organs stop working as well. We accept that the ejection fraction of your heart drops as you get older. We accept that your brain function decreases as you get older. We accept as normal what is not normal," says Isales, who along with Fulzele and their other colleagues in the MCG Center for Healthy Aging want to help reestablish for most of us what they consider the ability to live a significantly longer, and healthier life.

Amino acids like tryptophan are the building blocks for protein production, and proteins are the product our cells produce, which determine their function and ultimately the function of our organs and tissues.

Working in the highly charged environment of COVID-19 has had a huge impact on the mental health of nurses, according to a new survey by researchers at the University of British Columbia and the Institute for Work & Health in Toronto.

The findings, described recently in the Annals of Epidemiology, is the first to compare Canadian nurses' mental health prior to and during the pandemic.

"Whether they worked in acute care settings, in community care or in long-term care homes, nurses experienced high rates of depression and anxiety as the pandemic accelerated," says lead researcher Dr. Farinaz Havaei, a professor of nursing at UBC who studies health systems and workplace psychological health and safety.

Prior to the pandemic, two out of 10 nurses reported that they felt depressed. By April 2020, this had increased, with three out of 10 nurses reporting they felt depressed.

And prior to the pandemic, three out of 10 nurses said they were feeling anxious, whereas during the COVID-19 outbreak, four out of 10 now reported they felt anxious.

"Heavy workloads, inadequate staffing and the mental and emotional stress of dealing with human suffering and death--these factors contributed to the decline in nurses' well-being," she added.

The survey was conducted in September 2019 and again in April and June the following year, drawing more than 10,000 respondents.

Long-term care nurses affected the most

While the pandemic affected many nurses, those in the long-term care (LTC) sector felt the greatest strain, with six out of 10 reporting anxiety in April, compared to four out of every 10 nurses in the acute care and community care sectors.

However, when surveyed two months later, LTC nurses reported their outlook had improved. In that survey, four out of 10 (37 per cent) reported they felt anxiety and three out of 10 (27 per cent) said they felt depressed.

Havaei says the disproportionate impact of the pandemic on LTC nurses isn't surprising given that COVID-19 hit the long-term care sector the hardest, adding that the apparent improvement in late spring could be related to some nurses leaving their jobs due to poor mental health.

"By the time we conducted the third survey round, many of the LTC nurses--likely burnt out by the strain of caring for ill patients--had quit their jobs, reducing the amount of reported mental health problems."

Mental health supports

Although the research draws on data from a single province--British Columbia--the findings highlight the need to critically examine the supports available for nurses across Canada, says study co-author Dr. Peter Smith, a senior scientist at the Institute for Work & Health in Toronto.

"Healthcare workers have been on the front lines of the COVID-19 response," says Dr. Smith. "Studies have shown that, when workers feel protected through adequate and effective infection control practices and personal protective equipment, rates of anxiety and depression are lower."

Dr. Smith added: "We need to ensure for the remainder of the COVID-19 pandemic, and for pandemics in the future, that we have adequate systems and resources to quickly and effectively protect workers on the frontline. We also need to understand the effect that the prolonged period of high anxiety and stress has already had on frontline workers who didn't feel protected."

Dr. Havaei explains, poor nurse mental health has devastating costs for healthcare organizations and patients through increased nurse absenteeism, "presenteeism"--and turnover.

"Preliminary analysis from our other research shows that poor nurse mental health decreases the quality and safety of patient care delivery by as much as 10-fold. There is an urgent need for better mental health supports and resources for nurses, especially those who work in long-term care," adds Dr. Havaei.

UNIVERSITY PARK, Pa. -- Using an unusually well-preserved subfossil jawbone, a team of researchers -- led by Penn State and with a multi-national team of collaborators including scientists from the Université d'Antananarivo in Madagascar -- has sequenced for the first time the nuclear genome of the koala lemur (Megaladapis edwardsi), one of the largest of the 17 or so giant lemur species that went extinct on the island of Madagascar between about 500 and 2,000 years ago. The findings reveal new information about this animal's position on the primate family tree and how it interacted with its environment, which could help in understanding the impacts of past lemur extinctions on Madagascar's ecosystems.

"More than 100 species of lemurs live on Madagascar today, but in recent history, the diversity of these animals was even greater," said George Perry, associate professor of anthropology and biology, Penn State. "From skeletal remains and radiocarbon dating, we know that at least 17 species of lemurs have gone extinct, and that these extinctions happened relatively recently. What's fascinating is that all the extinct lemurs were bigger than the ones that survived, and some substantially so; for example, the one we studied weighed about 180 pounds."

Perry explained that much is unknown about the biology of these extinct lemurs and what their ecosystems were like. There is even uncertainty about how they were related to each other and to the extant lemurs that are alive today. This is due, in part, he said, to the difficulty inherent in working with ancient DNA, especially from animals that lived in tropical and sub-tropical locations.

"While many nuclear genomes of extinct animals have now been sequenced since the first extinct animal -- the woolly mammoth -- had its nuclear genome sequenced at Penn State in 2008, relatively few of these species have been from warmer climates due to faster DNA degradation in these conditions," said Perry. "For example, to date, Penn State's Ancient DNA Laboratory has screened hundreds of extinct lemur subfossils [or ancient bones that have not yet gone through the process of turning into rock]. Yet only two of our samples had sufficient DNA preservation for us to attempt to sequence the nuclear genome. The M. edwardsi jawbone was the best preserved."

Part of the collection of the Laboratory of Primatology and Paleontology at the University of Antananarivo, the jawbone that the team used in its study -- which was published today (June 22) in the journal Proceedings of the National Academy of Sciences -- had originally been discovered at Beloha Anavoha in southern Madagascar. Carbon-14 dating, a commonly used method for determining the age of archeological artifacts of a biological origin, revealed that the M. edwardsi jawbone was about 1,475 years old.

The team used a fragment of the jawbone to sequence the nuclear genome of M. edwardsi. Nuclear DNA contains information about both parents, whereas mitochondrial DNA, which is also used to study extinct species, only contains information about the mother.

In addition to M. edwardsi, the team newly sequenced the genomes of two extant -- or currently living -- lemur species: the weasel sportive lemur (Lepilemur mustelinus) and the red-fronted lemur (Eulemur rufifrons). The DNA from these species came from ear punches that members of the team, led by Edward E. Louis Jr., director of conservation genetics at Omaha's Henry Doorly Zoo and Aquarium and general director of the Madagascar Biodiversity Partnership, obtained from wild-caught individuals.

"Previous studies based on skull and teeth comparisons suggested that M. edwardsi was closely related to L. mustelinus," said Stephanie Marciniak, postdoctoral scholar in anthropology, Penn State. "However, our genetic analyses revealed that M. edwardsi is more closely related to E. rufifrons."

According to Perry, the first genetic study of M. edwardsi -- conducted in 2005 by Anne Yoder, Braxton Craven Professor of Evolutionary Biology at Duke University and her team, and now a co-author of the current paper -- was an analysis of a small fragment of the species' mitochondrial DNA.

"When Anne and her team observed the phylogenetic placement of Megaladapis to be more closely related to Eulemur than to Lepilemur, it was somewhat of a shock, in a cool way," he said. "But uncertainty about the relationship between Megaladapis and other lemurs has continued to linger among scientists. That 2005 study was a really important one, and now with the more sophisticated technology available to us today, we robustly confirmed that major finding."

In addition to extant lemur species, the team also compared M. edwardsi's genome to the genomes of dozens of more distantly related species, including golden snub-nosed colobine monkeys, which are folivores, and horses, which are herbivores.

"We found similarities between M. edwardsi and these two species in some of the genes that encode protein products that function in the biodegradation of plant toxins and in nutrient absorption, consistent with dental evidence suggesting that M. edwardsi was folivorous," said Marciniak.

Specifically, the researchers identified similarities between M. edwardsi and the golden snub-nosed monkey across genes with hydrolase activity functions, and between M. edwardsi and horse across genes with brush border functions.

"Hydrolases help to break down plant secondary compounds, while brush border microvilli play crucial roles in nutrient absorption and chemical breakdown in the gut," said Marciniak.

In the future, the team plans to analyze DNA from additional extinct lemurs and non-lemur primates with the goal of continuing to fill in the gaps in the primate family tree.

"For now," said Perry, "we are excited to have been able to analyze M. edwardsi's nuclear genome sequence for insights into the evolutionary biology and behavioral ecology of this extinct animal and to have resolved its phylogenetic relationship with some other extant lemurs."

To better understand the role of bacteria in health and disease, National Institutes of Health researchers fed fruit flies antibiotics and monitored the lifetime activity of hundreds of genes that scientists have traditionally thought control aging. To their surprise, the antibiotics not only extended the lives of the flies but also dramatically changed the activity of many of these genes. Their results suggested that only about 30% of the genes traditionally associated with aging set an animal's internal clock while the rest reflect the body's response to bacteria.

"For decades scientists have been developing a hit list of common aging genes. These genes are thought to control the aging process throughout the animal kingdom, from worms to mice to humans," said Edward Giniger, Ph.D., senior investigator, at the NIH's National Institute of Neurological Disorders and Stroke (NINDS) and the senior author of the study published in iScience. "We were shocked to find that only about 30% of these genes may be directly involved in the aging process. We hope that these results will help medical researchers better understand the forces that underlie several age-related disorders."

The results happened by accident. Dr. Giniger's team studies the genetics of aging in a type of fruit fly called Drosophila. Previously, the team showed how a hyperactive immune system may play a critical role in the neural damage that underlies several aging brain disorders. However, that study did not examine the role that bacteria may have in this process.

To test this idea, they raised newborn male flies on antibiotics to prevent bacteria growth. At first, they thought that the antibiotics would have little or no effect. But, when they looked at the results, they saw something interesting. The antibiotics lengthened the fly's lives by about six days, from 57 days for control flies to 63 for the treated ones.

"This is a big jump in age for flies. In humans, it would be the equivalent of gaining about 20 years of life," said Arvind Kumar Shukla, Ph.D., a post-doctoral fellow on Dr. Giniger's team and the lead author of the study. "We were totally caught off guard and it made us wonder why these flies took so long to die."

Dr. Shukla and his colleagues looked for clues in the genes of the flies. Specially, they used advanced genetic techniques to monitor gene activity in the heads of 10, 30, and 45-day old flies. In a previous study, the team discovered links between the age of a fly and the activity of several genes. In this study, they found that raising the flies on antibiotics broke many of these links.

Overall, the gene activity of the flies fed antibiotics changed very little with age. Regardless of their actual age, the treated flies genetically looked like 30-day old control flies. This appeared to be due to a flat line in the activity of about 70% of the genes the researchers surveyed, many of which are thought to control aging.

"At first, we had a hard time believing the results. Many of these genes are classical hallmarks of aging and yet our results suggested that their activity is more a function of the presence of bacteria rather than the aging process," said Dr. Shukla.

Notably, this included genes that control stress and immunity. The researchers tested the impact that the antibiotics had on these genes by starving some flies or infecting others with harmful bacteria and found no clear trend. At some ages, the antibiotics helped flies survive starvation or infection longer than normal whereas at other ages the drugs either had no effect or reduced the chances of survival.

Further experiments supported the results. For instance, the researchers saw similar results on gene activity when they prevented the growth of bacteria by raising the flies in a completely sterile environment without the antibiotics. They also saw a similar trend when they reanalyzed the data from another study that had raised flies on antibiotics. Again, the antibiotics severed many of the links between aging and hallmark gene activity.

Finally, the team found an explanation for why antibiotics extended the lives of flies in the remaining 30% of the genes they analyzed. In short, the rate at which the activity of these genes changed with age was slower than normal in flies that were fed antibiotics.

Interestingly, many of these genes are known to control sleep-wake cycles, the detection of odorants, and the maintenance of exoskeletons, or the crunchy shells that encase flies. Experiments on sleep-wake cycles supported the link between these genes and aging. The activity of awake flies decreased with age and this trend was enhanced by treating the flies with antibiotics.

"We found that there are some genes that are in fact setting the body's internal clock," said Dr. Giniger. "In the future, we plan to locate which genes are truly linked to the aging process. If we want to combat aging, then we need to know precisely which genes are setting the clock."

The development of therapeutic drugs for inflammatory bowel disease, an intractable immune disease, and multiple sclerosis - an autoimmune disorder - is gaining traction. A research team from the Department of Life Sciences at POSTECH and a joint research team at ImmunoBiome Inc. have uncovered that a yeast-derived polysaccharide mixture inhibits the onset and progression of immune disorders.

The number of cases of Crohn's disease and ulcerative colitis - both inflammatory bowel diseases - in Korea was about 18,000 and 37,000 respectively as of 2019, increasing about 2.3 times over the past decade. Multiple sclerosis is a rare and incurable disease that affects about 2,500 patients in Korea. Both diseases are intractable inflammatory diseases caused by abnormalities in the human immune system. The exact cause of the inflammatory bowel disease and multiple sclerosis is still unknown but it is presumed that environmental and genetic factors play a role.

Various immune cells such as monocytes, macrophages, dendritic cells, and T cells are involved in the onset and development of these diseases, but T cells in particular play a pivotal role. Currently, agents that suppress the overall inflammatory response are used in clinical practice, but this method has major side effects including vulnerability to infections and there are no clear effective treatments as of now.

To this, the POSTECH researchers and the joint research team from ImmunoBiome Inc. focused on the microbiome and the active substances derived from them, which have a big impact on the development and regulation of the immune system. The joint research team isolated specific polysaccharides from yeast - one of the symbiotic microorganisms in the human body - and first observed their anti-inflammatory effects. Then, using high-performance liquid chromatography and nuclear magnetic resonance (NMR) techniques, the researchers identified the constituents and chemical structures of the polysaccharides and named it MGCP (Mannan/β-1,6-Glucan-containing polysaccharides).

Using a mouse model for inflammatory bowel disease and multiple sclerosis, MGCP-administered mice suppressed the generation of inflammatory cells, which are T helper type 1 cells (Th1 cells). On the other hand, it selectively inhibited the progression of inflammatory diseases by inducing the generation of regulatory T cells (Regulatory T cells, hereinafter Treg cells) with anti-inflammatory function. The researchers additionally confirmed that the mechanism of action of the immunosuppressive response by MGCP is mediated by TLR2 and Dectin1, which are the two different innate immune receptors expressed in dendritic cells.

This study also presents a clear solution to an unsolved immunological question about beta-glucan (β-glucan), which is known to suppress hypersensitivity while inducing immune enhancement at the same time. The research team has uncovered that the immune response enhancing effect of β-glucan identified so far is due to β-1,3-glucan, and found that β-1,6-glucan that makes up the MGCP has a hypersensitivity immunosuppressive effect. These findings show that β-glucan of a specific structure is applicable as an immune enhancing or anti-inflammatory response inducer. These active substances show promise to be developed into the next-generation microbiome treatment.

This study revealed that the immunological efficacy is determined by the chemical structure of the obscure polysaccharide, which was largely unknown. It is significant that a novel polysaccharide MGCP that effectively inhibits inflammatory diseases has been discovered. "We have successfully demonstrated that MGCP can selectively suppress inflammatory T-cells," explained Professor Sin-Hyeog Im. "This will help to provide a great turning point for a new anti-inflammatory treatment with no side effects that can selectively suppress the inflammatory response."

The findings from this research were published online in the June 14 issue of Nature Communications.