Culture

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.

BIRMINGHAM, Ala. - A bout with flu virus can be hard, but when Streptococcus pneumonia enters the mix, it can turn deadly.

Now researchers have found a further reason for the severity of this dual infection by identifying a new virulence mechanism for a surface protein on the pneumonia-causing bacteria S. pneumoniae. This insight comes more than three decades after discovery of that surface protein, called pneumococcal surface protein A, or PspA.

This new mechanism had been missed in the past because it facilitates bacterial adherence only to dead or dying lung epithelial cells, not to living cells. Heretofore, researchers typically used healthy lung cell monolayers to search for bacterial adhesins that aid infection. Virus killing of lung cells during flu was found to set the stage for S. pneumonia attachment to the airway, thereby worsening disease and pneumonia.

The research, published in the journal Cell Reports, was led by Carlos Orihuela, Ph.D., and David Briles, Ph.D., professor and professor emeritus in the University of Alabama at Birmingham Department of Microbiology. Orihuela and Briles say their findings provide further explanation for how an infection by influenza A flu virus -- followed by S. pneumoniae superinfection -- causes severe pneumonia and a high death rate. The mechanism also points to possible improvements for disease treatment and vaccination.

A historical example of the deadly synergy of flu infection followed by S. pneumoniae superinfection is found in banked lung samples from the 1918 Spanish influenza pandemic that killed 40 million to 50 million people -- the vast majority of these samples showed co-infection or secondary infection with S. pneumonia.

The UAB research on PspA began with some head-scratching results from experimental lung infections of mice with influenza A, followed by either wild-type S. pneumonia that has the intact PspA gene, or a mutant S. pneumoniae that lacks PspA. Lung homogenates from mice infected with the wild-type had much higher numbers of S. pneumonia bacteria than lungs infected with the mutant. However, when researchers washed the interiors of the lungs and collected that bronchoalveolar lavage fluid, they counted similar numbers of the wild-type S. pneumonia and the mutant.

"This unexpected result was interpreted to mean that wild-type S. pneumoniae were more resistant to dislodgement than S. pneumonia with a pspA gene deletion, and it served as rationale for further experimentation," Orihuela said.

From this clue, the researchers were able to show that PspA functions as an adhesin to dying host cells, in addition to its several other previously established virulence mechanisms. The researchers also detailed the molecular mechanism of this bacterial adherence.

Both influenza A infection and release of the S. pneumoniae toxin pneumolysin cause death of lung epithelial cells. As they are dying, cells' phosphatidylserine residues get flipped to the outer cell membrane, where they bind the host enzyme glyceraldehyde-3-phosphate dehydrogenase, or GAPDH. In turn, the S. pneumoniae PspA on the surface of the bacteria binds to the GAPDH. PspA-GAPDH-mediated binding to lung cells increased S. pneumoniae localization in the lower airway, and this was enhanced by pneumolysin exposure or co-infection with influenza A virus.

Tests with fragments of the PspA protein showed that a 52-amino acid portion of the protein -- from amino acid 230 to 281 -- was required for GAPDH binding. Instilling one of those binding fragments into the lungs of influenza-infected mice reduced the disease severity of S. pneumoniae superinfection, presumably through binding competition.

"Our findings support the targeting of regions of PspA for therapeutic and vaccine development against influenza A/Streptococcus pneumoniae superinfections," Orihuela said. "Importantly, and despite more than 30 years since its discovery, PspA was not previously shown to function as an adhesin. Thus, our finding of PspA's role in adherence substantially advances our knowledge on the interactions of S. pneumoniae with its host."

Ultrasound can overcome some of the detrimental effects of ageing and dementia without the need to cross the blood-brain barrier, Queensland Brain Institute researchers have found.

Professor Jürgen Götz led a multidisciplinary team at QBI's Clem Jones Centre for Ageing Dementia Research who showed low-intensity ultrasound effectively restored cognition without opening the barrier in mice models.

The findings provide a potential new avenue for the non-invasive technology and will help clinicians tailor medical treatments that consider an individual's disease progression and cognitive decline.

"Historically, we have been using ultrasound together with small gas-filled bubbles to open the almost-impenetrable blood-brain barrier and get therapeutics from the bloodstream into the brain," Professor Götz said.

The new research involved a designated control group who received ultrasound without the barrier-opening microbubbles.

"The entire research team was surprised by the remarkable restoration in cognition," he said.

"We conclude therapeutic ultrasound is a non-invasive way to enhance cognition in the elderly."

Ageing is associated with impaired cognition and a reduction in the learning induced plasticity of the signalling between neurons called long-term potentiation (LTP).

Dr Daniel Blackmore, senior postdoctoral researcher on the team, said the new research aimed to use ultrasound to restore LTP and improved spatial learning in aged mice.

Professor Götz said the brain was "not particularly accessible", but ultrasound provided a tool for overcoming challenges like the blood-brain barrier.

"Using ultrasound could enhance cognition independently of clearing amyloid and tau, which form plaques and tangles in people with Alzheimer's disease," he said.

"Microbubbles will continue to be used in combination with ultrasound in ongoing Alzheimer's research."

About 400,000 people in Australia have dementia and numbers are projected to increase to one million by 2050, with ageing the single biggest risk factor.

Previous research has shown the long-term safety of ultrasound technology and that pathological changes and cognitive deficits could be improved by using ultrasound to treat Alzheimer's disease.

Professor Götz said there were still questions about the differences between normal "physiological" ageing and the "pathological" ageing that happens in Alzheimer's disease.

''We believe there may be some overlap between physiological and pathological ageing in the brain and the potential for this to be corrected with ultrasound is meaningful for those living with Alzheimer's disease," he said.

''We are taking these findings and implementing them in our Alzheimer's research as we go forward to clinical trials.''

Professor Götz's research team aims to understand how brain diseases begin and their progression at molecular and cellular levels in the hope of ultimately developing therapies.

The research has been published in Nature journal Molecular Psychiatry.

Are the traditional practices tied to endangered species at risk of being lost? The answer is yes, according to the authors of an ethnographic study published in the University of Guam peer-reviewed journal Pacific Asia Inquiry. But the authors also say a recovery plan can protect both the species as well as the traditional CHamoru practice of consuming them.

Else Demeulenaere, lead author of the study and associate director of the UOG Center for Island Sustainability, presented on their findings during the Marianas Terrestrial Conservation Conference on June 8.

Strong cultural ties

The researchers interviewed CHamorus about their recollections of preparing and eating the endangered fanihi, the fruit bat found only in the Mariana Islands, and the endangered fadang, a cycad endemic to Micronesia, as sources of food.

"Gathering and processing the [fadang] seeds into titiyas fadang was a family activity. Manåmko' spoke vividly about their exquisite taste and smell during my ethnobotanical research," Demeulenaere said. "CHamoru conservation managers told me they were afraid their kids would never acquire the taste of fanihi and hoped that one day the fanihi population would be restored so they could hunt them sustainably and restore this traditional practice."

Important roles in the ecosystem

Demeulenaere said the CHamoru culture's strong ties to these species only makes a stronger argument for preserving what are both ecologically important species in their own rights and important players in Guam's biodiversity.

"The fadang is a very special tree, as it belongs to the ancient genus Cycas, which originated during the Triassic Period, when dinosaurs were around. The leaves were most likely dinosaur food," Demeulenaere said.

The fadang, known scientifically as Cycas micronesica, was once the most common tree in Guam's limestone forests, but "an invasive scale insect has caused a rapid decline in the health of the cycad populations, which is further exacerbated by habitat loss," Demeulenaere said.

The fanihi, known scientifically as Pteropus mariannus, is an important seed disperser, she said, in particular for fadang seeds.

"They love to eat the seed coat of the fadang [...]," Demeulenaere said. "Restoration efforts consist of adding food sources for the fanihi in degraded forests. [Restoring the] fadang [population] is an important part of this effort."

Today, it is estimated that only 45 to 50 fruit bats remain in the wild in Guam -- down from 400-500 in 1984 and around 3,000 in the 1950s -- because of poaching and habitat destruction, according to the U.S. Fish & Wildlife Service.

Restoration work moving forward

Most of the study's interviewees said they would like to eat fanihi again once the populations are restored. Endemic foods can also significantly contribute to food security in the region, the paper states. But scientist-led protection and restoration of limestone habitats as well as snake suppression are important to recover the species and make sustainable harvest possible.

Moving forward, Demeulenaere said, "A co-production of knowledge consisting of traditional holders and scientists can outline harvesting practices and the recovery actions."

In the recent decade, scientists have paid more attention to studying light harvest for producing novel bionic materials or integrating naturally biological components into synthetic systems. Inspiration is the imitation of natural photosynthesis in green plants, algae, and cyanobacteria to convert light energy into chemical energy. Photosystem II (PSII) is a light-intervened protein complex responsible for the light harvest and water splitting to release O2, protons, and electrons. The development of PSII-based biomimetic assembly in vitro is favorable for the investigation of photocatalysis, biological solar cells, and bionic photosynthesis, further help us reveal more secret of photosynthesis.

The combination of PSII and artificially synthetic structures is successful for making biohybrid assemblies to harvest light. The evolution of material science advances the development of PSII-based assemblies, PSII-mimicking hybrid systems, and utilization of PSII-related products for energy conversion. Relative applications and explorations occur through coupling PSII within lipid membranes, multilayer polymeric structures, and nanoparticles to maximize the efficient range of light absorbance and offer a high PSII payload yield.

The desired light-harvest performance enables a dramatic energy conversion from sunlight to electric power or biochemical energy. Apart from integrating with synthetic materials, naturally active components, photosystem I (PSI), bacteriorhodopsin (BR), or ATP synthase (ATPase), attain in vitro reassembly with PSII to form artificial chloroplasts and achieve partial natural photosynthesis process, including electron generation and transfer as well as ATP synthesis. Subsequent studies found that manipulation of light absorption range is critical to improving the photosynthetic activity of PSII. Synthetic luminescent materials (e.g., fluorescent polymers, quantum dots) are applied to help PSII or chloroplast convert UV light into visible light, resulting in productivity improvement of ATP synthesis.

At present, although reassembly of PSII-based hybrid systems is successful, this system suffers from typical drawbacks shares by common protein species in terms of stability, durability, biological activity, and environmental restrictions for applying PSII-based systems in the near future. Therefore, efforts and explorations still focus on investigating PSII-based biomimetic assembly to challenge these above weaknesses.

This Reviews Article published in National Science Review by Prof. Junbai Li's group at Beijing National Laboratory for Molecular Sciences, CAS Key Lab of Colloid, Interface and Chemical Thermodynamics, Institute of Chemistry of Chinese Academy of Sciences, summarizes recent studies on how PSII protein complex combines with artificial structures via molecular assembly, and highlights PSII-based semi-natural biosystems. Moreover, they discuss this biomimetic systems regarding the remaining problem, challenges, and outlooks.

Toxoplasma gondii, the parasite responsible for toxoplasmosis, is capable of infecting almost all cell types. It is estimated that up to 30% of the world's population is chronically infected, the vast majority asymptomatically. However, infection during pregnancy can result in severe developmental pathology in the unborn child. Like the other members of the large phylum of Apicomplexa, Toxoplasma gondii is an obligate intracellular parasite which, to survive, must absolutely penetrate its host's cells and hijack their functions to its own advantage. Understanding how the parasite manages to enter host cells offers new opportunities to develop more effective prevention and control strategies than those currently available. A team from the University of Geneva (UNIGE), in collaboration with the University of Zurich (UZH) and the Paul Scherrer Institute (PSI) in Villigen, Switzerland, have identified the key role of RON13, a protein of the parasite, which is essential for the invasion process. The three-dimensional structure and the site of action of this enzyme are atypical, thus offering the possibility of designing specific inhibitors to stop the infection. These results are published in the journal Nature Communications.

Specific types of enzymes named kinases are key regulators of a wide range of basic biological processes. "These enzymes modify proteins by adding or removing phosphate groups that, like a switch, turn cellular functions on or off as needed", explains Oscar Vadas, a lecturer in the Department of Microbiology and Molecular Medicine at UNIGE Faculty of Medicine, a specialist in protein biochemistry and co-author of this study. "Kinases are great targets for drug development because, on the one hand, they are relatively easy to inhibit and, on the other hand, they are involved in many pathologies. They are therefore the subject of intense research." Identifying a kinase essential to the survival of a pathogen would thus pave the way for the development of new therapies.

A kinase seen from all its angles

The identification of RON13, a Toxoplasma gondii kinase, quickly became a very attractive subject of study in light of its major role in the invasive capacity of the parasite. "To understand the biological processes controlled by this enzyme, both at the cellular and molecular level, we combined several state-of-the-art technologies", explains Professor Adrian Hehl of UZH. Cryo-electronic microscopy identified an additional modular structure that was absent in all other kinases previously studied, but essential for RON13 activity. Expansion microscopy demonstrated morphological changes in the parasite using high-resolution images. In addition, proteomics was used to identify the kinase targets that are released into host cells to promote its invasion, and genetics was performed to study the impact of the absence of this kinase on the parasite's growth.

"These sophisticated analyses were also made possible thanks to the high-precision technology facilities of the UNIGE Faculty of Medicine, which were made available to the research teams", says Dominique Soldati-Favre, Director of UNIGE Faculty of Medicine Department of Microbiology and Molecular Medicine, who directed this work. "By pooling together all our expertise, we were able to identify precisely the interactions at work and understand the structure of this kinase at the atomic level", underlines Volodymyr Korkhov, a professor at PSI.

Without RON13, there is no invasion

RON13 is a kinase located in a unique compartment of the parasite, an organelle containing proteins to be injected into the host. Without RON13, host cells infection is impossible. "To confirm these results, we infected mice with a strain of the parasite that does not express RON13: it became completely harmless, to the extent that the mice did not show any specific immune response", explains Dominique Soldati-Favre.

Moreover, these very particular characteristics make RON13 insensitive to an inhibitor that is effective on the majority of kinases. "From a therapeutic point of view, this is excellent news", says Oscar Vadas. "This means that we can target it very precisely without affecting human kinases, thus limiting the side effects of the treatment." Moreover, although this work focused on the toxoplasmosis parasite, other pathogens of the Apicomplexa phylum share the same invasion process. It is therefore conceivable that a kinase similar to RON13 plays an essential role in infection by other parasites, and in particular by Plasmodium falciparum, the agent responsible for malaria.

This work was carried out thanks to the support of the Carigest SA Foundation and the Swiss National Science Foundation (SNSF).

An international study led by Helmholtz Zentrum München has revealed the structure of a membrane-remodeling protein that builds and maintains photosynthetic membranes. These fundamental insights lay the groundwork for bioengineering efforts to strengthen plants against environmental stress, helping to sustaining human food supply and fight against climate change.

Plants, algae, and cyanobacteria perform photosynthesis, using the energy of sunlight to produce the oxygen and biochemical energy that power most life on Earth. They also adsorb carbon dioxide (CO?) from the atmosphere, counteracting the accumulation of this greenhouse gas. However, climate change is exposing photosynthetic organisms to increasing environmental stress, which inhibits their growth, and in the long term, endangers the food supply of humankind.

The important first steps of photosynthesis are performed within the thylakoid membranes, which contain protein complexes that harvest sunlight. For decades, it has been known that the protein VIPP1 (vesicle-inducing protein in plastids) is critical for forming thylakoid membranes in almost all photosynthetic organisms - from plants on land to algae and cyanobacteria in the ocean. However, it has remained a mystery how VIPP1 performs this essential function. In the latest issue of the journal Cell, a new study by an international consortium of researchers led by Ben Engel from the Helmholtz Pioneer Campus at Helmholtz Zentrum München reveals the structure and mechanism of VIPP1 with molecular detail.

Building and protecting photosynthetic membranes

The researchers used cryo-electron microscopy to generate the first high-resolution structure of VIPP1. Combining this structural analysis with functional assays revealed how VIPP1 assembles into an interwoven membrane coat that shapes the thylakoid membranes. The research group also used the cutting-edge approach of cryo-electron tomography to image VIPP1 coats within the native environment of algae cells. By using the structural information to make specific mutations to VIPP1, the researchers observed that the interaction of VIPP1 with thylakoid membranes is critical to maintain the structural integrity of these membranes under high-light stress. "Our study shows how VIPP1 plays a central role in both thylakoid biogenesis and adaptation of thylakoids to environmental changes," explains first author Tilak Kumar Gupta from the Max Planck Institute of Biochemistry.

This study lays the foundation for a mechanistic understanding of thylakoid biogenesis and maintenance. It also provides new opportunities for engineering plants that are more resistant to extreme environmental conditions. "Insights into the molecular mechanisms controlling thylakoid remodeling are an important step towards developing crops that not only grow faster, have higher yield and resistance to environmental stress, but also absorb more atmospheric CO? to counteract climate change," says study leader Ben Engel.

International team research

This interdisciplinary study brought together the talents of research teams from the Technische Universität Kaiserslautern (Michael Schroda), Philipps-Universität Marburg (Jan Schuller), Ludwig-Maximilians-Universität München (Jörg Nickelsen), Okayama University in Japan (Wataru Sakamoto), McGill University in Canada (Mike Strauss), Ruhr-Universität Bochum (Till Rudack), the Max Planck Institute of Biochemistry (Wolfgang Baumeister and Jürgen Plitzko) and Helmholtz Zentrum München. "Our study covers a lot of new ground using a wide variety of techniques. This was only possible thanks to the tremendous collective efforts of the researchers in our international consortium," says Ben Engel.

Men - more often than women - need passion to succeed at things. At the same time, boys are diagnosed as being on the autism spectrum four times as often as girls.

Both statistics may be related to dopamine, one of our body's neurotransmitters.

"This is interesting. Research shows a more active dopamine system in most men" than in women, says Hermundur Sigmundsson, a professor at the Norwegian University of Science and Technology's (NTNU)Department of Psychology.

He is behind a new study that addresses gender differences in key motivating factors for what it takes to become good at something. The study uses men's and women's differing activity in the dopamine system as an explanatory model.

"We looked at gender differences around passion, self-discipline and positive attitude," Sigmundsson says.

The study refers to these qualities as passion, grit and mindset. The researchers also applied theories to possible links with dopamine levels.

Dopamine is linked to learning, attention and our ability to focus.

Dopamine is a neurotransmitter that is released in the brain. It can contribute to a feeling of satisfaction.

Men normally secrete more dopamine, which is often called the "happy hormone," but it plays a far more complex role than that. The effects of dopamine are linked to learning, attention and our ability to focus.

Previous studies on Icelandic students have shown that men are more dependent on passion in order to succeed at something. This study confirms the earlier findings. Men require more passion. In six out of eight test questions, men score higher on passion than women.

However, the association with dopamine levels has not been established previously.

"The fact that we've developed a test to measure passion for goal achievement means that we can now relate dopamine levels to passion and goal achievement," says Sigmundsson.

Women, on the other hand, may have greater self-discipline - or grit - and be more conscientious, according to other studies. Their level of passion may not be as pronounced in general, but they still are able to do what it takes to be good.

The results for the women, however, are somewhat more ambiguous than men's strong need to burn for something, and this study found no such gender difference.

Nor did the researchers find any difference between the sexes in terms of growth mindset.

In the past, the dopamine system has been associated with many different conditions, such as ADHD, psychoses, manias and Parkinson's disease. But it may also be related to a certain form of autistic behaviour.

Some individuals with autism may become very interested in certain topics, which can be a bit unusual, or even strange, for most people. People on the autism spectrum can focus intensely on these topics or pursuits, at least for a while. Dopamine may play a role.

"Other research in neuroscience has shown hyperactivity in the dopamine system in individuals with autism, and boys make up four out of five children on the autism spectrum. This, and dopamine's relationship to passion, might be a mechanism that helps to explain this behaviour," says Sigmundsson.

The research group tested 917 people aged 14 to 77, consisting of 502 women and 415 men. This is considered a major study in this context.

Sigmundsson collaborated with Stéfan Guðnason from the University of Akureyri and Sigurrós Jóhannsdóttir from the Icelandic State Diagnostic and Counselling Centre (SDCC).