Culture

Global study on bird song frequency

image: A global study of songbirds like this field warbler shows that song frequencies primarily depend on body size.

Image: 
Tomáš Albrecht

An analysis of the songs of most of the world's passerine birds reveals that the frequency at which birds sing mostly depends on body size, but is also influenced by sexual selection. The new study from researchers of the Max Planck Institute for Ornithology and colleagues suggests that habitat characteristics do not affect song frequency, thereby refuting a long-standing theory.

Many animals use acoustic signals for communication. These signals have evolved to maximize the effectiveness of the transmission and reception of the sounds, because this helps finding a mate or avoiding predation. One of the fundamental characteristics of acoustic signals is the frequency of the sound. In forested habitats, acoustic signals become attenuated because of sound absorption and scattering from foliage, which is particularly problematic for high-frequency sounds. Hence, a theory from the 1970s predicts that animals living in habitats with dense vegetation emit lower-frequency sounds compared to those living in open areas.

A team of researchers led by Bart Kempenaers from the Max Planck Institute for Ornithology in Seewiesen and Tomáš Albrecht from the Charles University in Praha and the Czech Academy of Sciences analysed the variation in song frequency of more than 5.000 passerine bird species, encompassing 85% of all passerines and half of all avian taxa. PhD student Peter Mikula collected song recordings primarily from xeno-canto, a citizen science repository of bird vocalizations, and from the Macaulay Library of the Cornell Lab of Ornithology.

Relationship between song frequency and body size.

Contrary to the theory, the study reveals that the peak frequency of passerine song does not depend on habitat type. If anything, the data suggest that species living in densely vegetated habitats sing at lower frequencies, which is the opposite of what was predicted. As expected from basic physical principles, the researchers found a strong relationship between song frequency and body size and an effect of shared ancestry. "Both limit the range of sound frequencies an animal can produce", says first author Peter Mikula. Heavier species sing at lower frequencies simply due to the larger vibratory structures of the vocal apparatus.

The study further reveals that species in which males are larger than females produce songs with lower frequencies than expected from their size. "This supports the hypothesis that the frequency of acoustic signals is affected by competition for access to mates", says Bart Kempenaers. Song frequency may act as an indicator of an individual's size and therefore of its dominance or fighting abilities. Thus, song frequency could influence reproductive success through competition with other males or even because it influences male attractiveness to females.

"Our results suggest that the global variation in passerine song frequency is mostly driven by natural and sexual selection causing evolutionary shifts in body size rather than by habitat-related selection on sound propagation", summarizes Tomáš Albrecht.

Credit: 
Max-Planck-Gesellschaft

COVID-19 isolation hurting women more than men

A study by University of Calgary researchers with the Hotchkiss Brain Institute examining sex and gender differences on sleep, empathy and mood during months of isolation due to COVID-19 has found that women are suffering more than men with poorer sleep and more anxiety, depression and trauma, while also feeling more empathetic than men.

The findings published in Frontiers in Global Women's Health is one of the first studies to look at changes in mood and sleep quality during the pandemic. Dr. Veronica Guadagni, PhD, led an online survey of Canadians between March 23 and June 7 of this year. During this time, schools and many businesses were closed, and people stayed home as much as possible as part of a general lock down to prevent transmission of the virus.

The researchers examined data from 573 participants, 112 men and 459 women with a mean age of 25.9 years. More than 66 per cent of the volunteer participants reported poor quality of sleep, more than 39 per cent reported increased symptoms of insomnia, and anxiety and distress were increased in the whole sample. Sleep, depression and anxiety symptoms were more prevalent in women.

"Generally, the study found women reporting more anxiety and depression," says Guadagni, a postdoctoral scholar at the Cumming School of Medicine (CSM). "Their symptoms worsened over time and with greater length of the isolation period. There was a progressive increase in anxiety, depression, poor sleep quality and trauma for males and females. But it was greater for females over time."

The study also found that women reported higher scores on a scale measuring empathy, the ability to understand the emotions of others and to care for others. The greater empathy was, however, associated with greater anxiety, depression and trauma. The authors speculate women's greater concern and anxiety in relation to being caregivers reflects differences in gender roles and norms.

"I was not surprised by the findings; women are the ones who carry the additional load," says Dr. Giuseppe Iaria, PhD, the senior investigator of the study. "Taking care of family and critical situations has always been a huge load on women and females."

When it came to feeling for others, the higher scores for women on the empathy scale may mean they're more likely to follow public health guidelines, such as washing hands, social distancing, and wearing a mask. "If we see that higher empathy is connected to prosocial behaviour we could expect that the people who actually care more for others would be more respectful of the rules. Future studies should test this specific hypothesis," says Guadagni.

The researchers were not able to glean any pre-pandemic sleep or anxiety issues from the participant's data. "We don't know what the interplay between sleep, mental health and empathy was before the isolation for these participants" says Iaria. He hopes the study will "trigger some insights" into the public awareness that some suffer more than others, leading to some acknowledgement and accommodation for women from their partners, employers, and institutions.

The researchers suggest sex and gender differences may play a role in psychological and behavioral reactions to the pandemic. And, they say, these differences need to be considered in planning targeted psychological interventions.

Credit: 
University of Calgary

Mayo Clinic Model of Care and Research leads to favorable outcomes for patients with COVID-19

ROCHESTER, Minn. -- Patients with COVID-19 who received care at Mayo Clinic, whether in the hospital or at home, had outcomes that compared favorably to those reported nationally and internationally. These results demonstrate the value of an integrated, team-based approach to patient care and monitoring, according to a retrospective study of all patients with COVID-19 treated at Mayo Clinic March 1-July 31.

Included in the research during the study period were 7,891 patients who tested positive for COVID-19 and were treated at Mayo Clinic. Of those patients, 897 required hospitalization ? 354 in an ICU. An intensive, multilayered approach was used to manage patient care, leveraging clinical trials and available therapies, and using remote monitoring tools for patients before or after hospital care.

Just over 77.5% of hospitalized patients received at least one COVID-19 therapy, such as an antiviral drug, systemic steroid, immunomodulatory monoclonal antibody or convalescent plasma. Nearly one-quarter of hospitalized patients received two therapies, most commonly a combination of steroids and antiviral medications.

The research, published in Mayo Clinic Proceedings, finds that mortality rates were lower than the national and international averages, and lower than what has been reported in other major studies and expanded-access programs. An overall mortality rate of 1.1% was reported for patients treated at Mayo, with inpatient mortality of 7.1% and ICU mortality of 11.9%.

Watch: Dr. Andrew Badley discusses COVID-19 research

Journalists: Broadcast-quality soundbites with Dr. Badley are in the downloads on the Mayo Clinic News Network. Please "Courtesy: Andrew Badley, M.D./COVID-19 Research Task Force/Mayo Clinic."

"COVID-19 patients treated at Mayo Clinic were diagnosed, monitored and treated with a team- based approach that was designed to ensure that all patients were treated with the most up-to-date, evidence-based, treatments available," says Andrew Badley, M.D., chair of Mayo Clinic's COVID-19 Research Task Force. "By including subject matter experts from a range of disciplines in our treatment teams, and having those treatment teams reviewing the care and progress of each patient daily, our outcomes were better than what had previously been reported."

Most patients who were cared for at Mayo Clinic were not part of the first wave of infections. "Mayo physicians and scientists were able to learn from the experience of other hospitals and adopt the best practices learned into our treatment paradigms," Dr. Badley says. "That knowledge, together with the increased access to experimental agents, is likely the major reason for the outcomes we observed."

Most cases occurred June 1-July 31, accounting for 87.5% of total cases during the study period. Mayo Clinic locations across the Upper Midwest saw 59% of patients with COVID-19, with Mayo Clinic in Arizona seeing 23% and Mayo Clinic in Florida seeing 18%. Of the patients treated, 674 were under 18. Only 13 pediatric patients were admitted to the hospital, and no deaths were reported. Given the low rates of complications, pediatric patients were excluded from subsequent analyses.

Among the 7,217 adults included in the analysis, 87.6% did not require hospitalization. Of these outpatients, 30 died, primarily in hospice or skilled nursing facilities. The median age of adult patients treated at Mayo was 59. There were slightly more male patients than female patients, and male patients were more likely to require hospitalization. The most common comorbidities were chronic obstructive pulmonary disease, 11.8%; diabetes, 9.4%; renal disease, 6.5%; and peripheral vascular disease, 6.2%.

The article notes that COVID-19 mortality rates have declined as the pandemic has progressed, with one possible factor being that testing initially was prioritized for those with specific symptoms and later expanded to asymptomatic people. "The support offered by Mayo Clinic labs to allow us to start aggressive testing was critical to these outcomes," says John O'Horo, M.D., a Mayo Clinic infectious diseases physician and the study's first author. "We were able to stand up drive-thru and hospital testing quickly, identify COVID-19 patients earlier, and initiate care in a more timely manner than would have otherwise been possible."

Another factor contributing to these favorable outcomes was Mayo Clinic's outpatient COVID-19 management teams and its remote monitoring capabilities, says Dr. Badley. These programs allow for high-risk patients to be monitored at home, and detect complications or clinical deterioration early, so that hospital admission and advanced care can be provided in a timely manner. "The high proportion of our patients who were able to participate in these programs was likely a contributor to our outcomes," he says.

Another possible contributor to improved outcomes was the growing acceptance of masks and social distancing, which reduce exposure and potentially reduce the severity of illness.

Mayo Clinic has been a leader in caring for, researching and testing patients with COVID-19 since the pandemic began, with teams developing experimental therapies and clinical trials. Mayo Clinic Laboratories has developed highly accurate diagnostic and antibody tests for COVID-19, and has performed more than 2 million molecular tests for patients. Mayo Clinic was the lead institution for the national Expanded Access Program for Convalescent Plasma, which led to emergency authorization for the use of plasma to help critically ill patients.

As the pandemic continues to surge in many parts of the country, Dr. Badley says the lessons learned by Mayo Clinic and other health care providers in the early phase continue to guide patient care and research going forward.

"The volume of patients that we now are seeing in the Midwest and nationally is vastly greater than it was last spring and summer, but all of the processes that we have put in place and have optimized are continuing," Dr. Badley says. "As this global pandemic approaches its first anniversary, we should be heartened by the advances that have been made in testing, diagnosis and management of COVID-19 and its complications. By adopting best practices learned from all institutions, we can continue to improve outcomes for patients."

Credit: 
Mayo Clinic

New drug inhibits the growth of cancer cells

image: Cartoon representation of the POLRMT-Inhibitor complex.

Image: 
Hauke S. Hillen

A newly developed compound starves cancer cells by attacking their "power plants" - the so-called mitochondria. The new compound prevents the genetic information within mitochondria from being read. Researchers from the Max Planck Institute for Biology of Ageing in Cologne, the Karolinska Institute in Stockholm and the University of Gothenburg report in their study that this compound could be used as a potential anti-tumour drug in the future; not only in mice but also in human patients.

Mitochondria provide our cells with energy and cellular building blocks necessary for normal tissue and organ function. For a long time, the growth of cancer cells was assumed to be independent of mitochondrial function. However, this long-standing dogma has been challenged in recent years. Especially cancer stem cells are highly dependent on mitochondrial metabolism. Due to the central role of mitochondria for normal tissue function, and because drugs that target mitochondrial functions are usually very toxic, it has so far proven difficult to target mitochondria for cancer treatment.

Now an international team of researchers has found a way to overcome these difficulties. "We managed to establish a potential cancer drug that targets mitochondrial function without severe side effects and without harming healthy cells", explains Nina Bonekamp, one of the lead authors of the study. Mitochondria contain their own genetic material, the mitochondrial DNA molecules (mtDNA), whose gene expression is mediated by a dedicated set of proteins. One such protein is the enzyme "mitochondrial RNA polymerase", abbreviated to POLRMT. "Previous findings of our group have shown that rapidly proliferating cells, such as embryonic cells, are very sensitive to inhibition of mtDNA expression, whereas differentiated tissues such as skeletal muscle can tolerate this condition for a surprisingly long time. We reasoned that POLRMT as a key regulator of mtDNA expression might provide a promising target", says Nils-Göran Larsson, head of the research team.

Compound inhibits mitochondrial RNA polymerase

In collaboration with the Lead Discovery Center, a translational drug discovery organization established by Max Planck Innovation, the research team designed a high-throughput test method for identifying a chemical compound that inhibits POLRMT. The POLRMT inhibitor strongly decreased cancer cell viability and tumour growth in tumour-bearing mice, but was generally well tolerated by the animals. "Our data suggest that we basically starve cancer cells into dying without large toxic side effects, at least for a certain amount of time. This provides us with a potential window of opportunity for treatment of cancer", says Nina Bonekamp. "Another advantage of our inhibitor is that we exactly know where it binds to POLRMT and what it does to the protein. This is in contrast to some other drugs that are even in clinical use." With the help of ACUS Laboratories in Cologne and the Max Planck Institute for Biophysical Chemistry in Göttingen, the team identified the chemical binding site of the inhibitor and obtained structural information of the POLRMT-Inhibitor complex.

Bonekamp and Larsson agree that it has been an exciting journey to translate basic findings into a potential drug. They are all the more excited about the possibilities that their findings will open up. "Given the central role of mitochondrial metabolism within the cell, I am sure that our inhibitor of mitochondrial gene expression can be used as a tool in a variety of different areas", explains Bonekamp. "Of course, it is intriguing to further pursue its potential as an anti-cancer drug, but also as a model compound to further understand the cellular effects of mitochondrial dysfunction and mitochondrial diseases."

Credit: 
Max-Planck-Gesellschaft

Study: Bumble bees lacking high-quality habitat have higher pathogen loads

image: Researchers found that bumble bees in landscapes that lacked quality nesting sites and spring flowers for forage had higher levels of pathogens. Their results can inform management practices to support the conservation of bee species that provide essential pollination services, they said.

Image: 
David Cappaert, Bugwood.org

Bumble bees found in low-quality landscapes -- characterized by a relative lack of spring flowers and quality nesting habitat -- had higher levels of disease pathogens, as did bumble bees in areas with higher numbers of managed honey bee hives, according to research led by Penn State scientists.

The results of the study, which examined how a variety of environmental and landscape characteristics influence infectious disease prevalence and bee health, can be used to inform management practices to support the conservation of bee species that provide essential pollination services in natural and agricultural ecosystems, the researchers said.

"Recent worldwide declines in wild and managed bee populations have been attributed to several factors," said the study's lead author, D.J. McNeil, postdoctoral fellow in the Insect Biodiversity Center in Penn State's College of Agricultural Sciences. "For example, extensive habitat loss and degradation has led to a lack of flowers and nest sites, which in turn has contributed to the loss of wild bee abundance and diversity."

He pointed out that more recently, some bee losses -- especially among honey bees and bumble bees -- have been blamed on rising levels of novel bee pathogens, perhaps exacerbated by other factors that weaken bee immunity or resistance.

"Many of the factors known to undermine bee health, such as poor nutrition or exposure to pesticides, can increase susceptibility to disease," McNeil said. "Bees are more likely to be nutritionally deprived in landscapes with fewer and less diverse flowering plants, and poor nutrition can reduce the immune response and increase pathogen and parasite loads."

The incidence and loads of a particular pathogen or parasite in bee populations likely are influenced by the composition of bee communities as well, noted study co-author Heather Hines, associate professor of biology and entomology, Penn State. She explained that the incidence of viruses and parasites in wild bumble bees was higher in the presence of honey bee colonies, which often harbor higher loads of pathogens that are transmissible to native bees.

"Given all these interacting factors, disease prevalence and virulence can be challenging to predict in wild bee populations," Hines said. "Our study is among the first to use data from a large geographic scale to evaluate the relative role of landscape features on the distribution and loads of key pathogens and parasites in wild bees."

To measure pathogen loads, the researchers analyzed specimens of the common eastern bumble bee -- Bombus impatiens, the most abundant bumble bee species in the region. The team collected bumble bee workers from sites across Pennsylvania during peak bumble bee abundance from late June to mid-July in 2018 and 2019. These sites, which included 38 of Pennsylvania's 67 counties, were selected to represent evenly the span of the state and to include a diversity of habitat types and land use patterns.

The researchers then screened for three pathogens known to infect bees -- deformed wing virus, black queen cell virus and Vairimorpha, a microsporidian parasite -- as well as for expression of a gene that regulates immunity. Using statistical analysis techniques, they correlated pathogen presence and loads with several recognized landscape-scale stressors, such as floral abundance, nesting habitat quality, insecticide loading, climatic conditions and interactions with managed honey bees.

Their findings, reported in Scientific Reports, suggested that bumble bees collected within low-quality landscapes exhibited the highest pathogen loads, with spring floral resources and nesting habitat availability serving as the main drivers. The study also found higher loads of bumble bee pathogens where honey bee apiaries are more abundant, as well as a positive relationship between Vairimorpha loads and rainfall, and differences in pathogens by geographic region.

McNeil said results of the study highlight the need to maintain and create high-quality landscapes, such as those with abundant floral and nesting resources, to support healthy wild bee populations. The findings also draw particular focus to the value of spring floral resources, which often are less emphasized in pollinator garden plantings than mid-summer forage.

"Our results suggest that it may be possible to predict potential risks from pathogens and parasites based on these landscape indices, which can help inform decisions as to where habitat restoration and conservation practices should be applied," he said. "This is particularly timely in light of widespread population declines in many insect groups, especially pollinators like bumble bees."

The researchers said they hope to incorporate this information into Beescape, an online tool that allows people across the United States to evaluate their landscape quality. They encourage Pennsylvania homeowners, growers and conservationists to read the Pennsylvania Pollinator Protection Plan, which contains a chapter on best practices for creating forage and habitat for bees in urban, agricultural and natural landscapes.

Credit: 
Penn State

New flower from 100 million years ago brings fresh holiday beauty to 2020

image: Valviloculus pleristaminis.

Image: 
George Poinar Jr., OSU

CORVALLIS, Ore. - Oregon State University researchers have identified a spectacular new genus and species of flower from the mid-Cretaceous period, a male specimen whose sunburst-like reach for the heavens was frozen in time by Burmese amber.

"This isn't quite a Christmas flower but it is a beauty, especially considering it was part of a forest that existed 100 million years ago," said George Poinar Jr., professor emeritus in the OSU College of Science.

Findings were published in the Journal of the Botanical Research Institute of Texas.

"The male flower is tiny, about 2 millimeters across, but it has some 50 stamens arranged like a spiral, with anthers pointing toward the sky," said Poinar, an international expert in using plant and animal life forms preserved in amber to learn more about the biology and ecology of the distant past.

A stamen consists of an anther - the pollen-producing head - and a filament, the stalk that connects the anther to the flower.

"Despite being so small, the detail still remaining is amazing," Poinar said. "Our specimen was probably part of a cluster on the plant that contained many similar flowers, some possibly female."

The new discovery has an egg-shaped, hollow floral cup - the part of the flower from which the stamens emanate; an outer layer consisting of six petal-like components known as tepals; and two-chamber anthers, with pollen sacs that split open via laterally hinged valves.

Poinar and collaborators at OSU and the U.S. Department of Agriculture named the new flower Valviloculus pleristaminis. Valva is the Latin term for the leaf on a folding door, loculus means compartment, plerus refers to many, and staminis reflects the flower's dozens of male sex organs.

The flower became encased in amber on the ancient supercontinent of Gondwana and rafted on a continental plate some 4,000 miles across the ocean from Australia to Southeast Asia, Poinar said.

Geologists have been debating just when this chunk of land - known as the West Burma Block - broke away from Gondwana. Some believe it was 200 million years ago; others claim it was more like 500 million years ago.

Numerous angiosperm flowers have been discovered in Burmese amber, the majority of which have been described by Poinar and a colleague at Oregon State, Kenton Chambers, who also collaborated on this research.

Angiosperms are vascular plants with stems, roots and leaves, with eggs that are fertilized and develop inside the flower.

Since angiosperms only evolved and diversified about 100 million years ago, the West Burma Block could not have broken off from Gondwana before then, Poinar said, which is much later than dates that have been suggested by geologists.

Joining Poinar and Chambers, a botany and plant pathology researcher in the OSU College of Agricultural Sciences, on the paper were Oregon State's Urszula Iwaniec and the USDA's Fernando Vega. Iwaniec is a researcher in the Skeletal Biology Laboratory in the College of Public Health and Human Sciences and Vega works in the Sustainable Perennial Crops Laboratory in Beltsville, Maryland.

Credit: 
Oregon State University

Development of plaques in Alzheimer's disease resolved

A team of researchers from Ruhr-Universität Bochum (RUB) and Vrije Universteit Amsterdam (VU) has determined the development stages of Aβ fibrils and has thus been able to understand the development of plaques. The researchers report in the academic journal Acta Neuropathologica Communications on 11 December 2020.

Joining forces

The team from the Centre for Protein Diagnostics (Prodi) at RUB is working with the Vrije Universiteit Medical Center (VUmc) in order to pool expertise in protein and dementia research. Medical experts such as Baayla Boon from VUmc attends to patients with dementia in the clinic and examines the post mortem brain tissue, which is diligently collected by the Netherlands Brain Bank (NBB). Razor-thin slices are cut from the brain for examination. "Such slices of tissue allow us to look deep within the convolutions of the brain," says Baaylas supervisor Professor Annemieke Rozemuller, Head of Neuropathology at VUmc.

The groups exchange samples and findings at regular meetings. In Bochum, protein researchers led by Professor Klaus Gerwert, Head of Biophysics and Founding Director of Prodi at RUB, examine the brain tissue. The plaques contained in this are illuminated with infrared light in special microscopes. "This allows us to determine the folding of biomarker proteins in the tissue," says Dominik Röhr from Prodi.

A new timeline for plaques

The formation of Aβ fibrils is well known from laboratory experiments. First, Aβ folds like a sheet of paper to form so-called β-sheets. These clump together into small groups, which are known as oligomers. Over time, the β-sheets come together like a deck of cards to form fibrils. The Bochum-based researchers led by Klaus Gerwert utilize this process as an internal clock for plaques. Newly developed plaques contain many oligomers. Over the course of plaque development, fibrils are continuously formed. The researchers thereby concluded that plaques pass through different stages during their development. "It has not been possible to directly observe the development of plaques so far. By combining methods from medicine and physics, new possibilities are now opening up," says Klaus Gerwert, delighted.

On the left is a fully developed plaque of brown-stained Aβ. On the right, the structure of Aβ determined by infrared microscopy is shown. In core are fibrils (red), around are mainly oligomers (blue).

Aβ is the focus in the fight against Alzheimer's disease. A central approach in the search for a cure is dissolving the plaques in the patients' brains. "Early diagnosis of Alzheimer's disease is crucial to prevent Aβ from causing irreparable damage in the brain," says Dominik Röhr. Promising medications are currently undergoing approval testing. These include the antibody aducanumab, which can break down plaques in the brain. The new findings from infrared microscopy indicate that the development of plaques could be stopped at an early stage by preventing the formation of oligomers. These are considered to be particularly harmful to the brain. The toxic effect of Aβ could thus be minimised with suitable drugs.

Credit: 
Ruhr-University Bochum

Blood alcohol levels much lower than the legal limit impair hand-eye coordination

image: The eye measurement assessment set-up (shown above) consists of a chin/forehead rest, an infra-red camera and lamp, high-resolution gamer display and game controller, with appropriate software to generate our moving visual stimuli and compute 21 specific eye measurements.

Image: 
NASA

In previous studies, eye movements and vision were only affected at blood alcohol concentrations (BACs) approaching the legal limit for driving (0.08% BAC), in England, Wales and Northern Ireland (1).

New research published in The Journal of Physiology however found for the first time that hand-eye coordination is dramatically more sensitive to alcohol with some measures of coordination impaired by more than 20% at BAC levels as low as 0.015%.

In particular, the ability to process visual motion, which is crucial for hand-eye coordination in driving and other activities, is compromised after consuming the equivalent of less than a half of beer, for a person around 75 kilograms in weight.

The findings from the research team based at NASA's Ames Research Center provide new information on the potential impact of even minimal alcohol consumption on high-risk human activities that rely on keen visual and visuomotor control, like driving, piloting, or working heavy machinery.

NASA is interested in developing sensitive yet non-invasive methods for detecting mild impairments. The researchers used low-dose alcohol to mildly, and reversibly, impair brain function as a proxy for other stressors that could affect performance in aerospace settings, such as altered gravity or atmospheric conditions, or in earth-based situations, such as neural illness, head injury or sleep deprivation.

Using this technique, they show that a set of eye measurements represents an ultra-sensitive new approach for detecting performance deficits, valuable for studying brain impairments in people on Earth and also in space.

Apart from this finding specific to alcohol-induced impairment, this study further demonstrates how a specially designed collection of non-invasive eye measurements can be used to measure mild deficits of processing in the brain.

To conduct the study, the researchers measured volunteers' eye movements, pupil responses, and BAC, multiple times during a day while they performed a specially designed task, before and after they drank alcohol.

At random, the volunteers were assigned a mixed drink containing a certain quantity of alcohol achieving either the higher (0.06%) or lower (0.02%) peak BAC levels so that they were not aware of exactly how much they drank on a given day.

The special task involved looking at a set of stationary points on a computer screen, then following with their eyes a dot that moved in a random direction, at a random speed. The dot started moving at a random time so that guessing did not help.

The researchers then computed 21 different ocular measures that have been shown to assess neural processing in specific brain areas that contribute to different components of the eye-movement and pupillary responses.

The study participants were men and women, mostly in their 20s, who drink on average 1-2 drinks per week. Therefore, the researchers haven't looked at the impact of age, nor have they tested heavy drinkers. The researchers made sure that participants had a full-night's sleep the night before, and asked that they abstain from both alcohol and caffeine consumption for several nights in a row prior to testing.

In future studies, the researchers plan to look at how their eye measurements are affected by other types of neurological conditions, such as those caused by degenerative diseases or toxic exposures. By using alcohol as a heuristic reference, they'll be able to compare any new-found impairments to that caused by consuming a certain number of alcoholic beverages.

Terence Tyson, first author on the study, said:
"Our findings provide a cautionary tale that the subjective experience of drunkenness is often not aligned with objective impairment of sensorimotor coordination. In other words, most people feel they are unimpaired after one drink, yet they are to a significant degree."

Thus, driving may be affected by drinking just a small amount of alcohol, even though the driver may feel fine and be well within the legal limit.

Credit: 
The Physiological Society

New model reveals previously unrecognized complexity of oceanic earthquake zones

image: Overview of the study area and the schematic illustration of interaction of fault motion and the seafloor subsidence.

Image: 
University of Tsukuba

Tsukuba, Japan - Researchers from the University of Tsukuba applied seismic data from around the world to build a model of the 2020 Caribbean earthquake. Oceanic transform faults are generally considered to be linear and simple and have been widely used in studies of earthquake dynamics. However, the research team found that high complexity in rupture speed and direction can occur even in a supposedly simple linear fault system.

On 28 January 2020, a large oceanic earthquake with magnitude 7.7 occurred at the Oriente transform fault in the Caribbean Sea, between Jamaica and Cuba. It caused a minor tsunami of 0.11 m height and was felt as far afield as Florida.

A research team at the University of Tsukuba have developed a new finite-fault inversion method for building models based on teleseismic waveform data from earthquake monitoring stations. This new approach to using the data takes a more flexible approach to resolving the fault geometry. Rather than relying on prior assumptions, the faulting components are separately evaluated in a wider model in both time and space, allowing all possible rupture evolutions to be considered. The team were keen to use the Caribbean earthquake to help to understand the faulting processes that occur during these shallow oceanic quakes.

"Some cases of complex rupture dynamics have recently been reported in previous earthquake studies, raising the question of whether or not we are correctly modeling these even in supposedly simple fault systems," says study author Professor Yuji Yagi. "The initial monitoring of this January 2020 event suggested variations in the waveform shape between two stations at similar distances from the epicenter, suggesting that there remains complexity to be explored at this fault."

This was an excellent opportunity to test the new method developed by the team, which used data from 52 seismic stations to construct a detailed model of the geophysical processes within the fault that gave rise to the earthquake.

"The results revealed complex rupture during the earthquake, caused by a bend in the fault that led to the changes in rupture speed and direction detected in the monitoring data," explains author Professor Ryo Okuwaki. "These variations triggered several successive rupture episodes that occurred along the 300-km-long fault." The modeling approach also allows some suggestions to be made about the possible occurrence of subsidence and the shape of the surrounding seabed following the earthquake event.

These findings reveal that oceanic transform faults, considered to be simple and linear, may be much more complicated than previously accepted, and therefore require a more comprehensive approach to earthquake modeling. This work will shed light on a possible interaction between the earthquake-fault motion and the evolution of the ocean floor around the transform boundary.

Credit: 
University of Tsukuba

Fungal RNA viruses: Unexpected complexity affecting more than your breakfast omelet

We've all suffered from viruses, but did you know that they are also a problem for mushrooms and molds? Mycoviruses are viruses that specifically infect fungi and have the potential to impact ecology, agriculture, food security, and public health. Understanding the nature of these viruses, including their number and evolution, can help us understand their origins and inform our understanding of viruses in general.

Previous research into RNA mycoviruses has relied on their sequence similarity to viruses that have already been described. However, this approach leaves viruses with different genetic structures or sequences undiscovered. Using an advanced technological approach called Fragmented and Primer Ligated Double Stranded RNA sequencing, or FLDS for short, researchers from the University of Tsukuba were able to identify viral sequences that were previously overlooked.

Summarizing the importance of this work, Professor Hagiwara said: "The current approaches used to identify RNA viruses mean that their genetic diversity has been underestimated. Using FLDS, we were able to study RNA viruses without relying on sequence similarity, which allows us to identify RNA viral sequences that are dissimilar to those previously identified."

Using FLDS, Professors Urayama and Hagiwara, and their colleagues, identified 19 RNA viruses in a fungus called Aspergillus. Highlighting the value of this approach, 9 of the 19 viruses identified had been undetected using conventional methods of examination. Moreover, 42% of identified viruses had genomes that were segmented, or spread throughout the host genome, and others identified had novel genome architectures.

RNA-dependent RNA polymerase (RdRp) is an essential gene found in all RNA viruses and allows RNA genome replication from an RNA template. It was commonly understood that all RNA viruses encode RdRp as a single, continuous gene.

"Unexpectedly, we found that viruses within a certain clade of Narnaviridae encode an RdRp gene lacking the catalytic domains," Professor Urayama explains, "but we also found a different open reading frame containing the missing domains." Although some RdRp sequences lacking the catalytic domains have been described previously, those viral genomes also lack the catalytic domains and produce imperfect RdRp proteins. The functional, yet divided, RdRp described by Professors Urayama and Hagiwara, and their colleagues, indicates that researchers should reconsider the structural plasticity of RdRp.

Credit: 
University of Tsukuba

Hardly any sports -- but more physical activity during lockdown

image: By playing outside, children and adolescents found ways to be physically active during the lockdown. (Photo: Martin Köhler, Motorik-Modul Study)

Image: 
Martin Köhler, Motorik-Modul Study

In spring 2020, when soccer and sports clubs closed for sever-al weeks due to the Corona pandemic, children and adoles-cents looked for alternative physical activities. According to a supplementary study covering more than 1700 children and adolescents aged from 4 to 17 as part of the Motorik-Modul Study (MoMo) conducted by Karlsruhe Institute of Technology (KIT) and Karlsruhe University of Education (PHKA), the chil-dren were physically active about 36 minutes longer every day, but also spent an hour more in front of screens and monitors. The results are reported in Scientific Reports. (DOI: 10.1038/s41598-020-78438-4)

"Surprisingly, boys and girls looked for a replacement of the cancelled sports offers, also those, who had not been physically active before," says Dr. Claudia Niessner. The scientist from KIT's Institute of Sports and Sports Science (IfSS) and her colleague Dr. Doris Oriwol, KIT and PHKA, manage the project, the findings of which are now published in the Scientific Reports of Nature Research. Closure of schools, sports facilities, and playgrounds from mid-March to early May to contain the Corona pandemic was both bad luck and an opportunity for the ten researchers. They had to suspend the field studies of their Motorik-Modul Study (MoMo) on motor skills and physical activities of children and adolescents during the lockdown, but seized the opportunity to organize online surveys. "We responded quickly and used the lockdown phase well. Comparison of the situations before and after lockdown was only possible, because we have long-term data, the only database of this kind worldwide," Niessner says. Among others, the researchers found that both the time of general physical activities and the time spent in front of screens and monitors increased." More time spent for using media does not necessarily mean less physical activity. In both areas, there are U-shaped relationships with a healthy lifestyle," says Dr. Steffen Schmidt, first author of the scientific publication made as part of the MoMo research project.

Everyday Physical Activities Are Less Intensive than Organized Sports

"According to our survey, everyday activity increased. Still, it was just a snapshot in an extraordinarily warm spring, and quantity is not quality," says Professor Alexander Woll, Head of IfSS and Director of the MoMo study started in 2003. "Playing outside, cycling, gardening or housework do not have the same intensity as training and competitions in organized sports. Moreover, social aspects are lacking when clubs and schools are closed," says the sports scientist. "Before the lockdown, we had the highest level of organized sports ever. About 60% of the children and adolescents in Germany are active in sports clubs. The long-term impact of lacking sports at schools and clubs on motor skills or overweight are not yet known," Woll says. According to the study, closure of sports clubs resulted in an average daily decline in sports by 28.5 minutes. "Digital offers of physical activities have increased and will continue to increase, but there is a difference between physical activity in front of the screen or running across a green meadow," Woll says. In addition to their everyday activities, children and adolescents spent about 18 minutes per day more for "non-organized sports," such as playing football, basketball or badminton, i.e. about 24 minutes instead of just seven minutes prior to the lockdown. Although the 60 minutes of physical activity per day recommended by WHO were not reached, the lockdown turned out to promote physical activity, Woll says. As regards the activity behavior during the current lockdown in winter, the sports scientist is more skeptical. He thinks that it is positive that schools are still open. But outdoor activities will presumably decrease in the cold and dark season, he says.

Living Environment Plays an Important Role

"Our study shows that the living environment of children and adolescents plays a major role," says sports scientist Niessner. While physical activity was highest for children living in a single-family house in a small municipality, it was lowest for children and adolescents living in multi-story buildings in large cities. "Free movement spaces are disappearing in urban planning. Countermeasures are urgently required," Woll says.

The MoMo Study is a joint project of KIT and PHKA. Deputy Project Director Professor Annette Worth, PHKA, explains: "As regards physical activity in times of Corona, school plays an important role. Teachers instruct, assist, give a feedback, and motivate. This is particularly important for children, where physical activities, games, and sports play a minor role at home."

The MoMo Study on the development of motor skills and physical activities of children and adolescents is part of the Germany-wide study on the health of children and adolescents in Germany (KiGGS) of Robert Koch Institute (RKI) and is funded by the Federal Ministry of Education and Research (BMBF). If possible, MoMo will be continued in 2021 to study long-term impacts of quantitative and qualitative changes of physical activities, including changes resulting from the pandemic, on the development of motor skills and health of children and adolescents in Germany.

Credit: 
Karlsruher Institut für Technologie (KIT)

Cellular exclusion of mitochondria protects cells from damage

image: Defective mitochondria are eliminated by mitophagy as well as extracellular release.

Image: 
Osaka University

Osaka, Japan - Mitochondria are cellular organelles that generate most of the energy cells need to function, and thus play an important role in maintaining cell health. In a new study, researchers from Osaka University discovered a novel mechanism by which cells turn over mitochondria and contribute to cellular maintenance. They further showed how this novel pathway is involved in the development of Parkinson's disease (PD).

Most cells in the body require mitochondria to function and survive. Various disease processes and toxic agents can harm cells by damaging mitochondria, and failure to eliminate damaged mitochondria can cause neurodegenerative diseases such as PD. Unsurprisingly, cells have a quality control system that ensures the health and function of mitochondria within cells. For a long time, it was thought that this control system would consist of mitophagy only, a process by which cells degrade damaged mitochondria and recycle their individual components to then build new mitochondria. While recent studies have shown that cells in addition have the ability to transfer mitochondria out, this process remains incompletely understood.

"The release of mitochondria into the extracellular space is a fascinating topic, but we know very little about it," says co-author Tatsusada Okuno. "The goal of our study was to investigate to which extent cells transfer mitochondria out in response to mitochondrial stress."

To achieve their goal, the researchers generated a cell line in which mitochondria are fluorescently labeled and thus can be investigated under a fluorescence microscope. By performing time-lapse imaging over a prolonged period of time, the researchers were able to watch the release of mitochondria in real-time. Intriguingly, they were able to show by correlative light-electron microscopy, a technique that allows cellular structures to be examined at ultra-high magnification, that mitochondria were mostly released in free form and were rarely enclosed in vesicles.

The researchers then asked what the role of mitochondrial release might be in PD. By studying cells deficient in parkin, the protein responsible for the hereditary form of PD, they were able to show markedly increased mitochondrial release in the absence of the protein. Likewise, the blood of parkin-deficient mice contained higher levels of mitochondrial proteins, further demonstrating how the absence of parkin facilitates extracellular mitochondrial release. Most importantly, however, the researchers were able to show that cerebrospinal fluids of PD patients with a mutation in parkin that renders the protein dysfunctional contained higher levels of mitochondria, demonstrating the significance of this novel mitochondrial quality control system in the development of PD in humans.

"These are striking results that demonstrate a novel mechanism for clearing defective mitochondria and an important role for mitochondrial homeostasis in the onset of Parkinson's disease," says corresponding author Hideki Mochizuki. "These findings may lead to the development of new biomarkers and therapeutics."

Credit: 
Osaka University

The Achilles' heel of cancer stem cells

image: Expanding cancer stem cells (green) in a colon tumor with an oncogenic activated Wnt/beta-catenin signaling pathway (red).

Image: 
Birchmer Lab, MDC

Since colonoscopies were introduced in Germany for early cancer detection, the number of diagnoses of advanced cancer every year has decreased, as precancerous lesions can now be detected and immediately removed as part of the examination. As a result, the death rate from colon cancer has also gone down - by 26 percent in women and 21 percent in men. Nevertheless, it remains the fourth deadliest cancer in the Western world - just behind lung, prostate and breast cancer. This is because the slow-growing tumors only become noticeable in the advanced stages of the disease and are therefore often diagnosed too late. Survival rate for advanced colorectal cancer is just five percent.

"Treatment options are very limited - not least because the cancer can return even after successful chemotherapy," explains Johanna Grinat, the study's lead author and a doctoral student in the Signal Transduction in Development and Cancer Lab. "The recurrent cancer is often more aggressive than the original tumor, which is thought to be caused by cancer stem cells. So we took a closer look at these cells."

Molecular switch found in cancer stem cells

The researchers led by Professor Walter Birchmeier identified Mll1, a protein that regulates stem cell genes in mice and in human colon cancer cells. In mice, the team was able to genetically trigger the formation of intestinal tumors. However, if the mice lacked the gene for Mll1, no tumors were able to be induced. And this seems to be the case in humans as well: Human colon cancer cell cultures that the scientists enriched with cancer stem cells lost some of their stem cell properties and behaved less aggressively when Mll1 was blocked. Together with Professor Eduard Batlle and bioinformaticians at the IRB in Barcelona, the MDC group used clinical data to show that colon cancer patients whose tumors have a large amount of this protein have a worse prognosis than patients with tumors that contain little Mll1.

Mll1 is an enzyme that sits on the DNA and controls the expression of certain genes "epigenetically," as the researchers say. "It primarily does this in cancer stem cells, where the Wnt signaling pathway is strongly activated," Grinat explains. "This means that, by deactivating it, we can specifically treat cancer stem cells."

The Wnt signaling pathway regulates the self-renewal and division of stem cells. If mutations occur that trigger a more active Wnt signaling cascade, the affected stem cells become more resistant than healthy stem cells. They then multiply uncontrollably and form tumors. Although chemotherapy slows down the cell division, it can also increase the selection pressure on cancer stem cells: "They become resistant to the treatment and form new tumors that, due to the mutation, grow more rapidly and are even more aggressive," says Dr. Julian Heuberger. This is why it is so important, he explains, to understand the regulatory mechanisms of cancer stem cells in particular. The postdoctoral researcher is also lead author and head of the study and now works in the Division of Hepatology and Gastroenterology in the Medical Department of Charité - Universitätsmedizin Berlin. "With Mll1," he adds, "we have found a molecular switch that primarily controls the self-renewal and division of cancer stem cells in colon cancer"

Hope and more effective therapies

Genetically "knocking out" a gene, as the scientists did with mice, is not possible in humans. In mice, the formation of cancer stem cells can be followed over time and there are always enough stem cells available for experiments. However, MII1 could be blocked with a chemical drug. Small molecules have already been developed for this research, for example, the inhibitors MI-2 and MM-401, which bind to essential Mll1 complexes and thereby inactivate its function. "Understanding the way these molecules work will enable us to develop and test these and even more clinically effective Mll1 inhibitors," says Birchmeier, who is the study's last author.

Healthy stem cells in the intestine are apparently not blocked in the process. "We were able to use another system in mice, salivary gland cancer cells, to show that Mll1 only affects cancer cells and not healthy stem cells," says Birchmeier. This also provides hope for the treatment of other types of cancer, as animal models have shown that head and neck tumors have the same Achilles' heel. "On the basis of our mouse studies, clinical trials are currently being conducted at the University Hospital of Düsseldorf to evaluate the use of Mll1 inhibitors in the treatment of head and neck tumors."

If they are successful, patients with colon cancer could be treated in the future with both chemotherapy and Mll1 inhibitors, i.e., therapeutics that specifically impede cancer stem cells. This increases the chances of a successful treatment - even with advanced colon cancer.

Credit: 
Max Delbrück Center for Molecular Medicine in the Helmholtz Association

Discovery of 66 new Roman Army sites shows more clues about one of the empire

image: Roman military presence in Castile

Image: 
romanarmy.eu

The discovery of dozens of new Roman Army sites thanks to remote sensing technology has revealed more about one of the empire's most infamous conflicts.

Analysis of the 66 camps shows the Roman army had a larger presence in the region than previously thought during the 200-year battle to conquer the Iberian Peninsula.

The discovery of camps of different sizes - used for training and shelter - has allowed experts to map how soldiers attacked indigenous groups from different directions and to learn more about the footprint of the Roman military presence in the northern fringe of the River Duero basin - the León, Palencia, Burgos and Cantabria provinces.

Experts analysed aerial photography and satellite images, created three-dimensional models of the terrain from LiDAR data and used drones to create detailed maps of the sites. This included resources from the Spanish National Geographic Institute (IGN) and geoportals such as Google Earth or Bing Maps. Pinpointing locations allowed fieldwork to then take place.

These temporary occupations usually left fragile and subtle traces on the surface. The ditches or the earth and stone ramparts protecting these fortifications have been filled in and flattened. Combining different remote sensing images and fieldwork shows the perimeter shape of the temporary Roman military camps, often a rectangle like a playing card.

These new sites are located at the foothills of the Cantabrian Mountains, where the conflict between Romans and natives was focused at the end of the 1st century BC. This suggests soldiers crossed between lowlands and uplands, using ridges in the mountains to stay out of site and give themselves more protection.

The fact there were so many army camps in the region shows the immense logistical support which allowed soldiers to conquer the area. Sites were used to aid movement to remote locations and to help soldiers stay in the area over the cold winter months. Some of the camps may have housed soldiers for weeks or months, and overs overnight.

The aim of the occupation was to expand the empire and to be able to exploit natural resources such as tin and gold.

The research, published in the journal Geosciences, was carried out by Andrés Menéndez Blanco, Jesús García Sánchez from the Archaeology Institute of Mérida, José Manuel Costa-García and Víctor Vicente García from the University of Santiago de Compostela, João Fonte from the University of Exeter and David González-Álvarez from the Institute of Heritage Sciences, Spanish National Research Council.

Dr Fonte said: "We have identified so many sites because we used different types of remote sensing. Airborne laser scanning gave good results for some sites in more remote places because it showed earthworks really well. Aerial photography worked better in lowland areas for the detection of cropmarks."

"The remains are of the temporary camps that the Roman army set up when moving through hostile territory or when carrying out manoeuveres around their permanent bases. They reveal the intense Roman activity at the entrance to the Cantabrian Mountains during the last phase of the Roman conquest of Hispania."

There is an important concentration of 25 sites along the valleys of northern Palencia and Burgos, as well as southern Cantabria. In the province of León, as many as 41 sites have been documented in different valleys. These range from small forts of a few hundred square meters to large fortified enclosures of 15 hectares.

Most of these Roman military sites were located in close proximity of later important Roman towns. Sasamón, a village in Burgos that was probably where nearby the Emperor Augusto established his camp during his presence in the front.

The research will continue so experts can examine the relationships the Romans established with indigenous communities, named Vaccaei, Turmogi, Cantabri, Astures and Callaeci, according to the Greek and Latin sources.

The team is currently developing a project to catalogue and document all the Roman camps in the province of León by means of drones, in order to gain a better understanding of their structures or the evolution of their state of conservation. Work is also continuing in Burgos and in Sasamón, including a study of the Cerro de Castarreño settlement and its conquest in the 1st century BC.

Credit: 
University of Exeter

Doctors should change the way that they ask patients about self-harm and suicide

Doctors can better help patients with mental health concerns by adopting a different questioning style around self-harm and suicide, experts have said.

New research warns patients may find it difficult to disclose thoughts of self-harm because of the way in which GPs ask about them.

Academics who examined consultations found that GPs were prone to ask questions in a way that invited a "no" response (e.g. "You're not having any thoughts of harming yourself?") and that patients were subsequently more hesitant when reporting thoughts of self-harm.

The study says that discussions about self-harm could be improved by GPs adopting a more open questioning style. This would mean acknowledging the possibility that patients might say "yes" when asked about thoughts of self-harm.

Researchers also say doctors can better help patients with mental health concerns if they ask them separate questions about self-harm and suicide, Doctors should do more to encourage discussion when responses are ambiguous and carry out more extensive checks to see if patients are having distressing thoughts.

Academics studied video-recorded consultations from the One in a Million data archive. These consultations took place between 2014 and 2015. The researchers selected all consultations featuring discussion of self-harm and suicide (18 in total) and carried out an in-depth analysis of how these discussions unfolded.

The research was conducted by Joseph Ford and Felicity Thomas from the University of Exeter, Richard Byng from the University of Plymouth and Rose McCabe from City, University of London and is published in the journal Patient Education and Counseling.

Dr Ford said: "Many patients who die by suicide have seen their GP in the month before death, which shows how important these conversations are. We know from earlier research, though, that many GPs find these conversations to be difficult. They worry about exacerbating a patient's thoughts of suicide, or even putting those thoughts in their head.

"Our aim with this research was to find out how these conversations unfold in practice. By looking at real-life recordings in detail, we have been able to identify ways to improve communication around these important topics."

During the consultations, patients who admitted to having thoughts of self-harm often did so in a hesitant way that downplayed the seriousness of those thoughts. This could mean leaving a long pause before responding or offering a response such as "I have in some ways" rather than a clear "yes".

Professor McCabe said: "People experiencing thoughts of self-harm and/or suicide do not tend to share them with friends or family so conversations with professionals are very important. It is difficult to admit to yourself and to others that you are having these distressing thoughts and people feel a lot of shame and guilt. So questions that further keep these thoughts beneath the surface of the conversation are problematic. GPs and other professionals should be aware of this and ask, for example, 'Sometimes people have thoughts of harming themselves when they are feeling this way, is this something you have experienced?' or 'Sometimes people have thoughts of ending their lives when they are feeling this way, is this something you have experienced?'".

Patients also distanced themselves from the negative stigma associated with self-harm, describing how they would not act upon their thoughts because of the impact it would have on their family. The study suggests that GPs can allay such stigma by asking about the patient's positive reasons for wanting to stay alive rather than the negative impact that their suicide would have on those around them.

The study also found that GPs were overwhelmingly focused on the possibility that patients might act upon their thoughts. While this allowed them to put appropriate measures in place, it risked ignoring those patients who found thoughts of self-harm distressing in themselves. It also potentially avoids examining what some patients want to actively do to address their situation.

Professor Byng said: "While understanding the distress felt by patients and anxiety felt by doctors in these encounters, we propose that practitioners can be supported to shift conversations to either a more therapeutic listening mode or even further around to help individuals see hope through the results of their own positive future actions."

Credit: 
University of Exeter