Culture

Tadpole nerve regeneration capacity provides clue to treating spinal cord injury

image: Introducing Neurod4 into neural stem cells derived from ependymal cells in mice just after spinal cord injury promotes neuronal differentiation. The differentiated neurons form synapses, which leads to an improvement in the motor function of their hind legs.

Image: 
Atsushi Natsume

Nagoya University researchers have identified a gene that plays a crucial role in regenerating neurons of African clawed frog tadpoles, which has an unusually high capacity for nerve regeneration. Their study, recently published in the journal iScience, showed that introducing the gene into mice with spinal cord injury (SCI) led to a partial recovery of their lost motor functions. These findings could contribute to the development of a new therapy for SCI, which often causes a person to experience permanent and severe physical and neurological disabilities.

Repairing spinal cord injuries in humans and other mammals is difficult, partly because of their limited ability to repair and regenerate neural tissues in the spinal cord. In contrast, there are animals with a high capacity for nerve regeneration, such as the African clawed frog. "As a tadpole, it is fully capable of functional recovery after a spinal cord injury," said Drs. Dasfne Lee-Liu and Juan Larrain from the P. Universidad Catolica de Chile in their study, "Genome-wide expression profile of the response to spinal cord injury in Xenopus laevis reveals extensive differences between regenerative and non-regenerative stages," published in 2014.

In this context, the Nagoya University research team conducted a collaborative study with Drs. Lee-Liu and Larrain to identify transcription factors that regulate nerve regeneration in the African clawed frog tadpole, with the aim of inducing regenerative effects in mammals. The team comprehensively analyzed the gene expression profiles of tadpoles in response to SCI, and found that a gene called Neurod4 was expressed predominantly during nerve regeneration. The team thus hypothesized that this gene is a key factor in the regeneration of neural tissues after an injury.

In this study, the team also focused on the fact that in mammals, neural stem cells (known as self-renewing cells) derived from the ependymal cells lining the central canal of the spinal cord are activated and proliferate in the early stage of SCI, although these types of neural stem cells eventually transform into astrocytes -- a type of cell that forms rigid glial scars.

"Taking these things together, we thought that introducing Neurod4 into activated neural stem cells may help regenerate neurons," said Associate Professor Atsushi Natsume of the Nagoya University Graduate School of Medicine, the corresponding author of the study.

To that end, the team conducted experiments in which the Neurod4 gene was introduced to activated neural stem cells in mice just after SCI. The researchers observed that the neural stem cells were successfully converted into neurons and, interestingly, the mice occasionally moved their paralyzed hind legs. Dr. Natsume explained, "Neurod4 introduced into activated neural stem cells facilitates the production of relay neurons, which project to motor neurons of the hind legs. As a secondary effect, glial scar formation was suppressed after the subacute phase of spinal cord injury. This effect allows an environment that was conducive for axons to elongate beyond the injury site and form synapses, thereby improving the motor function of the hind legs."

"Our method is to introduce a neuro regenerative gene directly into neural stem cells that are already present in the spinal cord. This could lessen the problems of rejection and tumor formation, which often occur in conventional stem cell transplantation methods. We believe this study will contribute to the development of new therapeutic approaches to spinal cord injury," he added.

Credit: 
Nagoya University

Scientists from Russia and Germany measured how the brain learn new words

image: Yuri Pavlov and Germany colleagues are studying the brain signals of people in a vegetative state.

Image: 
Urfu / Nadezhda Pavlova.

Researchers from University of Tübingen (Tübingen, Germany) and Ural Federal University (Ekaterinburg, Russia) have developed and experimentally tested new method to understand how the brain builds associations between previously unrelated words. The findings are published in Journal of Neurolinguistics.

The scientists conducted used electroencephalography to measure how the brain responds to the incongruent sentence endings. So, the brain responses to the last word in the phrase "I like my coffee with cream and sugar" have much smaller magnitude as compared to the phrase "I like my coffee with cream and socks". The brain reacts in a similar way to words in pairs such as cat-dog and cat-sky.

"We get a neural index of how people learn new associations between words, in fact - a language," said researcher of Department of Psychology at Ural Federal University and Institute of Medical Psychology and Behavioral Neurobiology at University of Tübingen Yuri Pavlov. "At the same time, this index is completely independent from behavioral responses. The brain itself informs us what it has learnt."

At first stage of the experiment the participants listened to five pairs of semantically unrelated words, each pair repeated twenty times. To give an example, the participants could hear such word pairs as carriage-text, death-fruit, seriousness-cow. Then, to the freshly learnt pairs, new similarly weird but new pairs were added. The experiment showed that the brain responses to the learnt word pairs rapidly attenuated and, after twenty repetitions, did not differ from the responses to familiar word pairs such as coffee-cream.

In the future, the scientists plan to apply the developed experimental paradigm to patients in disorders of consciousness.

"Perhaps those patients whose brains preserve the ability to learn new semantic associations have a chance to regain consciousness," said Yuri Pavlov. "Indeed, such an ability depends on a multiverse of cognitive functions such as long-term and working memory, speech perceptionThis means that we can suspect that the underlying anatomical and functional connections within the brain are not entirely destroyed. It is even possible that the patient is conscious, but cannot inform us about this by speech or gestures."

Credit: 
Ural Federal University

New approach for the development of a drug treatment for obesity and the resulting diseases

image: Beige adipocytes within white adipose tissue (beige adipocytes stained with UCP-1 in green. Lipids are stained in red and F-actin outlining cells especially blood vessels in grey, DNA ist blue)

Image: 
Ruth Karlina

The protein Asc-1 regulates whether fat-burning beige or fat-storing white adipocytes are formed, which can have an impact on the development of metabolic diseases. This is shown by a current study of the Helmholtz Zentrum München and the German Center for Diabetes Research (DZD). The results open up new approaches to prevent the development of metabolic diseases. The study has now been published in Nature Communications.

Not all fat is the same: there is white, brown and beige adipose tissue *. While white fat cells serve as energy stores, excess energy is burned in brown and beige fat tissue. Too much white fat is considered unhealthy. If the white adipose tissue increases significantly in adults with obesity, metabolic diseases such as diabetes or metabolic syndrome can develop. The situation is different in children: There, the initial formation of white adipose tissue is a prerequisite for a healthy metabolism. But how does adolescent adipose tissue differs from adult white adipose tissue? To answer this question, researchers have investigated the composition of white adipose tissue of young and adult mice using single cell RNA sequencing**.

Asc-1 promotes the formation of white adipocytes

The researchers found that adolescent adipose tissue differs greatly from adult white fat, especially in terms of the properties and composition of fat precursor cells. The researchers discovered a special subgroup of fat precursor cells in adolescent adipose tissue that contain the protein Asc-1, which is otherwise present in mature adipocytes. These precursor cells differentiate predominantly into white adipocytes, and the formation of "healthy" beige adipocytes is actively suppressed. In further cell biological investigations, the team around first author Lisa Suwandhi were able to show that the loss of Asc-1 function promotes the formation of beige adipocytes.

"These insights into the physiological processes of adipose tissue growth enable us to develop new strategies to prevent the harmful metabolic consequences of obesity," said last author Dr. Siegfried Ussar. The researchers are already pursuing this approach further. They are currently establishing strategies to modulate Asc-1 function in adipose tissue in the living organism and exploring ways to promote healthy adipose tissue expansion. The goal is to help obese patients maintain a healthy metabolism in the future and thus gain time to treat obesity with a holistic approach.

Credit: 
Deutsches Zentrum fuer Diabetesforschung DZD

Heat conduction record with tantalum nitride

image: Tantalum nitride can concuct heat faster than almost all other materials

Image: 
TU Wien

A thermos bottle has the task of preserving the temperature - but sometimes you want to achieve the opposite: Computer chips generate heat that must be dissipated as quickly as possible so that the chip is not destroyed. This requires special materials with particularly good heat conduction properties.

In collaboration with groups from China and the United States, a research team from TU Wien therefore set out to find the optimal heat conductor. They finally found what they were looking for in a very specific form of tantalum nitride - no other known metallic material has a higher thermal conductivity. In order to be able to identify this record-breaking material, they first had to analyse which processes play a role in heat conduction in such materials at the atomic level. The results have now been published in the scientific journal Physical Review Letters.

Electrons and lattice vibrations

"Basically, there are two mechanisms by which heat propagates in a material," explains Prof. Georg Madsen from the Institute of Materials Chemistry at TU Wien. "Firstly, through the electrons that travel through the material, taking energy with them. This is the main mechanism in good electrical conductors. And secondly through the phonons, which are collective lattice vibrations in the material." The atoms move, causing other atoms to wobble. At higher temperatures, heat conduction through propagation of these vibrations is usually the decisive effect.

But neither the electrons nor the lattice vibrations can propagate completely unhindered through the material. There are various processes that slow down this propagation of thermal energy. Electrons and lattice vibrations can interact with each other, they can scatter, they can be stopped by irregularities in the material.

In some cases, heat conduction can even be dramatically limited by the fact that different isotopes of an element are built into the material - i.e. similar atoms with different numbers of neutrons. In that case, the atoms do not have exactly the same mass, and this affects the collective vibrational behaviour of the atoms in the material.

"Some of these effects can be suppressed - but usually not all at the same time," says Georg Madsen. "It's like playing Whack-A-Mole: You solve one problem, and at the same time a new one arises somewhere else."

Tantalum nitride, the all-rounder

Despite our everyday experience of burning our hands on a hot metal plate, metals typically have a mediocre thermal conductivity. The metal with the highest known thermal conductivity is silver - with only a fraction of the conductivity of the record holding material diamond. But diamonds are expensive and very difficult to process.

With elaborate theoretical analyses and computer simulations, the team finally succeeded in identifying a suitable material: The hexagonal θ-phase of tantalum nitride. Tantalum is particularly favourable because there are hardly any different isotopes. Almost 99.99% of the naturally occurring tantalum is the isotope tantalum 181, other variants hardly occur.

"The combination with nitrogen and the special atomic scale geometry make the phase metallic, and it suppresses interactions of the heat carrying vibrations with other vibrations and with the conducting electrons. It is exactly those interactions that inhibit heat conduction in other materials," says Georg Madsen. "These interactions are not possible in this material because they would violate the law of energy conservation."

Therefore, this form of tantalum nitride combines several important advantages, making it a record-breaking material with a thermal conductivity several times higher than silver and comparable to diamond.

"For the chip industry, tantalum nitride is a highly promising material," Madsen is convinced. "Chips are getting smaller and more powerful, so conducting heat is becoming a bigger and bigger problem. No other material solves this problem better than the θ-phase tantalum nitride."

Credit: 
Vienna University of Technology

Dementia and COVID: What families and physicians should know

NEW YORK, NY (March 30, 2021)--Early in the pandemic, neurologists expressed concern that COVID-19 patients with dementia may be at higher risk for complications and mortality.

But those fears have not been realized, according to a new study of patients who were hospitalized with COVID-19 during the first wave of the pandemic in New York City. The study, led by James Noble, MD, MS, associate professor of neurology at Columbia University Vagelos College of Physicians and Surgeons and the Taub Institute for Research on Alzheimer's Disease and the Aging Brain, and Amro Harb, a Vagelos medical student, was published this month in the Journal of Alzheimer's Disease

Though the study found a greater proportion of patients with dementia had died, "other factors, including age and comorbidities, were really the driving factors and not dementia itself," Noble says.

One unmistakable difference among patients, however, was the greater incidence of delirium in those with dementia. 

"Early in the pandemic, we received many calls from caregivers about the sudden development of confusion and delirium in our dementia patients, even in those with only mild COVID symptoms," Noble says. "Delirium and confusion are common in elderly patients with other types of infections, including pneumonia, influenza, and urinary tract infections, and we realized delirium might be an unrecognized symptom of COVID-19 in this population."

That observation was reflected in the data from the hospitalized patients, where delirium was found in more than 36% of patients with dementia versus less than 12% of patients without dementia.

The dementia patients with COVID-19 were also less likely to report subjective symptoms such as shortness of breath, muscle aches, chills, nausea, or headaches compared with patients without dementia.

"It's hard to say if all of these are true differences," Noble says. "We know that, in general, people with dementia may be less likely to report some of the symptoms that we have come to recognize as typical COVID-19 symptoms because of poor awareness or they just don't remember to report these things." 

Regardless of the reason behind the differences, Noble says the study suggests we may need to look beyond conventional symptoms associated with COVID-19 in this population and consider confusion and delirium as possible common signs of infection.

"The CDC has recognized new confusion is a 'warning sign' of COVID-19, and this study suggests this symptom was especially common in people with dementia hospitalized with COVID-19," Noble says. "This is important for caregivers and health care providers of homebound Alzheimer's patients who have not been vaccinated yet."

Credit: 
Columbia University Irving Medical Center

Endangered songbird challenging assumptions about evolution

Not all species may travel the same path to existence, at least according to new findings from the University of Colorado Boulder and collaborators.

This new research, out now in Science, looked at a newly discovered, endangered songbird located only in South America--the Iberá Seedeater--and found that this bird followed a very rare evolutionary path to come into existence at a much faster pace than the grand majority of species.

By comparing this bird to a closely related neighbor (the Tawny-Bellied Seedeater) in the same group (the southern capuchino seedeaters), the researchers determined that genetic shuffling of existing variations, rather than new random mutations, brought this species into existence--and their own behaviors are keeping them apart.

This species is one of only two known examples across the globe to have traveled this path, challenging the typical assumptions of how new species form.

"One of the aspects of this paper that makes it so cool is that we were able to address this question of how the Iberá Seedeaters formed from multiple different perspectives," said Sheela Turbek, a graduate student in ecology and evolutionary biology (EBIO) at University of Colorado Boulder and the study's lead author.

"Not only did we collect on-the-ground data on who mated with one another and the identity of their offspring, but we also generated genomic data to examine how similar these two species are on a genetic level. We then zoomed out further to look at where the Iberá Seedeater fits in the context of the broader capuchino group."

"Many studies will address one of these aspects or questions but not combine all of these different pieces of information into a single study."

The southern capuchino seedeaters are a group of recently evolved songbirds found throughout South America that is branching rapidly, with many of its species in the early stages of evolution. This family is best known for the dramatic variation with the males in terms of songs and plumage color, while the females are largely indistinguishable even to the most familiar researchers.

The Iberá Seedeater, the most recent member of this family, was first discovered in the remote, swampy grasslands of Iberá National Park in northern Argentina by study co-authors Adrián S. Di Giacomo and Cecilia Kopuchian from Centro de Ecología Aplicada del Litoral, Argentina, in 2001, and then described in scientific literature in 2016.

In that national park, though, are six other closely related species of capuchinos, including the Tawny-Bellied Seedeater, that breed closely beside each other. These species, despite occupying the same environment and eating the same food, rarely interbreed.

And so, researchers wondered why--and how--the Iberá Seedeater even came to be.

They explored these questions in two ways: First, they looked at how this new species may have formed by examining the ways in which its DNA differs from the Tawny-Bellied Seedeater, and second, looking at what mechanisms might be preventing it from interbreeding with the other species that occur in the park.

To do that, Turbek went down to Argentina for the breeding season for three years, staying two and a half to three months at a time, searching for and monitoring nests, collecting blood samples from adults and nestlings, and then, in the final year, performed a behavioral experiment to see whether plumage or song played a roll in terms of species recognition.

"The field work involved in collecting the assortative mating and behavioral data is extraordinarily hard, which is why these kinds of datasets rarely exist. This study and publication are a testament to Sheela's skill and hard work in the field," said Scott Taylor, an assistant professor in EBIO at University of Colorado Boulder, an author on the paper and Turbek's advisor.

What they found is that the two birds are closely related genetically, only distinguishable by the genes involved in plumage coloration. As well, they found that the males responded most aggressively to songs and plumage variations aligning with their own species.

This all means that the species could very well reproduce and hybridize--they just choose not to, therefore reinforcing their own reproductive barriers.

On a broader level, though, when comparing the Iberá Seedeater to other capuchino species, the researchers found that the Iberá Seedeater shares genomic variants with other capuchinos in these regions, but the variants have been shuffled to form a unique combination, which, the researchers argue, could be an evolutionary shortcut that most likely underlies much of the diversity among the different subspecies of this family.

"This is a really beautiful story about a process that we have never seen in quite this way before," says co-author Irby Lovette, director of the Fuller Evolutionary Biology Program at the Cornell Lab of Ornithology.

"The classic and most common evolutionary model for new species is the accumulation of genetic mutations when those species are separated by a geographic barrier over perhaps millions of years. But here we found that genetic shuffling can happen quickly and without geographical isolation. It's almost like 'instant speciation.'"

Leonardo Campagna, a research associate at the Cornell Lab of Ornithology and the senior author on the paper, agrees:

"This is the clearest example in birds of how reshuffling of genetic variation can generate a brand-new species."

The only other organism where this type of evolution has been seen, according to Turbek, is a group of fish found in Africa called the Lake Victoria cichlids.

"It's interesting to see this mechanism operating in something as different as birds," Turbek commented.

While this study focused in part on the role of male behaviors, the researchers are very interested in taking it one step further, examining the role that female choice may also play in reproduction.

"There are many more questions that we have to address," Turbek said.

Credit: 
University of Colorado at Boulder

Scientists discover new genetic disease that delays brain development in children

image: Xenopus froglet finishing metamorphosis.

Image: 
Gretel Nicholson, EXRC

Scientists have discovered a new genetic disease, which causes some children's brains to develop abnormally, resulting in delayed intellectual development and often early onset cataracts.

The majority of patients with the condition, which is so new it doesn't have a name yet, were also microcephalic, a birth defect where a baby's head is smaller than expected when compared to babies of the same sex and age.

Researchers from the universities of Portsmouth and Southampton found that changes in a gene called coat protein complex 1 (COPB1) caused this rare genetic disease.

Now the variant has been identified, it will help clinicians come up with targeted interventions to help patients and their families, also opening the door to screening and prenatal diagnosis.

The research team, made up of frog geneticists, medical genomic research scientists and clinical geneticists, sequenced the DNA of affected patients and their family members, which identified COPB1 as the potential underlying cause of the disease. Using tadpoles to mimic the human gene variants, the tadpoles with the COPB1 gene changes had variably smaller brains than the control tadpoles and many of them had cataracts, just like the patients. This showed the link between the gene and disease very clearly.

The findings are published in the journal Genome Medicine.

Study co-author Professor Matt Guille, who leads a laboratory in the Epigenetics and Developmental Biology research group at the University of Portsmouth, said: "This is the first time that the tadpole has been used in such a direct way to help solve a clinical challenge.

"In our initial experiments to test the link between a genetic variation and a disease we found to our surprise that by altering the DNA of tadpoles, four times out of five we could re-create the disease-related changes seen in human patients. This will allow us to support our colleagues in providing more timely, accurate diagnosis that patients and their families so desperately need."

Co-author Diana Baralle, Professor of Genomic medicine and a clinical geneticist at the University of Southampton, said: "Next generation sequencing is transforming our ability to make new diagnoses and discover new causes for rare disorders. This story started with sisters I saw in clinic without a known underlying cause for their signs and symptoms. Looking closely at their genes, along with further functional molecular work and xenopus studies, we saw that this was a new previously undescribed syndrome. A diagnosis is so important to the family."

One in 17 people will suffer from a rare disease at some time in their lives. Most of these rare diseases have a genetic cause and often affect children, but proving which gene change causes a disease is a huge challenge.

Professor Guille said that previously, while studies connecting a gene and a disease were mainly performed in mice; several labs, including his own at the University of Portsmouth, have recently shown that experiments in tadpoles can also provide very strong evidence about the function of variant human genes. The process of re-creating some gene variants in tadpoles is straightforward and can be done in as little as three days.

Professor Guille added: "We now need to extend and improve our technology to make it applicable to the wider range of disease-related DNA changes provided to us by our clinical collaborators.

"If the clinical researchers find the information sufficiently useful, then we will continue to work together to scale up the pipeline of gene function analysis so it can be used to direct effective interventions for a significant number of patients."

Credit: 
University of Portsmouth

Study investigates non-verbal signs of resistance

A new study examining how people with severe and profound intellectual disabilities resist activities while in care recommends that institutions improve training to help carers better understand non-verbal cues, as well as offer greater flexibility to allow individual preferences to take priority over institutional schedules.

The research, published in the journal Sociology of Health and Illness, investigated how people with limited language ability expressed their wishes and preferences, and how their support workers responded. It was carried out at a residential home and a day care centre in the UK.

The study, by Dr Clare Nicholson of St Mary's University, Twickenham, and Dr Mick Finlay and Dr Steven Stagg of Anglia Ruskin University (ARU), involved taking notes and filming everyday interactions such as feeding, drinking, art and music activities, and physiotherapy, over the course of a year.

The research found that the service users signalled in very subtle ways, usually non-verbally, when they did not want to do something. For people with severe disabilities, how well their care workers recognise and respond to these subtle behaviours is crucial to their autonomy and empowerment.

Behaviour which appeared to signal resistance to activities included pretending to be asleep, dropping tools such as paint brushes, turning the head or the gaze away from the care worker, pushing objects away, dragging feet along the ground to slow movement in a wheelchair, and making loud vocalisations.

When these behaviours were not responded to by care workers, who instead continued with the activity, the person would sometimes escalate their resistance to behaviour involving self-injury, such as thrashing their body around in a wheelchair, striking their own face, and digging their fingernails into their hands.

In addition to encouraging care workers to adopt greater flexibility around which activities take place and when, the authors believe further training using real life examples, such as those outlined in the study, could help staff better understand some of the common signs of resistance.

Co-author Dr Mick Finlay, Reader in Social Psychology at Anglia Ruskin University (ARU), said: "Our research shows that people with severe intellectual disabilities can and do make responsible decisions regarding their wellbeing and wishes, and are able to indicate when they want to remove themselves from situations which make them distressed, bored or unhappy.

"However, for a person to act in a self-determined manner, they need to be able to communicate with others. Communication for people with severe intellectual disabilities is often non-verbal and can be ambiguous, and we found that this can present a challenge for their carers.

"We found that staff often continued to promote or even complete activities on behalf of the people they support, despite signs of resistance. This could be because the carer failed to pick up on the non-verbal cues. Or it could be because of a desire to maximise participation in activities or stick to a schedule.

"Institutional timetables need to be flexible enough to respect the everyday rights and choices of people with severe intellectual disabilities, and support staff need to have the ability to depart from fixed institutional agendas where appropriate, particularly when it would not cause detriment to the people in their care."

Credit: 
Anglia Ruskin University

Study finds microbial-plant interactions affect the microbial response to climate change

image: Surface litter samples were collected from the Loma Ridge Global Change Experiment (LRGCE) field site located 5 km north of Irvine, California.

Image: 
Ecology and Evolutionary Biology Professor Steven Allison

University of California, Irvine, biologists have discovered that plants influence how their bacterial and fungal neighbors react to climate change. This finding contributes crucial new information to a hot topic in environmental science: in what manner will climate change alter the diversity of both plants and microbiomes on the landscape? The paper appears in Elementa: Sciences of the Anthropocene.

The research took place at the Loma Ridge Global Change Experiment, a decade-long study in which scientists simulate the impacts of climate change on neighboring grasslands and coastal scrublands in Southern California. Experimental treatments there include nitrogen addition, a common result of local fossil fuel burning, and simulated drought imposed by covering patches of land with waterproof roofs during rainstorms.

In the project's early years, researchers focused on answering climate questions involving plants only. A research team led by Jennifer Martiny, professor of ecology & evolutionary biology and co-director of the UCI Microbiome Initiative, decided to examine whether the vegetation itself influences how climate change affects the bacteria and fungi in the ground. Soil microbes decompose dead plants, regulating the amount of carbon dioxide exchanged with the atmosphere.

The scientists sequenced microbial DNA in the grassland and scrubland, finding that the types and number of bacteria and fungi differed between them. Next, the team compared how the microbes reacted to nitrogen fertilizer and drought by monitoring the microbial DNA in plant litter, primarily dropped leaves and stems, over a three-year period.

"We thought diminished water might cause the scrubland microbial community to become more similar to that of the grasslands because there is evidence that scrublands start to grow increased grasses under drought conditions," said Sarai Finks, the paper's first author and UCI graduate student. "However, it didn't happen. The two microbial communities remained distinct."

The team also discovered that while simulated drought affected both bacteria and fungi in grassland and scrubland, there were some unexpected differences. Nitrogen addition only affected the bacteria and its impact was far less than that of drought.

"Researchers have looked at this kind of interaction previously, but not on the scale we have done here. We were able to investigate two different kinds of plant communities right next to each other," Finks said, adding that the team hopes their findings will be helpful to other scientists investigating microbial communities. "Microbes are crucial to the carbon cycle and we need to learn what changes in microbial diversity mean for the environment."

The researchers' paper was the latest to be published from scientific data collected before the Silverado wildfire struck the Loma Ridge Global Change Experiment in October 2020. "Scientists are now looking into researching post-fire interactions between plants and the microbial communities at the site," Finks said.

Credit: 
University of California - Irvine

Engineers use tiny device to change songbird pitch, improve understanding of human speech

image: Songbird with active implant with the capability of broadcasting high resolution temperature readings and cell type specific neuronal stimulation

Image: 
University of Arizona Gutruf Lab

The human brain regions responsible for speech and communication keep our world running by allowing us to do things like talk with friends, shout for help in an emergency and present information in meetings.

However, scientific understanding of just how these parts of the brain work is limited. Consequently, knowledge of how to improve challenges such as speech impediments or language acquisition is limited as well.

Using an ultra-lightweight, wireless implant, a University of Arizona team is researching songbirds - one of the few species that share humans' ability to learn new vocalizations - to improve scientific understanding of human speech. A paper about their work was published today in the journal Nature Communications.

"Using new methods of antenna design and optimized electronics, we were able to shrink the devices dramatically compared to existing versions, to about a third of the size of a dime and as thin as a sheet of paper," said lead author Jokubas Ausra, a biomedical engineering doctoral student in the Gutruf Lab, where the devices were created.

There are several ways the device can be used to study the link between brain behavior and vocalization. It can monitor the bird for slight temperature changes that indicate when a bird is most likely to sing. Using a technique called optogenetics, researchers can modulate neuron groups in the brain regions used for birdsong. In this study, the team found that remotely controlling specific neurons during birdsong using their unique device caused the song to change pitch.

"We are excited to expand the toolbox of neuroscientists and hope to enable many exciting studies that decipher the working principles of the brain," said senior author Philipp Gutruf, assistant professor of biomedical engineering and Craig M. Berge Fellow in the UArizona College of Engineering.

The Gutruf Lab has developed other wireless lightweight devices used to monitor brain activity in rodents, but birds' ability to move in 3D space represents an added challenge. This tiny device allows the birds to move without restriction - a breakthrough enabled by careful management of the energy sent wirelessly to the implant.

"Because of the small size and light weight, the birds can move freely and live permanently with the implant without affecting their behavior or health, which opens up many possibilities to study the basis for vocal communication," said co-senior author Julie Miller, an assistant professor of neuroscience and speech, language and hearing sciences at UArizona.

The team's next goal is to expand device capabilities to also record neuron activity. This could allow researchers to visualize brain activity during song learning and performance to gain a deeper understanding of the underlying brain mechanisms.

Credit: 
University of Arizona College of Engineering

How Streptococcus pyogenes can survive on skin and cause skin infections

image: WT indicates wild-type S. pyogenes (blue cells) that up-regulate ADI under low-glucose conditions, such as the skin surface. When ADI is activated, the bacteria can survive using arginine instead of glucose: virulent bacteria penetrate and damage the skin. ΔADI indicates S. pyogenes that has been genetically modified to inactivate the ADI pathway (red cells), leading to low virulence. In blood, ADI is suppressed by high glucose levels.

Image: 
Osaka University

Osaka, Japan - Streptococcus pyogenes is one of the most important bacterial causes of human skin infections. If S. pyogenes invades deep into the tissue, it can cause life-threatening illnesses, such as sepsis and toxic shock. With its limited supply of carbohydrates, the skin is generally an effective barrier against infection and not a good surface for the survival of S. pyogenes. To survive successfully and invade deep into the tissue, bacteria must be able to find a source of nutrients and also evade the skin's immune defenses.

Now, an international team led by Osaka University, Japan, in collaboration with Keio University, Japan, and University of California San Diego, USA, has discovered a way this disease organism obtains nutrition from the skin surface. This knowledge could lead to new therapeutic approaches to tackle infections. The team recently published the work in Cell Reports.

It was already known that some bacteria break down arginine (an amino acid - one of the building blocks of proteins) via a biochemical pathway named the arginine deaminase (ADI) pathway. The team confirmed that S. pyogenes can survive using arginine even when starved of glucose. When they deleted the bacterial gene (named arcA) encoding the first enzyme in the ADI pathway, the S. pyogenes lost that ability and also became less toxic towards human skin cells grown in culture.

When arginine is supplied, the ADI pathway of S. pyogenes is activated but there are also widespread changes in gene expression. Some genes are down-regulated but large numbers of genes are up-regulated, including genes associated with virulence of S. pyogenes, such as those that produce bacterial toxins.

Using mouse skin as a model system for human skin, the team showed for the first time that S. pyogenes can use arginine to survive on the skin surface. S. pyogenes lacking the arcA gene survived poorly and were less virulent on mouse skin, confirming the importance of this pathway in the disease process. In contrast, in blood (containing plentiful glucose), the altered S. pyogenes appeared no different to normal S. pyogenes since the ADI pathway was not needed.

"We showed that arginine from stratum corneum-derived filaggrin was a key substrate for the ADI pathway of S. pyogenes," says lead researcher Dr. Yujiro Hirose. "In mice that do not produce filaggrin, less arginine is available and the S. pyogenes bacteria do not utilize ADI pathway to cause the skin lesion."

"This represents a significant step forward in understanding how S. pyogenes survives on the skin," explains Dr. Hirose. "We expect our study will lead to novel treatment strategies: if we can block arginine metabolism in S. pyogenes it should restrict the pathogen's survival and virulence."

Credit: 
Osaka University

Curved plasmonic fluxes reveal new way to practical light manipulation within nanoscal

Scientists from Tomsk Polytechnic University jointly with Russian colleagues and researchers from Technical University of Denmark the first time have experimentally proved the existence of a two-dimensional (2D) curved flux of plasmonic quasiparticles, a plasmonic hook. A flat 2D hook is smaller than a 3D hook and possesses new properties, due to them, the researchers consider it as the most promising transmitter in high-speed microoptical circuits. The research findings are published in Applied Physics Letters (IF: 3,597; Q1) academic journal.

Electrons transmit information in existing calculation devices. The scientists suppose if electrons are replaced by photons, light quanta, it will be possible to transmit the data literally at the speed of light. In order that microoptical circuits and optical computers would become ordinary devices and become mass-produced, it is required to find a way to compress light to the nanoscale.

"We are searching for new types of curved wave fluxes, which can solve this task. Previously, we simulated and experimentally proved the existence of photonic and acoustic hooks and now we have proved the existence of a plasmonic hook. Nowadays, it is the most promising method to transmit a signal. The plasmonic wavelength is shorter than a 3D wavelength in free space and the area of radiation localization is in nanoscale. It is a crucial indicator for miniaturization," Igor Minin, Professor of the TPU Division for Electronic Engineering, a supervisor of the research work, says.

The authors of the article obtained a flat plasmonic hook using a simple and cheap focusing element. The flat plasmonic hook is an asymmetric dielectric particle sized 4-5 μm and about 0.25 μm thick. According to the scientists, the participle shape can be various, in this case, it was a microcube with a docked prism. This particle was placed on the 0.1 μm thick gold film, on the other side of the film, the diffraction grating was deposited.

During the experiments, the laser ray was directed at the diffraction grating. Plasmon resonance occurred next to the surface of the diffraction grafting under sunlight that is the sunlight was converted into plasmonic waves. These waves passed through the asymmetric dielectric particle focused in a 2D curved ray.

"We obtained a 2D curved ray due to a special shape of a dielectric particle. One of the mechanisms of sub-wave structured focusing is based on the phenomenon of a plasmonic nanojet that we managed to experimentally fix for the first time earlier. When we shift free 3D space to plasmon polaritons, in other words, 2D space, the quantum nature of matter reveals. It allows implementing implicitly new opportunities to control the interaction between matter and light, for instance, to implement biosensing methods based on the detection of micro- and nanoparticles, biomolecules in the near field. Of course, it is too early to speak about the application of results, it is a task for future research. Therefore, any research and experiments to transmit signals based on optical principles are still in the practice of fundamental research. Scientists of various fields will have to overcome many challenges to create, for instance, a productive optical computer or even efficient microcircuits. To overcome these challenges, 10-15 years might be spent," Igor Minin, TPU Professor, initiator of the research work, says.

Credit: 
Tomsk Polytechnic University

Confronting plastic pollution to protect environmental and public health

Some 8,300 million metric tons of plastics have been manufactured since production exploded in the 1950s, with more than 75 percent ending up as waste and 15 million metric tons reaching oceans every year. Plastic waste fragments into increasingly smaller but environmentally persistent "microplastics," with potentially harmful effects on the health of people, wildlife and ecosystems. A new collection, "Confronting Plastic Pollution to Protect Environmental and Public Health," is publishing on March 30th, 2021 in the open access journal PLOS Biology that addresses critical scientific challenges in understanding the impacts of microplastics.

The collection features three evidence-based commentaries from ecotoxicology and environmental health experts that address gaps in understanding and flag research priorities for improving methods to detect, evaluate, and mitigate threats associated with this emerging contaminant. The guest editor of the collection is Judith Enck, former EPA regional administrator, president of the nonprofit Beyond Plastics and visiting professor at Bennington College's Center for the Advancement of Public Action.

Plastic production increased from 2 million metric tons a year in 1950 to 380 million metric tons by 2015 and is expected to double by 2050. The plastic pollution crisis will worsen, experts say, as petrochemical companies shift from fossil fuels to fracking, which produces the plastic feedstock ethane.

The commentaries explores pressing challenges in three areas: the difficulty of developing health protective policies for emerging contaminants, the migration of toxic and undisclosed plastic additives into food and understanding how microplastics, a form of carbon themselves, impact carbon cycling in soils.

In the Essay, "Addressing the environmental and health impacts of microplastics requires open collaboration between diverse sectors," ecotoxicologist Scott Coffin and colleagues use California as a case study to suggest strategies to design research, policies and regulations for a contaminant scientists are just starting to understand, drawing on parallels with a similar class of emerging contaminants (per- and polyfluoroalkyl substances).

In her Essay, "Tackling the toxics in plastics packaging," environmental toxicologist Jane Muncke focuses on a major driver of the global plastic pollution crisis: single-use food packaging. Efforts to reduce plastic waste through recycling ignore evidence that chemicals in plastic migrate into food, she argues, making harmful chemicals an unintentional part of the human diet.

In their Essay, "Microplastic effects on carbon cycling processes in soils," plant ecologist Matthias Rillig and colleagues explore how microplastics appear to be interfering with the very fabric of the soil environment itself and call for a "major concerted effort" to understand the pervasive effects of these ubiquitous particles on the function of soils and terrestrial ecosystems.

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PLOS

First interstellar comet may be the most pristine ever found

image: This image was taken with the FORS2 instrument on ESO's Very Large Telescope in late 2019, when comet 2I/Borisov passed near the Sun.

Since the comet was travelling at breakneck speed, around 175 000 kilometres per hour, the background stars appeared as streaks of light as the telescope followed the comet's trajectory. The colours in these streaks give the image some disco flair and are the result of combining observations in different wavelength bands, highlighted by the various colours in this composite image.

Image: 
ESO/O. Hainaut

New observations with the European Southern Observatory's Very Large Telescope (ESO's VLT) indicate that the rogue comet 2I/Borisov, which is only the second and most recently detected interstellar visitor to our Solar System, is one of the most pristine ever observed. Astronomers suspect that the comet most likely never passed close to a star, making it an undisturbed relic of the cloud of gas and dust it formed from.

2I/Borisov was discovered by amateur astronomer Gennady Borisov in August 2019 and was confirmed to have come from beyond the Solar System a few weeks later. "2I/Borisov could represent the first truly pristine comet ever observed," says Stefano Bagnulo of the Armagh Observatory and Planetarium, Northern Ireland, UK, who led the new study published today in Nature Communications. The team believes that the comet had never passed close to any star before it flew by the Sun in 2019.

Bagnulo and his colleagues used the FORS2 instrument on ESO's VLT, located in northern Chile, to study 2I/Borisov in detail using a technique called polarimetry [1]. Since this technique is regularly used to study comets and other small bodies of our Solar System, this allowed the team to compare the interstellar visitor with our local comets.

The team found that 2I/Borisov has polarimetric properties distinct from those of Solar System comets, with the exception of Hale-Bopp. Comet Hale-Bopp received much public interest in the late 1990s as a result of being easily visible to the naked eye, and also because it was one of the most pristine comets astronomers had ever seen. Prior to its most recent passage, Hale-Bopp is thought to have passed by our Sun only once and had therefore barely been affected by solar wind and radiation. This means it was pristine, having a composition very similar to that of the cloud of gas and dust it -- and the rest of the Solar System -- formed from some 4.5 billion years ago.

By analysing the polarisation together with the colour of the comet to gather clues on its composition, the team concluded that 2I/Borisov is in fact even more pristine than Hale-Bopp. This means it carries untarnished signatures of the cloud of gas and dust it formed from.

"The fact that the two comets are remarkably similar suggests that the environment in which 2I/Borisov originated is not so different in composition from the environment in the early Solar System," says Alberto Cellino, a co-author of the study, from the Astrophysical Observatory of Torino, National Institute for Astrophysics (INAF), Italy.

Olivier Hainaut, an astronomer at ESO in Germany who studies comets and other near-Earth objects but was not involved in this new study, agrees. "The main result -- that 2I/Borisov is not like any other comet except Hale-Bopp -- is very strong," he says, adding that "it is very plausible they formed in very similar conditions."

"The arrival of 2I/Borisov from interstellar space represented the first opportunity to study the composition of a comet from another planetary system and check if the material that comes from this comet is somehow different from our native variety," explains Ludmilla Kolokolova, of the University of Maryland in the US, who was involved in the Nature Communications research.

Bagnulo hopes astronomers will have another, even better, opportunity to study a rogue comet in detail before the end of the decade. "ESA is planning to launch Comet Interceptor in 2029, which will have the capability of reaching another visiting interstellar object, if one on a suitable trajectory is discovered," he says, referring to an upcoming mission by the European Space Agency.

An origin story hidden in the dust

Even without a space mission, astronomers can use Earth's many telescopes to gain insight into the different properties of rogue comets like 2I/Borisov. "Imagine how lucky we were that a comet from a system light-years away simply took a trip to our doorstep by chance," says Bin Yang, an astronomer at ESO in Chile, who also took advantage of 2I/Borisov's passage through our Solar System to study this mysterious comet. Her team's results are published in Nature Astronomy.

Yang and her team used data from the Atacama Large Millimeter/submillimeter Array (ALMA), in which ESO is a partner, as well as from ESO's VLT, to study 2I/Borisov's dust grains to gather clues about the comet's birth and conditions in its home system.

They discovered that 2I/Borisov's coma -- an envelope of dust surrounding the main body of the comet -- contains compact pebbles, grains about one millimetre in size or larger. In addition, they found that the relative amounts of carbon monoxide and water in the comet changed drastically as it neared the Sun. The team, which also includes Olivier Hainaut, says this indicates that the comet is made up of materials that formed in different places in its planetary system.

The observations by Yang and her team suggest that matter in 2I/Borisov's planetary home was mixed from near its star to further out, perhaps because of the existence of giant planets, whose strong gravity stirs material in the system. Astronomers believe that a similar process occurred early in the life of our Solar System.

While 2I/Borisov was the first rogue comet to pass by the Sun, it was not the first interstellar visitor. The first interstellar object to have been observed passing by our Solar System was ?Oumuamua, another object studied with ESO's VLT back in 2017. Originally classified as a comet, ?Oumuamua was later reclassified as an asteroid as it lacked a coma.

Notes

[1] Polarimetry is a technique to measure the polarisation of light. Light becomes polarised, for example, when it goes through certain filters, like the lenses of polarised sunglasses or cometary material. By studying the properties of sunlight polarised by a comet's dust, researchers can gain insights into the physics and chemistry of comets.

More information

This research highlighted in the first part of this release was presented in the paper "Unusual polarimetric properties for interstellar comet 2I/Borisov" to appear in Nature Communications (doi: [10.1038/s41467-021-22000-x] - https://www.nature.com/articles/s41467-021-22000-x ). The second part of the release highlights the study "Compact pebbles and the evolution of volatiles in the interstellar comet 2I/Borisov" to appear in Nature Astronomy (doi: [10.1038/s41550-021-01336-w] - https://www.nature.com/articles/s41550-021-01336-w ).

The team who conducted the first study is composed of S. Bagnulo (Armagh Observatory & Planetarium, UK [Armagh]), A. Cellino (INAF - Osservatorio Astrofisico di Torino, Italy), L. Kolokolova (Department of Astronomy, University of Maryland, US), R. Nežič (Armagh; Mullard Space Science Laboratory, University College London, UK; Centre for Planetary Science, University College London/Birkbeck, UK), T. Santana-Ros (Departamento de Fisica, Ingeniería de Sistemas y Teoría de la Señal, Universidad de Alicante, Spain; Institut de Ciencies del Cosmos, Universitat de Barcelona, Spain), G. Borisov (Armagh; Institute of Astronomy and National Astronomical Observatory, Bulgarian Academy of Sciences, Bulgaria), A. A. Christou (Armagh), Ph. Bendjoya (Université Côte d'Azur, Observatoire de la Côte d'Azur, CNRS, Laboratoire Lagrange, Nice, France), and M. Devogele (Arecibo Observatory, University of Central Florida, US).

The team who conducted the second study is composed of Bin Yang (European Southern Observatory, Santiago, Chile [ESO Chile]), Aigen Li (Department of Physics and Astronomy, University of Missouri, Columbia, USA), Martin A. Cordiner (Astrochemistry Laboratory, NASA Goddard Space Flight Centre, USA and Department of Physics, Catholic University of America, Washington, DC, USA), Chin-Shin Chang (Joint ALMA Observatory, Santiago, Chile [JAO]), Olivier R. Hainaut (European Southern Observatory, Garching, Germany), Jonathan P. Williams (Institute for Astronomy, University of Hawai'i, Honolulu, USA [IfA Hawai'i]), Karen J. Meech (IfA Hawai'i), Jacqueline V. Keane (IfA Hawai'i), and Eric Villard (JAO and ESO Chile).

ESO is the foremost intergovernmental astronomy organisation in Europe and the world's most productive ground-based astronomical observatory by far. It has 16 Member States: Austria, Belgium, the Czech Republic, Denmark, France, Finland, Germany, Ireland, Italy, the Netherlands, Poland, Portugal, Spain, Sweden, Switzerland and the United Kingdom, along with the host state of Chile and with Australia as a Strategic Partner. ESO carries out an ambitious programme focused on the design, construction and operation of powerful ground-based observing facilities enabling astronomers to make important scientific discoveries. ESO also plays a leading role in promoting and organising cooperation in astronomical research. ESO operates three unique world-class observing sites in Chile: La Silla, Paranal and Chajnantor. At Paranal, ESO operates the Very Large Telescope and its world-leading Very Large Telescope Interferometer as well as two survey telescopes, VISTA working in the infrared and the visible-light VLT Survey Telescope. Also at Paranal ESO will host and operate the Cherenkov Telescope Array South, the world's largest and most sensitive gamma-ray observatory. ESO is also a major partner in two facilities on Chajnantor, APEX and ALMA, the largest astronomical project in existence. And on Cerro Armazones, close to Paranal, ESO is building the 39-metre Extremely Large Telescope, the ELT, which will become "the world's biggest eye on the sky".

The Atacama Large Millimeter/submillimeter Array (ALMA), an international astronomy facility, is a partnership of ESO, the U.S. National Science Foundation (NSF) and the National Institutes of Natural Sciences (NINS) of Japan in cooperation with the Republic of Chile. ALMA is funded by ESO on behalf of its Member States, by NSF in cooperation with the National Research Council of Canada (NRC) and the Ministry of Science and Technology (MOST) and by NINS in cooperation with the Academia Sinica (AS) in Taiwan and the Korea Astronomy and Space Science Institute (KASI). ALMA construction and operations are led by ESO on behalf of its Member States; by the National Radio Astronomy Observatory (NRAO), managed by Associated Universities, Inc. (AUI), on behalf of North America; and by the National Astronomical Observatory of Japan (NAOJ) on behalf of East Asia. The Joint ALMA Observatory (JAO) provides the unified leadership and management of the construction, commissioning and operation of ALMA.

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ESO

New statistical method eases data reproducibility crisis

UNIVERSITY PARK, Pa. -- A reproducibility crisis is ongoing in scientific research, where many studies may be difficult or impossible to replicate and thereby validate, especially when the study involves a very large sample size. For example, to evaluate the validity of a high-throughput genetic study's findings scientists must be able to replicate the study and achieve the same results. Now researchers at Penn State and the University of Minnesota have developed a statistical tool that can accurately estimate the replicability of a study, thus eliminating the need to duplicate the work and effectively mitigating the reproducibility crisis.

The team used its new method, which they describe in a paper publishing today (March 30) in Nature Communications, to confirm the findings of a 2019 study on the genetic factors that contribute to smoking and drinking addiction but noted that it also can be applied to other genome-wide association studies -- or studies that investigate the genetic underpinnings for diseases.

"While we applied the method to study smoking and drinking addiction-related outcomes, it could benefit other similar large-scale consortia studies, including current studies on the host genetic contribution to COVID-19 symptoms," said Dajiang Liu, associate professor of public health sciences and biochemistry and molecular biology, Penn State.

According to Liu, to detect patterns in genome-wide association studies it is important to obtain data from a large number of individuals. Scientists often acquire these data by combining many existing similarly designed studies, which is what Liu and his colleagues did for the 2019 smoking and drinking addiction study that ultimately comprised 1.2 million individuals.

"We worked really hard to collect all of the patient samples that we could manage," said Liu, noting that the data came from biobanks, epidemiology studies and direct-to-consumer genetic testing companies, such as 23andMe. However, he added, since the team used all of the available studies in its analysis, there were none leftover to use as comparisons for validation. "Our statistical method allows researchers to assess the replicability of genetic association signals without a replication dataset," he said. "It helps to maximize the power of genetic studies as no samples need to be reserved for replication; instead, all samples can be used for discoveries."

The team's method, which they call MAMBA (Meta-Analysis Model-Based Assessment of replicability), evaluates the strength and consistency of the associations between atypical bits of DNA, called single nucleotide polymorphisms (SNPs), and disease traits such as addiction. Specifically, MAMBA calculates the probability that if an experiment can be repeated with a different set of individuals, the relationships between the SNPs and those individuals' traits would be the same or similar as in the first experiment.

Qunhua Li, associate professor of statistics, Penn State, explained that MAMBA assigns a higher probability of replicability (PPR) for each SNP if the SNP is significantly associated with the trait being evaluated and if its estimated effect sizes are consistent across multiple studies.

"For example," said Li, "if the majority of participants who are addicted to smoking have a certain SNP that differs from non-addicted people, and if this SNP shows up across people in multiple smaller studies, then MAMBA will give it a higher PPR, which suggests that the SNP is probably important in addiction."

The researchers demonstrated the value of their method by applying it to Liu's 2019 study on smoking and drinking addiction. Among the 556 common and low-frequency SNP association signals, the team identified 529 with PPR greater than 99%. In an extended analysis of around 4,300 rare SNPs, the researchers identified 2,807 SNPs with PPR greater than 99%.

"Interestingly, we found that certain genes that are known to be responsible for lipid metabolism also influence smoking addiction," said Bibo Jiang, assistant professor of public health sciences, Penn State, noting that the phenomenon is known as pleiotropy -- when a gene influences two seemingly irrelevant traits. "If we want to design medications that target those genes to help people stop smoking, we should be mindful of any underlying conditions related to lipid metabolism, such as high cholesterol, that they may have."

Liu noted that the method can be applied to genome-wide association studies focused on a wide variety of traits. "I think in the next decade or so, an essential focus of biology will be to interpret and make sense of those genome-wide association study discoveries and whether we can translate some of them into medications to facilitate personalized medicine," he said. "We are excited to be able to offer this statistical approach as a service to the research community."

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Penn State