Culture

High density EEG produces dynamic image of brain signal source

Marking a major milestone on the path to meeting the objectives of the NIH BRAIN initiative, research by Carnegie Mellon's Biomedical Engineering Department Head Bin He advances high-density electroencephalography (EEG) as the future paradigm for dynamic functional neuroimaging.

The NIH Brain Research through Advancing Innovative Neurotechnologies (BRAIN) Initiative motivates researchers to "produce a revolutionary new dynamic picture of the brain that, for the first time, shows how individual cells and complex neural circuits interact in both time and space." An ideal technique for functional human brain imaging--one of the initiative's top priorities--would depict brain activity with high temporal resolution, high spatial resolution, and wide spatial coverage.

Carnegie Mellon's He has made a major leap forward for the field of functional neuroimaging. An NIH-funded study lasting several years and examining dozens of patients with epilepsy has produced a novel source imaging technology that uses high-density EEG recordings to map underlying brain networks. Published in Nature Communications, this research is a big step towards establishing the ability to dynamically image human brain function and dysfunction. This could provide important insight into both where and how underlying information-processing occurs.

EEG has long been one of the most effective functional methods available for human brain mapping. It takes readings in a matter of milliseconds, however the technology still struggles with determining the spatial extent of activity within the brain. The approach proposed by He and his team can accurately estimate for the first time the size and scope of active areas within the brain using high-density EEG, as well as interactions between regions that are functionally related. Their findings were validated using clinical recordings made at the Mayo Clinic, analyzing a total of 1,027 EEG spikes and 86 seizures recorded from 36 patients.

The team's method, termed the fast spatio-temporal iteratively reweighted edge sparsity (FAST-IRES) technique, uses machine learning to objectively estimate signal sources and activity as they vary over time. Unlike prior imaging techniques, it needs no ad hoc algorithm or human intervention for determining source extent and requires only minimal, intuitive input from physicians.

FAST-IRES could have a major impact on the research and treatment of various neurological and mental disorders like Alzheimer's, Parkinson's, stroke, chronic pain, and even depression. However, this method is uniquely and most immediately impactful for those suffering from drug-resistant epilepsy.

Around one percent of the global population suffers from epilepsy, and roughly one-third of cases are drug-resistant, requiring surgical intervention. Yet until now, no current non-invasive imaging modality has the spatial specificity to accurately determine the epileptogenic zone (EZ), which represents the minimum amount of tissue that must be removed to halt seizures.

"By analyzing epilepsy networks with our proposed FAST-IRES framework, we have demonstrated that the EZ can be determined objectively and noninvasively with high precision from scalp high density EEG recordings," wrote He and his co-authors.

There findings were validated against readings from conventional invasive intracranial recordings and surgical outcomes from each patient, proving FAST-IRES' effectiveness.

The study also marks one of the first times high-density EEG has been used to study epileptic seizures. The more powerful imaging technology, packing more than double the electrodes generally used in a clinical setting, is now available to patients treated at the Mayo Clinic. He believes that within the next five years, the FAST-IRES methodology will begin to impact the way we understand a number of neurological disorders.

"This work demonstrates that EEG source imaging may become the non-invasive high-spatial, high-temporal resolution paradigm for human brain imaging technology, an important goal of the BRAIN Initiative." said He, who served as a member of the NIH BRAIN Multi-Council Working Group from 2015-2019.

He's research may be life-changing for those suffering from epilepsy and could benefit researchers and physicians across the field of neurology, neurosurgery, and human neuroscience. This work brings the NIH and the scientific community one step closer to achieving a revolutionary new dynamic picture of the brain.

Credit: 
College of Engineering, Carnegie Mellon University

Seismic map of North America reveals geologic clues, earthquake hazards

image: This new-generation stress map of North America includes the first view of the style of faulting across the continent as well as more than 300 new measurements of the direction from which the greatest pressure occurs in the Earth's crust. The background color indicates relative stress magnitudes, or style of faulting. (Image credit: Jens-Erik Lund Snee and Mark Zoback)

Image: 
Jens-Erik Lund Snee and Mark Zoback

How do mountains form? What forces are needed to carve out a basin? Why does the Earth tremble and quake?

Earth scientists pursue these fundamental questions to gain a better understanding of our planet's deep past and present workings. Their discoveries also help us plan for the future by preparing us for earthquakes, determining where to drill for oil and gas, and more. Now, in a new, expanded map of the tectonic stresses acting on North America, Stanford researchers present the most comprehensive view yet of the forces at play beneath the Earth's surface.

The findings, published in Nature Communications on April 23, have implications for understanding and mitigating problems associated with induced seismicity - human-caused earthquakes - from unconventional oil and gas recovery, especially in Oklahoma, Texas and other areas targeted for energy exploration. But they also pose a whole new set of questions that the researchers hope will stimulate a wide range of modeling studies.

"Understanding the forces in the Earth's crust is fundamental science," said study co-author Mark Zoback, the Benjamin M. Page Professor of Geophysics in Stanford's School of Earth, Energy & Environmental Sciences (Stanford Earth). "In some cases, it has immediate application, in others, it may be applied decades later to practical questions that do not exist today."

First continental synthesis of data

The new research provides the first quantitative synthesis of faulting across the entire continent, as well as hundreds of measurements of compressive stress directions - the direction from which the greatest pressure occurs in the Earth's crust. The map was produced by compiling new and previously published measurements from boreholes as well as inferences about kinds or "styles" of faults based on earthquakes that have occurred in the past.

The three possible styles of faulting include extensional, or normal faulting, in which the crust extends horizontally; strike-slip faulting, in which the Earth slides past itself, like in the San Andreas fault; and reverse, or thrust, faulting in which the Earth moves over itself. Each one causes very different shaking from a hazard point of view.

"In our hazards maps right now, in most places, we don't have direct evidence of what kind of earthquake mechanisms could occur," said Jack Baker, a professor of civil and environmental engineering who was not involved with the study. "It's exciting that we have switched from this blind assumption of anything is possible to having some location-specific inferences about what types of earthquakes we might expect."

Zooming in

In addition to presenting a continent-level view of the processes governing the North American plate, the data - which incorporates nearly 2,000 stress orientations, 300 of which are new to this study - offer regional clues about the behavior of the subsurface.

"If you know an orientation of any fault and the state of stress nearby, you know how likely it is to fail and whether you should be concerned about it in both naturally-triggered and industry-triggered earthquake scenarios," said lead author Jens-Erik Lund Snee, PhD '20, now a postdoctoral fellow with the United States Geological Survey (USGS) in Lakewood, Colorado. "We've detailed a few places where previously published geodynamic models agree very well with the new data, and others where the models don't agree well at all."

In the Eastern U.S., for example, the style of faulting revealed by the study is exactly the opposite of what would be expected as the surface slowly "rebounds" following the melting of the ice sheets that covered most of Canada and the northern U.S. some 20,000 years ago, according to Lund Snee. The discovery that the rebound stresses are much less than those already stored in the crust from plate tectonics will advance scientists' understanding of the earthquake potential in that area.

In the Western U.S., the researchers were surprised to see changes in stress types and orientations over short distances, with major rotations occurring over only tens of miles - a feature that current models of Earth dynamics do not reveal.

"It's just much clearer now how stress can systematically vary on the scale of a sedimentary basin in some areas," Zoback said. "We see things we've never seen before that require geologic explanation. This will teach us new things about how the Earth works."

Credit: 
Stanford's School of Earth, Energy & Environmental Sciences

Coronaviruses and bats have been evolving together for millions of years

image: A mother fruit bat with her nursing pup. These fruit bats (Rousettus madagascariensis) from Ankarana in northern Madagascar are from a species that carries a form of coronavirus. The researchers have been studying the population dynamics of this species superimposed on different zoonotic diseases for seven years.

Image: 
Olivà S. Noroalintseheno Lalarivoniaina

Bats do a lot of good for the world--they pollinate plants, they eat disease-carrying insects, and they help disperse seeds that help with the regeneration of tropical forest trees. Bats and a range of other mammal groups are also natural carriers of coronaviruses. To better understand this very diverse family of viruses, which includes the specific coronavirus behind COVID-19, scientists compared the different kinds of coronaviruses living in 36 bat species from the western Indian Ocean and nearby areas of Africa. They found that different groups of bats at the genus and in some cases family level had their own unique strains of coronavirus, revealing that bats and coronaviruses have been evolving together for millions of years.

"We found that there's a deep evolutionary history between bats and coronaviruses," says Steve Goodman, MacArthur Field Biologist at Chicago's Field Museum and an author of a paper just released in Scientific Reports detailing the discovery. "Developing a better understanding of how coronaviruses evolved can help us build public health programs in the future." The study was led by Université de La Réunion scientists Léa Joffrin and Camille Lebarbenchon, who conducted the genetic analyses in the laboratory of "Processus infectieux en milieu insulaire tropical (PIMIT)" on Réunion Island, focusing on emerging infectious diseases on islands in the western Indian Ocean.

A lot of people use "coronavirus" as a synonym for "COVID-19," the kind of coronavirus causing the current pandemic. However, there are a vast number of types of different coronaviruses, potentially as many as bat species, and most of them are unknown to be transferred to humans and pose no known threat. The coronaviruses carried by the bats studied in this paper are different from the one behind COVID-19, but by learning about coronaviruses in bats in general, we can better understand the virus affecting us today.

All animals have viruses that live inside them, and bats, as well as a range of other mammal groups, happen to be natural carriers of coronaviruses. These coronaviruses don't appear to be harmful to the bats, but there's potential for them to be dangerous to other animals if the viruses have opportunities to jump between species. This study examines the genetic relationships between different strains of coronaviruses and the animals they live in, which sets the stage for a better understanding of the transfer of viruses from animals to humans.

Goodman, who has been based on Madagascar for several decades, and his colleagues took swab and some cases blood samples from more than a thousand bats representing 36 species found on islands in the western Indian Ocean and coastal areas of the African nation of Mozambique. Eight percent of the bats they sampled were carrying a coronavirus.

"This is a very rough estimate of the proportion of infected bats. There is increasing evidence for seasonal variation in the circulation of these viruses in bats, suggesting that this number may significantly vary according to the time of the year," says Camille Lebarbenchon, Disease Ecologist at the Université de La Réunion.

The researchers ran genetic analyses of the coronaviruses present in these bats. By comparing the coronaviruses isolated and sequenced in the context of this study with ones from other animals including dolphins, alpacas, and humans, they were able to build a giant coronavirus family tree. This family tree shows how the different kinds of coronavirus are related to each other.

"We found that for the most part, each of the different genera of families of bats for which coronavirus sequences were available had their own strains," says Goodman. "Moreover, based on the evolutionary history of the different bat groups, it is clear that there is a deep coexistence between bats (at the level of genus and family) and their associated coronaviruses." For example, fruit bats of the family Pteropodidae from different continents and islands formed a cluster in their tree and were genetically different than the coronavirus strains of other groups of bats found in the same geographical zones.

The team found that in rare cases, bats of different families, genera, and species that live in the same caves and have closely spaced day roost sites shared the same strain of coronavirus. But in this study, the transmission between species is the exception, not the rule. "It is quite reassuring that the transmission of coronavirus in the region between two bat species seems to be very rare given the high diversity of bat coronaviruses. Next, we need to understand environmental, biological, and molecular factors leading to these rare shifts" says Léa Joffrin, a disease ecologist who worked on bat coronavirus during her PhD at the Université de La Réunion.

Learning how different strains of coronavirus evolved could be key for preventing future coronavirus outbreaks. "Before you can actually figure out programs for public health and try to deal with the possible shift of certain diseases to humans, or from humans to animals, you have to know what's out there. This is kind of the blueprint," says Goodman.

Co-author Patrick Mavingui, microbial ecologist and head of the PIMIT Laboratory adds, "The development of serological methods targeting coronavirus strains circulating in the Indian Ocean will help show whether there have already been discrete passages in human populations, and their interaction with the hosts will allow a better understanding of the emergence risk."

The study also highlights the importance of museum collections, says Goodman. The researchers used, in part, bat specimens housed in the Field Museum, to confirm the identities of the animals employed in this study. These voucher specimens helped them confidently say which bats and from which geographical regions hosted the different strains of coronaviruses. The research also drew from genetic databases like GenBank. "This information is important for public health, and the point of departure is closely linked to museum specimens," says Goodman. "We're able to use museum material to study the evolution of a group of viruses and its potential applications across wildlife in the world."

Goodman also notes that despite the fact that bats carry coronaviruses, we shouldn't respond by harming or culling of bats in the name of public health. "There's abundant evidence that bats are important for ecosystem functioning, whether it be for the pollination of flowers, dispersal of fruits, or the consumption of insects, particularly insects that are responsible for transmission of different diseases to humans," he says. "The good they do for us outweighs any potential negatives."

Credit: 
Field Museum

Children who hold 'benevolent' sexist views are also likely to possess 'hostile' ones

Children who hold seemingly positive, "benevolent" views about women are also likely to hold negative ones, a team of psychology researchers has found. Their results also show differences between boys and girls in how these views change over time: "hostile" sexist perceptions decline for both boys and girls as they get older, but "benevolent" sexist ones diminish only for girls.

"It might seem cute when a boy acts in chivalrous ways toward girls, or when a girl pretends to be a princess who's waiting for a prince to rescue her," says Andrei Cimpian, an associate professor in New York University's Department of Psychology and one of the authors of the study, which appears in the journal Sex Roles. "Many times, this is just play, with no deeper meaning. But other times, these behaviors--even though they may seem inoffensive--might signal that children view women in a negative light, as weak, incompetent, and unable to survive or thrive without a man's help."

"It is encouraging to note that this work also reveals how these attitudes evolve with age for boys and girls, albeit unevenly," adds first author Matthew Hammond, a senior lecturer in the School of Psychology at New Zealand's Victoria University of Wellington.

Many understand the term "sexism" to refer to overtly negative attitudes toward women, Cimpian and Hammond observe. These could include perceptions that women are weak, incompetent, or overly emotional. However, they note, there's another aspect of sexism that is often overlooked--what researchers, notably Susan Fiske and Peter Glick, call "benevolent sexism." This consists of attitudes that may appear positive, but that are still undermining of and patronizing toward women--for instance, that women should be warm, caring, pure, and deserve to be put on a pedestal.

Previous studies have shown that adults who hold sexist views that are hostile also possess ones that are benevolent. But less clear is whether or not children also simultaneously hold these perceptions--and whether or not these views change through childhood.

To address this, the researchers looked at the attitudes of more than 200 children, aged 5 to 11, in two locations: New York City and Urbana-Champaign, Ill. They were asked if a series of statements were "right" or "wrong." The statements included both benevolent views (e.g., "Men need to protect women from danger") and hostile ones (e.g., "Women get more upset than men about small things").

In analyzing children's agreement and disagreement with these statements, the researchers found that children gave statistically distinct patterns of responses to the statements expressing hostile and benevolent views about women. Importantly, however, they also found an association between these types of views, meaning that if a child agreed with a hostile statement, then he or she was also likely to agree with a benevolent one.

"This is something we did not know before about young children's gender attitudes," observes Cimpian.

In addition, the findings showed that children's hostile sexism decreased with age for both boys and girls. However, benevolent sexism decreased with age only for girls--and not for boys.

"Boys may be less likely to recognize that their benevolent attitudes toward women are, in fact, patronizing," Cimpian suggests. "For instance, they may hold on to the belief that men ought to protect women because this view is in line with social norms and may be reinforced throughout their upbringing."

The study's authors see current circumstances as a chance to address concerns the study's findings raise.

"Parents and kids are spending a lot of time together these days, so there are plenty of opportunities for conversation," says Hammond. "It could be worthwhile to spend a few minutes discussing what they think men and women should be."

Credit: 
New York University

Recurrent genomic selection for wheat grain fructans

image: Swallowtail resting on winter wheat in Ithaca, New York.

Image: 
Lynn Veenstra

Fructans are naturally occurring plant polymers composed of fructose molecules. They are found in approximately 15% of flowering plant species, including wheat (Triticum aestivum L.). Fructans serve important physiological roles in plant stress tolerance as well as in human diets. Given the importance of wheat in diets across the world, targeting increases in wheat fructan levels through breeding would facilitate the development of climate-resilient, nutritionally improved wheat cultivars.

In an article recently published in Crop Science, researchers report on the effectiveness of breeding methodologies in developing winter wheat cultivars with increased fructan while minimizing phenotyping requirements.

The researchers found that development of wheat cultivars with increased fructan levels (range: 25-34%) was possible with methodologies that also reduce phenotyping requirements and maintain genetic diversity in populations.

The ability of researchers to develop wheat cultivars with increased fructan levels using the described methodology serves as an important proof-of-concept that these methodologies can be utilized in breeding for any phenotype-intensive traits, particularly in the development of nutritionally improved crops.

Credit: 
American Society of Agronomy

To combat COVID-19, behavioral pitfalls must be addressed

PRINCETON, N.J.--During any crisis, timely, and sometimes life-altering, decisions must be made, requiring an extreme amount of sound judgment under uncertainty. The Covid-19 pandemic is no different.

In a commentary piece for The Lancet, researchers from Princeton University and the Sunnybrook Research Institute review eight behavioral pitfalls that challenge these judgments. Among the issues they explore are common human traits: a fear of the unknown, personal embarrassment, and hindsight bias, among others.

The co-authors suggest that awareness of these pitfalls might help to maintain the behavior changes needed to fight the Covid-19 pandemic. They also offer solutions.

"Following the strong initial reactions to such a challenging and difficult time, awareness of judgmental pitfalls might help maintain things on the right path," said Eldar Shafir, Class of 1987 Professor in Behavioral Science and Public Policy at Princeton's Woodrow Wilson School of Public and International Affairs.

Shafir co-authored the piece with Dr. Donald Redelmeier, senior scientist at the Sunnybrook Research Institute.

The eight pitfalls, and solutions, they explore are as follows.

Fear of the unknown. Threats like Covid-19 are mysterious because they are unknown, but the initial mystery soon fades away. Repeated reminders linked to the situation are important to avoid complacency.

Personal embarrassment. To reduce the spread of Covid-19, people have been encouraged to engage in certain behaviors, like not touching their faces, but people do so reflexively. Some may see lapses as a personal failure. Opinion leaders can highlight one of many celebrities who have tested positive as a way of mitigating the stigma. Authorities should also counsel that momentary lapses are natural and should be followed by returning to best behaviors.

Neglect of competing risks. Many are so consumed by Covid-19, they may neglect sleep, exercise, or human companionship. Therefore, clinicians should advise their patients to promote safety against other harms.

Invisible diseases. Social distancing and isolation could potentially exacerbate chronic psychiatric disorder. Increased mental health care and communication supportive of a healthy home environment are warranted.

No clear feedback. Time delays associated with Covid-19 -- incubation period, intervention, and test results -- cause unnerving emotions and feelings. Authorities should urge caution against acting on daily epidemic reports, like momentary declines or sudden increases, because random volatility might be mistaken for a real trend.

Status quo bias abounds. People want to maintain normalcy during a crisis, but a temporary shaking of the status quo is an opportunity to refocus and look at things anew. Once the initial urgency is diminished, hospitals could reconsider how clinicians adapt to new forms of telemedicine. A more radical suggestion, the co-authors write, is revisiting the broader policy debates on whether nations without universal health care might return to a new normal.

Ingrained societal norms. Human behavior is shaped by norms like shaking hands, hugging, and other forms of human contact, and these norms are not easy to change. Slogans, images and other reminders could help facilitate the necessary change. Doctors and nurses should model the right behaviors, and can also spread the information, as they are role models to patients.

Hindsight bias. Once Covid-19 subsides, hindsight bias will lead to castigating medical authorities who might have overreacted or underreacted. The uneven distribution of cases within and between countries will further lead to charges of inequality and injustice. Some of the critiques will be correct and justified, but dynamic and contradictory data might make it difficult to establish exactly what was known at what time, and how differently things could have turned out otherwise. A collective mentality that we are all in this together may prove difficult but highly useful.

The commentary, "Pitfalls of judgment during the COVID-19 pandemic," will appear online April 23 in The Lancet.

Credit: 
Princeton School of Public and International Affairs

Simple 'do it yourself' circuit to ventilate two patients at once is technically feasible

A simple 'do it yourself' breathing circuit, using accessories that are readily available in intensive care, can be used to ventilate two critically ill patients at once, should clinicians be faced with equipment shortages, suggests research published online in the journal Thorax.

But although technically feasible, it isn't clear if the pros of split ventilation outweigh the cons, and the approach is fraught with ethical issues, so this circuit should only be used as a last resort, say critical care and respiratory disease doctors in linked opinion pieces.

Prompted by the rapid rise in COVID-19 cases in the Lombardy region of Italy, and the prospect of a ventilator shortage, Italian doctors assembled and tested a simple, easily built breathing circuit on two 'pretend' patients.

The circuit comprised routine and readily accessible tubing and accessories found in intensive care and operating theatres.

The 15-hour tests confirmed that it would be technically feasible to use the circuit to ventilate two patients at the same time.

What's more, the technique is safer for staff than manual bag ventilation and avoids the constant need for a 'human ventilator' to work the bag, so freeing up staff, say the researchers.

But the tests also showed that the level of ventilation provided wasn't evenly distributed when lung function and capacity differed between the two 'patients.'

It should therefore only be used as a last resort, caution the researchers, because of the need to closely match the physiology of both patients, and the impossibility of being able to monitor separately changes in each patient's respiratory response.

There are also ethical issues to consider, they point out. "Indeed, the most difficult choice during such an emergency would be to either accept a grim triage reality (in which not all patients receive a ventilator), or accept the fact that trying to save two patients with one ventilator could mean harming at least one of them," they write.

These concerns are picked up in a linked editorial by respiratory disease and critical care doctors from the University of Chicago.

The idea of ventilator sharing isn't new, explain Drs Steven Pearson, Jesse Hall, and William Parker. It was first suggested in 2006, for coping with equipment shortages in dire emergencies, and has been revived in anticipation of ventilator supply problems during the COVID-19 pandemic.

But they warn that even if patients can be matched before ventilation, the dynamic nature of the respiratory response means that these initial characteristics could subsequently diverge.

Daily pauses in the sedation needed for mechanical ventilation to check on the patient's ability to breathe unaided--which seems to help patients recover--would be extremely difficult if two people were connected to the same device, they point out.

The technical challenges also require other resources in short supply: intensivists and respiratory therapists, they say.

During a severe equipment shortage, clinical decisions would need to be based on ensuring the greatest good for the greatest number of patients, they explain. But what would happen if two patients each had a 50% chance of survival with a single ventilator, but only 20% on split ventilation, they ask?

"Whether or not the benefit of providing support to one additional patient outweighs the harms suffered by the two patients receiving co-ventilation is an impossible question to answer at this point, given the lack of evidence and experience, and these harms are unlikely to be amenable to rigorous quantification at any point in the near future," they write.

Ideally, in the absence of adequate supply, or other breathing support devices, patient (and family) consent should be obtained and strict protocols applied for the circumstances in which split ventilation can be used, and then only as a last resort, they emphasise.

"The role for co-ventilation appeals to the rule of rescue, the natural impulse to save those facing certain death, by freeing mechanical ventilators to support those in respiratory failure who would die without them," they write.

"But to use the lifeboat analogy, is taking on more passengers than the boat was designed to accommodate, worth the risk of sinking the lifeboat?"

Given current supply and demand, doctors will most likely be faced with such decisions, they suggest. "Humankind should realise it has been forced into a lifeboat by this pandemic without the luxury of yesterday's ethical postures until rescue arrives," they conclude.

In a further linked commentary, emergency care doctors in Detroit and New York agree that one patient per ventilator is best. Their YouTube video, setting out the experimental technique for ventilating four patients at the same time, inspired the Italian doctors to experiment with the approach for two patients.

"Everyone agrees one patient on one ventilator will always be the gold standard," write Drs Charlene Babcock and Lorenzo Paladino. "Use of one ventilator for two patients is clearly outside the manufacturer's recommendations and only appropriate in dire circumstances during a disaster."

But reporting on further experiences of the technique can only assist the understanding of how to expand ventilator options, they suggest.

"We commend the [Italian] authors of this study for further advancing documentation of this potential expansion of ventilator availability as a life-saving intervention during a disaster and hope the additional information we have provided may be informative," they conclude.

Credit: 
BMJ Group

TGen adds to international studies identifying cells susceptible to SARS-CoV-2 infection

PHOENIX, Ariz. -- April 23, 2020 -- Two significant international studies involving hundreds of scientists, including a human geneticist at the Translational Genomics Research Institute (TGen), an affiliate of City of Hope, suggest that specific cells in the human nasal passage shaped like a champagne glass, known as goblet cells, may play a significant role in enabling COVID-19 infections.

Two studies, one published today in Nature Medicine and a similar study published April 22 in the journal Cell, indicate that goblet cells highly express a receptor enzyme called ACE2 that binds to the spikes covering the outer surface of SARS-CoV-2, the virus that causes the COVID-19 disease.

"These studies largely agree with each other and provide new insights into the specific type of cells targeted by the SARS-CoV-2 infection," said Dr. Nicholas Banovich, a TGen Assistant Professor and member of the Lung Biological Network of the Human Cell Atlas, an international effort to create comprehensive reference maps of all human cells as a basis for diagnosing, monitoring and treating disease.

"When the COVID-19 crisis began, it became clear that these large datasets generated by members of the Human Cell Atlas community were a valuable resource to study which cell types were expressing key genes related to the SARS-CoV-2 infection," Dr. Banovich said.

In both studies, goblet cells -- which produce mucus in the nasal passages -- were found to overly express angiotensin-converting enzyme 2 (ACE2), which serves as the entry point into cells for some coronaviruses.

"A lot of information was known about the path of infection from previous studies of SARS-CoV, including the fact that the first step in viral entry into the human body is the binding of the coronavirus spike protein to the ACE2 human receptor and an associated gene called TMPRSS2, which helps activate the coronavirus spike protein, enabling it to enter the cell," Dr. Banovich said.

Using data sets from the Human Cell Atlas, the Nature Medicine study used single-cell profiling of healthy samples to examine cells exclusively in the human airways, including nasal passages, lower airways and the lungs. The study revealed that two types of cells in the nasal passage --goblet and ciliated cells -- most highly expressed ACE2 and TMPRSS2. In addition, it found that ACE2 also is expressed in AT2 cells in the lungs.

"The results of these studies suggest that these cells in the nasal passage may serve as a viral reservoir, helping to disseminate the virus within an individual and spread the disease between individuals," Dr. Banovich said.

Using existing and new data, the Cell study looked at multiple human, primate and mouse tissues. This study also found that nasal goblet cells highly express ACE2. In addition, researchers found expression of ACE2 in absorptive enterocytes within the gut, which could help explain why many COVID-19 patients have GI symptoms.

The most significant finding in this study, however, is that ACE2 is stimulated by interferon, which is released by the body's immune system in response to viral infections.

"The body's own immune system may be causing neighboring cells to become targets of the virus," Dr. Banovich explained. "A patient's own immune response may be creating new shots on goal for the virus' target."

Both studies represent the first major collaborative effort by the Human Cell Atlas' Lung Biological Network.

"These two studies really demonstrate the power of the Human Cell Atlas community and of single cell RNA sequencing. Pulling together this large group of researchers and data sets allowed the science to move at incredible speed," Dr. Banovich said.

Both studies rely on a relatively new technology called single cell RNA sequencing (scRNA-seq), which allows researchers to delve into the specific molecular characteristics of individual cells, the fundamental units of all life. Dr. Banovich and Assistant Professor Dr. Johathan Keats, TGen Director of Bioinformatics, were selected in 2017 by the Chan Zuckerberg Initiative to optimize the processing of samples for scRNA-seq analysis as part of the Human Cell Atlas project.

Credit: 
The Translational Genomics Research Institute

SMU professors detail how homeless students are doing educationally in Houston ISD

image: Simmons professors Alexandra Pavlakis and Meredith Richards look at research information with Kessa Roberts, post doctoral fellow.

Image: 
SMU

DALLAS (SMU) - A new report by SMU professors Alexandra Pavlakis and Meredith Richards details how homeless students in Houston ISD are faring educationally.

Released by the Houston Education Research Consortium at Rice University, the report makes clear that homeless students are at an elevated risk of a range of adverse educational outcomes, and the findings also highlight the complexity of the relationship between homelessness and student outcomes. Pavlakis and Richards, who are both assistant professors at SMU's Simmons School of Education & Human Development, looked at students who were homeless from 2012-13 to 2016-17, the years immediately preceding Hurricane Harvey.

Some of the key findings include:

Students experiencing homelessness were more likely to drop out of school than their matched, non-homeless peers.

Students who were homeless four and five years tended to have higher attendance than students who were homeless for shorter periods of time.

Unaccompanied youth had substantially lower attendance than accompanied homeless students, and less likely to pass the STAAR exams than accompanied homeless students.

Where students sleep matters. Attendance gaps were large for unsheltered students and students in motels.

Interestingly, homeless students tended to perform better on STAAR exams than their matched peers. This could hint at the potential value of educational supports and resources inherent in McKinney-Vento Act or provided at shelters or drop-in centers for homelessness. However, homeless students were also somewhat less likely to take STAAR tests--particularly in math.

Credit: 
Southern Methodist University

Researchers restore injured man's sense of touch using brain-computer interface technology

While we might often take our sense of touch for granted, for researchers developing technologies to restore limb function in people paralyzed due to spinal cord injury or disease, re-establishing the sense of touch is an essential part of the process. And on April 23 in the journal Cell, a team of researchers at Battelle and the Ohio State University Wexner Medical Center report that they have been able to restore sensation to the hand of a research participant with a severe spinal cord injury using a brain-computer interface (BCI) system. The technology harnesses neural signals that are so miniscule they can't be perceived and enhances them via artificial sensory feedback sent back to the participant, resulting in greatly enriched motor function.

"We're taking subperceptual touch events and boosting them into conscious perception," says first author Patrick Ganzer, a principal research scientist at Battelle. "When we did this, we saw several functional improvements. It was a big eureka moment when we first restored the participant's sense of touch."

The participant in this study is Ian Burkhart, a 28-year-old man who suffered a spinal cord injury during a diving accident in 2010. Since 2014, Burkhart has been working with investigators on a project called NeuroLife that aims to restore function to his right arm. The device they have developed works through a system of electrodes on his skin and a small computer chip implanted in his motor cortex. This setup, which uses wires to route movement signals from the brain to the muscles, bypassing his spinal cord injury, gives Burkhart enough control over his arm and hand to lift a coffee mug, swipe a credit card, and play Guitar Hero.

"Until now, at times Ian has felt like his hand was foreign due to lack of sensory feedback," Ganzer says. "He also has trouble with controlling his hand unless he is watching his movements closely. This requires a lot of concentration and makes simple multitasking like drinking a soda while watching TV almost impossible."

The investigators found that although Burkhart had almost no sensation in his hand, when they stimulated his skin, a neural signal--so small it was his brain was unable to perceive it--was still getting to his brain. Ganzer explains that even in people like Burkhart who have what is considered a "clinically complete" spinal cord injury, there are almost always a few wisps of nerve fiber that remain intact. The Cell paper explains how they were able to boost these signals to the level where the brain would respond.

The subperceptual touch signals were artificially sent back to Burkhart using haptic feedback. Common examples of haptic feedback are the vibration from a mobile phone or game controller that lets the user feel that something is working. The new system allows the subperceptual touch signals coming from Burkhart's skin to travel back to his brain through artificial haptic feedback that he can perceive.

The advances in the BCI system led to three important improvements. They enable Burkhart to reliably detect something by touch alone: in the future, this may be used to find and pick up an object without being able to see it. The system also is the first BCI that allows for restoration of movement and touch at once, and this ability to experience enhanced touch during movement gives him a greater sense of control and lets him to do things more quickly. Finally, these improvements allow the BCI system to sense how much pressure to use when handling an object or picking something up--for example, using a light touch when picking up a fragile object like a Styrofoam cup but a firmer grip when picking up something heavy.

The investigators' long-term goal is to develop a BCI system that works as well in the home as it does in the laboratory. They are working on creating a next-generation sleeve containing the required electrodes and sensors that could be easily put on and taken off. They also aim to develop a system that can be controlled with a tablet rather than a computer, making it smaller and more portable.

"It has been amazing to see the possibilities of sensory information coming from a device that was originally created to only allow me to control my hand in a one-way direction," Burkhart says.

Credit: 
Cell Press

Environment: Satellite data used to detect marine plastic

A new method of detecting patches of floating plastics in marine environments is presented in Scientific Reports this week. The approach, which uses data from the European Space Agency Sentinel-2 satellites, is able to distinguish plastics from other materials with 86% accuracy.

Lauren Biermann and colleagues identified patches of floating debris from Sentinel-2 data based on their spectral signatures - the wavelengths of visible and infrared light they absorbed and reflected. The authors then trained a machine-learning algorithm to classify the individual materials that made up these patches according to the specific spectral signatures of different plastic and natural materials. These signatures were obtained from satellite data on plastic litter washed up in the Durban Harbour in South Africa on 24 April 2019 and floating plastic deployed by the authors off the coast of Mytilene (Greece) in 2018 and 2019. They also used previously obtained satellite data on natural materials likely to be found together with marine plastic, such as seaweed, woody debris, foam and volcanic rock.

The authors tested their method on Sentinel-2 data from coastal waters in four different locations: Accra (Ghana), the San Juan islands (Canada), Da Nang (Vietnam) and east Scotland (UK). The method successfully distinguished plastics from other floating materials or seawater with an average accuracy of 86% across the four locations and 100% accuracy off the San Juan islands.

The findings demonstrate that the method was successful across four different coastal areas. The authors hope that it could be used with drones or high-resolution satellites to improve global monitoring of marine plastic littering and aid clean-up operations.

Credit: 
Scientific Reports

Avoid making exceptions for research quality during COVID-19 pandemic

Global crises are no excuse for lowering scientific standards, argue Alex London and Jonathan Kimmelman in a Policy Forum. The authors suggest that the urgencies of crises situations like COVID-19 require researchers, medical professionals, health authorities and other stakeholders to triage low-quality research efforts, and they present five criteria stakeholders can use to do so. As the global COVID-19 pandemic evolves, scientists worldwide are conducting studies to address the crisis at unprecedented rates. However, according to London and Kimmelman, these efforts are threatened by the widespread perception that public health emergencies demand exceptions to the usually high standards of research, in order for science to become feasible during such challenging times. The result has been a veritable flood of low-quality studies - many published on preprint servers and lacking peer-review - some of which have caught the public's attention, as well as the resources of policymakers. But the problems that rigorous scientific methods are designed to identify do not simply go away in the face of urgency, the authors write. Ultimately, the proliferation of poorly designed studies amplifies the risk of diverting scarce resources towards false leads and ineffective practices, while increasing uncertainty about how best to treat patients or develop public health interventions. London and Kimmelman present five criteria of quality: importance, rigor, analytical integrity, transparency and feasibility. Research and public health stakeholders have a responsibility to evaluate and triage studies that fail to meet these conditions, they say, and to combine efforts, labor and resources to quickly and efficiently complete high-quality investigations that have the greatest potential to advance public health.

Credit: 
American Association for the Advancement of Science (AAAS)

Everything is not fine: Kids can tell when parents suppress their stress

VANCOUVER, Wash. - Stress is common in a family setting, especially when people are spending so much time together under stay-at-home measures meant to slow the spread of COVID-19. New research finds that parents suppressing feelings of stress around their kids can actually transmit those feelings to the children.

In a paper published in Journal of Family Psychology, Sara Waters, assistant professor in Washington State University's Department of Human Development, and her colleagues studied interactions between parents and children between the ages of seven and 11. They found that children had a physical response when parents tried to hide their emotions.

"We show that the response happens under the skin," said Waters, the corresponding author on the paper. "It shows what happens when we tell kids that we're fine when we're not. It comes from a good place; we don't want to stress them out. But we may be doing the exact opposite."

The researchers studied 107 parents, nearly half of whom were fathers, and their children. They first got baseline measurements from both parent and child, and asked each to list the top five topics that caused conflict between them. Then, they separated the parents from children and asked each parent to perform a stressful activity, like public speaking, to activate the physiological stress response system.

Next, with the parent suitably stressed, they brought the child back in and asked them to have a conversation about the topic that ranked highest on both of their conflict lists. Half of those parents were asked to suppress their emotions during the conversation.

The interactions were all filmed and scored by third party viewers who didn't know which parents were in which group. The parents and children also had sensors on their bodies to measure the physiological responses.

They found that for the groups suppressing emotions, both parents and children were less warm and engaged with each other.

"That makes sense for a parent distracted by trying to keep their stress hidden, but the kids very quickly changed their behavior to match the parent," Waters said. "So if you're stressed and just say, 'Oh, I'm fine', that only makes you less available to your child. We found that the kids picked up on that and reciprocated, which becomes a self-fulfilling dynamic."

In the study, mothers in the control group did not transmit their stress to their children. But, for mothers asked to suppress their emotions, their children exhibited more signs of stress, both physiologically and externally. It wasn't the same for fathers.

"We found that moms and dads were different," Waters said. "We were looking for a physiological response, but there wasn't one in either the control or the experimental condition where dads transmitted stress to their kids."

"We think that fathers not transmitting their suppressed stress may be because, often, fathers tend to suppress their emotions around their children more than mothers do," Waters said. "The kids have experience with their dad saying things are fine even when they're not. But it was more abnormal for kids to see their mom suppressing their emotions and they reacted to that."

The more out of control parents feel, and during a global pandemic that feeling is likely exacerbated, the stronger they have an impulse to reassure their kids that everything is ok.

"Research shows that it's more comforting for kids to have their feelings honored than just be told 'It's going to be fine,'" Waters said.

For instance, if a child tells their parents it sucks not to see their friends anymore, don't immediately try to fix that problem, Waters said.

"Just sit with them and give them a chance to regulate those emotions on their own," she said. "Try not to show that you're frustrated with them, or solve their problem. And try to do the same for yourself, give yourself permission to be frustrated and emotional."

Waters said her biggest fear with this study is it will cause parents more stress.

"We don't want this to be another thing that parents stress out about when raising their kids," she said. "It's not that you are screwing up--but honor your feelings and your child's feelings. Be brave enough to look at it. Kids will work their way through it; they're good at it. Giving yourself permission to feel opens up your mind to more and better problem solving. It's a good thing."

Credit: 
Washington State University

How birds evolved big brains

image: Visualizations of brain endocasts (blue) from the skulls of a dinosaur and a modern bird.

Image: 
Image courtesy of WitmerLab at Ohio University.

An international team of evolutionary biologists and paleontologists have reconstructed the evolution of the avian brain using a massive dataset of brain volumes from dinosaurs, extinct birds like Archaeopteryx and the Great Auk, and modern birds.

The study, published online today in the journal Current Biology, reveals that prior to the mass extinction at the end of the Cretaceous Period, birds and non-avian dinosaurs had similar relative brain sizes. After the extinction, the brain-body scaling relationship shifted dramatically as some types of birds underwent an explosive radiation to re-occupy ecological space vacated by extinct groups.

"One of the big surprises was that selection for small body size turns out to be a major factor in the evolution of large-brained birds," says Dr. Daniel Ksepka, Curator of Science at the Bruce Museum and lead author of the study. "Many successful bird families evolved proportionally large brains by shrinking down to smaller body sizes while their brain sizes stayed close to those of their larger-bodied ancestors."

In order to understand how bird brains changed, a team of 37 scientists used CT scan data to create endocasts (models of the brain based on the shape of the skull cavity) of hundreds of birds and dinosaurs, which they combined with a large existing database of brain measurements from modern birds. They then analyzed brain-body allometry: the way brain size scales with body size.

"There is no clear line between the brains of advanced dinosaurs and primitive birds," notes co-author Dr. Amy Balanoff of Johns Hopkins University. "Birds like emus and pigeons have the same brains sizes you would expect for a theropod dinosaur of the same body size, and in fact some species like moa have smaller-than-expected brains."

The two groups of birds with truly exceptional brain sizes evolved relatively recently: parrots and corvids (crows, ravens, and kin). These birds show tremendous cognitive capacity, including the ability to use tools and language, and to remember human faces. The new study finds that parrots and crows exhibited very high rates of brain evolution that may have helped them achieve such high proportional brain sizes.

"Several groups of birds show above average rates of brain and body size evolution," remarks co-author Dr. N. Adam Smith of the Campbell Geology Museum at Clemson University. "But crows are really off the charts - they outpaced all other birds. Our results suggest that calling someone 'bird-brained' is actually quite a compliment!"

"Crows are the hominins of the bird kingdom," says co-author Dr. Jeroen Smaers of Stony Brook University. "Like our own ancestors, they evolved proportionally massive brains by increasing both their body size and brain size at the same time, with the brain size increase happening even more rapidly."

Credit: 
Bruce Museum

The basis of glyphosate resistance in amaranth

image: Glyphosate-resistant Palmer amaranth in a cotton field.

Image: 
William T. Molin

William T. Molin (U.S. Department of Agriculture-Agricultural Research Service, Stoneville, MS) teamed up with Allison Yaguchi, Mark Blenner, and Christopher A. Saski (Clemson University, SC) to sequence and dissect the structure of the extrachromosomal DNA replicon that underlies the molecular and biochemical basis of resistance to the herbicide glyphosate in Palmer amaranth (Amaranthus palmeri). This work aids our understanding of adaptive evolution in plants and has implications for optimizing pesticide use in the environment.

Glyphosate is a widely used broad-spectrum herbicide that targets both broadleaf plants and grasses (dicots and monocots). It kills plants by inhibiting the enzyme 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS), found only in plants and in some bacteria. EPSPS is a key enzyme for the biosynthesis of essential amino acids and is an ideal target for herbicides because animals and humans use another enzyme that is insensitive to glyphosate to fulfill the same function. Some plants, including A. palmeri, can develop resistance to glyphosate toxicity by massively raising the expression of the EPSPS gene during glyphosate stress, essentially flooding the system with extra EPSPS enzyme and thereby counteracting the effects of the herbicide.

Making more copies of a gene is one possible means to increase gene expression: the phenomenon of amplification of genes or gene clusters is a common stress-avoidance mechanism in animals, plants, and microorganisms and is at play here. The amplified genes are often contained within extrachromosomal circular DNA (eccDNA) fragments known as replicons, circles of DNA that are maintained and replicated outside of the normal linear chromosomes in an organism. In humans, eccDNA is a prevalent feature of many cancers and a variety of diseases associated with developmental defects and premature aging. In such cases, eccDNAs carry oncogenes and other genes that may boost the survival and proliferation of diseased cells.

Molin et al. provide the complete sequence of the eccDNA replicon responsible for glyphosate resistance in A. palmeri, reveal its structural organization and genomic content, and examine some of the features that enable it to replicate and persist in the genome through multiple generations. The eccDNA replicon was found to contain 59 genes, a subset of which (including the EPSPS gene) show higher expression after treatment of the resistant plants with glyphosate. In addition to the presence of amplified genes, the eccDNA structure consists of a complex arrangement of repeated sequences and mobile genetic elements--so-called transposable elements--that might play a role in its maintenance and replication based on analogy with other eccDNAs. Author Christopher Saski noted that "the DNA content of the eccDNA replicon is sophisticated. Sequencing this element was difficult, and this complete assembly became possible only when DNA sequencing technology advanced to the single-molecule level, such as developed by Pacific Biosciences" (the biotechnology company that pioneered these methods, based in Menlo Park, CA).

Since the introduction of glyphosate in the 1970s, the rise of glyphosate-resistant weeds has been a growing problem in agricultural settings. The original glyphosate-resistant amaranth weedy plant that started this project was collected from a soybean field that had been routinely sprayed with the herbicide for a decade. The origin of this eccDNA replicon is unknown but is likely a result of transposable element activation and genomic shuffling that might have been pushed along by the use of glyphosate. That is, plants like A. palmeri that contain the eccDNA are able to survive and propagate where glyphosate is used frequently; additionally, glyphosate stress might contribute to the activation of the transposable elements that influence eccDNA formation and activity. Understanding the complete genomic structure and function of the eccDNA replicon will aid our knowledge of how glyphosate resistance develops and evolves in plants and help to further refine herbicide treatment strategies and combat the rise of resistant weeds.

The authors also identified structural features consistent with tethering of the eccDNA to chromosomes, which may facilitate maintenance of the fragment during normal cellular mitosis. Future work will focus on how the eccDNA self-replicates in plant cells, and identifying the essential functional elements of the replicon. This discovery could lead to "new approaches to genome engineering and the possibility of expressing useful agronomic traits outside of the nuclear genome," said Saski.

Credit: 
American Society of Plant Biologists