Earth

The diamonds and other crystals on view in science museum exhibits are a delight to the eye. What contributes to their sometimes dazzling geometric shapes and colors is their highly ordered arrangement of atoms. For the crystalline materials in battery electrodes, their ordered microstructure has practical benefits for ease of the ion transfer within the electrode during charge and discharge.

Scientists at the U.S. Department of Energy’s (DOE) Argonne National Laboratory have created and tested a single-crystal electrode that promises to yield pivotal discoveries for advanced batteries under development worldwide for electric vehicles, consumer electronics and other applications. Collaborating on the project were researchers from Northwestern University and the University of Illinois at Chicago.

“We recognized that single crystals can play a vital role in identifying promising new ways to understand, at atomic and molecular levels, the chemistries that control charge–discharge processes in batteries with polycrystalline electrodes.” — Sanja Tepavcevic, Argonne’s Materials Science division

The electrode materials in advanced batteries are “polycrystalline,” meaning they have numerous differently oriented crystalline regions. Because polycrystalline electrodes are relatively simple to fabricate, scientists have focused past battery research on experimenting with these materials, which are full of different kinds of defects within the ordered structures that often can affect performance.

“We recognized that single crystals can play a vital role in identifying promising new ways to understand, at atomic and molecular levels, the chemistries that control charge–discharge processes in batteries with polycrystalline electrodes,” noted Sanja Tepavcevic, assistant scientist in Argonne’s Materials Science division.

As a model system to investigate their single-crystal cathode, the team chose the sodium-ion battery under development to compete with current lithium-ion batteries. The main attraction of these batteries is that sodium is far more abundant an element than the lithium used for lithium-ion batteries.

The team prepared single crystals of a sodium-iridium oxide (Na2IrO3) and used them as the cathode material in small test cells. For comparison, they also tested similar cells with polycrystalline cathodes. By drawing upon the scientific facilities at Argonne — in particular, the Advanced Photon Source (APS), a DOE Office of Science User Facility — they could determine the precise position of every atom in the crystal structure for different states of cell charge and discharge.

“This project simply would not have been possible without the extraordinary material characterization resources of the APS,” said Tepavcevic. “We also greatly benefitted from the expertise of team member Jennifer Hong Zheng in her world-class capability at growing single crystals to precise specifications.”

Much was learned about the cathode chemistry during charge–discharge cycling of the test cells. In particular, the team investigated the origin of the extra capacity beyond that expected for the NaIrO3 endpoint structure.  “With our single crystals, we could separate surface from bulk effects that were not apparent in earlier work with polycrystalline materials alone,” said Tepavcevic. The team demonstrated that the extra capacity derives from surface reactions, not the bulk of the material as previously thought.

Important to improved battery design is knowing how and why material changes occur during cycling. From their test results, the team determined the chemical structure of the three distinct phases that form during charge, two of which were not known before. They also found that cell capacity faded with cycling because of the formation of a new detrimental phase on charge, which persisted during discharge and grew in size with cycle number.

“We learned more about sodium-ion batteries with our single-crystal electrodes than we ever thought possible at the project start,” said John Mitchell, Argonne Distinguished Fellow in the Materials Science division. “Clearly, single crystals open the window to a far better understanding of the chemical and electronic transformations that control energy storage and release in all battery types, as well as their degradation mechanisms with cycling.” With such knowledge, future battery researchers will be able to develop design rules for synthesizing new and improved polycrystalline materials with desired functionality.

Physical exercise may not be top of mind for older adults during the COVID-19 outbreak. But according to one UBC Okanagan researcher, strength training can be an effective way to stay healthy while at home.

A recent study from UBCO professor Jenn Jakobi shows that strength training with free-weights that progresses in intensity is effective in combating declining health often observed with adult aging.

"Inactivity and social isolation are key contributors to age-related frailty," says Jakobi. "While social isolation is a complex challenge these days, there is absolutely some work we can do on enhancing exercise at home."

She adds that physical movement and exercise, inclusive of weight training, can be readily adapted for the home but advises that anyone looking to start a new exercise program should consult with their physician first.

Jakobi, a professor in UBC Okanagan's School of Health and Exercise Sciences, defines frailty as reduced function and health in older adults. Features include unintentional weight loss, slow walking speed, muscle weakness, fatigue and low activity levels. If left unchecked this may lead to declines in health and functional independence which might require longer-term care.

"Age isn't necessarily always associated with being frail, and frailty isn't reserved for just old age--it can occur at any point in adulthood," says Jakobi. "Yet, it is dynamic and can be reversed. Maintaining and building muscle strength is key."

Jakobi and her research team wanted to explore whether progressive-resistance exercises can be effective at altering the path to this vulnerability.

After an initial screening of 53 older adults, the lab-based study evaluated 21 pre-frail women over the age of 65, divided into two groups. One group participated in a progressively intense free weight exercise program three-times-a-week for 12 weeks. Their exercises mimicked movements of normal life, and which may become difficult for some as they age.

"For example, we asked participants to complete a series of squats, replicating sitting-down and standing up," explains Nick Bray, former UBCO graduate student and co-author of the study. "We also asked them to perform dead-lifts, which mimic picking-up groceries."

The other group simply maintained their normal routines.

Measurements of muscle strength and performance were compared between the groups after the 12-week session. Not only did the exercise group improve their muscle performance and become less frail, they did so without injury.

"The exercise group improved in all measures including walking speed, grip strength and sit-to-stand time," says Jakobi. "Also, these changes were seen as early as nine weeks into the program."

She adds that their findings dispel the myth of strength training being unsuitable for pre-frail older adults.

"Traditionally, older adults opt for low-intensity, and low-resistance exercise because they believe that heavy free-weight exercise isn't right for them. Our findings show the opposite."

Although the research into heavy resistance training is novel and in its early phases this style of exercise is showing great promise. None of the exercise participants opted-out of the program or reported negative events and all improved in functional movement.

To help those interested in using this new research in their home during this period of physical distancing, Jakobi and her team have created an exercise worksheet and other at-home resources that highlight beginning phases of these progressive movements.

"This type of activity is appropriate and can be enjoyable," says Jakobi. She suggests just going for it.

"Try something new and lift progressively more. You should feel a good healthy challenge."

Susan Fowler turned Silicon Valley upside down in 2017 when she posted an essay on her website about the sexual harassment she experienced while working for Uber.

Uber's human resources department ignored claims against Fowler's male manager and the company then told her to quit. Fowler argued the company prioritized keeping the male manager, who was a key player in Uber's sales.

In her essay, Fowler stated the win-at-all-costs culture was driven by "competitiveness, aggression and paranoia," and one where casual sexism and racism flourished.

Shortly after Fowler published her essay, federal authorities began investigations and lawsuits were filed.

Stories like Fowler's reflect Silicon Valley's male-dominated corporate culture that at times enables sexual harassment to go unchecked and female careers to be sidelined.

A new study from The School of Business at Portland State University suggests that the aggressive cultures of private equity firms, like venture capitalists, might spill over into the companies that they fund. Venture capitalists are often the hidden players in business decision making, and they are funding startups like Uber, SpaceX and AirBnB.

With money, comes expectations

As a company grows through early developmental milestones, it becomes accountable to key stakeholders.

According to the study, companies often face challenges when balancing the tension between long-term socially responsible strategies and short-term demands associated with financial performance.

PSU Associate Professor of Management Theodore Khoury and colleagues published their study, "Is venture capital socially responsible? Exploring the imprinting effect of VC funding on CSR practices," in the Journal of Business Venturing.

The study found that venture capitalist investors often push a business they are financing to prioritize long-term financially-based goals instead of socially responsible business ones, like fair wages, reducing carbon footprints or improving labor policies.

Venture capitalists often hold a large portion of the equity in the companies in which they invest, which gives them voting power to challenge or advocate for specific strategic directions and influence decisions that might jeopardize company returns.

The prioritization of financial success opens a floodgate, allowing behaviors such as sexual harassment at new companies like Uber to go unchecked.

"We find that venture capitalist-backed companies have poorer socially responsible practice records, which do improve over time, but at a comparatively slower rate than non-venture capitalist-backed companies," Khoury said.

Unexpected consequence of greed

The PSU study also highlights how venture capitalists' desires for financial surplus might end up causing more harm than good.

Uber agreed to pay $4.4 million dollars to settle federal charges of fostering a work culture wrought with sexual harassment. It's just one of the dozens of Silicon Valley companies facing huge fines related to sexual harassment charges.

The researchers assert that socially responsible practices positively impact, rather than reduce, a company's financial performance.

"Compared to non-venture capitalist-backed companies, venture capitalist-backed companies presented significantly lower assets, sales, tangible assets, inventories, returns on assets, profit margins and debt levels, as well as higher intangibles and current ratios," the study said.

In addition to financial success, socially responsible practices help satisfy multiple stakeholders (like employees), enhance a company's market value, preempt government regulations, reduce risk, develop business resources and lower capital costs.

However, the researchers add that when venture capitalist-backed companies receive funding from firms with a responsible investment orientation and a broader stakeholder view, their socially responsible practice records are significantly better.

"Early-stage imprinting can happen from many sources, but when businesses take funding from certain investors, certain cultures, operating modes and ways of conducting business may start to take shape for the long term to affect a broader group of stakeholders," Khoury said. "The effects of early-stage imprinting from venture capital funding can be hard to 'undo,' and there are social consequences."

Today and as sea level continues to rise in the future, extreme high tide events cause Honolulu, Hawai'i's primary urban center to experience flooding not just from water washing directly over the shoreline, but also from groundwater inundation as the water table is pushed toward the surface, and reverse flow through the municipal drainage system. In a study published in Scientific Reports, researchers at the University of Hawai'i at Mānoa School of Ocean and Earth Science and Technology, found in the next few decades, sea level rise will likely cause large and increasing percentages of land area to be impacted simultaneously by the three flood mechanisms.

Further, they found that groundwater inundation represents the most extensive flood source, while direct marine inundation represents the least extensive--only three percent of the predicted flooding. 

"This is significant because many people think that sea level rise can be mitigated by seawalls," said Shellie Habel, lead author of the study and coastal geologist and extension agent with the University of Hawai'i Sea Grant College Program and UH Coastal Geology Group. "But a seawall will not stop groundwater inundation. Our results highlight the need to readjust our thinking regarding the flooding that accompanies sea level rise. We want to be sure to implement flood management strategies that will be effective at mitigating flooding."

This requires that all types of flooding be thoroughly assessed.

Identifying vulnerable locations, infrastructure

Habel and co-authors developed a method that identified the various flood types and their extent. Flood maps were produced by simulating flood locations and depths generated by each of the three mechanisms and by overlapping the simulations to identify areas vulnerable to combined flooding over the coming decades.

Colleagues at the UH Sea Level Center then developed a statistical model that considers predicted tide and projected magnitudes of local sea level rise to establish the frequency with which flooding is likely to occur in given locations.
 

With these flood simulations, the research team assessed critical infrastructure that is likely to fail and cause direct impacts, such as dangerous or impassable roadways, storm drainage inlets likely to fail or act as pathways for additional flooding, and non-functional or flooded cesspools.

The impacts were found to be widespread among Honolulu's heavily densified primary urban center.

Planning for the future

"Because each type of flooding infiltrates through unique pathways, they will require unique engineering strategies to manage," said Habel. "The design of flood management strategies required to mitigate these impacts necessitate site-specific consideration of each mechanism to avoid being ineffective."

In partnership with the Honolulu Board of Water Supply, the University of Hawai'i, Hawai'i Sea Grant, and other stakeholders, the authors plan to develop a real-time coastal groundwater monitoring network. Data collected through the monitoring network will help improve the capabilities of the modeling such as the ability to incorporate the effects of extreme rainfall. The network would also provide information that could inform the development of short, mid and long-term flood management strategies.

May 4, 2020 - In the debate about nature versus nurture for developing reading skills, cognitive neuroscientists have a clear message: both matter. From infancy, children have a neural scaffolding in place upon which environmental factors refine and build reading skills. In new work being presented today at the Cognitive Neuroscience Society (CNS) virtual meeting, scientists are reporting on these biological and environmental factors -- including early screen time -- as they uncover biomarkers that can identify children at risk for dyslexia and other reading acquisition disorders.

"Reading is a relatively new human invention. To read, our brains have to 'recycle' neural circuits originally used for other abilities such as visual and language processing, as well as attention and cognitive abilities," says Tzipi Horowitz-Kraus of The Technion in Israel and Cincinnati Children's Hospital, who is chairing the CNS symposium about the new work. "The fact that 5-10% of children worldwide, across cultures and genetic backgrounds, suffer from dyslexia suggests that this disability is not limited to a specific language."

Indeed, the research being presented by Horowitz-Kraus and others suggests a variety of biological precursors are present in children prior to school age across languages, and several environmental factors can help or hinder reading acquisition. The goal is to identify children at risk early, to provide the best possible interventions that will improve literacy.

The reading brain in infancy

One of the biggest insights to come in recent years in the study of reading acquisition is that most interventions to identify and treat dyslexia in school were coming too late. Over the past decade, longitudinal studies of young children coming out of the lab of Nadine Gaab at Harvard Medical School and others at labs globally have shown that the brains of children who will develop dyslexia are already atypical even before they start into kindergarten.

"We knew that the brain of someone with dyslexia was different from a control, but we didn't know if it was something that developed before the onset of formal reading instruction or if it developed in response to a daily failure to learn to read over a significant period of time," she says. "Our work was the first time MRI imaging could show that some of the brain characteristics predate the onset of reading development," Gaab says.

And in new work being presented at the CNS meeting and available via preprint, Gaab's team has shown that, as a group, babies as young as 3 months old have an underlying infrastructure that helps predict success in reading years later.

As part of the BOLD (Boston Longitudinal Dyslexia) study, Gaab's team has scanned the brains of 140 infants who have a familial risk for dyslexia and then followed them over time to study changes in the structure and function of their brains. For the newest data, 45 of the once-infant subjects have now turned 5 or 6 years old, allowing the researchers to map their brain scans from infancy to their pre-reading skills.

"What our infant data suggest is that there is a structural brain scaffold in infancy that serves as a foundation," Gaaab explains. "Language and reading may be a process that refines this pre-existing brain scaffold."

Studying the brains of young children in an MRI machine is far from simple, Gaab explains. When they are babies, the goal is to have the participants sleep in the scanner. So her lab looks like an elaborate daycare center -- with adaptable rocking chairs, swings, cribs, and other gear optimized for use with the scanner. While safely sleeping in the MRI, the babies hear stories read to them, allowing the researchers to capture both structural information about their brains but also, surprisingly, functional data. "We were very surprised to see robust language networks activated while the infants sleep," Gaab says.

As 5- and 6-year-olds returning to the lab, the children identify word sounds in games designed to test their pre-reading skills. As they get older, the children will do increasingly more advanced tasks, such as reading in the scanner. This longitudinal work gives the researchers a big-picture view of reading development rather than just a snapshot view.

Gaab's lab is next working to understand the co-occurrence of disorders such as ADHD and dyscalculia (a math learning disorder) with dyslexia. They also want to understand techniques children successfully use to compensate for dyslexia in the brain. "We now see children are not a clean slate for reading experience," Gaab says, and they want to not only better understand the determining factors but also inform policy-makers and the public.

The reading brain on screen

While studying neurobiochemistry for her master's program, Horowitz-Kraus worked on SAT preparation with her younger brother who was struggling with reading despite his high intelligence in nonverbal tasks. "Observing my brother's frustration in executing a task that is very intuitive for individuals without dyslexia made me set the goal to seek neurobiological correlates for reading difficulties and to find ways to improve reading ability," she says. "This way, I thought, the difficulty can be diagnosed objectively, maybe even before reading is formally acquired, and can prove without a doubt that the difficulty is real."

Fifteen years later, Horowitz-Kraus has done just that and, in new research, is seeking to understand how day-to-day conditions affect the neurobiological foundation for reading in the brain. "Although dyslexia is a genetic disorder, the environment has an impact wherein it can reduce or increase reading challenges," she says. "The brain is extremely plastic at the pre-reading age, and hence negative stimuli, such as exposure to screens, may have an amplifying effect on a child's outcomes."

In a series of studies, Horowitz-Kraus and colleagues examined how the home literacy environment, including screen exposure, affects the brain circuits of children 3- to 5-years old, in particular executive functions, language and visual processing. As published recently in JAMA Pediatrics, screen-based media use beyond American Academy of Pediatrics guidelines was associated with "lower microstructural integrity of brain white matter tracts supporting language and emergent literacy skills in prekindergarten children."

Earlier work using EEG had found reduced narrative comprehension in preschool children using screens compared to in-person reading. They also have found that screen exposure engages different brain networks in children with dyslexia compared to typical readers.

The results suggest, Horowitz-Kraus says, that listening to stories through screens is not similar to joint reading when seeking to nurture the developing brain. "There is no replacement for joint storytelling in engaging neuronal circuits related to future reading," she says.

Such studies enabled by modern neuroimaging data are allowing researchers for the first time to determine what infrastructure is needed to be able to read and to track the typical and atypical development of this infrastructure -- and to develop appropriate early interventions.

Both Horowitz-Karus and Gaab envision moving to a more preventative model for reading disorders. "This preventive model is something we embrace a lot in medicine but for some reason, we have not yet done so in education," Gaab says. She cites cholesterol screening to help identify those at risk for heart disease as a model that could work for dyslexia and other learning disorders.

Already their research and others' have led to new educational policies, including early dyslexia screening in 29 states to identify children at risk in kindergarten. "We and other cognitive neuroscientists hope to continue to contribute to that shift in this model," Gaab says.

The team from the University of Nottingham's Schools of Pharmacy and Life Sciences have found that the surface shape (topography) and chemical composition of polymer materials can be changed to create materials that control the body's immune response. This could have future applications in the fight against rejection of medical devices including artificial joints, dental implants and vascular implants. The results from two recent studies have been published in Advanced Science and Matter.

Artificial joints, stents and dental implants are among the most common devices that use biomaterials to restore function or completely replace diseased or damaged tissues. However, following the implantation of biomaterials in the body, a host reaction is common, including responses such as inflammation, a foreign body reaction (FBR), and fibrous capsule development which can result in the implant failing.

These reactions are driven by the activation of immune cells called monocytes and macrophages attaching to the implant surface. The physical features on the surface of a material or implant known as 'topography' is known to influence macrophage attachment.

Professor Amir Ghaemmaghami has co-led the research, he explains: "We are looking at ways to create materials that can be safely put inside the body without the immune system attacking it and causing rejection. To do this we are exploring materials that can control the immune response. We have used high throughput screening technology to examine how the topography and chemical properties of a material can be used to design "immune?instructive" surfaces for potential use in implants, which influence macrophage function and consequently the foreign body responses to biomaterials."
 

Taking control of the immune response

A state-of-the-art high throughput screening approach was used to investigate the relationship between material topographies and immune cell attachment and behaviours for 2176 different micropatterns. 

The results indicated that micron-scale pillars 5-10um in diameter were key in driving macrophage attachment, and that the density of the micropillars proved key in controlling inflammatory reactions.

The team also discovered immune instructive polymer chemistries that successfully controlled the immune response in a pre-clinical rodent model. This was achieved through screening libraries of diverse polymers and identifying materials that control the behaviour of macrophages.

An AI algorithm was used to model the relationships between the material chemistries and the cell responses they produced. These results suggest that different immune-instructive polymers attract different amounts of protein adsorption which was key to the macrophage responses. 

Professor Morgan Alexander also co-led the research, he said: "These latest discoveries add to a wealth of materials research taking place at the University of Nottingham and it is exciting to have discovered these biomaterials that could be a real game-changer in the area of medical implants. Getting these materials used in a commercial product would be our ultimate aim for this research, there is still a way to go to get there but these discoveries are a significant step towards that."

This research was conducted in collaboration with Technical University Eindhoven, La Trobe University Australia and Maastricht University. It has been funded by an EPSRC Programme Grant in Next Generation Biomaterials Discovery that aims to find new biomaterials. The aim is to allow us to move beyond the existing limited range of polymeric drug and cell delivery agents and medical device polymers that are currently licensed for use in man, to bespoke materials identified to function optimally for specific applications.

Children with long-term health conditions may be more likely to experience mental illness in early adolescence than healthy children, according to new research from Queen Mary University of London.

In the study, published in Development and Psychopathology, children reported to have chronic health problems showed higher rates of mental illness at 10 years, and those health problems continued to be associated with poor mental health at the ages of 13 and 15.

To carry out the study, researchers reviewed a sample of approximately 7000 children to investigate the occurrence of mental health disorders, including anxiety or depression, and chronic illness. The measure of chronic illness was based on mothers assessing their child's health at 10 and 13. Since chronic conditions are defined as those that cannot be cured but can be controlled by medication and other therapies, and may have little disease activity, this measure included children presenting with minor health problems.

The researchers found that children with chronic health conditions were approximately twice as likely at 10 and at 13 to present with a mental health disorder than the control group (children reported by their mothers to be 'healthy, no problems'). At age 15, children with chronic health problems were 60% more likely to present with such disorders.

Study author, Dr Ann Marie Brady from Queen Mary University of London, said: "Although the link between chronic health conditions and mental health problems in childhood has been made before, this study provides the strongest evidence of it to date in the years of late childhood and early adolescence. The difference chronic conditions make to mental health are concerning, and the first impact can be seen even before adolescence, in late childhood."

To investigate this pattern further, the researchers looked at a subset of the children with chronic illness: those who had been diagnosed with asthma. Asthma symptoms are generally mild and well-controlled. Nevertheless, researchers found that asthmatic children showed a similar pattern, having a higher rate of mental illness at 10, 13 and 15 than healthy children.

The study also reviewed what additional factors might account for the link between chronic conditions and mental illness. The sample was taken from the Children of the 90s study, which also contains information from parents and children about other issues including family functioning, friendships, children's activity levels, bullying and health-related absenteeism from school. Researchers analysed which of these might contribute to mental illness rates among children with chronic illness.

They found that bullying and health-related school absenteeism emerged as the most significant additional factors for children with mental health issues. Health-related school absenteeism was identified as the most consistent factor predicting mental health problems over time.

Dr Brady said: "Chronic illness disrupts children's normal lives, and this can affect their development and wellbeing. Even children with asthma, a generally treatable and less debilitating chronic condition, had higher rates of mental illness than the healthy children in our study. If children with chronic conditions are more likely to miss school, or experience bullying, that can make the situation worse. Keeping an eye on school attendance and looking out for evidence of bullying amongst children with chronic illness may help to identify those who are most at risk."

Carbon nanotubes, the tiny hollow tube of hexagonal carbon lattices has been touted as one of the most promising materials for building items with fascinating electrical, thermal and mechanical properties. Selective functionality is realized by adding elements to the carbon nanotubes to make transistors, composite additives, field emitters and transparent conductive films. Carbon nanotubes doped with boron makes the structure of the tubes more functional while increasing the ability to modulate the electrical properties. Boron-doping into coaxially aligned two single-walled carbon nanotubes (double-walled carbon nanotubes :DWNTs) show promise for use in electronic devices, composite materials, energy storage and power generation materials.

A research group led by Hiroyuki Muramatsu of Shinshu University succeeded in selectively doping the outer nanotube of the DWNTs with boron. Previously, there was no method to control the incorporation of boron atoms to carbon nanotubes. The tubes would fuse together or the structure would drastically change through treatments of boron-doping, frustrating researchers. In this study, Muramatsu and his team were able to selectively add boron to the outer tubes of DWNTs. This significantly increased the electrical conductivity and the Seebeck coefficient which resulted in a highly enhanced thermoelectric performance of the DWNTs.

This advancement in technique allows for an extremely effective method to add functionality such as high electrical conductivity, chemical activation and improvement of thermoelectric properties while maintaining the function of the inner CNT. Muramatsu and his team succeeded in discovering the conditions for intricately doping boron on a single outermost layer of CNT without changing the coaxial structure of DWNTs. Only then were they able to actually demonstrate and confirm the characteristics of the synthesized DWNTs.

In the future boron-doped DWNTs could be used in thermoelectric applications to harvest waste heat for electricity generation and other advanced applications. However, DWNTs are still not very well understood. Muramatsu believes that through fundamental research and understanding the basic properties of outer tube-selectively boron-doped DWNTs, more applications can be found while enhancing performance relevant to various applications. The ultimate goal is to strategically use the characteristics of the structure and physical properties of DWNTs to add unique functions and characteristics. New principles and methods must be investigated in detail to establish a more selective high-concentration doping method and study its effect on the structure and function.

Low blood sugar levels, known as hypoglycemia, can be a life-threatening situation, especially for people with type 1 diabetes who rely on intensive insulin therapy to prevent blood sugar from going too high. Solutions to this problem may come from a better understanding of the basic mechanisms keeping blood sugar in balance.

At Baylor College of Medicine and other institutions, researchers led by Dr. Yong Xu, associate professor of pediatrics-nutrition and of molecular and cellular biology at Baylor, have identified a group of unique glucose-sensing neurons in the brain and how they work together to prevent severe hypoglycemia in mice. Their results appear in the journal Nature Communications.

"Glucose-sensing neurons sense fluctuations in blood sugar levels and respond by rapidly decreasing or increasing their firing activities. This response can trigger changes in behavior to increase glucose levels. For instance, the animals may begin eating," Xu said. "Glucose-sensing neurons also can affect the production of hormones such as glucagon that can directly regulate glucose production or uptake by peripheral tissues. It's a feedback system that keeps the balance of blood glucose."

Glucose-sensing neurons are found in several brain regions. Xu and his colleagues focused on neurons located in a small area called the ventrolateral subdivision of the ventromedial hypothalamic nucleus (vlVMH). Many neurons in this region express estrogen receptor-alpha and respond to glucose fluctuations in the blood, but their functions in glucose metabolism had not been specifically investigated.

A unique population of neurons

The researchers found that neurons in the vlVMH nucleus of murine brains had unique characteristics.

First, Xu and his colleagues were surprised that, while in other VMH subdivisions about half of the neurons were glucose-sensing, in the ventrolateral subdivision all the estrogen receptor-alpha neurons were glucose-sensing. "Just this fact makes this group of neurons quite unique," Xu said.

They also found that, although all the neurons in this area sense glucose, they do not respond to changes in glucose level in the same way. About half of the neurons are 'glucose-excited' - their firing activity increases when they sense high glucose levels and decreases when glucose levels are low. In contrast, the other half of the neurons are glucose-inhibited - they decrease firing when glucose is high and increase it when glucose is low.

"We wondered why these neurons responded in opposite ways to the same glucose challenge," Xu said.

The researchers combined genetic profiling, pharmacological, electrophysiological and CRISPR gene-editing approaches to look into this question. They investigated the ion channels that each type of glucose-sensing neuron uses to respond to glucose levels. Ion channels are large molecules spanning across the cell membranes of neurons. The channels control the traffic of ions - electrically charged atoms or molecules - in and out of neurons, a process that is crucial for regulating neuronal firing activities.

The researchers found that glucose-excited neurons use a KATP ion channel, but the glucose-inhibited neurons used a different ion channel called Ano4. "The KATP ion channel is well known in our field, but the role of Ano4 ion channel in glucose sensing has never been reported. We have identified a new ion channel that is important for glucose-inhibited neurons."

A coordinated effect regulates blood glucose

In addition, Xu and colleagues identified the neuronal circuits that are involved when glucose-excited and glucose-inhibited neurons respond to low blood glucose levels. They discovered that the circuits were different - glucose-excited neurons project neuronal connections to a brain region that is different from the one reached by glucose-inhibited neurons.

Using optogenetics, a combination of genetic modifications and light to activate specific neuronal circuits, the researchers showed in mice that when glucose-inhibited neurons responded to low glucose levels, they activated a particular circuit, and the result was an increase of blood glucose. On the other hand, when glucose-excited neurons responded to low blood glucose, they inhibited a different circuit, but the result also was an increase in blood glucose levels.

"When the mice were hypoglycemic, these two circuits were regulated in an opposite manner - one was excited while the other was inhibited - but the outcome was the same, bringing blood glucose to normal levels," Xu said. "This forms a perfect feedback system to regulate blood glucose levels."

Interestingly, all the neurons in this important group express estrogen receptor-alpha, a well-known mediator of the ovarian hormone, estrogen. In the future, Xu and colleagues want to investigate whether estrogen plays a role in the glucose-sensing process and whether there are gender differences in the functions of these neurons on glucose balance.

SILVER SPRING, Md. - A study led by scientists at the Walter Reed Army Institute of Research sheds new light on the body's initial response to dengue virus (DENV) infection, describing the molecular diversity and specificity of the antibody response. These results, published in EBioMedicine, a journal published by The Lancet, identify a heretofore unappreciated role for DENV-reactive IgA antibodies.

DENV is a member of the clinically-relevant Flavivirus genus alongside Zika virus, yellow fever virus and others. With four distinct serotypes, DENV is thought to infect between 280 and 550 million people worldwide every year.

While the majority of individuals suffering from dengue fever recover without showing severe symptoms or requiring extensive medical intervention, approximately 500,000 individuals per year develop severe dengue which has a mortality rate of up to 20%. Dengue is of particular concern for deploying Service Members, and the development of effective countermeasures to prevent dengue infection is a priority for the Department of Defense.

Subclinical exposure is a significantly complicating factor for public health and vaccine development, as those individuals previously exposed to one DENV serotype are at greater risk for severe symptoms than those with no previous exposure. Therefore, determining the previous exposure history of a patient experiencing symptoms of DENV infection can provide insight to the patient's risk of developing severe disease.

In this study, researchers used single cell RNA sequencing technology to measure the products of B cell plasmablasts, the antibody-producing cells found in greatest numbers immediately after DENV exposure. They also used a range of analyses to describe the ability of these antibodies to neutralize DENV and characterize their structure.

They discovered that IgA represented a significant fraction of antibodies expressed by B cell plasmablasts circulating after DENV infection, most dramatically in individuals experiencing their first DENV infection. "The fact that we observed such a profound IgA signature in individuals experiencing their first DENV infection may improve our ability to rapidly determine a patient's DENV exposure history and risk of developing severe disease" says Dr. Adam Waickman, the lead author on the study.

Though these data were generated from a small group of children, this is the first study to measure and characterize the entire output of plasmablasts without limitations to specific types of antibodies. These insights set the stage for future work to fully characterize the body's immune response to DENV, understand risk factors to severe dengue and ultimately could be critical to the development of new diagnostic tools as well as a safe, efficacious dengue vaccine.

GAINESVILLE, Fla. --- More than a thousand years ago, people from across the Southeast regularly traveled to a small island on Florida's Gulf Coast to bond over oysters, likely as a means of coping with climate change and social upheaval.

Archaeologists' analysis of present-day Roberts Island, about 50 miles north of Tampa Bay, showed that ancient people continued their centuries-long tradition of meeting to socialize and feast, even after an unknown crisis around A.D. 650 triggered the abandonment of most other such ceremonial sites in the region. For the next 400 years, out-of-towners made trips to the island, where shell mounds and a stepped pyramid were maintained by a small group of locals. But unlike the lavish spreads of the past, the menu primarily consisted of oysters, possibly a reflection of lower sea levels and cool, dry conditions.

People's persistence in gathering at Roberts Island, despite regional hardship, underscores their commitment to community, said study lead author C. Trevor Duke, a researcher in the Florida Museum of Natural History's Ceramic Technology Lab.

"What I found most compelling was the fact that people were so interested in keeping their ties to that landscape in the midst of all this potential climate change and abandonment," said Duke, a Ph.D. candidate in the University of Florida department of anthropology. "They still put forth the effort to harvest all these oysters and keep these social relationships active. These gatherings probably occurred when different groups of people were getting together and trying to figure out the future."

Duke and his collaborators compared animal remains from shell mounds and middens - essentially kitchen trash heaps - at Roberts Island and Crystal River, home to an older, more prominent ceremonial site. Their findings showed Crystal River residents "pulled out all the stops" for ritual feasts, regaling visitors with deer, alligator, sharks and dozens of other dishes, while at Roberts Island, feasts consisted of "oysters and very little else," Duke said.

The Roberts Island ceremonial site, which was vacated around A.D. 1050, was one of the last outposts in what was once a flourishing network of religious sites across the Eastern U.S. These sites were characterized by burial grounds with distinctly decorated ceramics known as Swift Creek and Weeden Island pottery. What differentiated Roberts Island and Crystal River from other sites was that their continuous occupation by a small group of residents who prepared for the influx of hundreds of visitors - not unlike Florida's tourist towns today.

"These were very cosmopolitan communities," Duke said. "I'm from Broward County, but I also spent time in the Panhandle, so I'm used to being part of a small residential community that deals with a massive population boom for a month or two months a year. That has been a Florida phenomenon for at least two thousand years."

Archaeologists estimate small-scale ceremonies began at Crystal River around A.D. 50, growing substantially after a residential community settled the site around A.D. 200. Excavations have uncovered minerals and artifacts from the Midwest, including copper breastplates from the Great Lakes. Similarly, conch shells from the Gulf Coast have been found at Midwestern archaeological sites.

"There was this long-distance reciprocal exchange network going on across much of the Eastern U.S. that Crystal River was very much a part of," Duke said.

Religious ceremonies at Crystal River included ritual burials and marriage alliances, Duke said, solidifying social ties between different groups of people. But the community was not immune to the environmental and social crises that swept the region, and the site was abandoned around A.D. 650. A smaller ceremonial site was soon established less than a mile downstream on Roberts Island, likely by a remnant of the Crystal River population.

Duke and his collaborators collected samples from mounds and middens at the two ceremonial sites, identifying the species present and calculating the weight of the meat they would have contained. They found that feasts at hard-strapped Roberts Island featured far fewer species. Meat from oysters and other bivalves accounted for 75% of the weight of Robert Island samples and roughly 25% of the weight from Crystal River. Meat from deer and other mammals made up 45% of the weight in Crystal River samples and less then 3% from Roberts Island.

Duke said evidence suggests that Roberts Island residents also had to travel farther to harvest food. As sea levels fell, oyster beds may have shifted seaward, possibly explaining why the Crystal River population relocated to the island, which was small and had few resources.

"Previous research suggests that environmental change completely rearranged the distribution of reefs and the ecosystem," Duke said. "They had to go far out to harvest these things to keep their ritual program active."

No one knows what caused the widespread abandonment of most of the region's ceremonial sites in A.D. 650, Duke said. But the production of Weeden Island pottery, likely associated with religious activities, ramped up as bustling sites became ghost towns.

"That's kind of counterintuitive," he said. "This religious movement comes on really strong right as this abandonment is happening. It almost seems like people were trying to do something, create some kind of intervention to stop whatever was happening."

JUPITER, Fla.--May 1, 2020--Many people with Parkinson's disease eventually develop debilitating movements called dyskinesia, a side effect of their much-needed dopamine replacement medication. The mechanism underlying this unwanted side effect has been unknown, until now. An international collaboration led by Scripps Research, Florida has found a key cause, and with it, potentially, a new route to providing relief.

Dopamine replacement therapy makes Parkinson's symptoms much better at first, but eventually treatment gives way to uncontrollable, jerky body movements. But why? New research shows that underlying this development is the therapy's unintended boost of a protein with the unwieldy name Ras-guanine nucleotide-releasing factor 1, or RasGRP1 for short. This boost in RasGRP1 produces a cascade of effects which lead to abnormal, involuntary movements known as LID, or L-DOPA-induced dyskinesia, says co-lead author Srinivasa Subramaniam, PhD, associate professor of neuroscience at Scripps Research, Florida.

Encouragingly, the collaboration found that in dopamine-depleted mice and other animal models, inhibiting production of RasGRP1 in the brain during dopamine replacement diminished the involuntary movements without negating the useful effects of the dopamine therapy.

Taken together, the research offers a new path to easing Parkinson's dyskinesia while allowing maintenance of dopamine replacement therapy, Subramaniam says.

Subramaniam's group has long been interested in cellular signaling in the brain underlying motor movements, and how it is affected by brain diseases, including Huntington's and Parkinson's.

"Parkinson's patients describe treatment-induced dyskinesia as one of the most debilitating features of their illness," Subramaniam says. "These studies show that if we can down-regulate RasGRP1 signaling before dopamine replacement, we have an opportunity to greatly improve their quality of life."

The study, "RasGRP1 is a causal factor in the development of L-DOPA-induced dyskinesia in Parkinson's disease," published in the journal Science Advances May 1. In addition to Subramaniam, the co-lead author is Alessandro Usiello, PhD, of the University of Campania Luigi Vanvitelli, Caserta, Italy, and the Behavioural Neuroscience Laboratory at Ceinge Biotecnologie Avanzate, Naples, Italy.

Dopamine is a neurotransmitter and hormone that plays a key role in movement, learning, memory, motivation, and emotion. Parkinson's develops when dopamine-producing neurons in a region of the mid-brain called the substantia nigra stop working or die. It's a brain region associated with both movement initiation and reward, so its impairment causes a wide variety of symptoms, including stiffness, balance problems, walking difficulty, tremor, depression and memory issues.

Doctors treat Parkinson's with dopamine replacement therapy, often a medicine called levodopa. The brain converts levodopa into dopamine, and at proper doses, this leads to resolution of symptoms. But as dose and duration grow, a side effect called dyskinesia can develop. After a decade, about 95 percent of Parkinson's patients will experience some degree of involuntary dyskinesia, Subramaniam says.

Dyskinesia is different than tremor, according to the Michael J. Fox Foundation.

"It can look like fidgeting, writhing, wriggling, head bobbing or body swaying," the foundation explains. "Many people say they prefer dyskinesia to stiffness or decreased mobility. Others, though, have painful dyskinesia or movements that interfere with exercise or social or daily activities."

The reason for its development has eluded scientists. Subramaniam and his team had studied the problem over the past decade, leading them eventually to the discovery that RasGRP1 signaling was a main culprit.

"There is an immediate need for new therapeutic targets to stop LID, or L-DOPA-induced dyskinesia in Parkinson's disease," Subramaniam says. "The treatments now available work poorly and have many additional unwanted side effects. We believe this represents an important step toward better options for people with Parkinson's."

The next steps in the research will be discovering the best route to selectively reducing expression of RasGRP1 in the striatum while not affecting its expression in other areas of the body, Subramaniam says.

"The good news is that in mice, a total lack of RasGRP1 is not lethal, so we think that blocking RasGRP1 with drugs, or even with gene therapy, may have very little or no major side effects," Subramaniam says.

"It's rare for a nonprofit institution to possess the medicinal chemistry and drug development expertise needed to identify and develop such a therapy, but we have that at Scripps Research," Subramaniam says. "Our next task is to develop suitable compounds capable of blocking RasGRP1 in the striatum."

Crystals can be made artificially but a lot of energy is used to melt the ingredients together, and this can make them expensive. This problem can be overcome by using appropriate solvents. Called the flux method, crystals are grown in a crucible that contains solvents that allow the crystal to form with less energy because dissolution will happen easier. Imagine having table salt, and wanting to form crystals of a desirable structure. The salt can be heated to its melting point which would take a lot of energy, or, it can be dissolved in a solvent such as water, and the water can be evaporated at a much lower temperature than trying to heat the salt on its own. Finding the right condition is key for having good crystal recipes.

Katsuya Teshima of Shinshu University is an expert on flux recipes for crystal growth, and continues research to produce optimal crystals of desirable properties. With Effect of Holding Temperature on Growth of Ruby Crystal Films... Teshima, first author Shunsuke Ayuzawa and their team investigated rubies (Al2O3:Cr) and its solubility curve in flux. The flux method of growing crystals is currently the preferable method of procuring crystals because it has negligible environmental impact. With this research, Teshima and his team at Shinshu University investigated the partial solubility curve of ruby crystal growth in Molybdenum Trioxide (MoO3).

The solubility curve is a graph that shows how much dissolves at what temperature. It is crucial to know this information in order to grow crystals with precision. With this research, the solubility curve of Al2O3:Cr in MoO3 for 1050 to 1200? was obtained. Figuring out the solubility curve of this crystal which vaporizes at such high temperatures had been extremely difficult, but this team managed to figure out a way by using the guiding principle of epitaxial growth on a single crystal sapphire substrate to measure a small amount of ruby crystal growth. The key was to distinguish between the red ruby layer and the transparent sapphire layer as the flux evaporated.

Ruby is the Latin word for red, and as the name suggests, is renowned for their beautiful pink and maroon color. Rubies are one of the five cardinal gems because they were rare in the past. Other cardinal gems are diamonds, emeralds, sapphire and amethyst. What is becoming more apparent is that rubies are not only nice to look at, but have properties that can be used in a variety of industry. Rubies have mechanical strength, excellent optical properties and are chemically stable. Single crystals of ruby make great optical devices. The first reported solid laser in 1960 was made of ruby crystal.

Unlike diamonds which are made of pure carbon, rubies are made of a mix of the mineral corundum- a crystalline form of aluminum oxide with a trace of chromium that gives it the red color. The holding temperature, which is the temperature at which the solution is kept, produces different types of rubies with differing properties. The newly discovered solubility curve will enable scientists to be more precise when making crystals.

Teshima, a university researcher hopes to systemize the phase diagram of flux methods for all materials. Having relied on experience and knowledge in the past, he will conduct more research performed through analytical chemistry and computational science from a process chemistry standpoint. He believes that new substances can be discovered and created to perform new functions through the systemization of the flux method.

LA JOLLA--(May 1, 2020) Salk and Scripps Research Institute scientists, along with collaborators at the pharmaceutical company Lundbeck, identified two genes that can regulate levels of healthy fats, called FAHFAs, in mice. The team found that the loss of the two genes led to higher-than-normal levels of the beneficial FAHFAs, while blocking the genes' activity with an experimental drug also increased FAHFA levels.

Because FAHFAs decrease inflammation and increase insulin sensitivity, a better understanding of the activity of their regulatory genes may eventually lead to therapies for people with diabetes and inflammation.

"This study is a really great starting point to answer important questions about FAHFAs," says Alan Saghatelian, a professor in Salk's Clayton Foundation Laboratories for Peptide Biology and corresponding author of the new paper, which appeared in the Journal of Biological Chemistry on May 1, 2020. "Targeting them in this way might have important implications for treating metabolic and inflammatory diseases."

In 2014, Saghatelian and collaborators discovered FAHFAs (short for fatty acid esters of hydroxy fatty acids) when studying a strain of obese mice that were unexpectedly resistant to diabetes. The mice, they found, had sixteen times more FAHFAs than usual. The researchers went on to show that people with pre-diabetes have lower-than-average levels of FAHFAs in their fat and blood. Together, the results suggested that higher levels of FAHFAs may be beneficial to health. Further studies also found a connection between FAHFAs and reduced inflammation in the body.

While many types of fat are ingested through food, FAHFAs are naturally produced by the body, so altering their levels is more difficult. But in 2016, Saghatelian's group, with Benjamin Cravatt of The Scripps Research Institute, reported that two proteins, AIG1 and ADTRP, seemed to alter levels of FAHFAs in isolated cells.

In the new work, Saghatelian and Cravatt's labs, along with the Saez lab at Scripps and industrial partners at Lundbeck, collaborated to further study how AIG1 and ADTRP regulate FAHFAs in living animals. The researchers found that when mice lacked both AIG1 and ADTRP, levels of FAHFAs in their fat tissues were up to nine times higher than levels seen in normal mice. Experiments confirmed that FAHFAs were increasing because AIG1 and ADTRP weren't there to break down the beneficial fats, as they usually would. No other types of fat were affected, however.

"What this tells us is that these proteins are very, very specific for this biochemical activity," says Salk postdoctoral fellow Meriç Erikci Ertunc, the first author of the new paper.

The researchers then worked with Lundbeck researchers to test a library of compounds for molecules that could block the activity of both AIG1 and ADTRP. They found one, called ABD-110207, and tested its effect on mice.

"Until this point, we'd only ever studied the therapeutic potential of FAHFAs by feeding FAHFAs to mice," says Erikci Ertunc. "That's not a very natural situation, but we didn't have any other way to alter levels until we generated mice lacking FAHFA degrading enzymes and found ABD-110207."

The drug-like small molecule successfully increased FAHFA levels, mimicking the results seen in the mice lacking both proteins. In mice lacking the proteins, metabolic benefits were not observed compared to what has been seen in mice that directly consumed FAHFAs. This isn't surprising, the researchers say, given that fats ingested are processed differently than those made naturally by the body.

The team next hopes to study more about the role of FAHFAs in the body and how their levels are normally regulated.

"This could have implications in studying and treating not only diabetes and inflammation but things like cardiovascular disease or even neurodegenerative diseases in which FAHFAs may play a role," says Saghatelian, who holds the Dr. Frederik Paulsen Chair.

The new development, recently reported in the scientific journal Nature Communications, was led by Christopher Li, PhD, a professor in Drexel's College of Engineering whose research has centered around engineering polymer structures for special applications, in collaboration with Bin Zhao, PhD, a professor in the Chemistry Department at the University of Tennessee, Knoxville. Their work shows how these structures, like polymer crystal spheres, can be formed simply by mixing chemicals in a solution - rather than physically manipulating their growth.

"Most crystals grow in a regular pattern, if you think about snowflakes, there is a translational symmetry that guides the unit cell repeating throughout the crystalline flake. What we've discovered is a way to chemically manipulate the macromolecular structure so that this translational symmetry is broken when the molecule crystallizes," Li said. "This means we can control the overall shape of the crystal as it forms - which is a very exciting development, both for its scientific significance and the implications it could have for mass production of targeted therapies."

The technique Li uses to compel what would normally be a flake-like crystal to draw itself up into a sphere builds on his previous work with polymers that look like brushes and polymer crystals formed from emulsion droplets. Incorporating these pliable "bottle-brush" polymers as the structural system of the crystal, allows Li to shape its growth by adjusting the "bristles" of the brush.

"A bottle-brush polymer has lining bristles surrounding a spine, what we discovered is that we can make that spine bend upon crystallization by packing bristles on to one side of it," Li said. "This sets the pattern that is repeated as the crystal grows - so instead of growing flat it curves three-dimensionally to form a sphere."

This means the amount of bristle polymers in the solution will determine how much the bottle-brush spine bends and thus the shape and size of the crystal ball.

Li's team also reports on how to pause the formation of the crystal, leaving holes in the sphere that could be useful for inserting a medicinal payload during the manufacturing process. Once filled, it can be closed with polymers tailored to help direct it to its target in the body.

"We have been working toward this achievement for some time," Li said. "This spherical crystallography manifest itself in robust structures that we see in nature from egg shells to virus capsids, so we believe it is the ideal form to survive the rigors of delivering medication in the body. Being able to control the properties of the crystal as it forms is an important step toward realizing this application."