Culture

A KAIST research team's computational simulations demonstrated that the waves of spontaneous neural activity in the retinas of still-closed eyes in mammals develop long-range horizontal connections in the visual cortex during early developmental stages.

This new finding featured in the August 19 edition of Journal of Neuroscience as a cover article has resolved a long-standing puzzle for understanding visual neuroscience regarding the early organization of functional architectures in the mammalian visual cortex before eye-opening, especially the long-range horizontal connectivity known as "feature-specific" circuitry.

To prepare the animal to see when its eyes open, neural circuits in the brain's visual system must begin developing earlier. However, the proper development of many brain regions involved in vision generally requires sensory input through the eyes.

In the primary visual cortex of the higher mammalian taxa, cortical neurons of similar functional tuning to a visual feature are linked together by long-range horizontal circuits that play a crucial role in visual information processing.

Surprisingly, these long-range horizontal connections in the primary visual cortex of higher mammals emerge before the onset of sensory experience, and the mechanism underlying this phenomenon has remained elusive.

To investigate this mechanism, a group of researchers led by Professor Se-Bum Paik from the Department of Bio and Brain Engineering at KAIST implemented computational simulations of early visual pathways using data obtained from the retinal circuits in young animals before eye-opening, including cats, monkeys, and mice.

From these simulations, the researchers found that spontaneous waves propagating in ON and OFF retinal mosaics can initialize the wiring of long-range horizontal connections by selectively co-activating cortical neurons of similar functional tuning, whereas equivalent random activities cannot induce such organizations.

The simulations also showed that emerged long-range horizontal connections can induce the patterned cortical activities, matching the topography of underlying functional maps even in salt-and-pepper type organizations observed in rodents. This result implies that the model developed by Professor Paik and his group can provide a universal principle for the developmental mechanism of long-range horizontal connections in both higher mammals as well as rodents.

Professor Paik said, "Our model provides a deeper understanding of how the functional architectures in the visual cortex can originate from the spatial organization of the periphery, without sensory experience during early developmental periods."

He continued, "We believe that our findings will be of great interest to scientists working in a wide range of fields such as neuroscience, vision science, and developmental biology."

In a new study from the Danish psychiatry project iPSYCH, researchers have identified genetic risk factors for developing bipolar disorder and psychoses among people with depression. In the longer term, the results may contribute to ensuring the correct diagnosis is made earlier, so that the patients can receive the correct treatment as quickly as possible.

Bipolar disorder and psychoses such as schizophrenia are serious mental disorders, which often have a great impact on a person's life and well-being. In a number of cases, bipolar disorder and schizophrenia are first diagnosed several years after the onset of the disorder. This is associated with unfavourable prognosis for the course of the disorders. The sooner the patient gets the correct diagnosis and begins targeted treatment, the better the prognosis. For this reason, researchers are aiming at identifying risk factors that will aid psychiatrists to reach the correct diagnosis as early as possible.

Depression often precedes bipolar disorder and psychoses

Many people who develop bipolar disorder or psychoses initially come into contact with the mental health services due to depression. A research team from iPSYCH therefore set out to examine a dataset consisting of 16,949 people aged 10-35 who had been treated for depression at a psychiatric hospital in Denmark.

"Our goal with the study was to investigate whether genetic factors are associated with an increased risk of developing bipolar disorder or psychosis among patients with depression. This knowledge can potentially be used in clinical practice to identify patients who should be monitored even more closely," explains the lead author of the research article based on the study, Senior Researcher Katherine Musliner from the National Centre for Register-based Research.

Among the factors the researchers looked into in the study was whether the genetic risk scores for bipolar disorder and schizophrenia - i.e. a person's individual genetic risk of developing these disorders - could possibly help psychiatrists determine which of their patients with depression was at greatest risk of subsequently developing bipolar disorder or a psychosis.

"One thing we discovered was that the genetic risk score for bipolar disorder is associated with an increased risk of developing bipolar disorder, and that the genetic risk score for schizophrenia is associated with an increased risk of developing a psychosis among patients who have been diagnosed with depression," says Katherine Musliner, stressing that the effect of the genetic risk scores were relatively small.

Family history weighs heavily

Another member of the research group behind the study, Professor Søren Dinesen Østergaard from the Department of Clinical Medicine and Aarhus University Hospital - Psychiatry, emphasises that caution is needed when interpreting the results.

"At present, the genetic risk scores cannot contribute to early diagnosis of bipolar disorder and psychoses in clinical practice, but it cannot be ruled out that this could be the future scenario. On the other hand, our study confirms that having a parent with bipolar disorder or a psychosis is a strong predictor for the development of these particular disorders after depression. This underlines the importance of getting information about mental disorders in the family as part of the assessment of people suffering from depression," he explains.

The results have been published in the American Journal of Psychiatry.

Background for the results

The study is a register-based study with data from 16,949 people who were treated for depression at a psychiatric hospital in Denmark in the period from 1994 to 2016.

Scientists from Queen Mary University of London have found that harmful mutations accumulating in the fire ant social chromosome are causing its breakdown.

The chromosome, first discovered by researchers at the University in 2013, controls whether the fire ant colony has either one queen or multiple queens. Having these two different forms of social organisation means the species can adapt easily to different environments and has resulted in them becoming a highly invasive pest all over the world, living up to their Latin name Solenopsis invicta, meaning "the invincible".

For the new study, published in eLife, the research team performed detailed analyses of the activity levels of all the genes within the social chromosome for the first time to understand how it works and its evolution. They found that damaging mutations are accumulating in one version of the social chromosomes, causing it to degenerate. The findings also showed that most of the recent evolution of these chromosomes stems from attempts to compensate for these harmful mutations.

Natural selection is the main evolutionary mechanism that helps to optimise genes over generations but normally, it cannot simultaneously optimise genes for two different types of social organisation within one species.

To overcome this evolutionary conflict, social chromosomes group together genes adapted to each type of social form. The results of the new study show that this solution prevents the removal of harmful mutations from the genome and as a result, these mutations accumulate over time and begin to dominate the fate of the system.

The social chromosomes in fire ants are a rare example of a direct link between genes and social behaviour. They work in a similar way to the X and Y chromosomes in humans, which determine sex.

This discovery has wider ecological and medical implications because genomic structures similar to social and sex chromosomes can not only help species adapt to changing environments but also underpin diseases such as cancer.

Dr. Martínez-Ruiz, lead author of the study from Queen Mary University of London, said: "Our results show that the initial benefit of nature combining genes into a social chromosome has a cost. One million years later, most of the differences we see between social chromosomes are due to the accumulation of negative mutations."

"We also see that the rest of the genome adapts very quickly in response to negative mutations," added Dr. Wurm, Reader in Bioinformatics at Queen Mary and senior author of the study. "This is how evolution works, by adding patches to imperfect solutions, rather than by finding the most efficient solution."

"Despite the degeneration of the social chromosomes, the fire ants are unlikely to lose them anytime soon. This would require another major chromosomal reshuffling - such events are rare and usually lethal," Dr Wurm continues. "However, over long evolutionary timescales, anything is possible. Most of the 20,000 species of ants either have only single-queen colonies or only multiple-queen colonies. We are now trying to understand whether social chromosomes are required for changes in social organisation."

The study builds on earlier research by the authors on the evolution of social chromosomes. They have previously identified differences in genes for chemical communication that may be responsible for perceiving queens*, showed that one social chromosome has doubled in size**, and that this social chromosome lacks genetic diversity***.

SARS-CoV-2 can infect human neural progenitor cells and brain organoids, as shown by researchers from the Shenzhen Institutes of Advanced Technology (SIAT) of the Chinese Academy of Sciences and their collaborators from The University of Hong Kong (HKU).

Their study was published in Cell Research on August 4.

Coronavirus disease 2019 (COVID-19) is caused by SARS-CoV-2, also known as the novel severe acute respiratory syndrome coronavirus 2. Over 17 million confirmed cases of COVID-19 and more than 686,703 associated deaths have been reported across 218 countries and geographical regions as of August 3.

This novel coronavirus primarily causes respiratory illness with clinical manifestations largely resembling those of SARS. However, neurological symptoms including headache, anosmia, ageusia, confusion, seizure and encephalopathy have also been frequently reported in COVID-19 patients.

A study of 214 hospitalized COVID-19 patients in Wuhan reported that 36.4% of all patients and 45.5% of severe cases had neurologic symptoms. In addition, studies from France and Germany have revealed that 84.5% and 36.4%, respectively, of COVID-19 patients had viral infections in the brain.

However, there has been no direct experimental evidence of SARS-CoV-2 infection in the human central nervous system (CNS).

To explore the direct involvement of SARS-CoV-2 in the CNS in physiologically relevant models, the research team assessed SARS-CoV-2 infection in human neural progenitor cells (hNPCs), neurospheres and brain organoids derived from induced pluripotent stem cells (iPSCs).

The results demonstrated that iPSC-derived hNPCs were permissive to SARS-CoV-2 infection, but not SARS-CoV infection. Extensive protein expression and infectious viral particles were detected in neurospheres and brain organoids infected with SARS-CoV-2, which suggested SARS-CoV-2 could productively infect the human brain.

Importantly, SARS-CoV-2 infection in 3D human brain organoids was localised to TUJ1 (neuronal marker) - and NESTIN (NPC marker)-positive cells, suggesting SARS-CoV-2 could directly target cortical neurons and NPCs.

"Overall, our study provides the first evidence of direct SARS-CoV-2 infection in human brain organoids, which contributes to our understanding of the pathogenesis of neurological complications in COVID-19," said Prof. HUANG Jiandong from HKU, who led the study.

The research team suggested that chronic and long-term consequences of SARS-CoV-2 infection of the CNS should be closely monitored.

Clinging to the walls of tropical caves is a type of plant with a single leaf that continues to grow larger for as long as the plant survives. Researchers at the University of Tokyo hope that their study of this unusual species may help inspire future genetic tools to control the size of common crop plants.

"We are pleased that we finally made a small breakthrough studying this plant," said Professor Hirokazu Tsukaya, who led the recent research project.

The plant's scientific name, Monophyllaea glabra, means "hairless species of one-leaf plant." M. glabra sprouts from a seed with two embryonic leaves called cotyledons, but only one of the cotyledons continues to develop into a leaf.

All Monophyllaea species grow one leaf that, as far as scientists have observed, can continue growing bigger as long as the plant lives. Most plants have no limit on the number of leaves they can grow, but those leaves do have a predetermined maximum size.

Tsukaya first tried working with Monophyllaea in the early 1990s after a trip to see the plants growing in their native habitat in Thailand.

"Monophyllaea like to live in limestone caves in Southeast Asia. If you have a chance to go there, you can see these plants easily," said Tsukaya.

The same curious biology that made the plants so interesting also made them challenging to study with new genetic tools being designed at the time for more common species with immediate agricultural or medical relevance. After a decadeslong hiatus while other molecular techniques developed, the project to understand Monophyllaea began again recently when doctoral student and first author of the research paper Ayaka Kinoshita joined the lab.

"I believe ours is the only lab in the world currently studying this species," said Tsukaya.

Understanding what makes Monophyllaea unique required tools that could see the location and activity level of genes early in the leaf's development. A technique known as whole-mount in situ hybridization allows researchers to preserve whole chunks of an organism, not just thin slices, and lock in place all of the genetic material the cells were using at the time of their death. The technique is commonly used in animal tissue, but is more complicated to use in plants because of the stiff outer cell wall around plant cells.

"Luckily, another of our lab members, Assistant Professor Hiroyuki Koga, is a true professional at using the whole-mount system and he persisted to develop a suitable method for plants," said Tsukaya. Koga is the second author of the research publication and was able to perfect a technique to preserve entire three-week-old Monophyllaea plants.

In plants with standard anatomy, the gene SHOOT MERISTEMLESS (STM) is expressed in cells at the growing tips of stems, referred to as the shoot meristem. Additionally, the gene ANGUSTIFOLIA3 (AN3) is expressed in very young leaves to promote the multiplication of cells that form the leaf.

"With our naked eye, we cannot see any shoot meristem in Monophyllaea. So we want to know, is it lost or is it modified?" explained Tsukaya.

Instead of separating the location and timing of STM and AN3 gene expression, young Monophyllaea showed overlapping expression of the two genes. Researchers say that what looks like a simple leaf in Monophyllaea is actually a combination or fusing of the shoot meristem and leaf.

"In Monophyllaea, the expression areas overlap, suggesting this plant is a hybrid of a normal leaf and shoot meristem. We suppose this curious gene expression pattern is one reason why the plant has such a curious appearance," said Tsukaya.

Researchers state that understanding how unusual species like M. glabra evolved to use common genes in uncommon ways will help agricultural scientists develop tools for controlling the size of leaves for optimal farming cultivation in the future.

"We study M. glabra because the characteristics of Monophyllaea development are very unique and they cannot be found in any mutants of common laboratory plants. Dealing with the unique phenomenon can definitely provide new insights to plant science," said Tsukaya.

In the transmission of signals within the cell which, for example, stimulate cell growth or trigger metabolic processes, phosphate groups play an important biochemical role. The phosphate groups are often attached to proteins or removed to control activity. In this process, a change in the protein triggers the next one and the signal is transmitted in a signaling cascade. The target is usually the cell nucleus, where genes are switched on or off.

For the first time, biochemists and virologists from Goethe University have now succeeded in documenting the full picture of all the communication pathways in a human cell infected with SARS-CoV-2 and observed what changes the infection triggers. To do so, they analyzed all proteins carrying a phosphate group at a given moment in time - what is known as the phosphoproteome. The result: SARS-CoV-2 evidently uses above all those signaling pathways of the host cell where a growth signal is transmitted into the cell from outside. If these signaling pathways are interrupted, the virus is no longer able to replicate.

Dr. Christian Münch from the Institute of Biochemistry II at Goethe University explains: "The signaling pathways of the growth factors can be blocked precisely at the point where the signal from outside the cell docks onto a signal receiver - a growth factor receptor. There are, however, a number of very effective cancer drugs that interrupt growth factor signaling pathways slightly further down the cascade, through which the signals of different growth factor receptors are blocked. We've tested five of these substances on our cells, and all five led to a complete stop of SARS-CoV-2 replication."

Professor Jindrich Cinatl from the Institute of Medical Virology at University Hospital Frankfurt says: "We conducted our experiments on cultivated cells in the laboratory. This means that the results cannot be transferred to humans without further tests. However, from trials with other infectious viruses we know that viruses often alter signaling pathways in their human host cells and that this is important for virus replication. At the same time, already approved drugs have a gigantic lead in terms of development so that it would be possible - on the basis of our results and just a few more experiments - to start clinical studies very quickly."

Via INNOVECTIS, the researchers have patented their method of interrupting signaling pathways by means of specific inhibitors in order to treat COVID-19. INNOVECTIS was founded in 2000 as a subsidiary of Goethe University and has operated successfully since then as a service provider in the transfer of academic know-how into business practice.

Researchers have identified a potential new degradation mechanism for electric vehicle batteries - a key step to designing effective methods to improve battery lifespan.

The researchers, from the Universities of Cambridge and Liverpool, and the Diamond Light Source, have identified one of the reasons why state-of-the-art 'nickel-rich' battery materials become fatigued, and can no longer be fully charged after prolonged use.

Their results, reported in the journal Nature Materials, open the door to the development of new strategies to improve battery lifespans.

As part of efforts to combat climate change, many countries have announced ambitious plans to replace petrol or diesel vehicles with electric vehicles (EVs) by 2050 or earlier.

The lithium-ion batteries used by EVs are likely to dominate the EV market for the foreseeable future, and nickel-rich lithium transition-metal oxides are the state-of-the-art choice for the positive electrode, or cathode, in these batteries.

Currently, most EV batteries contain significant amounts of cobalt in their cathode materials. However, cobalt can cause severe environmental damage, so researchers have been looking to replace it with nickel, which also offers higher practical capacities than cobalt. However, nickel-rich materials degrade much faster than existing technology and require additional study to be commercially viable for applications such as EVs.

"Unlike consumable electronics which typically have lifetimes of only a few years, vehicles are expected to last much longer and therefore it is essential to increase the lifetime of an EV battery," said Dr Chao Xu from Cambridge's Department of Chemistry, and the first author of the article. "That's why a comprehensive, in-depth understanding of how they work and why they fail over a long time is crucial to improving their performance."

To monitor the changes of the battery materials in real time over several months of battery testing, the researchers used laser technology to design a new coin cell, also known as button cell. "This design offers a new possibility of studying degradation mechanisms over a long period of cycling for many battery chemistries," said Xu. During the study, the researchers found that a proportion of the cathode material becomes fatigued after repetitive charging and discharging of the cell, and the amount of the fatigued material increases as the cycling continues.

Xu and his colleagues dived deep into the structure of the material at the atomic scale to seek answers as to why such fatigue process occurs. "In order to fully function, battery materials need to expand and shrink as the lithium ions move in and out," said Xu. "However, after prolonged use, we found that the atoms at the surface of the material had rearranged to form new structures that are no longer able to store energy."

What's worse is that these areas of reconstructed surface apparently act as stakes that pin the rest of the material in place and prevent it from the contraction which is required to reach the fully charged state. As a result, the lithium remains stuck in the lattice and this fatigued material can hold less charge.

With this knowledge, the researchers are now seeking effective countermeasures, such as protective coatings and functional electrolyte additives, to mitigate this degradation process and extend the lifetime of such batteries.

STONY BROOK, NY, August 25, 2020 - More than two decades ago scientists discovered the Arp2/3 complex, an actin (cellular protein) cytoskeketal nucleator which plays a crucial role in cell division, immune response, neurodevelopment other biological processes. But there has been no determined structure of the activated state of the complex until now, an achievement that may lay the foundation for uncovering its role in biology and in the development of disease. Researchers at Stony Brook University led by Saikat Chowdhury, PhD, determined the structure of Arp2/3 and describe it in a paper published in Nature Structural and Molecular Biology.

Chowdhury, and graduate student and first author Mohammed Shaaban determined the first near-atomic resolution structure of Arp2/3 in its active state by using cryo-electron microscopy. The structure shows the complex in its active form and bound to a signaling molecule. It also shows the nucleated actin filament, thus providing a structural snapshot of the global and local conformational changes in the Arp2/3 complex that help grow new actin filament in cells.

"Obtaining the macromolecular structure of activated Arp2/3 complex has been a long-standing goal for scientists," says Chowdhury, senior author and an Assistant Professor in the Department of Biochemistry and Cell Biology in the College of Arts and Sciences at Stony Brook University. "Our structure reveals a level of molecular details which show the individual components of the complex and how they are positioned relative to each other in the active state."

Having a structure of Arp2/3 in its active state will help drive more detailed research of the complex. Chowdhury explains that this is extremely important because when Arp2/3 is deregulated in the biological state, it is associated with cancer metastasis, neurodegeneration, bacterial and viral infections and wound healing problems.

"So not only does this structure enable us to fill a knowledge gap in the actin cell biology field, it potentially helps to build our understanding of the underlying causes of a number of diseases with the ultimate goal of developing new therapeutics," emphasizes Chowdhury.

Determining the Arp2/3 structure in its activated state required the researchers to use technologies available in Stony Brook University's Cryo-Electron Microscopy Facility, a center supported by the National Institutes of Health (NIH), and the High Performance Computing capabilities in the Division of Information Technology.

Chowdhury is also affiliated with the Institute of Engineering Driven Medicine and Institute of Chemical Biology & Drug Discovery at Stony Brook University, as well as an affiliated scientist at Brookhaven National Laboratory. The research was done in collaboration with Brad Nolen at the University of Oregon and supported in part by the NIH and SUNY, Stony Brook University.

(Santa Barbara, Calif.) -- Once in a while, over the history of life, a new trait evolves that leads to an explosion of diversity in a group of organisms. Take wings, for instance. Every group of animals that evolved them has spun off into a host of different species -- birds, bats, insects and pterosaurs. Scientists call these "key innovations."

Understanding the development of key innovations is critical to understanding the evolution of the amazing array of organisms on Earth. Most of these happened deep in the distant past, making them difficult to study from a genetic perspective. Fortunately, one group of plants has acquired just such a trait in the past few million years.

Columbines, with their elegant nectar spurs, promise scientists an opportunity to investigate the genetic changes that underpin a key innovation. After much research, UC Santa Barbara professor Scott Hodges, research associate Evangeline Ballerini, and their coauthors at Harvard University have identified a gene critical to the development of these structures. And to their knowledge, this is among the first key innovations for which a critical developmental gene has been identified. Their findings appear in the journal PNAS.

The researchers named the gene after Gregg Popovich, head coach of the San Antonio Spurs basketball team. "This gene is a transcription factor, which means it controls spur development in columbines by regulating the activity of other genes," explained Ballerini. "So I chose the name POPOVICH because as coach, Popovich controls San Antonio Spurs development, in a sense, by regulating the activity of his players."

The evolution of spurs in columbines' ancestors seems to have led to rapid expansion in the genus. Around 70 species evolved over the past 5 to 7 million years, compared to its spurless sister genus, which counts only four species among its members.

And columbines aren't the only flowers with spurs. The trait evolved independently in many different plants, including nasturtiums, larkspurs and impatiens. "And in each of those groups, the ones that have spurs have far more species than their closest relatives that don't have spurs," said Hodges.

"We think that diversity is linked to the evolution of this spur because the spur produces nectar, which attracts animal pollinators," Ballerini said. Changing the length or shape of the spur changes the animals that can pollinate the flower. "Bees are only moving pollen between bee flowers, hummingbirds are only moving pollen between hummingbird flowers, so you're not exchanging genes between those two different populations." Eventually, the two can split into different species.

The question the researchers were trying to answer was how innovations like these develop in the first place. "If we can find genes that are important in the development of a key innovation, that will help us understand this kind of process," said Hodges.

"In most of these cases -- like in the wing example with birds, bats and insects -- those evolved so long ago that it's hard to find a particular gene that was critical for evolving that trait," he added. "Here we have a fairly recent origin of a key innovation, only 5 to 7 million years ago, and it's a fairly simple trait, so it's a little more straightforward."

Finding POPOVICH

Since columbines evolved so recently, most of them can form fertile hybrids with each other. In the 1950s and '60s, a Polish geneticist crossed a spurless species -- appropriately named the spurless columbine -- with its spurred cousins. She found that in the first generation of offspring all had spurs, but self-pollinating these yielded a second generation where spurlessness reappeared in a quarter of the plants.

That ratio was crucial to Hodges and Ballerini's work some half a century later. This simple fraction suggested that a single gene controlled the development of spurs. But columbines have roughly 30,000 genes, and only one was the gene they were looking for.

Following in the footsteps of his predecessor, Hodges also crossed the spurless columbine with a spurred species, and then self-pollinated the offspring. But unlike in the previous experiment, Ballerini and Hodges now had the tools to search the plants' genetic code.

Ballerini sequenced the genome of each of the nearly 300 second generation plants and looked for instances in which the spurless plants had inherited two copies from their spurless grandparent. This narrowed the search to around 1,100 genes on one of the plants' chromosomes.

Still, 1,100 genes are a lot to sort through. "There was no guarantee that these methods would lead us to the gene we were looking for," Ballerini said. "There was definitely quite a bit of work that went into all of the experiments and analyses, but in the end there was a bit of luck too."

Ballerini examined the expression of genes during five stages of early petal development in the spurless columbine and three other spurred species. She sequenced all the genes that were turned on in each stage and looked for consistent differences between the spurless and spurred plants. Eventually, with input from one of her collaborators at Harvard, Ballerini suspected she had identified the right gene. It was always turned off in the spurless species, turned on in the spurred species and was one of the 1,100 genes previously identified as associated with spurless flowers in the genetic cross. Now it was time to test her hypothesis.

She used a genetically modified virus to knock down the expression of the gene in question as well as a gene critical for producing red pigment. This way they could tell which petals were affected just by looking at the color.

Wherever POPOVICH was sidelined, the flowers developed diminutive spurs. But spur length depends both on the number and the size of cells. So the researchers worked with collaborators to count the number and measure the length of each cell making up these diminutive spurs.

"The longer spurs had more cells, and the shorter spurs had fewer cells," Hodges noted. "So the gene must have been acting by affecting how many cells were produced."

Ballerini remembers sitting in her office after finishing her final analyses. She began throwing out potential gene names to graduate student Zac Cabin, a fellow sports enthusiast. "At the same time Zac and I turned to each other and both said 'POPOVICH!'" she recalled. The name seemed a perfect fit. "And it leaves open the possibility that, if we identify other genes at play in spur development, we can name them after some of the players on the Spurs."

A path to new discoveries

While identifying POPOVICH is certainly an achievement, the true value of the discovery lies in what it reveals about the evolution of key innovations. Before this work, none of the plant groups that had well-known genomes also made spurs. "We had no idea where to start," said Hodges. "This discovery provides us a foothold."

"Once we identify one gene -- like this gene, which seems to be key in the process of forming spurs -- then we can start to figure out all of the components," he added. The team can now begin investigating which genes POPOVICH regulates, and which genes regulate POPOVICH. "This is a place to start to understand the whole system."

While the researchers don't know how POPOVICH functions in other groups of plants, it appears to influence the number of leaflets that grow on bur clovers. Columbines also express the gene in their leaves; perhaps it was recruited from the leaves into petal development, Ballerini suggested.

Novel adaptations don't appear out of nowhere, she explained. "When you're evolving a new structure, usually you're not evolving a whole brand new gene." Generally, organisms repurpose or add a purpose to an existing gene.

The authors are also interested in identifying genes involved in the second phase of spur formation: the elongation of the cells in the spur cup.

"These are things that we will want to do now that we've identified this gene," Hodges said. "And since it's a transcription factor, it must have particular genes that it's affecting. The next logical step would be to identify the targets of this gene, and that would tell us a lot more about how it functions."

The researchers expressed their gratitude toward Harvey Karp, who generously funded the Karp Discovery Award that made their research possible. "We really couldn't have done this project without it," Ballerini said.

New research has revealed the locations and industries in the USA where efforts to improve water consumption would have the greatest benefit for economic activity and the environment.

The study, led by researchers from Virginia Tech, used a spatially detailed database of water productivity to set realistic benchmarks for more than 400 industries and products. It is published today in the IOP Publishing journal Environmental Research Letters.

Lead author Dr Landon Marston, from Virginia Tech, said: "Nearly one-sixth of U.S. river basins cannot consistently meet society's water demands while also providing sufficient water for the environment. Water scarcity is expected to intensify and spread as populations increase, new water demands emerge, and climate changes.

"However, improving water productivity by meeting realistic benchmarks for all water users could enable US communities to expand economic activity and improve environmental flows. We asked ourselves the questions: if water productivity is improved across the US economy, how much water can be saved and in which industries and locations?' Our study is the first attempt to answer this question on a nationwide scale, and develop benchmarks to inform future action."

Using their data, the research team looked at how much water savings or how much improvement in water productivity (production or dollars earned per unit of water consumed) could be achieved by improving all users' water productivity to meet a target benchmark, such as up to the 50th percentile (median productivity), 25th percentile (high productivity), or 10th percentile (outstanding productivity).

Co-author Dr Kyle Davis, from the University of Delaware, said: "One of the good things about a benchmarking approach is that it is not prescriptive in the practices or technologies used to reduce water consumption. Instead, it enables individuals and companies to select from a portfolio of strategies, tailored to the constraints and opportunities they face in their businesses and geographic or climatic context.

"The benchmarks we've developed represent actual water productivities achieved by a water user's regional industry peers and are therefore realistically achievable in most cases. Our study provides an upper bound of potential water savings, because we recognise that financial and regulatory barriers may prevent some water users from attaining water productivities achieved by their peers."

The study also found that some of the most water stressed areas in the US West and South have the greatest potential for water savings, with around half the savings obtained by improving water productivity in the production of corn, cotton, and alfalfa.

Dr Marston added: "By incorporating benchmark-meeting water savings within a national hydrological model, we show that depletion of river flows across Western US regions can be reduced on average by 6.2 to 23.2 per cent, without reducing economic production.

"We also identified the US industries and locations that can make the biggest impact by working with their suppliers to reduce water use 'upstream' in their supply chain. The agriculture and manufacturing sectors have the largest indirect water footprint, due to their reliance on water-intensive inputs, but these sectors also show the greatest capacity to reduce water consumption throughout their supply chains.

"Our study is an important first step towards understanding locations and industries where improved water productivity has the greatest potential to conserve water. Meeting the direct and indirect water demands of a growing population while providing enough water to meet local environmental flow requirements will be a key challenge in the coming decades. Improving water productivity will be critical in meeting this challenge, by putting water to more economically-beneficial uses, reducing unsustainable water use, and making water available for other uses, including the environment."

ADELPHI, Md. -- Something is different, and you can't quite put your finger on it. But your robot can.

Even small changes in your surroundings could indicate danger. Imagine a robot could detect those changes, and a warning could immediately alert you through a display in your eyeglasses. That is what U.S. Army scientists are developing with sensors, robots, real-time change detection and augmented reality wearables.

Army researchers demonstrated in a real-world environment the first human-robot team in which the robot detects physical changes in 3D and shares that information with a human in real-time through augmented reality, who is then able to evaluate the information received and decide follow-on action.

"This could let robots inform their Soldier teammates of changes in the environment that might be overlooked by or not perceptible to the Soldier, giving them increased situational awareness and offset from potential adversaries," said Dr. Christopher Reardon, a researcher at the U.S. Army Combat Capabilities Development Command's Army Research Laboratory. "This could detect anything from camouflaged enemy soldiers to IEDs."

Part of the lab's effort in contextual understanding through the Artificial Intelligence for Mobility and Maneuver Essential Research Program, this research explores how to provide contextual awareness to autonomous robotic ground platforms in maneuver and mobility scenarios. Researchers also participate with international coalition partners in the Technical Cooperation Program's Contested Urban Environment Strategic Challenge, or TTCP CUESC, events to test and evaluate human-robot teaming technologies.

Most academic research in the use of mixed reality interfaces for human-robot teaming does not enter real-world environments, but rather uses external instrumentation in a lab to manage the calculations necessary to share information between a human and robot. Likewise, most engineering efforts to provide humans with mixed-reality interfaces do not examine teaming with autonomous mobile robots, Reardon said.

Reardon and his colleagues from the Army and the University of California, San Diego, published their research, Enabling Situational Awareness via Augmented Reality of Autonomous Robot-Based Environmental Change Detection, at the 12th International Conference on Virtual, Augmented, and Mixed Reality, part of the International Conference on Human-Computer Interaction.

The research paired a small autonomous mobile ground robot, equipped with laser ranging sensors, known as LIDAR, to build a representation of the environment, with a human teammate wearing augmented reality glasses. As the robot patrolled the environment, it compared its current and previous readings to detect changes in the environment. Those changes were then instantly displayed in the human's eyewear to determine whether the human could interpret the changes in the environment.

In studying communication between the robot and human team, the researchers tested different resolution LIDAR sensors on the robot to collect measurements of the environment and detect changes. When those changes were shared using augmented reality to the human, the researchers found that human teammates could interpret changes that even the lower-resolution LIDARs detected. This indicates that--depending on the size of the changes expected to encounter--lighter, smaller and less expensive sensors could perform just as well, and run faster in the process.

This capability has the potential to be incorporated into future Soldier mixed-reality interfaces such as the Army's Integrated Visual Augmentation System goggles, or IVAS.

"Incorporating mixed reality into Soldiers' eye protection is inevitable," Reardon said. "This research aims to fill gaps by incorporating useful information from robot teammates into the Soldier-worn visual augmentation ecosystem, while simultaneously making the robots better teammates to the Soldier."

Future studies will continue to explore how to strengthen the teaming between humans and autonomous agents by allowing the human to interact with the detected changes, which will provide more information to the robot about the context of the change-for example, changes made by adversaries versus natural environmental changes or false positives, Reardon said. This will improve the autonomous context understanding and reasoning capabilities of the robotic platform, such as by enabling the robot to learn and predict what types of changes constitute a threat. In turn, providing this understanding to autonomy will help researchers learn how improve teaming of Soldiers with autonomous platforms.

The old adage about a frog that gets put in a pot of cold water on a stove, and doesn't leap out even as the heat slowly climbs to boiling, might seem like a strange metaphor for primary care.
But for many primary care providers around the country, it might feel like an increasingly apt one.

And they feel like the frogs.

The heat that has gradually increased under them in recent years came from a range of sources:

Insurance companies that make them the gatekeeper for patients who need specialty care.

The electronic health record systems that eat up hours after the 'work day' is done, to document diagnoses, orders and treatment authorizations.

The increased expectations from patients and specialists that they'll respond to messages, test results or requests instantly.

The performance metrics that come with a threat of financial penalty.

The growing number of medical decisions that demand in-depth discussions with patients.

And now the rapid rise in telemedicine visits due to COVID-19.

And all of this with little or no increase in the time they have to get it all done, or reduction in the number of patients assigned to them.

Two teams of primary care providers from Michigan Medicine, the University of Michigan's academic medical center, have just published papers in the Journal of General Internal Medicine looking at issues facing primary care practitioners in the third decade of the 21st Century.

More demands, same amount of time

One of the papers documents the electronic medical record demands faced by general internists at Michigan Medicine, U-M's academic medical center.

Each one reported an average of 390 "in-basket" tasks each week, and reported spending an average of 20 hours each week handling the tasks and the additional work that most of them resulted in. That's far more than the eight hours of administrative time per week allowed for each full-time clinician.

The findings build on other studies showing that primary care providers nationwide face the highest number of incoming tasks on EMR systems.

Lead author Laurence McMahon, M.D., M.P.H., chief of general medicine at U-M, notes that the burden has driven many primary care providers across the country to cut back their clinical schedule, just to make their work hours manageable.

"Fully 70% of Michigan Medicine's general medicine faculty now work 'part-time', because it is the only way they can manage the explosion in work - in essence they are taking a pay cut in order to deal with what has become a full-time body of work," says McMahon.

Some have decided to go into hospital medicine, which comes with defined shifts providing general care to hospitalized patients. The new paper's senior author, Vineet Chopra, M.D., M.Sc., leads Michigan Medicine's Division of Hospital Medicine.

"If we are the frogs in the story, I was there when they put the pot on the stove," says McMahon, who has practiced medicine for more than 30 years. "I've had the opportunity to live through all this change, and I remember when each day would mean you'd finish your work and be done. This is no longer the case, and I fear that it will mean fewer physicians choosing primary care careers at a time when our country needs them more than ever. We need a rational way of dividing up that workload so that it's supportive of patient care and of the workforce that's delivering it."

McMahon is quick to point out that the current situation didn't come about all of a sudden, or on purpose.

"This has happened by accident, because of incremental steps," he explains. "Each time we just altered how we practice, and what we do outside our official work hours, to accommodate the additional tasks. But for many, this has made it a job that's not doable within the time we have to see the patients we need to see."

It's no wonder, he says, that some of the "frogs" have chosen to leave the pot, or climb the sides by reducing their hours.

He and his colleagues call for a serious examination of the appropriate size and composition of the panels of patients that primary care providers are expected to maintain, the ability to customize EMRs for primary care, and attention to the actual demands on providers' time. Because of the importance of lifestyle and work-life balance to the current generation of new physicians, time is of the essence to make this change.

Sharing decision making - express style

The other new paper, by U-M and VA Ann Arbor Healthcare System internists Tanner Caverly, M.D., M.P.H., and Rodney Hayward, M.D., focuses on one of the expectations that has arisen in recent years for primary care providers: shared decision making.

They put forth a framework for an abbreviated version that busy providers can practice, to help patients play a larger role in deciding what's right for them and avoiding the patriarchal approach of yesteryear. They call it "everyday shared decision making."

It takes a concept originally developed for high-stakes decisions about cancer treatment or major surgery, and adapts it for the kinds of decisions made at the primary care level.

"An emphasis in recent years has been on improving discussions between the physician and patient--about medical evidence, personal preference and overall goals. But the picture is different in primary care, where most decisions are not high-stakes. Primary care providers most often guide patients about lower-stakes decisions such as whether and when to get screened for different diseases - and only have a minute or two within a clinic visit to make those decisions," says Caverly.

In fact, some studies have shown that as a result of the short time allowed for primary care encounters, many patients aren't getting a true chance to share in the decisions about their health. Efforts to involve other clinic staff in the shared decision making process aren't working either.

In the framework that the authors and their colleagues have proposed, the primary care provider must be able to quickly use information about the individual patient's risk factors to formulate a personalized recommendation about the potential positives and negatives of the decision at hand.

But instead of trying to go over all of the odds ratios and statistics in the minute or two they can allot for such discussions, they instead give the patient their evidence-based, personalized recommendation, and then put the ball in the patient's court by saying they'll support whatever they decide. If the patient asks for more details, they can provide them.

In order to make this approach possible, primary care providers will need more information at the time of care about how much any given treatment, screening or other intervention is likely to help that patient in particular, given their health history and risk factors.

Such information needs to be at their fingertips, including in the computer systems they use during appointments, and a good sense of how much patient preference varies for each decision.
This could flag for providers which patients fall into the "preference sensitive zone" for any given decision, so the provider can let them know the decision isn't clear-cut and inform them about key factors that affect the decision.

Caverly and Hayward give as an example a website created to help providers determine quickly which patients will get the most benefit from a CT scan to screen for lung cancer, https://screenlc.com/.

They note that in their future efforts to test the everyday SDM model, a main task for providers is to frame the decision for that individual patient and then let them decide. For instance, for one patient, they might say about a lung cancer screening,

"For someone like you, I think the potential benefits outweigh the harms" but for another patient they might say "This is very clear-cut, and the benefits far outweigh the potential harms."

Washington, August 24, 2020--A new study finds evidence that contradicts claims in legal complaints to the U.S. Department of Justice arguing that Asian American students face negative consequences while in college as a result of not being admitted to and not attending their first-choice institution. These complaints led to the Trump administration launching formal investigations into the race-conscious admissions practices of Harvard and Yale universities. The findings were published today in Educational Researcher, a peer-reviewed journal of the American Educational Research Association.

The Justice Department issued its findings on the Yale investigation on August 13; its investigation of Harvard is still ongoing.

The nearly identical complaints filed by the Coalition of Asian American Associations (CAAA) and the Asian American Coalition for Education (AACE) specifically cited several negative consequences for these students: reduced time spent on leadership, public service, and co-curricular activities; diminished satisfaction in their academic institutions; a negative attitude toward academics and lower academic achievement; a lack of self-confidence and assertiveness; and negative racial interactions.

To test the groups' claims, a team of seven researchers at the University of Denver and the University of California, Los Angeles (UCLA), examined differences in Asian American student outcomes while in college, based on their college admission and enrollment decisions. For their study, the researchers analyzed longitudinal data from two national surveys administered by the Higher Education Research Institute at UCLA: the 2012 Freshman Survey and 2016 College Senior Survey. The study's sample included 1,023 students who self-identified as Asian American and completed both surveys.

The researchers assessed 27 student outcome measures spread across six general categories. The categories included academic performance and perception of academic abilities; satisfaction with college; self-confidence and self-esteem; level of student involvement; willingness and ability to contribute to society; and diversity of racial interactions.

"Overall, our findings countered the claims made by the two groups that served as the impetus of the Justice Department's investigation," said study coauthor Mike Hoa Nguyen, an assistant professor of higher education at the University of Denver. "We found that only small differences, if any, exist between the self-reported outcomes of Asian American students who were admitted to and attending their first-choice university and those students who were not."

Nguyen's coauthors include Connie Y. Chang, Victoria Kim, Rose Ann E. Gutierrez, Annie Le, and Robert T. Teranishi at UCLA, and University of Denver scholar Denis Dumas.

On 23 of the 27 outcome measures, Nguyen and his colleagues found no difference between the two groups of students, after controlling for students' SAT score, high school grade point average, gender, and first-generation college status. On one other measure--"time spent participating in student clubs or groups"--students not accepted by their first-choice institution reported higher levels of involvement than their peers. The remaining three outcome measures showed marginally higher outcomes for students at their first-choice university, with a very small magnitude of difference between the two groups.

In the "academic performance and perception of academic abilities" category, only one of the 11 measures--"time spent studying and doing homework"--showed a difference between the two groups, with students at their first-choice institution indicating more time on schoolwork. At the same time, the two groups reported similar levels of academic performance and perception of their academic ability.

In the "diversity of racial interactions" category, four of the five measures--including "positive cross-racial interaction"--found no differences between the two groups of students. On the fifth measure--"negative cross-racial interaction"--students at their first-choice university reported fewer negative experiences.

In the "satisfaction with college" category, students at their first-choice university scored higher on one measure--overall satisfaction with the college experience--than their peers. On the other measure in the category--"satisfaction with coursework"--there was no difference between the two groups.

"It is important to note that college choice and admission outcomes are not the only factor contributing to students' college satisfaction," Nguyen said. "Prior research indicates that feeling welcome and valued, instructional effectiveness, racial identity, and faculty and student interactions all impact college satisfaction."

In the "willingness and ability to contribute to society" and the "self-confidence and self-esteem" categories, across seven indicators, both groups showed no differences.

"The bottom line is that our findings reject the claims that Asian American students face negative consequences if they are not accepted by and do not attend their first-choice college," said Nguyen. "Our study shows that the claims are inconsistent and inaccurate."

Furthermore, Nguyen added, the findings support prior research that emphasizes the benefits of attending college, in general, even if it is not at one's first-choice institution.

"Although college choice is of vast importance for many students, including Asian Americans, our study suggests that simply relying on rankings and perceived prestige at elite universities to determine one's first-choice schools might be a disservice to students," Nguyen said. "It is what students do in college, rather than the level of institutional prestige alone, that most determines educational outcomes."

While the CAAA and AACE indicate that they broadly represent the Asian American and Pacific Islander community, public opinion research, including the Spring 2016 Asian American Voter Survey, has found that a majority of Asian Americans support race-conscious university admissions.

UNIVERSITY PARK, Pa. -- The risk of transmitting the livestock virus PPRV, which threatens 80 percent of the world's sheep and goats, increases with certain husbandry practices but not herd size. A new study, led by researchers at Penn State, investigated how transmission of PPRV might change at different scales and identified specific husbandry practices associated with increased odds of infection -- including the introduction of sheep and goats to the herd, sheep or goat attendance at seasonal grazing camps, and the sales or gifting of goats from the herd.

The sheep and goat plague virus, formally known as peste des petits ruminants virus (PPRV) and now known as small ruminant morbillivirus (SRMV), produces a highly infectious and often fatal disease. This study, which appears online Aug. 24 in the journal Viruses, is the third from an international team of researchers who hope to inform strategies for the global campaign to eradicate the virus.

"If we can identify behaviors that increase transmission risk, we can better inform how we allocate resources to manage the virus," said Catherine Herzog, epidemiologist and Huck postdoctoral scholar at the Center for Infectious Disease Dynamics at Penn State and first author of the paper.

The researchers previously found that transmission risk of PPRV was greater among herds in pastoral villages, where people rely almost solely on livestock for their livelihood, compared to herds from agropastoral villages, where people rely on a mix of livestock and agriculture. However, the factors driving these differences were unclear.

Because pastoral villages typically have much larger herds than agropastoral villages, the researchers first investigated whether herd size was related to the rate at which animals become infected--the force of infection. One might expect the rate of infection to increase with herd size, because an animal in a larger herd would have the potential to closely interact with more individuals.

"We hypothesized that the force of infection would increase with herd size--a pattern known as density-dependent transmission--but interestingly this is not what we observed," said Ottar Bjørnstad, Distinguished Professor of Entomology and Biology and J. Lloyd and Dorothy Foehr Huck Chair of Epidemiology at Penn State and a member of the research team.

Instead, Bjornstad explained that at the level of an individual compound, which might contain animals from multiple households living together in a herd, the data suggest that transmission is not related to herd size--a pattern known as frequency dependent transmission. The researchers believe this is due to the formation of social cliques, whose size is unaffected by the overall herd size.

"Having a clear understanding of this relationship and if it varies across geographic scales will improve how we model the disease," he said.

Transmission risk, however, did increase with specific husbandry practices such as the attendance of sheep or goats at seasonal grazing camps, where many herds come to aggregate, and introduction of livestock to the herd. Introductions occur when animals are purchased from or returned home from the market after a failure to sell, or if they returned from being loaned to another herd for breeding opportunities or milk production. Transmission risk also increased when cattle or goats were recently removed from the herd, through gifting, sale, or death.

The researchers hope their ongoing work will help clarify the ecological mechanisms driving PPRV transmission.

"Now that we have evidence that these husbandry practices are associated with higher rates of infection in the Tanzanian setting, we can take a closer look at these practices and recommend improvements or modifications that could help mitigate the transmission risk," said Herzog. "For example, we could explore quarantine procedures around the introduction of animals from sales or gifting, and the return of animals from seasonal grazing camps. We could also focus our veterinary care on settings or events where risk is the highest."

BROOKLYN, New York, Friday, August 14, 2020 – Teleporting is a science fiction trope often associated with Star Trek. But a different kind of teleporting is being explored at the NYU Tandon School of Engineering, one that could let researchers investigate the very basis of social behavior, study interactions between invasive and native species to preserve natural ecosystems, explore predator/prey relationship without posing a risk to the welfare of the animals, and even fine-tune human/robot interfaces.

The team, led by Maurizio Porfiri, Institute Professor at NYU Tandon, devised a novel approach to getting physically separated fish to interact with each other, leading to insights about what kinds of cues influence social behavior.

The innovative system, called “behavioral teleporting” — the transfer of the complete inventory of behaviors and actions (ethogram) of a live zebrafish onto a remotely located robotic replica — allowed the investigators to independently manipulate multiple factors underpinning social interactions in real-time. The research, “Behavioral teleporting of individual ethograms onto inanimate robots: experiments on social interactions in live zebrafish,” appears in the Cell Press journal iScience.

The team, including Mert Karakaya, a Ph.D. candidate in the Department of Mechanical and Aerospace Engineering at NYU Tandon, and Simone Macrì of the Centre for Behavioral Sciences and Mental Health, Istituto Superiore di Sanità, Rome, devised a setup consisting of two separate tanks, each containing one fish and one robotic replica. Within each tank, the live fish of the pair swam with the zebrafish replica matching the morphology and locomotory pattern of the live fish located in the other tank.

An automated tracking system scored each of the live subjects’ locomotory patterns, which were, in turn, used to control the robotic replica swimming in the other tank via an external manipulator. Therefore, the system allowed the transfer of the complete ethogram of each fish across tanks within a fraction of a second, establishing a complex robotics-mediated interaction between two remotely-located live animals. By independently controlling the morphology of these robots, the team explored the link between appearance and movements in social behavior.

The investigators found that the replica teleported the fish motion in almost all trials (85% of the total experimental time), with a 95% accuracy at a maximum time lag of less than two-tenths of a second. The high accuracy in the replication of fish trajectory was confirmed by equivalent analysis on speed, turn rate, and acceleration.

Porfiri explained that the behavioral teleporting system avoids the limits of typical modeling using robots.

“Since existing approaches involve the use of a mathematical representation of social behavior for controlling the movements of the replica, they often lead to unnatural behavioral responses of live animals,” he said. “But because behavioral teleporting ‘copy/pastes’ the behavior of a live fish onto robotic proxies, it confers a high degree of precision with respect to such factors as position, speed, turn rate, and acceleration.”

Porfiri’s previous research proving robots are viable as behavior models for zebrafish showed that schools of zebrafish could be made to follow the lead of their robotic counterparts.

“In humans, social behavior unfolds in actions, habits, and practices that ultimately define our individual life and our society,” added Macrì. “These depend on complex processes, mediated by individual traits —baldness, height, voice pitch, and outfit, for example — and behavioral feedback, vectors that are often difficult to isolate. This new approach demonstrates that we can isolate influences on the quality of social interaction and determine which visual features really matter.”

The research included experiments to understand the asymmetric relationship between large and small fish and identify leader/follower roles, in which a large fish swam with a small replica that mirrored the behavior of the small fish positioned in the other tank and vice-versa.

Karakaya said the team was surprised to find that the smaller — not larger — fish “led” the interactions.

“There are no strongly conclusive results on why that could be, but one reason might be due to the ‘curious’ nature of the smaller individuals to explore a novel space,” he said. “In known environments, large fish tend to lead; however, in new environments larger and older animals can be cautious in their approach, whereas the smaller and younger ones could be ‘bolder.’”

The method also led to the discovery that interaction between fish was not determined by locomotor patterns alone, but also by appearance.

“It is interesting to see that, as is the case with our own species, there is a relationship between appearance and social interaction,” he added.

Karakaya added that this could serve as an important tool for human interactions in the near future, whereby, through the closed-loop teleporting, people could use robots as proxies of themselves.

“One example would be the colonies on Mars, where experts from Earth could use humanoid robots as an extension of themselves to interact with the environment and people there. This would provide easier and more accurate medical examination, improve human contact, and reduce isolation. Detailed studies on the behavioral and psychological effects of these proxies must be completed to better understand how these techniques can be implemented into daily life.”