Culture

We've all heard the saying that individuals learn at their own pace. Researchers at Carnegie Mellon University have developed an automated, robotic training device that allows mice to learn at their leisure. The technology stands to further neuroscience research by allowing researchers to train animals under more natural conditions and identify mechanisms of circuit rewiring that occur during learning.

A research team led by Carnegie Mellon neuroscientist Alison Barth has used the automated technology to identify new, previously unidentified pathways activated when the brain rewires its circuits in response to experience. Their findings are published in the July 17 issue of Neuron.

Barth's lab focuses on understanding the process by which cortical circuits receive sensory information and adapt to it in order to learn. Understanding the algorithm that underlies the changes in the brain's learning circuitry will have important implications for creating engineered systems that use deep learning and artificial intelligence.

"Neural circuits in the cerebral cortex have had 3.5 billion years to evolve to become perfectly adapted to learning things," said Barth, a professor of biological sciences and member of the Carnegie Mellon Neuroscience Institute. "There is valuable information about what happens in the brain that can be used to inform computations that need to change based on experience."

To better study how the brain changes during sensory learning, the researchers constructed an army of automated robotic devices, in an effort that was spearheaded by Sarah Bernhard, an undergraduate student in Carnegie Mellon's Department of Biological Sciences. These devices allowed mice to voluntarily approach a water port in their home cage where they would receive a gentle puff of air to their whiskers followed by a drop of water. If they approached the port and didn't feel a puff of air, they wouldn't get a drop of water. Eventually, they learned that a puff of air meant water and they would start to drink when they felt it.

"It was almost like we gave the mice homework. Some took 50 tries to learn, others took 400. Some learned early in the evening, others learned late at night. But they all learned and learned quickly," said Barth. "One thing that is critical to learning is that you have to be ready to learn. This device let mice learn when they wanted and at their own pace."

They found that when they used the device, the mice learned quickly and independently, with no intervention from the researchers. As a result, they could capture a larger data set that more accurately reflects the individual diversity in learning.

In the Neuron study, Barth and colleagues used the robotic device to determine what sensory learning pathways were conserved across the population, regardless of how long learning took. They found some surprising results.

The pathways that changed the most in response to the sensory stimulus, indicating learning, were not the ones they expected. It was commonly thought that in sensory learning information came from the skin, traveling rapidly to the neocortex through the thalamus. However, the research team found that this pathway remained relatively unchanged during sensory learning. Instead, they were surprised to find that the cortical synapses, responding to a high-order and more integrative part of the thalamus, were much more plastic.

"Our results suggest that the brain maintains the pathway that represents the fast sensory input, things that you want to know for certain in any given situation. The pathway that is responsible for processing more context-rich information is the one that is flexible," Barth said. "The brain keeps the original file but edits a copy of it."

The results provide insight into the algorithm that the neocortex uses to rewire itself during learning. Barth plans to use this training paradigm to understand how and when different types of tasks and rewards can change the brain.

Restricted oxygen during early life development might result in lasting heart damage for many creatures, but not for alligators. Low oxygen doesn't hurt their hearts; it makes them stronger.

Now, University of Guelph researchers are beginning to understand why, pinpointing how alligator hearts benefit from tough early conditions in the egg, in a new study published in Scientific Reports.

It's foundational research that has significant potential to benefit humans.

Alligators, like many lizards and turtles, begin life as eggs buried in deep nests, with the ones buried deepest receiving the least amount of oxygen.

"Low oxygen at this early stage of life affects normal growth and developmental processes, especially in the heart. In placental mammals, like us, these changes are negative and last into adulthood. But in alligators we're seeing something different: the ones with the least oxygen in the nest might actually thrive," said Sarah Alderman, an adjunct professor in U of G's Department of Integrative Biology who led the study.

The alligators that develop under low oxygen conditions - or hypoxia - emerge from the nest with hearts that are bigger and stronger than their siblings that had access to more air as embryos. Their hearts also perform better during exertion, which might help them hold their breath longer or endure through a chase.

What Alderman and her collaborators wanted to understand was which changes occur that create these stronger, more efficient hearts. So they set out to identify what protein differences mark the hypoxic gator heart.

A team from the Rockefeller Wildlife Refuge in Louisiana retrieved alligator eggs from the refuge's wetlands and sent them to colleagues at the University of North Texas. There, some of the eggs were kept in incubators with hypoxia while the rest were raised in incubators with normal levels of oxygen.

The U of G team received samples of the alligator hearts and, with funding from the Natural Sciences and Engineering Research Council of Canada (NSERC), analyzed the proteins inside these hearts using a method known as "shotgun proteomics."

They found signs that the low oxygen in the egg induced a shift in the abundance of certain key molecules the heart uses for making heart proteins, for integrating these proteins into their cells, and for quickly removing and recycling any damaged proteins.

"Essentially, these alligators ramped up the machinery they needed for these processes," Alderman said.

Most of the changes they found in the embryo hearts were still evident two years later in the hearts of juvenile alligators also raised in hypoxia.

As well, Alderman found the hypoxic hearts had more proteins involved in the breakdown of lipids, or fats, needed for energy.

"Hearts are most efficient when they burn fats for energy," Alderman said, noting that athletes' hearts are especially good at this. "But in humans, when the heart progresses into heart failure, it switches to burning sugars."

The fact that alligator hearts from the embryos raised in hypoxia develop an increased ability to use lipids for energy into later life might be key as to why hypoxia is not detrimental to them as similar condition would have been to a developing human heart.

While the Texas team was able to study the alligators only until they were two years old - "After that, it becomes a little dangerous to keep alligators in a lab," Alderman noted - all signs point to these changes in protein expression in the heart being permanent.

Prof. Todd Gillis, a professor in the Department of Integrative Biology, says this research shows how important environmental conditions during embryonic development are to the subsequent health of the adult.

"Clearly, stressors that occur at this early stage have long-term consequences because, as we see here, it changes the biology of the animal," he said.

Gillis, who is a founding member of U of G's Centre for Cardiovascular Investigations, says the next step is to identify what triggers these important changes in protein expression. If that can be identified, it opens a way of applying the findings to humans with weakened hearts, Gillis said.

"If you could find a way to turn on these pathways and then maintain that, that could be a way of improving cardiac function and keeping the heart healthy."

This research team recently received funding from the National Science Foundation in the U.S. to continue this work. Alderman looks forward to the next phase of research, noting that alligators are fascinating to study.

"Alligators have walked this planet far longer than humans have, and they haven't changed much in that time - so whatever their hearts are doing, they are doing really well."

Women's perceived competence has increased relative to men's,
consistent with their growing participation in the labor force and
education

The perception of women as more compassionate and
affectionate has strengthened over time

Researchers: Women's perceived advantage in competence and
communion should favor women's employment

Less positive -- women perceived as less ambitious and decisive,
a disadvantage in relation to leadership

EVANSTON, Ill. --- Good news for women -- they are no longer regarded as less competent than men on average, according to a nationally representative study of gender stereotypes in the United States. Less positive, however, is that women's gains in perceived competence have not propelled them to the top of hierarchies.

A new Northwestern University analysis investigated how gender stereotypes in the U.S. have evolved over seven decades (1946-2018), a span of time that brought considerable change in gender relations due in large part to women's increased participation in the labor force and education. Women now earn more bachelor's, master's and doctoral degrees than men, unlike decades ago.

The study, published in the journal American Psychologist, analyzed 16 nationally representative opinion polls conducted in the United States with more than 30,000 adult respondents. These polls asked respondents to compare women's and men's competence (e.g., intelligent, organized, creative), communion (e.g., affectionate, compassionate, emotional), and agency (e.g., ambitious, aggressive, decisive).

Most adults now report that women and men are equal in general competence. But among those who see a difference, most see women as more competent than men.

For instance, in the most recent poll, conducted in April 2018, most respondents (86%) said that men and women are equally intelligent. However, 9% said that women are more intelligent, compared to a smaller percentage (5%) who said that men are more intelligent.

Alice Eagly, lead author of the study and professor of psychology in the Weinberg College of Arts and Sciences at Northwestern, also said that the study's findings about communion and agency are surprising.

"The perceptions of women as communal and men as agentic have not eroded since the 1940s, contrary to conventional wisdom about convergence in gender roles," Eagly said. "Rather, communal stereotypes have changed but increasingly towards portraying women as more compassionate, affectionate and sensitive than men. Men are still viewed as more ambitious, aggressive and decisive than women, and that agency stereotype has not substantially changed since the 1940s."

The researchers note that different groups of respondents -- men, women, racial subgroups -- generally agree about these stereotypes. For instance, respondents in recent U.S. samples ascribed competence more often to women than men, regardless of the respondent's sex, race, ethnicity, college education, marital status, employment status or birth cohort.

Interpretation of these findings, said Eagly, also a faculty fellow with Northwestern's Institute for Policy Research, is that women's increasing labor force participation and education likely underlie the increase in their perceived competence, but that occupational segregation underlies the other findings.

"Specifically, women are concentrated in occupations that reward social skills or offer contribution to society," she said. "People observe the social roles of women and men and infer the traits that make up gender stereotypes. In general, stereotypes reflect the social position of groups in society and, therefore, change only when this social position shifts. That's why gender stereotypes have changed."

"The current stereotypes should favor women's employment, because competence is, of course, a job requirement for virtually all positions," Eagly said. "Also, jobs increasingly reward social skills, making women's greater communion an additional advantage."

But the findings are not all positive for women, she adds. "Most leadership roles require more agency than communion and the lesser ambition, aggressiveness and decisiveness ascribed to women than men are a disadvantage in relation to leadership."

The researchers' findings about change over time are novel, Eagly said.

"There are many studies on gender stereotypes, but no others have investigated change in these stereotypes over many decades using representative samples."

"Gender Stereotypes Have Changed: A Cross-Temporal Meta-Analysis of U.S. Public Opinion Polls From 1946 to 2018" will publish July 18 in the journal American Psychologist. In addition to Eagly, co-authors include Christa Nater, University of Bern; David I. Miller, American Institutes for Research; and Michéle Kaufmann and Sabine Sczesny, University of Bern.

For female mosquitoes, finding their next meal is all about smelling and seeing.

Through behavioral experiments and real-time recording of the female mosquito brain, a team of scientists, led by researchers at the University of Washington, has discovered how the mosquito brain integrates signals from two of its sensory systems -- visual and olfactory -- to identify, track and hone in on a potential host for her next blood meal.

Their findings, published July 18 in the journal Current Biology, indicate that, when the mosquito's olfactory system detects certain chemical cues, they trigger changes in the mosquito brain that initiate a behavioral response: The mosquito begins to use her visual system to scan her surroundings for specific types of shapes and fly toward them, presumably associating those shapes with potential hosts.

Only female mosquitoes feed on blood, and these results give scientists a much-needed glimpse of the sensory-integration process that the mosquito brain uses to locate a host. Scientists can use these findings to help develop new methods for mosquito control and reduce the spread of mosquito-borne diseases.

This study focused on the olfactory cue that triggers the hunt for a host: carbon dioxide, or CO2. For mosquitoes, smelling CO2 is a telltale sign that a potential meal is nearby.

"Our breath is just loaded with CO2," said corresponding author Jeffrey Riffell, a UW professor of biology. "It's a long-range attractant, which mosquitoes use to locate a potential host that could be more than 100 feet away."

That potential host could be a person or another warm-blooded animal. Prior research by Riffell and his collaborators has shown that smelling CO2 can "prime" the mosquito's visual system to hunt for a host. In this new research, they measure how CO2 triggers precise changes in mosquito flight behavior and visualize how the mosquito brain responds to combinations of olfactory and visual cues.

The team collected data from approximately 250 individual mosquitoes during behavioral trials conducted in a small circular arena, about 7 inches in diameter. A 360-degree LED display framed the arena and a tungsten wire tether in the middle held each mosquito. An optical sensor below the insect collected data about mosquito wingbeats, an air inlet and vacuum line streamed odors into the arena, and the LED display showed different types of visual stimuli.

The team tested how tethered Aedes aegypti mosquitoes responded to visual stimuli as well as puffs of CO2-rich air. They found that, in the arena, one-second puffs of air containing 5% CO2 -- just above the 4.5% CO2 air emitted by humans -- prompted the mosquitoes to beat their wings faster. Some visual elements like a fast-moving starfield had little effect on mosquito behavior. But if the arena showed a horizontally moving bar, mosquitoes beat their wings faster and attempted to steer in the same direction. This response was more pronounced if researchers introduced a puff of CO2 before showing the bar.

To get a clear picture of how smelling CO2 first affected flight behavior, they analyzed their data using a mathematical model of housefly flight behavior.

"We found that CO2 influences the mosquito's ability to turn toward an object that isn't directly in their flight path," said Riffell. "When they smell the CO2, they essentially turn toward the object in their visual field faster and more readily than they would without CO2."

The researchers repeated the arena experiments with a genetically modified Aedes aegypti strain created by Riffell and co-author Omar Akbari, an assistant professor at the University of California, San Diego. Cells in these mosquitoes glow fluorescent green if they contain high levels of calcium ions -- including neurons of the central nervous system when they are actively firing. In the arena, the researchers removed a small portion of the mosquito skull and used a microscope to view neuronal activity in sections of the brain in real time.

The team focused on 59 "regions of interest" that showed especially high levels of calcium ion levels in the lobula, a part of the mosquito brain's optic lobe. If the mosquito was shown a horizontal bar, two-thirds of those regions lit up, indicating increased neuronal firing in response to the visual stimulus. When the researchers introduced a puff of CO2 first and then showed the horizontal bar, 23% of the regions had even higher activity than before -- indicating that the CO2 odor prompted a larger-magnitude response in these areas of the brain that control vision.

The researchers tried the reverse experiment -- seeing if a horizontal bar triggered increased firing in the parts of the mosquito brain that control smell -- but saw no response.

"Smell triggers vision, but vision does not trigger the sense of smell," said Riffell.

Their findings align with the general picture of mosquito senses. The mosquito sense of smell operates at long distances, picking up scents more than 100 feet away. But their eyesight is most effective for objects 15 to 20 feet away, according to Riffell.

"Olfaction is a long-range sense for mosquitoes, while vision is for intermediate-range tracking," said Riffell. "So, it makes sense that we see an odor -- in this case CO2 -- affecting parts of the mosquito brain that control vision, and not the reverse."

In the future, Riffell wants to test whether other shapes affect mosquito behavior and activity in the optic lobe. Those results may further illuminate the hierarchical nature of mosquito host-hunting behaviors: smell first, then see. It may also provide new knowledge for mosquito control.

When making decisions that are important to the species' survival, zebrafish choose mating over fleeing from a threat. This decision, different compared to that of some other species, appears to be controlled by specific brain regions that respond to pheromone cues.

These findings by scientists at Harvard University and Novartis Institutes of BioMedical Research (NIBR) illuminate an aspect of basic biology that will be important as researchers use zebrafish to model neurological diseases that affect social behavior, such as autism and schizophrenia. The study is published in Current Biology.

"Animals and people make behavioral decisions, ones controlled by environmental challenges and modulated by their internal drives, but little is known about the biology of these choices," said Mark Fishman, M.D., Harvard professor of stem cell and regenerative biology and senior author of the study. "We looked at a critical decision for the survival of the species in zebrafish, giving them the choice between mating and fleeing a threat."

Wired for survival

To simulate a threat, the researchers used "skin extract," a complicated mixture of pheromones that is released when a zebrafish is injured. When exposed to the substance, zebrafish usually show a strong alarm reponse, swimming quickly near the bottom of the tank and then freezing.

But when the zebrafish were mating, they ignored the threat. Moreover, they did not need to be mating to ignore the threat -- being exposed to "mating water" that was previously conditioned by mating zebrafish was enough. This indicated to the researchers that the behavior was due to reproductive pheromones released in the water.

Digging deeper, the researchers used live imaging to identify specific brain regions that were activated by the mating and threat stimuli.

"When we presented both stimuli at the same time and looked at the brain, by and large we saw a response to just the reproductive stimulus, not the fear-inducing stimulus. And even further, the areas that were previously activated by the fear-inducing stimulus were now being suppressed," said Gerald Sun, Ph.D., former NIBR postdoctoral scholar and co-lead author of the study.

An unexpected response

The zebrafish's choice to continue mating in the face of a threat is the opposite of many other animals, including humans.

"The fish completely disregarded what is normally a very noxious, fearful stimulus, and that was really unexpected," Sun said. "One potential explanation for why zebrafish have adopted this strategy is that they lay eggs that are externally fertilized. Humans and live-bearing fish make the opposite decision to flee a threat, because they need to survive for the next generation to be propagated."

A model to study behavioral decisions

With a better understanding of zebrafish biology, researchers can use the animal model to study social and other behaviors.

"It's important to establish what are the normal behaviors of zebrafish. Then you can study zebrafish as a model for diseases that affect social behavior, like autism and schizophrenia," said Carmen Diaz-Verdugo, NIBR postdoctoral scholar and co-lead author of the study. "Once you define a well-established behavior and know the brain area responsible for it, then you can create genetic models that behave differently and use them for drug discovery."

Although human brains are more complex than those of zebrafish, they still have a primitive component.

"We all have certain innate responses to the world around us. One hopes that with humans, you can modulate these to a certain degree. But on the other hand, your limbic system -- your 'fish brain' -- will play a big part in how you respond in different situations," Fishman said. "We anticipate that elements of the underlying circuitry will be conserved and used for similar purposes in other species, although playing out in a species-specific manner."

Robots and prosthetic devices may soon have a sense of touch equivalent to, or better than, the human skin with the Asynchronous Coded Electronic Skin (ACES), an artificial nervous system developed by a team of researchers at the National University of Singapore (NUS).

The new electronic skin system achieved ultra-high responsiveness and robustness to damage, and can be paired with any kind of sensor skin layers to function effectively as an electronic skin.

The innovation, achieved by Assistant Professor Benjamin Tee and his team from the Department of Materials Science and Engineering at the NUS Faculty of Engineering, was first reported in prestigious scientific journal Science Robotics on 18 July 2019.

Faster than the human sensory nervous system

"Humans use our sense of touch to accomplish almost every daily task, such as picking up a cup of coffee or making a handshake. Without it, we will even lose our sense of balance when walking. Similarly, robots need to have a sense of touch in order to interact better with humans, but robots today still cannot feel objects very well," explained Asst Prof Tee, who has been working on electronic skin technologies for over a decade in hope of giving robots and prosthetic devices a better sense of touch.

Drawing inspiration from the human sensory nervous system, the NUS team spent a year and a half developing a sensor system that could potentially perform better. While the ACES electronic nervous system detects signals like the human sensor nervous system, it is made up of a network of sensors connected via a single electrical conductor, unlike the nerve bundles in the human skin. It is also unlike existing electronic skins which have interlinked wiring systems that can make them sensitive to damage and difficult to scale up.

Elaborating on the inspiration, Asst Prof Tee, who also holds appointments in the NUS Department of Electrical and Computer Engineering, NUS Institute for Health Innovation & Technology (iHealthTech), N.1 Institute for Health and the Hybrid Integrated Flexible Electronic Systems (HiFES) programme, said, "The human sensory nervous system is extremely efficient, and it works all the time to the extent that we often take it for granted. It is also very robust to damage. Our sense of touch, for example, does not get affected when we suffer a cut. If we can mimic how our biological system works and make it even better, we can bring about tremendous advancements in the field of robotics where electronic skins are predominantly applied."

ACES can detect touches more than 1,000 times faster than the human sensory nervous system. For example, it is capable of differentiating physical contacts between different sensors in less than 60 nanoseconds - the fastest ever achieved for an electronic skin technology - even with large numbers of sensors. ACES-enabled skin can also accurately identify the shape, texture and hardness of objects within 10 milliseconds, ten times faster than the blinking of an eye. This is enabled by the high fidelity and capture speed of the ACES system.

The ACES platform can also be designed to achieve high robustness to physical damage, an important property for electronic skins because they come into the frequent physical contact with the environment. Unlike the current system used to interconnect sensors in existing electronic skins, all the sensors in ACES can be connected to a common electrical conductor with each sensor operating independently. This allows ACES-enabled electronic skins to continue functioning as long as there is one connection between the sensor and the conductor, making them less vulnerable to damage.

Smart electronic skins for robots and prosthetics

ACES' simple wiring system and remarkable responsiveness even with increasing numbers of sensors are key characteristics that will facilitate the scale-up of intelligent electronic skins for Artificial Intelligence (AI) applications in robots, prosthetic devices and other human machine interfaces.

"Scalability is a critical consideration as big pieces of high performing electronic skins are required to cover the relatively large surface areas of robots and prosthetic devices," explained Asst Prof Tee. "ACES can be easily paired with any kind of sensor skin layers, for example, those designed to sense temperatures and humidity, to create high performance ACES-enabled electronic skin with an exceptional sense of touch that can be used for a wide range of purposes," he added.

For instance, pairing ACES with the transparent, self-healing and water-resistant sensor skin layer also recently developed by Asst Prof Tee's team, creates an electronic skin that can self-repair, like the human skin. This type of electronic skin can be used to develop more realistic prosthetic limbs that will help disabled individuals restore their sense of touch.

Other potential applications include developing more intelligent robots that can perform disaster recovery tasks or take over mundane operations such as packing of items in warehouses. The NUS team is therefore looking to further apply the ACES platform on advanced robots and prosthetic devices in the next phase of their research.

Researchers have identified somatic mutations in the brain that could contribute to the development of Alzheimer's disease (AD). Their findings were published in the journal Nature Communications last week.

Decades worth of research has identified inherited mutations that lead to early-onset familial AD. Inherited mutations, however, are behind at most half the cases of late onset sporadic AD, in which there is no family history of the disease. But the genetic factors causing the other half of these sporadic cases have been unclear.

Professor Jeong Ho Lee at the KAIST Graduate School of Medical Science and Engineering and colleagues analysed the DNA present in post-mortem hippocampal formations and in blood samples from people aged 70 to 96 with AD and age-matched controls. They specifically looked for non-inherited somatic mutations in their brains using high-depth whole exome sequencing.

The team developed a bioinformatics pipeline that enabled them to detect low-level brain somatic single nucleotide variations (SNVs) - mutations that involve the substitution of a single nucleotide with another nucleotide. Brain somatic SNVs have been reported on and accumulate throughout our lives and can sometimes be associated with a range of neurological diseases.

The number of somatic SNVs did not differ between individuals with AD and non-demented controls. Interestingly, somatic SNVs in AD brains arise about 4.8 times more slowly than in blood. When the team performed gene-set enrichment tests, 26.9 percent of the AD brain samples had pathogenic brain somatic SNVs known to be linked to hyperphosphorylation of tau proteins, which is one of major hallmarks of AD.

Then, they pinpointed a pathogenic SNV in the PIN1 gene, a cis/trans isomerase that balances phosphorylation in tau proteins, found in one AD patient's brain. They found the mutation was 4.9 time more abundant in AT8-positive - a marker for hyper-phosphorylated tau proteins- neurons in the entorhinal cortex than the bulk hippocampal tissue. Furthermore, in a series of functional assays, they observed the mutation causing a loss of function in PIN1 and such haploinsufficiency increased the phosphorylation and aggregation of tau proteins.

"Our study provides new insights into the molecular genetic factors behind Alzheimer's disease and other neurodegenerative diseases potentially linked to somatic mutations in the brain," said Professor Lee.

The team is planning to expand their study to a larger cohort in order to establish stronger links between these brain somatic mutations and the pathogenesis of Alzheimer's disease.

WASHINGTON, July 18, 2019 -- There are some crazy poisons in this world of ours, and they're often found in things you'd least expect. In this week's episode of Reactions, we break down our top five strangest poisons: https://youtu.be/4hQ0G0GaYR8.

Researchers in the group of Jan Michiels (VIB-KU Leuven Center for Microbiology) identified a mechanism of how sleepy bacteria wake up. This finding is important, as sleepy cells are often responsible for the stubbornness of chronic infections. Findings published in Molecular Cell reveal new perspectives on how to treat chronic infections, for example by forcing bacteria to wake up.

Sleeping bacteria

Bacteria are able to fall into a deep sleep. These sleeping bacteria are called 'persisters' and they can be found in every type of bacterial population studied so far, including important human pathogens. From a patient's point of view, persisters are unwanted as their sleeping state makes them insensitive to antibiotics.

These sleeping bacteria may wake up spontaneously and colonize the host leading to a return of the infection. Hence, persisters are associated with the failure of antibiotic therapy when they are not killed by the immune system. Until now, it was unknown how these cells were able to revert from dormant to active state. These new results provide insight into how persisters wake up.

Breaking links to wake up

To investigate how persisters wake up, the scientists used an E. coli model system based on HokB. HokB is a peptide - a small cousin of proteins - which is known to promote the development of persister cells by forming pores in the bacterial cell membrane. This results into a rapid loss of energy, pushing the bacteria into a low energy state or deep sleep. Importantly, this pore formation is only possible when two HokB peptides are linked together. The awakening of these sleeping bacteria is possible only when the link between the peptides is broken. This in turn breaks up the pore. Only when the pore is degraded, cells are able to energize again by consuming available nutrients.

Lead author Dorien Wilmaerts (VIB-KU Leuven Center for Microbiology) says: "You can compare this process with a punctured tire: you take out the spike first, and then inflate it again. Doing it the other way around does not make sense."

Getting rid of chronic infections

Persister cells are responsible for chronic infections that keep returning. Examples are urinary tract infections by Escherichia coli, lung infections in cystic fibrosis patients by Pseudomonas aeruginosa, or tuberculosis by Mycobacterium tuberculosis. How persister cells wake up is a long-standing question in persistence research. This work is the first to provide a detailed mechanistic understanding of an awakening mechanism and opens up new perspectives on how to stimulate awakening of deeply dormant cells.

Prof. Jan Michiels (VIB-KU Leuven) says: "Results from this work may help us to discover novel molecules and to design new strategies to eradicate persisters. Combinations of molecules stimulating awakening together with classical antibiotics could eradicate chronic infections."

Ribosomes are molecular machines that produce proteins in cells. Having finished the job, the ribosomes need regenerating. This process is important for the quality of the proteins produced and thus for the whole cell homeostasis as well as for developmental and biological processes. Biochemists from Goethe University Frankfurt together with biophysicists at LMU Munich have now watched one of the most important enzymes for ribosome recycling at work - ABCE1 - and shown that it is unexpectedly versatile in terms of structure.

Ribosomes decode the genetic information from the messenger RNAs and translate it into proteins. Once they have produced a protein, but also if defective proteins have come to a halt in the ribosome, the ribosomes have to be "recycled" so that they are in good working order for a new round of synthesis. In all organisms (except bacteria), the enzyme ABCE1 coordinates this process, in which the ribosome is split into its two subunits. Biochemist Robert Tampé and LMU biophysicist Thorben Cordes, in collaboration with researchers at the University of Groningen (Netherlands), have shown that ABCE1 adopts three structural conformations to boost recycling. Their results are presented in the current issue of the journal Cell Report.

The ABCE1 enzyme can split ATP, the energy currency of cells, and use the energy released to separate the two ribosomal subunits. "Recent structural and functional data have shown that a conformational change of the enzyme, that is, a change in its spatial structure, is essential within this process for the diverse functions of ABCE1," says Cordes. Using an integrated test approach - among others with the help of what is known as the single-molecule FRET method - his team has now observed at first hand the structural variability of ABCE1 at the level of single molecules.

In the course of this work, the researchers established that the two ATP binding sites of ABCE1 can adopt three conformations - open, intermediate and closed - which are in a state of dynamic equilibrium. Interaction of ABCE1 with both the ribosome and the ATP influences the structural dynamics of the two ATP binding sites. This results in a complex network of different states, in which ribosome and ATP shift the equilibrium in the direction of the closed conformation.

"We assume that the conformations perform functionally different roles in the dissociation of the ribosome as well as for the many other diverse functions of ABCE1," says Cordes. "Ribosome recycling is governed by an extraordinarily complex and conserved machinery, which has medical significance as yet unimagined," adds Robert Tampé.

UCF student Veronica Urgiles has helped describe two new frog species discovered in Ecuador, and she named one of them after one of her professors.

Urgiles and an international team of researchers just published their findings in the journal ZooKeys.

"Frogs are by far my favorite," said Urgiles, who is pursuing a master's degree in biology. "So, getting to describe and name two of them is terrific. I have been looking at these frogs for years now, so going over the whole process of observing them in their habitats and then analyzing them and comparing them under the microscope, to finally naming them is a long, but very satisfying journey."

Urgiles, a 2017 Fulbright scholar and the lead author, said she chose to attend UCF for its integration of genetics and genomics in biodiversity research and the emphasis on real-world application. She works with Assistant Professor Anna Savage who specializes in species diversity based on molecular analyses.

"One of the things that I found most interesting about these guys is that they don't have metamorphosis like a regular frog, but instead they develop entirely inside eggs that adult females deposit in the ground," Urgiles said. "They really don't need water bodies for their development. Both of the new frog species inhabit high elevation ecosystems in the mountain range over 8,000 feet, so even though we are right there in the equator, it's very cold and windy most of the year."

The team of researchers has been studying frogs in Ecuador the past few years. In 2017, Urgiles found the first new species and named it Pristimantis quintanai, after one of her biology professors -- Pedro Quintana-Ascencio. She and Savage found the second species -- Pristimantis cajanuma -- in 2018. Both were found in the Paramo and montane forest of the southern Ecuadorean Andes.

The frogs are tiny, measuring .8 inch. Pristimantis quintanai females are brown and black and Pristimantis cajanuma are green and black, both easily blending into the foliage. They have a distinct call that is sharp and continuous, sounding like tik-tik-tik-tik.

Urgiles examined DNA samples collected by the international team back in Savage's lab at UCF, generated genetic sequences, and constructed the phylogenetic analysis. Other team members also worked the morphological diagnosis and comparisons with other frogs and an acoustic analysis of the frogs' calls.

"In these analyses, we use all of the genetic similarities and differences we find to build phylogenetic trees, and when we find that a 'branch' on the 'tree' has strong support and contains all of the individuals that share the same morphological characteristics, then we have good evidence to describe it as a new species," says Savage, whose expertise includes describing species diversity based on molecular analyses. "We used this method, along with vocalization and location data, to conclude that the two species we describe are distinct from any other species that have ever been characterized."

The work is critical because of the vast diversity that has yet to be discovered in the tropical Andes of South America, Urgiles says. In 2018, 13 new species of frogs were documented in the tropical Andes of Ecuador and so far in 2019 five new frogs have been documented.

There are potentially thousands of new plants and animals in the area that may hold the key to other discoveries. It's important to know what is there, to better understand the threats to habitat loss and disease so conservation methods can be established to protect the resources.

The first rule on the stock market is to buy low and sell high. Economists are well aware of how this behaviour changes the prices of stocks, but in reality, trades alone don't tell the whole story. Parties like banks and insurance companies rarely trade stocks themselves; instead, they place orders for traders to do so on their behalf, which can be canceled at any time if they are no longer interested. The amount payed by those placing orders is affected by a highly variable quantity called the bid-ask 'spread' - the difference between the price initially quoted for a stock, and the final bidding price. In a new study published in EPJ B, Stephan Grimm and Thomas Guhr from Duisburg-Essen University in Germany compare the influences that three price-changing events have on these spread changes. Their work sheds new light on the intricate inner workings of the stock market.

For 96 stocks in the NASDAQ100 index, Grimm and Guhr calculated the frequencies of trades, order placements and deletions over a span of four days. They found that order deletions actually increase the bid-ask spread more often than trades do, and that when the number of deletions exceeds the number of trades, the spreads associated with different stocks become far more varied. They also determined that the prices of individual stocks are raised by trades and order deletions which change their spread, but are lowered by spread-changing order placements. Finally, the duo showed that all three spread-changing events result in a cross-response to other stocks, thereby affecting the entire market.

Ultimately, Grimm and Guhr concluded that spread-changing order placements and deletions have nearly the same effect on stock prices as trades do. Their work improves economists' understanding of the deep-rooted interconnections which allow actions involving individual stocks to change the market as a whole.

Korea Brain Research Institute (KBRI, President Seo Pan-ghill) announced on July 10 that the international joint research team where Senior Researcher Jeong Yoon-ha and John Hopkins School of Medicine collaborated, found that 'cell autophagy* gene' called ATG7 is related to the onset of frontotemporal dementia and Lou Gehrig's disease.

Autophagy: It refers to the phenomenon where a cell discomposes and recycles unnecessary organelles or components. It can be regarded as the self-cleaning taking place within the cell.

The research outcome was published in the July issue of 'Autophagy', which is an international journal and the name of the paper and authors are as follows.

Paper: Upregulation of ATG7 Attenuates Motor Neuron Dysfunction Associated with Depletion of TARDBP/TDP-43

Author: Aneesh Donde*, Mingkuan Sun*, Yun Ha Jeong* (co-first author), Xinrui Wen, Jonathan Ling, Sophie Lin, Kerstin Braunstein, Shuke Nie, Sheng Wang, Liam Chen and Philip C. Wong (corresponding author)

The research team found that when the genes are manipulated to make sure that a certain protein called TDP-43* is not created in mice and fruit flies, then the activity of gene ATG7, which is essential for cell autophagy, was inhibited and neuronal degeneration occurred.

It is a transcriptional regulation protein and it is known as the major pathogenesis of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD).

ATG7: Essential gene for autophagy

On the contrary, when the gene is manipulated to increase the ATG7 gene expression for activation of autophagy in fruit flies, for which the TBPH* gene expression is inhibited, it is found that neurodegenerative and ataxia symptoms were improved.

TBPH: Gene of fruit flies that is equivalent to TDP-43 present in humans

The result of this study is meaningful in that the study confirmed the fact that TDP-43 protein regulates the activation of ATG7, which is responsible for the autophagy of neurons as well as the specific process of neuronal degeneration at the gene level.

Cells improve the activity of overall cells by consuming damaged or old organelles or some structures (This is what we call autophagy). If the activity of gene ATG7, which is key to this process, is reduced, then the damaged and old organelles still remain, causing problems in the muscle cells and neurons.

Dr. Jeong Yoon-ha of the KBRI expected that "this research would contribute towards the development of a new treatment for neuro-degenerative diseases, aiming to activate the autophagy function of cell".

The art of tattooing may have found a diagnostic twist. A team of scientists in Germany have developed permanent dermal sensors that can be applied as artistic tattoos. As detailed in the journal Angewandte Chemie, a colorimetric analytic formulation was injected into the skin instead of tattoo ink. The pigmented skin areas varied their color when blood pH or other health indicators changed.

A tattooist places ink directly in the dermis, a roughly one-millimeter-thick layer of tissue that hosts nerves, blood vessels, and hair follicles. The tattoo needle punctures the epidermis, the uppermost layer of skin, and releases the pigments into the dermis below, where the pigments stain the skin permanently.

Using tattoos for diagnostic rather than cosmetic purposes is a new concept. Researcher Ali K. Yetisen, who works at the Technical University of Munich, Germany, and his colleagues thought the technique could be helpful to place sensor formulations at spots in the body where they can record changes in metabolic substances directly, without any spatial distance or time delay, and perhaps for a very long period of time.

The researchers then identified and adapted three colorimetric chemical sensors that produce a color change in response to biomarkers. The first sensor was a rather simple pH indicator consisting of the dyes methyl red, bromothymol blue, and phenolphthalein. If injected into a model skin patch--a piece of pig skin--the resulting tattoo turned from yellow to blue if the pH was adjusted from five to nine.

The other two sensors probed the levels of glucose and albumin. Albumin is a carrier and transport protein in the blood. High glucose levels in the body may indicate diabetic dysfunction, whereas falling albumin levels can indicate liver or kidney failure. The glucose sensor consisted of the enzymatic reactions of glucose oxidase and peroxidase, which, depending on the glucose concentration, led to a structural change of an organic pigment, and a yellow to dark green color change. The albumin sensor was based on a yellow dye that, upon association with the albumin protein, turned green.

The scientists then applied several sensor tattoos onto patches of pig skin. When they changed the pH or the glucose or albumin concentrations, the colors of the decorated areas changed accordingly. They quantified these visible effects by evaluating the colors with a simple smartphone camera and an app.

The authors claim that such sensor tattoos could allow permanent monitoring of patients using a simple, low-cost technique. With the development of suitable colorimetric sensors, the technique could also extend to recording electrolyte and pathogen concentrations or the level of dehydration of a patient. Further studies will explore whether tattoo artwork can be applied in a diagnostic setting.

MINNEAPOLIS, MN- July 18, 2019 - New University of Minnesota Medical School research is the first to show that estrogen is essential to maintaining muscle stem cell health.

In an article recently published in Cell Reports, lead authors Dawn Lowe, PhD, Professor in the Department of Rehabilitation Medicine, Division of Physical Therapy and Rehabilitation Science Graduate Program, University of Minnesota Medical School and Michael Kyba, PhD, Professor of Pediatrics and Carrie Ramey/CCRF Endowed Professor in Pediatric Cancer Research, Department of Pediatrics, Division of Blood and Marrow Transplantation, University of Minnesota Medical School, are the first to establish that estrogen is essential in females for muscle stem cell maintenance and function.

The study investigates mice whose ovaries were surgically removed as well as mice without the estrogen receptor in their muscle stem cells and evaluated muscles' ability to regenerate. It found that the loss of estrogen or genetic deletion of the estrogen receptor in muscle stem cells led to a 30 to 60 percent drop in muscle stem cell (also known as satellite cell) numbers across five different muscles. The surviving cells had severe difficulty reproducing themselves and generating new muscle after injury. The study also included a collaboration with scientists in Finland who performed muscle biopsies in women shortly before and after the transition to menopause. This showed that in humans, the number of satellite cells correlated strongly with changing serum estrogen levels. "This is the first work to show that estrogen deficiency affects the number as well as the function of satellite cells," said Lowe.

It has been known that estrogen replacement therapy for menopausal symptoms can help maintain muscle health. But such hormone replacement therapy which treats weakening muscles also raises the risk of cancer due to estrogen's effects on tissues, such as those of the breast and endometrium. The team showed that a new class of drug, known to interact with estrogen receptors in a way that doesn't affect breast or endometrial tissue, was able to stimulate the estrogen signal in muscle stem cells and could potentially shield aging women from muscle stem cell decline due to menopause, without the risks associated with conventional hormone replacement therapy.

"It has long been known that male sex hormones promote muscle health, but we have been in the dark about what happens when females age," said Lowe. "What estrogen does in women in terms of reproduction has been known for decades. Now we're learning what estrogens do in women's muscles."