Culture

Whether you are playing Go in a park amid chirping birds, a gentle breeze and kids playing catch nearby or you are playing in a den with a ticking clock on a bookcase and a purring cat on the sofa, if the game situation is identical and clear, your next move likely would be, too, regardless of those different conditions. You'll still play the same next move despite a wide range of internal feelings or even if a few neurons here and there are just being a little erratic. How does the brain overcome unpredictable and varying disturbances to produce reliable and stable computations? A new study by MIT neuroscientists provides a mathematical model showing how such stability inherently arises from several known biological mechanisms.

More fundamental than the willful exertion of cognitive control over attention, the model the team developed describes an inclination toward robust stability that is built in to neural circuits by virtue of the connections, or "synapses" that neurons make with each other. The equations they derived and published in PLOS Computational Biology show that networks of neurons involved in the same computation will repeatedly converge toward the same patterns of electrical activity, or "firing rates," even if they are sometimes arbitrarily perturbed by the natural noisiness of individual neurons or arbitrary sensory stimuli the world can produce.

"How does the brain make sense of this highly dynamic, non-linear nature of neural activity?" said co-senior author Earl Miller, Picower Professor of Neuroscience in The Picower Institute for Learning and Memory and the Department of Brain and Cognitive Sciences (BCS) at MIT. "The brain is noisy, there are different starting conditions - how does the brain achieve a stable representation of information in the face of all these factors that can knock it around?"

To find out, Miller's lab, which studies how neural networks represent information, joined forces with BCS colleague and mechanical engineering Professor Jean-Jacques Slotine, who leads the Nonlinear Systems Laboratory at MIT. Slotine brought the mathematical method of "contraction analysis," a concept developed in control theory, to the problem along with tools his lab developed to apply the method. Contracting networks exhibit the property of trajectories that start from disparate points ultimately converging into one trajectory, like tributaries in a watershed. They do so even when the inputs vary with time. They are robust to noise and disturbance, and they allow for many other contracting networks to be combined together without a loss of overall stability - much like brain typically integrates information from many specialized regions.

"In a system like the brain where you have [hundreds of billions] of connections the questions of what will preserve stability and what kinds of constraints that imposes on the system's architecture become very important," Slotine said.

Math reflects natural mechanisms

Leo Kozachkov, a graduate student in both Miller's and Slotine's labs, led the study by applying contraction analysis to the problem of the stability of computations in the brain. What he found is that the variables and terms in the resulting equations that enforce stability directly mirror properties and processes of synapses: inhibitory circuit connections can get stronger, excitatory circuit connections can get weaker, both kinds of connections are typically tightly balanced relative to each other, and neurons make far fewer connections than they could (each neuron, on average, could make roughly 10 million more connections than it does).

"These are all things that neuroscientists have found, but they haven't linked them to this stability property," Kozachkov said. "In a sense, we're synthesizing some disparate findings in the field to explain this common phenomenon."

The new study, which also involved Miller lab postdoc Mikael Lundqvist, was hardly the first to grapple with stability in the brain, but the authors argue it has produced a more advanced model by accounting for the dynamics of synapses and by allowing for wide variations in starting conditions. It also offers mathematical proofs of stability, Kozachkov added.

Though focused on the factors that ensure stability, the authors noted, their model does not go so far as to doom the brain to inflexibility or determinism. The brain's ability to change - to learn and remember - is just as fundamental to its function as its ability to consistently reason and formulate stable behaviors.

"We're not asking how the brain changes," Miller said. "We're asking how the brain keeps from changing too much."

Still, the team plans to keep iterating on the model, for instance by encompassing a richer accounting for how neurons produce individual spikes of electrical activity, not just rates of that activity.

They are also working to compare the model's predictions with data from experiments in which animals repeatedly performed tasks in which they needed to perform the same neural computations, despite experiencing inevitable internal neural noise and at least small sensory input differences.

Finally, the team is considering how the models may inform understanding of different disease states of the brain. Aberrations in the delicate balance of excitatory and inhibitory neural activity in the brain is considered crucial in epilepsy, Kozachkov notes. A symptom of Parkinson's disease, as well, entails a neurally-rooted loss of motor stability. Miller adds that some patients with autism spectrum disorders struggle to stably repeat actions (e.g. brushing teeth) when external conditions vary (e.g. brushing in a different room).

Secondary school students perform better in natural sciences and mathematics and are more motivated when digital tools are used in instruction. However, success depends on the design of the tools used. Success levels are higher when children and young adults do not study alone and when digital instruction is accompanied by paper-based teaching materials, according to the conclusion reached by one of the largest investigations on the topic, evaluating approximately 90 individual studies.

Digitalization of school instruction has been hotly debated for years. What programs should teachers use on the computer, when and how often? The debate is characterized by a challenging abundance of research projects. The Center for International Student Assessment (ZIB) at the Technical University of Munich (TUM) has now evaluated a total of 92 studies published worldwide since the year 2000.

The meta-study shows that secondary school students in classes which work with digital teaching tools perform better than children and young adults in classes that are taught solely on a traditional basis. Furthermore these students are more motivated by the respective subject. This applies for all grades in secondary schools and for all the subjects investigated, i.e. mathematics, biology, chemistry and physics.

However, digital tools alone are no guarantee of success. Their impact on performance depends on how they are used in instruction:

Children and young adults benefit more from digital teaching tools when they work together in pairs instead of alone. The researchers assume that computer programs play a special role in stimulating discussions between the students which can positively impact the learning process.

Secondary school students perform better when accompanied by teachers while working with digital tools. When they work with computer programs entirely alone, the positive effect is minor.

The positive effect of digital tools is greater when the tools do not completely replace classic classroom materials. A promising approach is to use them in supplement to analog methods.

Digital tools increase performance more particularly when teachers have been professionally trained how to integrate them into the lessons.

Not even well-made programs can replace teachers

"Digital tools should be worked into instruction in moderation," says Prof. Kristina Reiss, head of the ZIB and dean of the TUM School of Education. "Getting rid of tried and proven analog formats would be going a step too far. In addition, we see that even very well-made learning programs cannot replace the teacher."

In well-planned application, the advantages of digital tools could be completely leveraged, in particular for complex and abstract content in natural sciences and mathematics, for example the visualization of chemical compounds and geometric shapes.

"If the new teaching methods can additionally increase the motivation of secondary school students, this will be a great opportunity for the STEM subjects," Reiss points out.

Some digital tools are more useful than others

The meta-study also indicates which types of digital tools are most promising. The greatest positive effect comes from what are referred to as intelligent tutor systems, programs which convey content in small units and also enable individual exercises. The decisive factor is that these programs adapt the speed, level of difficulty and amount of assistance to the user's skills. On the other hand, hypermedia systems configured for free exploration with video, audio and text materials that fail to define a learning objective are comparatively less effective.

PULLMAN, Wash. - Automatic gratuities leave restaurant patrons with a bad taste, even when the meal and the service were excellent, new research from Washington State University indicates.

"We thought if service quality was high, people wouldn't care if an automatic service charge was added to their bill," said Jeff Joireman, the study's coauthor and professor and chair of the Department of Marketing and International Business at the Carson College of Business.

But whether customers had a good experience or bad one, they reacted negatively when their bill came with a mandatory tip, preventing them from leaving the gratuity themselves. Surprisingly, customers with the best dining experiences expressed the most dissatisfaction with automatic gratuities. The research was published in Journal of Services Marketing and was based on four separate studies.

"People think non-voluntary tipping systems are unpopular because customers can't punish servers for poor quality service," Joireman said. But when the service was high, "we found that customers were equally frustrated by non-voluntary tipping - this time because they couldn't reward their servers."

In both service scenarios, customers said they were unlikely to patronize the restaurant in the future.

Non-voluntary tipping systems take control away from the customer, said Ismail Karabas, assistant professor of marketing at Murray State University and lead author of the research, which was part of his doctoral dissertation at WSU.

"Being able to reward the server makes customers feel good," Karabas said. "That's part of the restaurant experience."

When customers lose control of the tip, "their ability to show their gratitude has been blocked," he said. "They have fewer positive feelings about the restaurant experience, and they're less likely to eat there again."

Automatic gratuities growing in restaurant industry

North American customers spend about $66 billion annually on tips at restaurants and other establishments. Although voluntary tipping is still standard practice, a growing number of restaurants are moving toward automatic gratuities, Karabas said.

For restaurant owners, the switch to automatic gratuities is often about fairness, he said. They want to divide tips between servers and the kitchen staff, rewarding the entire team and equalizing pay.

"The person who cooks your meal may be working harder than the server, but servers end up making quite a bit more money when you add in the tips," Karabas said. "That's led to turnover of kitchen staff, which is a concern in the restaurant industry."

While the intent of using automatic gratuities to equalize pay and retain employees is laudable, restaurant owners and managers should be aware of the drawbacks, he said.

"High-quality service does not compensate for the negative customer response to a non-voluntary tipping system," Karabas said. "Managers may think 'We're fine as long as we provide good service,' but we found that's just not true."

Exploring other ways to reward good service

Restaurants thatswitch to automatic tipping could explore other ways to help customers keep their sense of control, the researchers said.

"Based on what we know about blocked gratitude, I would look for ways to give customers the feeling they are still the ones leaving the tip, even though it's added automatically," Karabas said. "It could be as simple as saying, 'You tipped your server 18% today. Thank you.'"

Restaurants could also encourage customers to reward their servers through other means, such as providing feedback on comment cards, voting for a server of the month, or even adding a separate line on the bill for an extra tip, the researchers said.

But restaurants should be careful about perceptions, according to Karabas, who said additional research is needed on alternate ways to reward servers. Some customers might react cynically to an extra line on their bill for an enhanced tip.

"You don't want customers to think you're being sneaky and trying to trick them into tipping twice," he said.

Scientists are closer to gaining the upper hand on a disease that has wiped out citrus orchards across the globe. New models of the bacterium linked to the disease reveal control methods that were previously unavailable.

Metabolic models of organisms are like road maps of cities.

"They show you all the biological processes, and how they work together," said UC Riverside microbiology professor James Borneman. "They also show you which molecular pathways, if blocked, will kill the organism."

In this case, researchers created the first models of the bacterium associated with Huanglongbing or HLB, also known as citrus greening disease. The team's work is described in a new paper published in Nature's npj Systems Biology and Applications.

The research team made models for six different strains of the bacterium known as CLas and doing so enabled them to identify as many as 94 enzymes essential for the bacterium's survival. These enzymes can now be considered targets for the creation of new antibacterial treatments.

In addition, the team identified metabolites required for the bacteria to grow.

"Just like when humans break down the food they eat into small components called metabolites, which feed our cells, bacterial cells also require metabolites for their growth," Borneman said.

Knowing the metabolites needed for CLas' growth could enable scientists to cultivate it in a laboratory setting. It is not currently possible to grow CLas on its own, hindering scientists' ability to study it and ultimately to manage it.

This research project involved a collaboration between UC Riverside, UC San Diego, Texas A&M University, and the U.S. Department of Agriculture. In addition to Borneman, members of the modeling team included UCR plant pathologist Georgios Vidalakis and UCSD systems biologist Karsten Zengler.

UC Riverside is at the forefront of efforts to combat Huanglongbing. Other important areas of research include antibacterial development and delivery, immune system fortification in citrus, engineering resistant citrus via a detailed understanding of host-microbe interactions, breeding resistant citrus, and insect management, among others.

Because microbes tend to mutate and acquire resistance mechanisms in response to drugs and other efforts to thwart them, Borneman cautions that any one solution to the problem may be short-lived.

"Microbes almost always adapt to control measures, perpetuating the 'arms race' between pathogens and hosts," Borneman said. "There won't be one thing that will fix this disease. We likely will need to address all three components associated with the disease -- the bacterium, the insect that transmits it, and the citrus plants -- to find a long-lasting solution."

To that end, the research team is constructing metabolic models of citrus and the insect, the Asian citrus psyllid.

"We expect that this multiorganism modeling endeavor will provide new insights into the mechanisms underlying this disease, which will lead to effective and sustainable Huanglongbing management strategies," Borneman said.

Modelling the predicted movements of pervasive sap-sucking tiny insects before they infest banana crops has the potential to become a key tactic in the fight against a devastating virus, according to QUT research.

Banana bunchy top virus (BBTV) is an aphid-transmitted banana disease that has been in Australia since 1913 and has been contained by biosecurity agencies to southeast Queensland and northern New South Wales.

Badly affected plants will not produce fruit if left unchecked and entire plantations can become infested.

BBTV cannot be cured and infected plants must be destroyed.

QUT researchers have designed a model that tracked the probability of a banana plant being infected by aphids that carried the disease, with the findings published in PLOS Computational Biology.

Keypoints:-

Aphids can fly long distances to new plantations and quickly infect nearby plants.

Current inspection measures by biosecurity agents are costly and time-consuming.

Mathematical and statistical models can help to predict areas of risk of infection.

A stochastic mathematical model describes disease spread, infectivity and recovery rates.

External environmental and seasonal factors influence virus spread.

The framework can be adapted to study dynamics of other vector-borne diseases.

A 2012 study estimated the benefits from eliminating the disease would be worth between $16-27 million to Australia each year.

Distinguished Professor Kerrie Mengersen said despite ongoing traditional methods of monitoring and management of the disease, eradication had proved elusive.

The latest study, conducted in collaboration with biosecurity agents, focused on a BBTV-infected banana plantation in northern New South Wales.

The location of every diseased plant in the plantation was recorded using GPS.

Associate Professor Chris Drovandi said the research expanded existing disease management strategies by calibrating the model to real field data.

"The new model we've developed quantifies the effects of seasonal changes, the plantation's configuration and spread of banana bunchy top virus while predicting high-risk areas," Associate Professor Drovandi said.

"Peak transmission occurs when temperatures reach 25-30 degrees, so weather is an important factor to consider in the complex dynamics of BBTV spread."

Since 2014, the banana farm has undergone monthly inspections implementing a "rogue-and-remove" disease management strategy.

QUT researcher Abhishek Varghese joined the study as part of an undergraduate vacation research scholarship, visiting the farm and meeting industry officials.

He said it was difficult to see the symptoms of virus on plants from the air, or by using drones, as the leaves needed to be viewed underneath for infestations.

"The banana trees grow along a steep slope and insects can be swept up and pushed to different parts of the plantation by seasonal forces," he said.

"Since the 1930s field surveyors have scoured the plantation attempting to individually identify infections by checking banana leaves showing a choked or bunched appearance.

"They mark the infected area without interrupting the insects and spray paraffin oil to ensure the aphids can't escape and inject a systemic insecticide and herbicide (glyphosate) slowly killing the banana plant and all the aphids inside it."

Mr Varghese, who is studying a dual engineering and economics degree at QUT, said stochastic mathematical modelling also helped pinpoint areas where the disease remained latent in the soil two or three months after trees had been removed.

"This is an expensive and laborious process for field surveyors so a precise forecasting tool may assist in pinpointing areas to inspect more carefully, reducing costs and making the job easier," he said.

BBTV was first introduced to Australia in 1913 via infected suckers from Fiji and spread locally through the banana aphid, Pentalonia nigronervosa.

"This is a fantastic example of talented students using mathematical and statistical skills to help solve real problems facing farmers and the agriculture industry," Professor Mengersen said.

Researchers from University of Missouri-Kansas City, University of Wisconsin-Milwaukee, and University of Pennsylvania published a new paper in the Journal of Marketing that examines the effectiveness of what they call "the dueling preferences approach" on prosocial giving.

The study, forthcoming in the Journal of Marketing, is titled "Penny for Your Preferences: Leveraging Self-Expression to Encourage Small Prosocial Gifts" and is authored by Jacqueline Rifkin, Katherine Du, and Jonah Berger.

BallotBin, a UK-based company, designs custom bins for the disposal of cigarette butts. These "ballot bins" have a fascinating feature: They pose a question and provide two bin compartments, each labeled with a possible answer to the question. Smokers can then answer the question through the disposal of a cigarette butt into either compartment. For example, one recent "ballot bin" in London asked smokers whether flying or invisibility is the better superpower, allowing them to express their preference by depositing their cigarette butts in one of two labeled compartments. This set-up can be found in a variety of other settings designed to increase prosocial acts. Cafés have started to position two tip jars rather than one, asking patrons whether they prefer Star Trek or Star Wars. Similarly, the ASPCA asked people to donate money by expressing their preference for cats or dogs ("Vote for your Paw-sident").

This set-up, in which the act of giving is framed as a choice between two options, is called the "dueling preferences" approach. But the question remains: Is the dueling preference approach really more effective at increasing prosocial giving than traditional approaches? And if so, why?

The research team set out to answer these questions. They conducted initial experiments in real cafés and with real charities using several different "duels" (summer vs. winter, mountains vs. beach, chocolate vs. vanilla ice cream) and discovered that the dueling preferences approach can indeed be more effective than traditional approaches at increasing small prosocial gifts. In particular, the dueling preferences approach increased people's likelihood to tip/donate and how much money they gave.

Next, the researchers sought to understand why this approach works. Several follow-up studies indicate this approach works because it provides people with the opportunity to say something about who they are. Du explains, "People love to talk about themselves and share their opinions. In fact, the parts of the brain that light up when we get to share our opinions also light up in response to finding $10 or getting a sweet treat. This fact about human psychology ultimately makes the dueling preferences approach an inherently attractive and motivating opportunity. People are willing to give money to share what they believe in."

Of course, the dueling preferences approach must be implemented tactfully. People may be willing to give money to share what they believe in, but what if a duel captures an issue people don't believe in? As Rifkin described, "When we tested a duel that asked people's preferences for the letter "A" vs. "B"--a relatively uninspiring issue--we were not able to increase prosocial giving. Similarly, when we tested a duel that was interesting to some, but not to all--one's preference for pets--we found that the duel only increased giving among those who found the issue to be important to them. Also, people do not always want or even need to express themselves." While the inherent need to say something about who we are is critical for harnessing the power of dueling preferences, people differ in what and when they want to share. As a result, it takes some thought to figure out exactly what options to choose, when, and among whom to deploy this approach.

Overall, those interested in increasing prosocial giving can benefit by leveraging the flexibility and ease of implementation of the dueling preferences approach. Ultimately, if managers can effectively harness people's desire to express themselves, this approach can be a powerful tool for increasing prosocial giving. The magic of dueling preferences lies in its ability to leverage any valued identity--whether a Star Trek fan, chocaholic, or lefty--to increase prosocial giving.

A Korean research team has reported important findings that could potentially improve the performance of retinal prostheses creating artificial vision for blind individuals. The Korea Institute of Science and Technology (KIST) announced that a research team led by Dr. Maesoon Im of the Center for BioMicrosystems, Brain Science Institute had found retinal neural signals arising from electric stimulation are altered depending on disease progression in mice affected by outer retinal degeneration. This research was done in collaboration with the lab of Professor Shelley Fried at Harvard Medical School, Massachusetts General Hospital.

Retinal degenerative diseases, such as retinitis pigmentosa and age-related macular degeneration, primarily destroy photoreceptor cells, which convert light into electrochemical signals, leading to profound vision loss. Currently, there are no available cure for these diseases.

Fortunately, retinal ganglion cells are known to survive those conditions, making "artificial vision" available. An array of microelectrodes can be implanted at the back of the eyeball so that electric pulses applied by those microelectrodes can stimulate ganglion cells to transmit visual neural signals to the brain again. This is the basic working principle of retinal prosthetic devices. Although several retinal prostheses have been commercialized, one of problems preventing broad application has been a huge performance variation across patients due to unidentified reason.

The KIST research team had delved into the potential source of the performance variation and has found the level of disease progression may be critical. They designed a longitudinal study and performed experiments using mice at various stages of retinal degeneration. Those mice lost their vision gradually due to a genetic mutation which is similar to people with retinitis pigmentosa . The researchers recorded electrically-evoked neural activities of retinal ganglion cells from animals at varying ages and tried to correlate those artificial vision signals to the disease progression. They uncovered that both the magnitude and the consistency of the electrically-evoked responses diminished as retinal degeneration advanced.

The response consistency is particularly important for retinal prostheses because they periodically refresh artificial visual percepts using repetitive electrical stimuli. For example, when a retinal prostheses user stares at a letter "K" repeating electrical stimuli need to create neural signals representing "K." Otherwise, i.e. if the response consistency is too low, the electrical stimuli might transmit neural signals meaning different letters such as "L," "R," or "S,", thus making the prosthetic user difficult to correctly interpret what he or she is seeing. The KIST study suggests it is likely to be the case in severly degenerate retinas. Throughout a seriese of experiments to assess the degree of similarities across different neural signals arising from repeated electrical stimuli of a same condition, they found that the response consistency considerably declined with the progressing retinal degeneration while normal retinas showed high consistencies.

Dr. Young-Jun Yoon and Dr. Jae-Ik Lee, the lead authors of the study, said, "Even if a user fixes his/her gaze, their degenerate retina is likely to keep transmitting considerably different neural signals to the brain across repeats of electric stimuli. Probably, it may have caused poor perception of electrically-evoked artificial vision."

"Retinal degenerative diseases exhibit different patterns of progression across patients. Our results suggest that it is crucial to carefully select candidate patients of retinal implants by thorough examinations assesing the progression level of each patient's retinal degeneration," said Dr. Maesoon Im. "We are studying hardware and software approaches for the improved quality of artificial vision for patients at the late-stage degeneration."

When the eye isn't getting enough oxygen in the face of common conditions like premature birth or diabetes, it sets in motion a state of frenzied energy production that can ultimately result in blindness, and now scientists have identified new points where they may be able to calm the frenzy and instead enable recovery.

In this high-energy environ, both the endothelial cells that will form new blood vessels in the retina -- which could improve oxygen levels -- and nearby microglia -- a type of macrophage that typically keeps watch over the retina -- prefer glycolysis as a means to turn glucose into their fuel.

Medical College of Georgia scientists have shown that in retinal disease, the excessive byproducts of this inefficient fuel production system initiate a crescendo of crosstalk between these two cell types. The talk promotes excessive inflammation and development of the classic mass of leaky, dysfunctional capillaries that can obstruct vision and lead to retinal detachment, says Dr. Yuqing Huo, director of the Vascular Inflammation Program at MCG's Vascular Biology Center.

The major byproduct of glycolysis is lactate, which also can be used as a fuel, for example, by our muscles in a strenuous workout. Microglia also need some lactate from the endothelial cells. But in disease, the lactate is in definite oversupply, which instead supports this destructive conversation between cells, says Huo, corresponding author of the study in the journal Science Translational Medicine.

"This is a major problem in our country, loss of vision because of compromised oxygen for a variety of reasons," says Dr. Zhiping Liu, postdoctoral fellow in Huo's lab and the study's first author. "We hope this additional insight into how that process destroys vision, will enable us to find better ways to intervene," Liu says.

In a low-oxygen environ, endothelial cells produce not only a lot of lactate, but also factors that encourage nearby microglia to be more active, and to use glycolysis to get more active, Huo says.

In reality, microglia don't need the encouragement because they already also seem to prefer this method of energy production. But the extra lactate sent their way does spur them to produce even more energy and consequently even more lactate, Huo says.

The normally supportive immune cells also start overproducing inflammation-promoting factors like cytokines and growth factors that promote blood vessel growth or angiogenesis, which, in a vicious loop, further turns up glycolysis by the endothelial cells, which are now inclined to proliferate excessively.

"The reciprocal interaction between macrophages and (endothelial cells) promotes a feed-forward relationship that strongly augments angiogenesis," they write.

The destructive bottom line is termed pathological angiogenesis, a major cause of irreversible blindness in people of all ages, the scientists say, with problems like diabetic retinopathy, retinopathy of prematurity and age-related macular degeneration.

"Our eyes clearly do not have sufficient oxygen, and they end up trying to generate more blood vessels through this process called pathological angiogenesis, which is really hard to control," Huo says.

The excessive sprouting and proliferation of endothelial cells is central to the destruction, and glycolysis is central to their sprouting and proliferation but the exact mechanisms that trigger all the glycolysis and crosstalk between endothelial cells and microglia have been unknown, they write.

"In all these conditions, there is something wrong with the tissue that causes the blood vessels to not behave properly," says coauthor Dr. Ruth B. Caldwell, cell biologist in the Vascular Biology Center. "It's a bad state," she says, which they want to help normalize.

As they are finding more about how the conversation goes bad between these two cells, they are seeing new logical points to do that. When they knock out the most potent activator of glycolysis, called Pfkfb3, from the microglia, lactate production clearly goes down and the cells no longer aid production of dysfunctional capillaries. Conversely, expression of both the messenger RNA that enables production of Pfkfb3 and lactate are significantly higher in the cells when oxygen levels are low.

Agents that stop these cells' over-the-top use of glycolysis could be good therapeutic approaches, they say. Blocking excessive lactate production could be another. Stopping the microglia from lapping up too much lactate also significantly suppresses pathological angiogenesis in their lab studies. Agents that normalize endothelial cell growth might work as well.

While genetic manipulation was used for much of their lab work to date, the scientists are now looking at chemicals that might work at these various points. A problem is that many drugs that suppress glycolysis have numerous unwanted effects, so they are working to more selectively intervene. They note that since the use of glycolysis by macrophages is critical to support of a healthy immune response, localized inhibition should yield the desired response without affecting the immune response.

Current treatments for abnormal blood vessel development and related leaking and swelling include suppressing vascular endothelial growth factor, or anti-VEGF, which, as the name implies, is a key factor in endothelial cell growth, may require ongoing injections in the eye and gets decent results in conditions like diabetic retinopathy. But anti-VEGF therapy really does not facilitate repair, says Caldwell. The scientists have early evidence their intervention strategies may, because they intervene earlier and help normalize the "bad" environment. "We get repair and restoration," Caldwell says.

Huo and his colleagues are among those who have shown that glycolysis is critical to the sprouting of endothelial cells and that mice lacking Pfkfb3 have impaired angiogenesis.

Endothelial cells, which line all our blood vessels, are one of the first things laid down when we make new blood vessels. In the retina, they start making tiny tunnels that ideally will become well-functioning capillaries, blood vessels so small that a single red blood cell may have to fold up just to get through. These thin-skinned blood vessels are the point where oxygen, fluid and nutrients are provided to body tissue, then blood gets routed back through the venous system to the heart where the process starts anew.

Endothelial cells grow accustomed to glycolysis when they are helping make our bodies in the early, no-oxygen days during development, Huo says.

The usual job of microglia includes keeping an eye out for invaders, like a virus, and keeping connections between nerves, called synapses, trimmed up.

A team of medical researchers has found that in human milk, pasteurisation inactivates the virus that causes COVID-19, confirming milk bank processes have been safe throughout the pandemic, and will remain safe going forward, too.

The study - published this month in the Journal of Paediatrics and Child Health - was a partnership between UNSW and a multidisciplinary team from Australian Red Cross Lifeblood Milk.

There are five human milk banks in Australia. As the COVID-19 pandemic evolves, these milk banks continue to provide donated breast milk to preterm babies who lack access to their mother's own milk. Donors are screened for diseases, and milk is tested and pasteurised to ensure that it is safe for medically fragile babies.

"While there is no evidence that the virus can be transmitted through breast milk, there is always a theoretical risk," says Greg Walker, lead author and PhD candidate in Professor Bill Rawlinson's group at UNSW Medicine.

"We've seen in previous pandemics that pasteurised donor human milk (PDHM) supplies may be interrupted because of safety considerations, so that's why we wanted to show that PDHM remains safe."

For this study, the team worked in the Kirby Institute's PC3 lab to experimentally infect small amounts of frozen and freshly expressed breast milk from healthy Lifeblood Milk donors.

"We then heated the milk samples - now infected with SARS-CoV-2 - to 63?C for 30 minutes to simulate the pasteurisation process that occurs in milk banks, and found that after this process, they did not contain any infectious, live virus," Mr Walker says.

"Our findings demonstrate that the SARS-CoV-2 virus can be effectively inactivated by pasteurisation."

The researchers say their experiments simulated a theoretical worst-case scenario.

"The amount of virus we use in the lab is a lot higher than what would be found in breast milk from women who have COVID-19 - so we can be really confident in these findings," Mr Walker says.

Dr Laura Klein, Research Fellow and Lifeblood Milk senior study author, explains that the purpose of the research was to provide evidence behind what people already expected.

"Pasteurisation is well known to inactivate many viruses, including the coronaviruses that cause SARS and MERS," she says.

"These findings are also consistent with a recent study that reported SARS-CoV-2 is inactivated by heat treatment in some contexts."

Kirby Institute researcher and study co-author, Associate Professor Stuart Turville, says this work was a first.

"We've been working in real time to grow and make tools against this new pathogen, which has been an exponential learning curve for everyone involved. This work and many others that are continuing in the PC3 lab tell us how we can be safe at the front line working with this virus in the real world."

Cold storage doesn't inactivate the virus

The researchers also tested if storing SARS-CoV-2 in human milk at 4°C or -30°C would inactivate the virus - the first time a study has assessed the stability of experimentally infected SARS-CoV-2 in human milk under common storage conditions.

"We found that cold storage did not significantly impact infectious viral load over a 48-hour period," Mr Walker says.

"While freezing the milk resulted in a slight reduction in the virus present, we still recovered viable virus after 48 hours of storage."

The researchers say the fact that SARS-CoV-2 was stable in refrigerated or frozen human milk could help inform guidelines around safe expressing and storing of milk from COVID-19 infected mothers.

"For example, we now know that it is particularly important for mothers with COVID-19 to ensure their expressed breast milk does not become contaminated with SARS-CoV-2," Dr Klein says.

"But it's also important to note that breastfeeding is still safe for mothers with COVID-19 - there is no evidence to suggest that SARS-CoV-2 can be transmitted through breastmilk."

Donated breast milk is recommended by the World Health Organisation when mother's own milk is not available to reduce the risks of some health challenges premature babies can face. Lifeblood Milk has provided donor milk to over 1500 babies born premature in 11 NICUs across New South Wales, South Australia, and Queensland since launching in 2018.

Uncertainties in the evolutionary tree of birds and their closest relatives have impeded deeper understanding of early flight in theropods, the group of dinosaurs that includes birds. To help address this, an international study led by HKU Research Assistant Professor Dr. Michael Pittman (Vertebrate Palaeontology Laboratory, Division of Earth and Planetary Science & Department of Earth Sciences) and co-first-authored by his former Postdoctoral Fellow Dr. Rui Pei (now an Associate Professor at the Institute of Vertebrate Paleontology and Paleoanthropology, Beijing), produced an updated evolutionary tree of early birds and their closest relatives to reconstruct powered flight potential, showing it evolved at least three times. Many ancestors of the closest bird relatives neared the thresholds of powered flight potential, suggesting broad experimentation with wing-assisted locomotion before flight evolved. The ten-man five-country team published their findings in the prestigious high-profile journal Current Biology.

"Our revised evolutionary tree supports the traditional relationship of dromaeosaurid ("raptors") and troodontid theropods as the closest relatives of birds. It also supports the status of the controversial anchiornithine theropods as the earliest birds," said Dr. Pei. With this improved evolutionary tree, the team reconstructed the potential of bird-like theropods for power flight, using proxies borrowed from the study flight in living birds. The team found that the potential for powered flight evolved at least three times in theropods: once in birds and twice in dromaeosaurids. "The capability for gliding flight in some dromaeosaurids is well established so us finding at least two origins of powered flight potential among dromaeosaurids is really exciting," said Dr. Pittman. Crucially, the team found that many ancestors of bird relatives neared the thresholds of powered flight potential. "This suggests that theropod dinosaurs broadly experimented with the use of their feathered wings before flight evolved, overturning the paradigm that this was limited to a much more exclusive club," added Dr. Pittman.

This study is the latest in the Vertebrate Palaeontology Laboratory's long-term research into the evolution of early birds and their closest relatives (see Notes). Asked about future plans, Dr. Pittman replied: "We have helped to better constrain the broader functional landscape of theropods just before flight evolved and in its earliest stages. We plan to now focus on the dromaeosaurids and early birds that we have shown to have the potential for powered flight to improve our understanding of what it took to fly and why."

LA JOLLA--(August 10, 2020) While your skeleton helps your body to move, fine skeleton-like filaments within your cells likewise help cellular structures to move. Now, Salk researchers have developed a new imaging method that lets them monitor a small subset of these filaments, called actin.

"Actin is the most abundant protein in the cell, so when you image it, it's all over the cell," says Uri Manor, director of Salk's Biophotonics Core facility and corresponding author of the paper. "Until now, it's been really hard to tell where individual actin molecules of interest are, because it's difficult to separate the relevant signal from all the background."

With the new imaging technique, the Salk team has been able to home in on how actin mediates an important function: helping the cellular "power stations" known as mitochondria divide in two. The work, which appeared in the journal Nature Methods on August 10, 2020, could provide a better understanding of mitochondrial dysfunction, which has been linked to cancer, aging, and neurodegenerative diseases.

Mitochondrial fission is the process by which these energy-generating structures, or organelles, divide and multiply as part of normal cellular maintenance; the organelles divide not only when a cell itself is dividing, but also when cells are under high amounts of stress or mitochondria are damaged. However, the exact way in which one mitochondrion pinches off into two mitochondria has been poorly understood, particularly how the initial constriction happens. Studies have found that removing actin from a cell entirely, among many other effects, leads to less mitochondrial fission, suggesting a role for actin in the process. But destroying all the actin causes so many cellular defects that it's hard to study the protein's exact role in any one process, the researchers say.

So, Manor and his colleagues developed a new way to image actin. Rather than tag all the actin in the cell with fluorescence, they created an actin probe targeted to the outer membrane of mitochondria. Only when actin is within 10 nanometers of the mitochondria does it attach to the sensor, causing the fluorescence signal to increase.

Rather than see actin scattered haphazardly around all mitochondrial membranes, as they might if there were no discrete interactions between actin and the organelles, Manor's team saw bright hotspots of actin. And when they looked closely, the hotspots were located at the same locations where another organelle called the endoplasmic reticulum crosses the mitochondria, previously found to be fission sites. Indeed, as the team watched actin hotspots light up and disappear over time, they discovered that 97 percent of mitochondrial fission sites had actin fluorescing around them. (They speculate that there was also actin at the other 3 percent of fission sites, but that it wasn't visible).

"This is the clearest evidence I've ever seen that actin is accumulating at fission sites," says Cara Schiavon, co-first author of the paper and a joint postdoctoral fellow in the labs of Uri Manor and Salk Professor Gerald Shadel. "It's much easier to see than when you use any other actin marker."

By altering the actin probe so that it attached to the endoplasmic reticulum membrane rather than the mitochondria, the researchers were able to piece together the order in which different components join the mitochondrial fission process. The team's results suggest that the actin attaches to the mitochondria before it reaches the endoplasmic reticulum. This lends important insight towards how the endoplasmic reticulum and mitochondria work together to coordinate mitochondrial fission.

In additional experiments described in a pre-print manuscript available on bioRxiv, Manor's team also reports that the same accumulation of endoplasmic reticulum-associated actin is seen at the sites where other cellular organelles--including endosomes, lysosomes and peroxisomes--divide. This suggests a broad new role for a subset of actin in organelle dynamics and homeostasis (physiological equilibrium).

In the future, the team hopes to look at how genetic mutations known to alter mitochondrial dynamics might also affect actin's interactions with the mitochondria. They also plan to adapt the actin probes to visualize actin that's close to other cellular membranes.

"This is a universal tool that can now be used for many different applications," says Tong Zhang, a light microscopy specialist at Salk and co-first author of the paper. "By switching out the targeting sequence or the nanobody, you can address other fundamental questions in cell biology."

"We're in a golden age of microscopy, where new instruments with ever higher resolution are always being invented; but in spite of that there are still major limitations to what you can see," says Manor. "I think combining these powerful microscopes with new methods that select for exactly what you want to see is the next generation of imaging."

Connections with friends and family are key to helping communities adapt to the devastating impact of climate change on their homes and livelihoods, a new study shows.

The research found people are more empowered to respond when they see others doing the same.

Scientists analysed how an island community in Papua New Guinea of around 700 people coped with the impact of encroaching sea-levels and dwindling fish stocks. The study, published in the journal Nature Climate Change, examined the actions households took to deal with these impacts.

Lead author Dr Michele Barnes, from the ARC Centre of Excellence for Coral Reef Studies (Coral CoE), said: "We found their actions were related to their social networks, the ways they are connected to other people within the community."

"To cope with the impacts of climate change, existing practices or behaviours can be tweaked--this is adaptation. However, in some cases this won't be enough, and people need to enact more fundamental changes--transformation."

"In our case, adaptation included things like building sea walls to protect existing land use," said co-author Dr Jacqueline Lau, from Coral CoE and WorldFish. "And transformation involved developing alternative food and income sources away from fish and fishing-related activities."

Essentially both sets of actions are necessary to combat the impacts of climate change. Dr Barnes says influence within social networks is what encouraged this: the households more socially connected to others taking action were more likely to do the same.

"It may be a situation of 'like-attracts-like' where households with particular mindsets are more socially connected to similar households," Dr Barnes said. "Another explanation is that households were influencing each other's actions. It's likely a combination of the two," she said.

The authors also found household connections with the marine environment played an important role in determining the responses to climate impacts.

"Climate change and other human impacts rapidly degrade coral reef ecosystems and alter the composition of reef fish communities," said co-author Professor Nick Graham, of Lancaster University in the UK.

"The adaptation of coastal communities is becoming essential. Our research highlights that interacting with and learning from the marine environment is one mechanism through which this adaptation can be achieved," he said.

Dr Barnes says the policies and programs seeking to reduce vulnerability to climate change often focus on building up material assets or creating infrastructure.

"Our research emphasises a broader set of factors can play an important part in the actions communities end up taking," she said.

Albert Einstein once said, "I see my life in terms of music." Perhaps inspired by his words, scientists at the Center for Self-assembly and Complexity (CSC), within the Institute for Basic Science (IBS, South Korea) now see chemical reactions in the presence of music. The IBS research team has reported that audible sound can control chemical reactions in solution by continuously supplying energy sources into the interface between air and the solution. The sound-controlled air-liquid chemical interactions "painted" intriguing and aesthetic patterns on the surface and bulk of the solution. "The Pied Piper of Hamelin tells the mythological story of a pied piper who lured rats away from the city of Hamelin by enchanting them with the music from his magical pipe. With music working like a fuel for such artistic control in chemistry, our study has shown that even synthetic molecules can exhibit life-like behavior - listening and following a musical track," says Dr. Rahul Dev Mukhopadhyay, the co-first and -corresponding author of the study.

Music (or audible sound with a frequency range of 20 to 20,000 Hz) in fact finds useful applications in various fields, such as boosting plant cultivation or livestock breeding and even for therapeutic purposes. Ultrasound (greater than 20,000 Hz) has long been used as an essential tool in medical diagnosis. However, audible sound has rarely been associated with chemical reactions due to its low energy. Previous studies have usually focused only on its effect on the movement of water surface.

In this study, the IBS research team has gone further than that. They hypothesized that sound-generated water waves may fuel chemical reactions between air and liquid. "In fact, one aspect of a climate change study is about how CO2 concentration in the ocean changes depending on the movement of ocean waves. In retrospect, it makes sense that a wavy ocean is a more suitable condition for CO2 to be absorbed in the ocean than a still ocean. Our study has revealed the function of audible sound as a source for controlling chemical reactions, which occurs all around us, but has not been noticed till now," explains Dr. HWANG Ilha, the co-first and -corresponding author of the study.

In their experimental set-up, the water was placed on a Petri dish and positioned on top of a speaker. When sound was played through the speaker, different surface wave patterns were generated - depending on the frequency and the amplitude of the audible sound source and the geometry of the vessel. To see how this vibrating air-water interphase controls the dissolution of atmospheric gases like oxygen or carbon dioxide into water, the researchers used O2-sensitive methyl viologen (MV2+/MV+* ) redox couple and CO2-sensitive pH indicator bromothymol blue (BTB).

Organic molecule methyl viologen is normally colorless or white, but turns deep blue upon chemical reduction. When a blue-colored solution of reduced methyl viologen in a Petri dish was exposed to air with sound playing, some regions of the solution slowly turned colorless. The sound waves generates oscillation of the fluid, prompting a streaming effect, and the solution underwent a distinct observable color change due to the gradual dissolution of atmospheric oxygen. Those not affected by the streaming retained their blue color. In the absence of sound, the uncontrolled dissolution of oxygen and natural convection currents of chemicals in solution resulted in a random pattern, which was different each time over the repetition of the same experiment. However, when the same solution was exposed to low frequency sounds below 90 Hz, very interesting and aesthetic patterns were generated. More specifically, two counter-rotating vortices emerged in blue and white contrast in the presence of 40 Hz sound. The same pattern repeated in the same condition during subsequent cycles.

The experiment indicates the reaction with oxygen, which is determined whether the solution is colorless or blue. In other words, by applying sound to a solution, the researchers could control the local molecular concentrations of oxygen in different regions that compose the same solution. Just like the surface waves, the patterns vary according to the frequency of the applied sound as well as the shape of the dish (Figure 1, Middle). The patterns also exhibited self-healing behavior, i.e., they recover their original pattern structure after being manually disturbed.

This concept was further extended to the dissolution of carbon dioxide gas using a pH indicator (bromothymol blue, BTB). BTB has a blue color in basic conditions (pH over 7.6), green color in neutral conditions (pH 6.0 to 7.6), and a yellow color in acidic conditions (pH under 6.0). Sound assisted dissolution of carbon dioxide in water turns it acidic due to the formation of carbonic acid. Therefore, when a blue-colored basic solution of BTB is exposed to carbon dioxide, the solution gradually turns green and eventually changes to yellow. During this process, if the solution is exposed to audible sound, a three-colored pattern having two vortices was generated (Figure 1, Bottom). Interestingly, the pattern represents the coexistence of acidic, neutral, and basic domains in a solution. "Our study visualized a chemical environment that is partitioned into different molecular environments without any physical barrier, resembling cellular microenvironments. This is a novel discovery that may replace the common sense belief that the pH of a solution is uniform throughout all of the vessel," notes Dr. Hwang.

Extending the concept beyond simple molecules, the researchers utilized their strategy to program the organization of organic molecules within solution. In all cases, the sound generated organic aggregate patterns were obtained transiently and maintained only in presence of a steady supply of chemical fuel, which may be either a reducing agent or a base. This type of behavior is generally exhibited by intracellular biochemical processes which are maintained with a steady supply of fuels or energy currencies, such as adenosine-5'-triphosphate (ATP) or guanosine-5'-triphosphate (GTP). Prof. Kimoon Kim, Director of the IBS Center for Self-assembly and Complexity, who supervised the overall research, added, "This is the first study to show that it is possible to control and visualize chemical reactions using audible sound. In the near future, we may further expand the scope of use of audible sound from chemistry to other fields, such as physics, fluid mechanics, chemical engineering and biology."

Animal behaviour scientists from the University of Lincoln, UK, have discovered that filling your home with appeasing pheromones could be the key to a happy household where both dogs and cats are living under the same roof.

The new research, led by Professor Daniel Mills and Dr Miriam Prior, explored the effects of two different pheromone products on cat-dog interactions in homes where owners could see room for improvement in their pets' relationships.

Their new scientific paper is now available to read online via the journal Frontiers in Veterinary Science.

The results show that both products used - Feliway Friends, which emits pheromones that are calming for cats, and Adaptil, which does the same for dogs - both had a positive impact on the interactions between cats and dogs living in the same home.

Over a six week period, both products led to a notable decrease in undesirable interactions - such as dog chasing cat, cat hiding from dog, cat and dog staring at each other, and dog barking at cat. Users of Adaptil even observed a significant increase in some desirable behaviours - friendly greetings between cat and dog, and time spent relaxing in the same room.

"Although we are all aware of the perceived tensions between cats and dogs, we believe this is the first study of its kind to explore the use of pheromone products to improve the relationship when the two species are living in the same household," explained Professor Mills, Professor of Veterinary Behavioural Medicine in Lincoln's School of Life Sciences.

"Seven per cent of households in the UK own both a cat and a dog, which represents a large number of pet owners and their animals living with potentially stressful animal relationships on a day-to-day basis. Many cat and dog owners report that their animals are comfortable in each other's' company, but where this isn't the case, a poor relationship between a resident cat and dog can have serious consequences for the welfare of individual animals. There may be an unacceptable level of social stress or restricted access to key resources such as food, water or suitable toilet areas. There will also be increased stress for the remainder of the family (both human and animal), and potential risks of injury due to conflict."

It has also been reported that a problematic relationship between a new pet and an existing pet is one of the main reasons for cats and dogs being taken to shelters for rehoming.

The pet owners involved in this new scientific trial reported weekly on the frequency of 10 specific undesirable interactions and seven specific desirable interactions between their cats and dogs. They were split into two groups; one group using Feliway Friends and the other using Adaptil, with the pheromones supplied in unlabelled packaging and randomly assigned by an independent staff member such that neither the participants nor the researchers knew which product was being trialled in each household until after the statistics had been collected.

The researchers were aware that in many households, the comfortability of the cat seems to have a stronger influence over the quality of the cat-dog relationship. It could therefore be seen as surprising that it was the product releasing dog pheromones which was seen to increase specific desirable interactions.

Miriam, a Lincoln-based vet who undertook the work as part of her postgraduate degree in Clinical Animal Behaviour at the University of Lincoln, said: "While it might be expected that Feliway Friends would be more effective in multi-species homes given the apparently stronger contribution of the cat's comfortability to the quality of the cat-dog relationship, this did not appear to be the case. Our results might be explained by the behaviour of the dog being the primary determinant of the cat's quality of interaction with it.

"We would like to investigate this further to really tease out the effects of these pheromone products individually and also to investigate their use in combination with each other. We suggest that Adaptil may have had such a beneficial effect because a more relaxed dog may be less likely to disturb the cat (e.g. by chasing it), resulting in a cat that is less stressed and more willing to form some form of social bond with the dog."

Leipzig/Halle. Human changes to the environment have been linked to widespread pollinator declines. New research published in Nature Communications shows that intensive land use will further decrease pollination and reproductive success of wild plants, especially of those plants that are highly specialized in their pollination. An international team of scientists led by researches from the German Centre for Integrative Biodiversity Research (iDiv), Martin Luther University Halle-Wittenberg (MLU) and the Helmholtz Centre for Environmental Research (UFZ) performed a global data analysis that provided conclusive evidence of the links of human land use and pollination of plants.

Plants provide resources including food and shelter to all other living organisms on earth. Most plants need pollinators to reproduce, which is why mounting research showing widespread pollinator declines is concerning. Despite concerns we are facing a pollination crisis, we do not know which types of plants will be most affected by pollinator declines and under which conditions declines in plant reproductive success are to be expected.

Changes in land-use are the leading threat to plants and pollinators. However, different groups of pollinators may have different responses to changes in land-use. For example, some farming practises may increase honeybee abundance on the one hand but reduce the abundance of other pollinators such as wild bees and butterflies on the other hand. Dr Joanne Bennett, who led the research as a postdoctoral researcher at iDiv and MLU and is now working at the University of Canberra, said: "Plants and their pollinators have evolved relationships over millions of years . Humans are now changing these relationships in just a few years."

A global data set on land use and pollen limitation

To determine if land use effects pollen limitation, an international team of researchers set out to compile a global dataset that quantified the degree to which pollenation limits plant reproductive success. For this, they analysed thousands of published pollen supplementation experiments - experiments that estimate the magnitude of pollen limitation by comparing the number of seeds produced by naturally pollinated flowers with flowers receiving hand supplemented pollen. Joanne Bennett said: "If naturally pollinated plants produce less fruits or seeds than plants that have received additional pollen by hand then the reproduction of that plant population is limited - this is called pollen limitation. In this way, pollen limitation experiments provide an unparalled opportunity to link plant reproductive function to the health of pollination services."

It was almost 20 years ago when Prof Dr Tiffany Knight, Alexander von Humboldt professor at MLU and head of the Spatial Interaction Ecology research group at iDiv and UFZ, started to compile the first data sets. Supported by iDiv's synthesis centre sDiv, Knight and Bennett took the project to a new level by forming a group of 16 experts from all over the world to expand the dataset and generate new ideas. The researchers started with 1,000 experiments on 306 plant species from Europe and North America. To date, it includes data from over 2,000 experiments and more than 1,200 plants and has a more global distribution. Tiffany Knight said: "One of the most rewarding components of this research has been the collaboration with the international team, and the inclusion of studies published in languages other than English."

Specialists and plants in intensely used landscape highly pollen limited

Ultimately, this data allowed for a global meta-analysis, which showed that wild plants in intensely used landscapes, such as urban areas, are highly pollen limited. The researchers found that plants that are specialized in their pollination are particularly at risk of pollen limitation, but this varies across the different land-use types and is based on which pollinator taxa they are specialized on. For example, plants specialized on bees were less pollen limited in agriculturally managed lands than those specialized on other pollinator types. This could be because domesticated honey bees support the pollination of wild plants in these lands.

The results show conclusively that intensive land use is linked to lower plant reproductive success due to lower pollination success. This suggests that future land-use change will decrease the pollination and reproductive success of plants, and can cause plant communities to become more dominated by species that are generalized in their pollination.