Culture

Research conducted at Cruzeiro do Sul University in São Paulo, Brazil, can contribute to earlier diagnosis of diabetic neuropathy, a disorder characterized by damage to peripheral nerves, with symptoms such as pain and paresthesia (pricking, burning and numbness), mainly in the legs and feet.

In the study, a group led by Professor Paulo Barbosa de Freitas Júnior measured grip force in diabetic patients while they were holding and handling objects. The results were compared with data for healthy subjects and patients with other neurological diseases, such as multiple sclerosis, Parkinson’s, and carpal tunnel syndrome (pain, numbness and tingling in the hand and arm caused by a pinched nerve in the wrist).

Freitas and his group tested volunteers to measure the grip force exerted by diabetics with and without a diagnosis of neuropathy, as well as healthy subjects, and developed a methodology that can be used to produce equipment for use in clinical practice. In future, the innovation should help physicians diagnose the disorder quickly and easily not long after the onset of initial symptoms of neuropathy in diabetics.

The analysis focused on grip force used to hold and manipulate objects, and on relative safety margin, i.e. grip force normalized by the coefficient of friction between skin in contact with the object and surface of the manipulated material. The central nervous system “calculates” the amount of force needed to hold an object, learning to do so better over time. “Every object has a contact surface with which our fingers create friction when we hold it. The smoother the surface, the more grip force needed to hold it. If it’s rough, we can use less grip force thanks to friction,” Freitas explained.

Considering grip force and safety margin, people with neurological disorders such as multiple sclerosis and Parkinson’s tend to use more force to grip objects than healthy people. The force needed to manipulate an object is moderately greater than the minimum force needed to hold it in the desired position. “In the case of people with neurological alterations, our hypothesis is that they grip objects more strongly as a conservative strategy,” Freitas said. “The nervous system detects a neurological deficiency and sends a command for the hand to use more force as it grips the objects. This process is entirely unconscious, of course.”

The test results showed that healthy volunteers used between 100% and 120% of the minimum force required to hold an object, whereas the force used by participants with neurological alterations was two and a half times to three times greater.

Freitas and his team then investigated the performance of diabetics, who typically suffer from neuropathy as the disease worsens. “There was no prior research on diabetics involving the type of experiment we used in our study,” he said.

The hypothesis was that diabetics would grip objects more tightly, as is the case with people who suffer from carpal tunnel syndrome, multiple sclerosis and Parkinson’s. “However, what we found was the opposite: diabetics used half as much force to hold an object as controls in the simplest task, which was the static test, in which the subject merely has to hold an object without manipulating it,” Freitas said.

An article published in the journal Human Movement Science reports the main findings of the study, which was funded by FAPESP via a Regular Research Grant and a scientific initiation scholarship.

Calculating grip force

Three types of test were conducted with 36 volunteers, including 24 diabetics divided into two groups: 12 who had developed neuropathy, and 12 who had neither been diagnosed with neuropathy nor displayed clinical signs of the disorder. The other 12 participants were healthy and formed the control group. Before testing began, the researchers measured each participant’s skin sensitivity, since the sense of touch is a key factor in conveying to the central nervous system the information required by the brain to calculate the force needed to hold and manipulate objects.

Volunteers were each asked to perform three tasks using the same type of object instrumented to measure force. In the static holding test, they had to hold the object with their dominant hand as if they were holding a glass of water. A beep sounded after ten seconds, and they were to unclasp their fingers slowly so as to release the object, while a researcher measured the friction between the fingers and the object. The second task consisted of picking up an object from a table, lifting it about 5 cm, holding it for 10 seconds, and putting it back on the table. In the third task, termed oscillation, the volunteers had to grasp the object, hold it in front of their navel, and move it about 20 cm up and down for 15 seconds.

In the second and third tasks, the results for diabetics and diabetics with neuropathy were similar to those for controls. The surprise came in the simplest task of all, which was static holding, as diabetics and diabetics with neuropathy used half the force applied by the controls.

The explanation is not exactly a loss of sensitivity in the fingers of diabetics, the researchers explained, but deficient tactile information sent from their fingertips to the central nervous system. There is not enough information of high quality for the brain to make the requisite calculations and the hand to use the right amount of force. “In addition, there are studies showing that certain areas of the spinal cord and cortex that receive and process this sensory information are smaller in diabetics than in healthy people,” Freitas said.

The study suggests diabetes does not only affect the periphery of the body, causing loss of sensitivity in the toes and fingers, for example, but also affects the central nervous system. “This happens early in diabetes. People tend to think these complications happen only after a certain age or when a person has had diabetes for some time, but actually patients have the problem before neuropathy is diagnosed,” Freitas said.

Novel device for rapid early diagnosis

Scientists do not fully understand what causes neuropathy in diabetics. One hypothesis has to do with neuron death or loss of function due to alterations in blood vessels and metabolism. “Because of metabolic alterations, blood doesn’t reach the nerve ends in the soles, palms, toes and fingers, leading to the death of neurons in these peripheral regions,” Freitas surmised. As the disease progresses, neurons in other regions closer to the torso, knees and so on, also suffer damage and may die.

Given this lack of knowledge, prevention is the best option, and the study discussed here will help in this regard, according to Freitas. “Our research provides a foundation on which a simple device could be developed for use in the doctor’s office with rapid results,” he said. Grip and load force can serve as behavioral biomarkers to detect neurological alterations even before the patient manifests clear symptoms of neuropathy. “The idea is to have a device that enables physicians to measure force in a straightforward test and see if the patient shows signs of incipient neurological alterations.”

Neuropathy is currently diagnosed by means of a painful invasive examination using a technique called electroneuromyography, in which an electric current is passed through small electrodes in the shape of needles inserted into the patient’s muscles and the reaction time is measured to assess nerve conduction velocity. Freitas proposes a procedure that can be used during a regular visit to the doctor. The patient would hold an object instrumented to measure grip force. “After 10 to 15 seconds of this test, the physician would have the result: the object was held with this or that level of force, and the value measured is below or above the level considered safe to the act of holding the object. It could evidence neurological alterations arising from diabetes,” he said.

The next steps envisaged by Freitas include developing the instrumented object for use in such testing, which could be simpler than the one used in research. To do so, he needs to determine the best combination between the object’s weight and surface smoothness or roughness, so as to evidence the difference between diabetics and nondiabetics. “We need various combinations of smoothness and roughness, as well as lighter and heavier weights, in order to measure the differences between the combinations, and choose the best for use in future tests,” he said. He is pursuing partnerships with hospitals and companies interested in participating in the development of a solution, as well as volunteers for forthcoming studies. He can be contacted at Paulo.deFreitas@cruzeirodosul.edu.br or defreitaspb@gmail.com.

Immunologists at St. Jude Children's Research Hospital have identified a biological pathway that selectively controls how key immune cells, called T follicular helper cells, mature into functional components of the immune system.

The finding offers the promise of developing drugs to activate the metabolic pathway to enhance the effectiveness of vaccines, including those that protect against COVID-19. Such medications could stimulate the immune system to respond more vigorously following immunization to produce more antibodies against a virus or bacterium.

The work also lays the foundation for drugs that dial down the pathway to alleviate autoimmune diseases such as lupus. In such disorders, an overactive immune system produces antibodies that attack the body's own tissues.

Led by Hongbo Chi, Ph.D. of the Department of Immunology, the researchers published their findings today in Nature.

Regulating the adaptive immune response

Chi and colleagues identified a metabolic control pathway that selectively regulates the development of specialized immune cells in the adaptive immune system. These cells are called T follicular helper cells.

The adaptive immune system is so named because when the body is infected by viruses or bacteria, it learns to target and attack them. T follicular helper cells activate the component of the adaptive immune system called humoral immunity. While humoral immunity attacks invaders circulating outside cells largely via the generation of antibodies, the other adaptive immune system component, cellular immunity, targets invaders inside infected cells.

In their experiments, the researchers sought to discover whether a metabolic control pathway existed that modified the T follicular helper cells to activate them. When such cells are activated, they help antibody-producing cells, called B cells, to mature and to generate infection-fighting antibodies.

Discovering a key pathway

To discover a possible control pathway, Chi and his colleagues used genetic techniques to delete in the T cells multiple enzymes known to be elements of such metabolic control pathways. Then, the scientists introduced the deletion-engineered T cells into mice followed by infection with a virus and tested whether the T cells lacking the enzyme were functional.

Their experiments revealed that one metabolic control pathway, called the CDP-ethanolamine pathway, selectively regulated the T follicular helper cells.

"This finding was a big surprise," Chi said. "First of all, this pathway was considered to have a housekeeping function leading to the production of building blocks for the cell membrane. But we discovered that it has a major signaling function. And secondly, we were surprised that this pathway--and not other parallel pathways of this type--was the only one involved in regulating T follicular helper cells."

As a complementary method to determine if the pathway selectively regulated the T follicular helper cells, the researchers deleted each of the key enzymes they identified in the CDP-ethanolamine pathway. They found that deletion of these enzymes, but not those of other parallel regulatory pathways, selectively impaired development of the T follicular helper cells, but not overall immune function.

Importantly, said Chi, those key enzymes could be targets for drugs that either enhance or inhibit the pathway, and thus the activity of the T cells.

"We are now exploring whether we can enhance the effectiveness of vaccines by using drugs that activate the pathway, to help these T cells mobilize the immune system to generate antibodies in response to a vaccine," he said.

"On the other hand, to treat autoimmune disease, we're interested in developing new ways to inhibit this pathway," he said. "This approach is promising because we know that such activation or inhibition is highly selective for T follicular helper cells and would not affect other immune functions."

The researchers are also delving into the structural mechanisms by which the enzymes work--insights that could offer such drug targets, Chi said.

ST. LOUIS -- In the United States, low-income and minority students are completing college at low rates compared to higher-income and majority peers -- a detriment to reducing economic inequality. Double-dose algebra could be a solution, according to a new study published in roceedings of the National Academy of Sciences of the United States of America (PNAS).

The paper, "Effects of Double-Dose Algebra on College Persistence and Degree Attainment," is the culmination of a series of studies that followed two cohorts of ninth-grade students over a period of 12 years in the Chicago Public Schools (CPS) where double-dose algebra was introduced in 2003.

The new policy required incoming ninth graders with eighth-grade math scores below the national median to complete two periods of math -- one period of algebra, plus an additional period of instruction designed to build foundational prealgebra skills. Research findings showed that, for median-skill students scoring at or above the 50th percentile in the 2003 cohort, double-dose algebra significantly increased semesters of college attended and college degree attainment.

"This provides unique insight for districts that provide extra instruction but are unable to rigorously study the impact of those programs," said Takako Nomi, Ph.D., associate professor of educational studies at Saint Louis University. Her work focuses on educational policy and equity.

Nomi, who also serves as research affiliate at the University of Chicago's Consortium on Chicago School Research, led the study. Other authors include Stephen W. Raudenbush, Ed.D., of the department of sociology at the University of Chicago; and Jake J. Smith, of Harris School of Public Policy at the University of Chicago.

A key takeaway from the study is how schools chose to implement the policy matters, Nomi said. Fewer schools adopted the cut-score-based double-dose algebra program in 2004 than in 2003. Most schools that did strongly comply in 2004, did so by placing their median-skill double-dose students in low-skill algebra classrooms, according to the study.

In terms of classroom peer composition, "the impact was largest when schools didn't group double-dose students with low-skilled students," Nomi said. Research findings demonstrate that when students were placed in double-dose classes with much lower-skilled peers, the program had no effect. Subsequent research should address the design of optimal policies for lower-skill students, Nomi said. A math intervention far more intensive than double-dose algebra is essential to improve their high school and postsecondary outcomes. The study also notes that ninth-grade students who fail math also tend to fail other core classes.

"It's not just a math issue," Nomi said. "The policy of giving extra math is not enough to change the trajectory for the students who struggle the most. It's important to support struggling students in general."

This study was supported by grant R305A170602 from the Institute of Education Sciences entitled, "Doubling Up? Understanding the Long-Term Effects of Ninth-Grade Algebra Reform on College Persistence and Graduation."

Nomi's research interests include urban education, education policy, inequality in education, school reforms, and college readiness. Nomi is associate director of the Sinquefield Center for Applied Economic Research where she collaborates with top SLU researchers. In a separate study, she's exploring why low-income and minority students -- particularly Black males -- are less likely to complete college. She is also a part of a faculty advisory board at SLU's Geospatial Institute.

"Equal pay for equal work," a motto touted by many people, turns out to be relevant to the plant world as well. According to new research by Stanford University ecologists, plants allocate resources to their microbial partners in proportion to how much they benefit from that partnership.

"The vast majority of plants rely on microbes to provide them with the nutrients they need to grow and reproduce," explained Brian Steidinger, a former postdoctoral researcher in the lab of Stanford ecologist, Kabir Peay. "The problem is that these microbes differ in how well they do the job. We wanted to see how the plants reward their microbial employees."

In a new study, published July 6 in the journal American Naturalist, the researchers investigated this question by analyzing data from several studies that detail how different plants "pay" their symbionts with carbon relative to the "work" those symbionts perform for the plants - in the form of supplying nutrients, like phosphorus and nitrogen. What they found was that plants don't quite achieve "equal pay" because they tend not to penalize low-performing microbes as much as would be expected in a truly equal system. The researchers were able to come up with a simple mathematical equation to represent most of the plant-microbe exchanges they observed.

"It's a square root relationship," said Peay, who is an associate professor of biology in the School of Humanities and Sciences. "Meaning, if microbe B does one-quarter as much work as microbe A, it still gets 50 percent as many resources - the square root of one-quarter."

When the researchers tested their equation against 13 measurements of plant resource exchange with microbe partners, they were able to explain around 66 percent of the variability in the ratio of plant payments to two different microbes.

"The biggest surprise was the simplicity of the model," said Steidinger. "You don't get a lot of short equations in ecology. Or anywhere else."

The fruit of frustration
When asked about the motivation for developing this equation, Steidinger summed it up with one word: frustration.

"There is a lot of really interesting literature in a field called 'biological market theory' that deals with how plants should preferentially allocate resources. But for the folks who actually run experiments, it is difficult to translate these models into clean predictions," said Steidinger. "We wanted to make that clean prediction."

An informal survey of the Peay lab members encouraged the researchers to start with the assumption of equal pay because most people agreed it was reasonable to guess that plants treat all microbes the same. To reach their final equation, Steidinger and Peay then factored in the diminishing returns seen in the fertilizer models and assessed them through the lens of biological market theory literature - which uses human markets as a mathematical analogy for exchanges of services in the natural world.

"It turns out if the plant is flush with resources - in this case, the sugars it feeds to its microbes - and if the nutrients are valuable enough, the plant pays its microbes according to a square-root law," said Peay.

The square-root model is a strong start to addressing Steidinger's original frustration but it is not quite at the level of realism he wants to eventually achieve.

"For instance, our model allows a useless microbe to be fired without the plant losing resources," said Steidinger. "But, just as in the human world, it takes an investment to hire a microbe and that initial investment is a gamble that microbial layabouts can consume at their leisure."

Weber's Law
In an attempt to explain why plants follow the square-root model, the researchers turned to a law in psychology. Weber's Law addresses how humans perceive differences in stimuli, such as noise, light or the size of different objects. It explains that, the stronger the stimuli, the worse we are at identifying when it changes. This law has been shown to hold for many non-human animals as well - describing, for example, how birds and bats forage for food and how fish school. Now the researchers suggest it's a good analogy for their plant payment scheme too.

"Our model says that plant should go easy on low-performing microbes, seemingly overpaying the 25-percent-as-good microbe with 50 percent as much resources," said Peay. "Well, it's long been known that humans and non-human animals sense differences in quantity in a way that might bias them towards similar leniency."

In other words, the researchers suggest that, like a human trying to detect the volumes of specific noises in a loud room, a plant making optimal payment decisions may be relatively insensitive to differences in the quality of its microbial employees. And the researchers argue that this insensitivity may be for the best, as it encourages plants to maintain a certain level of microbial diversity, which can help give the plant options for dealing with environmental changes it encounters throughout its lifetime.

"I think what we're seeing is plants behave like animals not because they have the same perceptional limitations - and certainly not because they think like animals - but because we face similar challenges in making the best choices when there are diminishing returns on investment," says Steidinger.

DURHAM, N.C. -- You dash into a convenience store for a quick snack, spot an apple and reach for a candy bar instead. Poor self-control may not be the only factor behind your choice, new research suggests. That's because our brains process taste information first, before factoring in health information, according to new research from Duke University.

"We spend billions of dollars every year on diet products, yet most people fail when they attempt to diet," said study co-author Scott Huettel, a professor of psychology and neuroscience at Duke. "Taste seems to have an advantage that sets us up for failure."

"For many individuals, health information enters the decision process too late (relative to taste information) to drive choices toward the healthier option."

The new paper, which appears July 5 in Nature Human Behaviour, describes the advantage taste has over healthfulness in the decision-making process.

"We've always assumed people make unhealthy choices because that's their preference or because they aren't good at self-control," said study co-author Nicolette Sullivan. "It turns out it's not just a matter of self-control. Health is slower for your brain to estimate - it takes longer for you to include that information into the process of choosing between options."

The research was undertaken when Sullivan was a postdoctoral associate at Duke. She is now an assistant professor of marketing at the London School of Economics and Political Science.

For the study, Sullivan and Huettel recruited 79 young adults of a median age of 24.4 years. Study participants were asked to fast for four hours before the experiment to ensure they arrived hungry.

Participants were asked to rate snack foods on their tastiness, healthfulness and desirability. They were then presented with pairs of foods and asked to choose between them - and the researchers timed their choices.

At the end of the experiment, participants were offered one of the foods they had chosen.

Study participants registered taste information early in their decision process - taking about 400 milliseconds on average to incorporate taste information. Participants took twice as long to incorporate information about a snack's healthfulness into their decisions.

That may not sound like much time. In many cases though, it's enough to alter the choice we make.

"Not every decision is made quickly - house purchases, going to college - people take time to make those choices," Huettel said. "But many decisions we make in the world are fast - people reach for something in the grocery store or click on something online."

The authors say their findings could apply to other choices, not just food. For instance, some financial decisions, such as saving and spending choices, may also be affected by how -
and when - the brain processes different types of information.

Meanwhile, all is not lost in the war against junk food cravings.

Half of study participants received a blurb before the experiment, stressing the importance of eating healthy. Those participants were less likely to choose an unhealthy snack.

The authors also identified something simple that can help people with their food choices: slowing down the decision-making process.

When study participants took longer to consider their options, they tended to pick healthier ones.

"There may be ways to set up environments so people have an easier time making healthy choices," Huettel said. "You want to make it easy for people to think about the healthfulness of foods, which would help nudge people toward better decisions."

When you insist you're not racist, you may unwittingly be sending the opposite message.

That's the conclusion of a new study* by three Berkeley Haas researchers who conducted experiments with white participants claiming to hold egalitarian views. After asking them to write statements explaining why they weren't prejudiced against Black people, they found that other white people could nevertheless gauge the writers' underlying prejudice.

"Americans almost universally espouse egalitarianism and wish to see themselves as non-biased, yet racial prejudice persists," says Berkeley Haas Asst. Prof. Drew Jacoby Senghor, one of the authors. "Our results suggest that the explicit goal of appearing egalitarian might blind people to the possibility that they could be communicating, and perpetuating, prejudicial attitudes."

Co-authored by Derek Brown, PhD 24, and Michael Rosenblum, PhD 20--a post-doctoral scholar at NYU Stern School of Business--the study builds on past research finding people's racial prejudice "leaks out" through nonverbal behavior, such as facial expressions or physical distance. In a series of experiments published in the Journal of Experimental Social Psychology, the researchers looked at perceptions based solely on written content.

They selected a group of white participants, screening out the small percentage who expressed overt prejudice, and scored subjects' racial attitudes with two widely used assessments. The subjects were then asked: "Do you believe that all people are equal and should have equality of opportunity? Why or why not?," and "Are you prejudiced toward Black people? Why or why not?" A second group of white participants, asked to read the written responses, accurately estimated how the writers had scored on the prejudice scale.

Linguistic cues

In a second experiment to parse out whether people were signaling racial attitudes intentionally or inadvertently, they asked one group to answer as honestly as possible and another group to answer "in the least prejudiced way possible." There was no difference to the readers, who accurately scored both groups' answers.

"That gave us some confidence that people are naturally trying to come across as egalitarian, but something about the language they choose is betraying them," Rosenblum said.

What were those linguistic cues? The most powerful indicator, they found, was language that dehumanized or objectified African Americans--for example, "I have a great relationship with the Blacks." Other characteristics such as defensiveness, references to personal responsibility, or a belief that equal opportunity exists were strongly associated with higher levels of prejudice, and cues such as focus on equity or an acknowledgement that inequality exists were associated with lower levels of prejudice. Interestingly, references to being colorblind or mentions of personal contact with Black people weren't indicative of the white participants' attitudes.

"This demonstrates that peoples' use of the cues are meaningful not only for how prejudice is expressed, but also how egalitarianism is perceived," said Brown.

Contagion effect

A third experiment had a sobering result. The researchers found that white participants reported greater prejudice towards Black people after reading statements from the self-avowed white egalitarians who scored high on underlying prejudice. In other words, the readers mirrored the attitudes of the writers, even when they identified themselves as ideologically dissimilar (conservative vs liberal).

"We don't know reading other people's views gave them permission to express more prejudice, or whether they thought that this is the norm and their actual prejudice level changed, but there seemed to be a contagion effect," Rosenblum said. "One of the lessons here is that words carry weight. It does seem that this is one way that prejudice is unwittingly spread."

FOR IMMEDIATE RELEASE

In what turned out to be one of the most important accidents of all time, Scottish bacteriologist Alexander Fleming returned to his laboratory after a vacation in 1928 to find a clear zone surrounding a piece of mold that had infiltrated a petri dish full of Staphylococcus aureus (S. aureus), a common skin bacterium he was growing.

That region of no bacterial growth was the unplanned birth of a medical miracle, penicillin, and would lead to the era of antibiotics. Now, in a paper published today in the journal Science Translational Medicine, researchers at Johns Hopkins Medicine have announced another accidentally discovered, potentially game-changing treatment -- one that may one day provide an alternative immune-based solution to the danger of antibiotic-resistant bacterial infections.

And like Fleming's surprise finding, the bacterium of note is once again S. aureus -- but this time, methicillin-resistant Staphylococcus aureus, the life-threatening strain unharmed by methicillin and other antibiotics, and better known by its acronym, MRSA.

The paper's senior author, Lloyd Miller, M.D., Ph.D., former professor of dermatology, infectious diseases and orthopaedic surgery at the Johns Hopkins University School of Medicine, and now with Janssen Research and Development, says the research team was originally intending to study the mechanisms behind MRSA skin infections in mice with and without the ability to manufacture interleukin-1 beta (IL-1β). This protein, transformed into its active form by enzymes called caspases, enhances protective immunity by helping immune cells called neutrophils, monocytes and macrophages fight bacterial infections.

"We gave the mice a blocker of all caspases [pancaspase inhibitor], a compound known as Q-VD-OPH, thinking it would leave both sets of mice more vulnerable to MRSA infection," Miller says. "To our surprise, blocking caspases had the opposite effect, resulting in a rapid and remarkable clearing of the MRSA bacteria by keeping the immune cells alive and boosting their protective function."

Sensing they might have accidentally uncovered a means of fighting bacterial "superbugs," Miller and his colleagues conducted their latest study to confirm the unexpected finding was not a fluke.

The results were encouraging.

"A single oral dose of Q-VD-OPH decreased the size of MRSA skin lesions and rapidly cleared the bacteria compared with vehicle-treated [given the carrier solution without Q-VD-OPH] and untreated mice," says study lead author Martin Alphonse, Ph.D., a dermatology postdoctoral fellow at the Johns Hopkins University School of Medicine. "And surprisingly, the treatment worked whether IL-1β was present or not -- and without administering any antibiotics."

The researchers, says Alphonse, found that the pancaspase inhibitor reduces apoptosis -- one of three main methods the body uses to remove worn-out or damaged cells -- of neutrophils and monocytes, leaving them in plentiful numbers and better able to remove MRSA bacteria.

"It's like a fire department where older firetrucks are kept operating to help put out blazes, when otherwise, they would have been taken out of service," says Miller.

The researchers also saw enhanced necroptosis -- a second controlled cell death process similar to apoptosis -- of macrophages, which are mature monocytes.

"The destruction of macrophages by necroptosis releases large amount of tumor necrosis factor, or TNF, a protein that triggers bacteria-fighting immune cells to swarm into an infected area of skin," says Alphonse.

Finally, the researchers tested whether Q-VD-OPH in mice could have broader activity against two other dangerous skin bacteria, Streptococcus pyogenes (the cause of multiple diseases, including scarlet fever, necrotizing fasciitis and toxic shock syndrome) and Pseudomonas aeruginosa (often a threat to hospitalized patients on ventilators, with catheters or suffering wounds from surgery or burns). The targeting of the body's immune system against bacteria via pancaspase inhibition -- referred to as "host-directed immunotherapy" -- proved just as successful as it had been for MRSA.

"It was an accidental finding by Alexander Fleming that led to the golden age of antibiotics, but now that's nearing the end because of antibiotic-resistant bacteria," says Miller. "It seems fitting that another surprise in the lab could be the start of a second golden age, the use of host-directed immunotherapy."

When someone is suspected of criminal activity, one of the most important questions they are asked is if they have a credible alibi. Playing back past events in our minds, however, is not like playing back a video recording. Recollections of locations, dates, and companions can become muddled with the passage of time. If a suspect's memories are out of line with documented events, a once-plausible alibi can crumble and may be seen as evidence of guilt.

To put people's memories of past whereabouts to the test, a team of researchers tracked the locations of 51 volunteers for one month and found that their recollections were wrong approximately 36% of the time.

"This is the first study to examine memory for where an event happened," said Simon J. Dennis, director of the Complex Human Data Hub at the University of Melbourne's School of Psychological Sciences and lead author of the study, which was published in the journal Psychological Science. "We were able to use experience-sampling methods to actually examine people's memories and analyze what is affecting memory error in their everyday life."

In the study, an app on the participants' smartphones continuously (and securely) recorded their locations and surroundings via GPS. The app also made sound recordings of the environment every 10 minutes. Participants had the freedom to turn off the app or to delete events--a mechanism designed to protect privacy.

At the end of the month, the participants received a memory test in which they were given a time and date and then asked to select one of four markers on Google Maps to show where they had been at that moment.

The results revealed that participants tended to confuse days across weeks. They also often confused weeks in general and hours across days. The participants had the poorest recall when memories of one event become entwined with memories of a similar experience, such as filling up a car with gas at a different location of the same gas-station chain.

Additionally, the researchers found that people tended to confuse places they had visited at similar times or locations, such as multiple bars visited in one evening. People also made mistakes--although less frequently--when events involved similar sounds or movement patterns, such as when they had walked through town on different days while listening to their favorite music.

"This has implications for alibi generation, as jurors tend to assume that a suspect who is wrong is lying," said Dennis. "These results can alert investigators to the questions they should ask in order to catch the memory errors that suspects are likely to make."

The protein actin is ubiquitous and essential for life. In mammals, every cell expresses two of its forms, beta-actin and gamma-nonmuscle-actin. Despite having distinct roles, the two forms are nearly identical, sharing 99% of their amino acid sequence.

Research by Anna Kashina of Penn's School of Veterinary Medicine and colleagues has shown that, contrary to scientific dogma, it's not the slight differences in amino acid sequence that govern these proteins' discrete functions in the cell. Rather, their nucleotide sequences--the "letters" that make up their DNA coding sequence, which differ by roughly 13% between the two forms--are responsible for their individual roles in organisms' survival and cell migration.

And in a new study the researchers offer an explanation for why: Beta-actin mRNA is translated into protein faster than gamma-actin. Both forms help cells move, but beta-actin's faster rate seems to cause cell to affix to a substrate more strongly, slowing down cell movement.

"On a global, philosophical level, this expands our understanding of genetic code," says Kashina, a professor of biochemistry at Penn Vet and the senior author on the study, which was published in the journal eLife. "We used to believe that the role of the nucleotides was to encode amino acids, but now we see that, actually, proteins with the same amino acid sequence have different translation rates, and that makes a difference in their function."

Kashina uses the term "silent code" to refer to the influence of these nucleotide differences. In earlier work, her team showed that, in mice, editing the amino acid sequence but maintaining the silent nucleotide code could cause gamma-actin to behave like beta-actin in the body. Normally, mice lacking beta-actin would die before birth, but the researchers showed that performing gene editing to the beta-actin gene so it had the same amino acid sequence as gamma-actin kept mice alive thanks to the nucleotide differences.

A finding from an earlier paper, also published in eLife, motivated the new work. In that earlier study the researchers found that beta-actin RNA had a much higher density of ribosomes than that of gamma-actin. Ribosomes are crucial to the synthesis of protein from RNA, leading the scientists to hypothesize that this difference in protein translation rate could be responsible for the different functions between gamma and beta-actin.

To test their idea, they used cell lines to express only the coding sections of beta- and gamma-actin in mouse cells, as well as their edited versions: the beta-actin that had been edited to have the same amino acid sequence as gamma-actin and vice versa for gamma-actin.

When put to the test in a wound-healing experiment, the researchers found that the nucleotide sequence was paramount in determining the speed at which actin facilitated cell movement. Cells expressing only the typical beta-actin migrated at typical rates, but gamma-actin-expressing cells moved twice as fast. The cells containing edited versions of actin proved that this difference is nucleotide-sequence dependent. Beta-actin edited to have the amino acid sequence of gamma moved like gamma-actin-expressing cells, and those with gamma-actin edited to have the amino acid sequence of beta-actin moved at the rate of beta-actin-expressing cells.

These results surprised the researchers since they expected the higher density of ribosomes in beta-actin mRNA could support faster translation and thus faster movement. And, indeed, when they measured the rate of translation on a single-molecule level, they found that translation occurs about twice as fast for beta-actin as for gamma-actin.

"We expected that faster translation would mean faster movement," Kashina says, "and that's not what we found. It took us a long time to explain why."

What they eventually discovered, was that although the subunits of beta-actin could be supplied faster than those of gamma-actin, that speed worked to the detriment of cell migration speed.

"We found that the faster you supply it, the better the cell attaches to the substrate," Kashina says. "It creates proper traction, which is essential for normal migration. And if you don't supply it fast enough the cell can't attach properly and starts sliding. So that explained our seemingly counterintuitive results."

Kashina and colleagues plan to continue to probe the role of the nucleotide sequence, including why evolutionary forces led to the production of such similar forms of actin and whether the "silent code" is at work in other proteins.

"We think this is part of a bigger story," Kashina says. "We believe actins are not the only proteins that behave this way. There are a number of protein families in the human genome that contain highly similar proteins encoded by different genes. This silent code could be at play in those families as well."

Researchers have produced vaccine-like immune responses to a dangerous bacterium by colonizing 26 healthy volunteers with a related, but harmless, commensal bacterial species. The first-in-human, controlled infection study showed the strategy was safe, as no side effects were reported and the volunteers didn't transmit the commensal bacteria to bedroom-sharers over the 90-day study. Neisseria lactamica is a member of the microbiome that usually resides in the upper airways of children but can also safely colonize the airways of adults. Some researchers theorize that these bacteria could serve as vehicles for immunization, by delivering molecules from more dangerous bacteria to the respiratory system. But commensal bacteria are usually tolerated by the immune system, and it has been difficult to genetically engineer N. lactamica to deliver bacterial antigens. However, Jay Laver and colleagues successfully engineered N. lactamica to express Neisseria Adhesin A as a vaccine antigen. Neisseria Adhesin A is a protein from a related species named Neisseria meningitidis, which can cause meningitis. The team intranasally inoculated 26 adult volunteers with the engineered N. lactamica, which persisted in 86% of the subjects for 90 days. The colonization produced immune responses against Neisseria Adhesin A from both plasma cells and memory B cells within 28 days, and the B cells persisted for at least 90 days after colonization. There were no adverse effects in the volunteers, none of them transmitted the N. lactamica to any contacts who shared the same bed, and the bacteria could be eradicated after 90 days with antibiotics. Laver et al. conclude their delivery system could be used in other applications, such as manipulating the respiratory microbiome or inducing immune tolerance to allergens.

The measures taken during the COVID-19 pandemic limited the access of citizens to natural objects. It is still unexplored, what consequences this had for the residents and what conclusions should be drawn for more effective urban planning. RUDN University scientists with colleagues from Australia and Germany studied how the restrictions associated with COVID-19 affected the use of blue and green infrastructure by citizens in Moscow (Russia) and Perth (Australia), and what consequences this had for their health. In the article "Human Dimensions of Urban Blue and Green Infrastructure during a Pandemic. The Case Study of Moscow (Russia) and Perth (Australia)", published in Sustainability, they presented the results of a study on the importance of green and blue infrastructure for the physical and mental health of the citizens. The results give a basis for developing a balanced strategy for landscape design and urban space planning based on the development of green infrastructure that allows effectively maintaining the well-being and health of citizens, especially during a crisis such as that caused by COVID-19.

The significant challenges caused by the COVID-19 pandemic emphasized that the concept and features of the modern environmentally balanced cities development should consider not only the implementation of economic and social urban strategies, but also functional urban design, related to the urban spaces planning and the development of green infrastructure. Using the results of a web questionnaire survey conducted in May-July 2020 in Moscow (Russia) and Perth (Australia), the article presents an analysis of the significance of contact with nature and various objects of green and blue infrastructure of cities, as well as their changes during and after the COVID-19 restrictions. In order to identify the way people relate to green and blue urban objects and what role they play in providing a comfortable environment, as well as how the general restrictions associated with COVID-19 affected the nature of their interaction with natural infrastructure, they developed a questionnaire of 25 questions, which became the basis of an online study.

216 Muscovites and 110 residents of Perth took part in the survey. The results were analysed statistically. The survey data collected during the isolation period provided information about access to green and blue urban spaces, inequalities in access, as well as changes in the development of urban green infrastructure that are necessary from the respondents' point of view. Scientists analysed the social aspects of citizens' perception of natural objects of the urban and emphasized the importance of contact with nature for maintaining physical and mental health, socio-cultural identification, and socialization (the importance of green and blue objects as social and multicultural spaces). In both cities, measures taken during the COVID-19 restricted people's access to green spaces and water bodies, which negatively affected their mental and physical health and well-being. The survey results showed that the quality, functionality, and location of open natural spaces illustrate the inequality in their distribution and accessibility to the population. In some cases, it was noted that residents of certain areas of cities suffered from limited access to natural objects.

"The COVID-19 circumstances, when access to natural urban facilities was limited for millions of people around the world, highlighted that in extraordinary situations, urban nature can play an essential role in contributing to human well-being and shaping human-nature relationships. Studies have confirmed that public green and blue spaces play a key role not only in maintaining a comfortable environmental situation, but also in restoring mental and physical health during and after an emergency. owever, the issues of how these differential impacts could influence future urban development that will make the cities sustainable and resilient towards addressing challenges, such as those associated with the COVID-19 pandemic and climate change, need to be better understood. In this sense, the comparison of experiences from cities in different countries could be very valuable," says Diana Dushkova, PhD, associate professor at the RUDN University and senior researcher at The Helmholtz-Centre for Environmental Research

The researchers compared Moscow and Perth as two cities with different approaches to the organization of natural objects and landscaping strategies. In Moscow, most of the green areas and water bodies are open to public. In Perth, more than half of the city's green infrastructure facilities are located on private territories. It turned out that residents of Perth and Moscow consider access to nature equally important, even though cities differ in size, climatic conditions, and planning approaches. In both cities, more than 60% of residents said that the opportunity of contact with nature is important or extremely important for physical and mental health. Among the main values of contact with nature, citizens noted fresh air (82.9% in Perth and 51.6% in Moscow), a sense of unity with nature (89.5% in Perth and 71.2% in Moscow), the scenic beauty (89.5% in Perth and 71.2% in Moscow). The differences in the responses of residents of the two cities are noticeable in questions that relate to the specifics of the restrictions adopted in the pandemic. Changes in visiting natural spaces before and during the pandemic are especially noticeable in Moscow, where strict restrictions were introduced. 56.9% of Muscovites visited green and water zones less often. In Perth, parks and other natural recreation areas remained open, and 59.4% of residents did not visit urban natural spaces less often, and 26.7% even began to do it even more often.

"Our results showed that urban residents are aware of the value of green and blue spaces and emphasize their important role in maintaining health and well-being, especially during the COVID-19 pandemic. This is new convincing evidence that the issues of accessibility of natural objects and their balanced distribution in urban areas should be considered in the development strategy of a modern city, which considers the new requirements of the modern world in ensuring safe and comfortable life and maintaining human health. In addition, it indicates that access to nature and public rights to use green spaces determine the overall resilience of cities to the crisis. The obtained results obtained provide the basis for further research in the development of modern approaches to landscape design and planning of urban green and water zones and allow us to see how effectively they can ensure and maintain the well-being and health of citizens, especially during a crisis such as that caused by COVID --19," says Diana Dushkova.

Astronomers have designed and trained a computer program which can classify tens of thousands of galaxies in just a few seconds, a task that usually takes months to accomplish.

In research published today, astrophysicists from Australia have used machine learning to speed up a process that is often done manually by astronomers and citizen scientists around the world.

"Galaxies come in different shapes and sizes" said lead author Mitchell Cavanagh, a PhD candidate based at The University of Western Australia node of the International Centre for Radio Astronomy Research (ICRAR).

"Classifying the shapes of galaxies is an important step in understanding their formation and evolution, and can even shed light on the nature of the Universe itself."

Mr Cavanagh said that with larger surveys of the sky happening all the time, astronomers are collecting too many galaxies to look at and classify on their own.

"We're talking several million galaxies over the next few years. Sometimes citizen scientists are recruited to help classify galaxy shapes in projects like Galaxy Zoo, but this still takes time."

This is where convolutional neural networks, or CNNs, come in. In today's high-tech world, these kinds of computer programs are everywhere, used in everything from medical imaging, stock markets and data analytics, to how Netflix generates recommendations based on your viewing history.

In recent years, CNNs have begun to see wider adoption in astronomy. Most of the existing CNNs that astronomers use are binary - is this a spiral galaxy or not? - but this new CNN uses multiclass classification - is this an elliptical, lenticular, spiral, or irregular galaxy? - with more accuracy than the existing binary networks.

Mr Cavanagh said that machine learning is becoming more widespread in astronomy.

"The massive advantage of neural networks is speed. Survey images that would otherwise have taken months to be classified by humans can instead be classified in mere minutes."

"Using a standard graphics card, we can classify 14,000 galaxies in less than 3 seconds."

"These neural networks are not necessarily going to be better than people because they're trained by people, but they're getting close with more than 80% accuracy, and up to 97% when classifying between ellipticals and spirals."

"If you place a group of astronomers into a room and ask them to classify a bunch of images, there will almost certainly be disagreements. This inherent uncertainty is the limiting factor in any AI model trained on labelled data."

One great advantage of this new AI is that the researchers will be able to classify more than 100,000,000 galaxies at different distances (or redshifts) from Earth and in different environments (groups, clusters etc). This will help them understand how galaxies are being transformed over time, and why it might happen in particular environments.

The CNNs that Mr Cavanagh has developed aren't just for astronomy. They can be repurposed for use in many other fields, as long as they have a large enough dataset to train with.

"CNNs will play an increasingly important role in the future of data processing, especially as fields like astronomy grapple with the challenges of big data," he said

A new screening method that can test the effectiveness of therapeutic molecules designed to 'glue' proteins together in the body has been developed by researchers at the University of Birmingham and the University of Leicester.

The research paves the way for drug developers to screen large numbers of potential new drug compounds to discover new treatments for diseases such as breast cancer and Parkinson's disease.

The ways in which proteins interact with each other are fundamental to all cell functions. These interactions underpin every function of a healthy body, with any slight change in these interactions resulting in disease.

A handful of drugs have been designed that can break apart these interactions, and this serves to disrupt the progress of the disease. However, in some diseases, the problem is caused by protein interactions not happening, or not happening in the right way. So new drugs that work by 'gluing' these proteins together would be highly effective, but finding them is not straightforward.

In this study, Chemical Science, researchers in the University of Birmingham's School of Biosciences have designed a system that uses mass spectrometry to measure the precise mass of a pair of proteins, plus the 'glue', to identify which 'glue' is the strongest and thus will likely be the most successful in treating the disease.

Lead author Dr Aneika Leney said: "A healthy body depends very much on the cells' proteins being able to signal effectively. Any wrong signal can lead to disease and that could be the wrong proteins sticking together - or proteins not joining up as they should. We want a drug that corrects for this. Our methods provides a 'snapshot' of what is happening to the proteins when we add a potential drug so we can see quickly whether the 'glue' is working"

The team worked with chemical biologists at the University of Leicester to test the method on therapeutic compounds being studied by co-lead author Dr Richard Doveston and his team.

Dr Doveston says: Looking for molecules that act as glues is not easy because things are complicated by having two proteins in the mix. At the early stage of development we often just want to find molecules that are good starting points for development, so they might not be that good as glues at this stage. The current high-throughput screening methods available to us are usually not very effective in this context. The mass spectrometry method is great because we can learn so much from the data and it can be gathered relatively easily and quickly.

Because the glue compounds are highly specific to the identified proteins, interactions with other proteins are rare, so the therapy is unlikely to produce any unlooked-for effects."

Dr Leney adds: "We hope our approach will be taken up by pharmaceutical companies and used to rapidly screen and test promising drug compounds that can bind proteins together to deliver a therapeutic benefit."

CLEVELAND, Ohio (July 7, 2021)--Estrogen has been thought to play a role in a woman's risk of developing Alzheimer disease (AD). A new study has taken a different approach to identifying risk factors for AD by examining the association between a woman's reproductive life span as an indicator of endogenous estrogen exposure and levels of cerebrospinal fluid biomarkers. Study results are published online in Menopause, the journal of The North American Menopause Society (NAMS).

Alzheimer disease represents 60% to 70% of all dementia diagnoses, making it the most common form of dementia. Approximately two-thirds of those with AD are women. This is not surprising, because age is the greatest known risk factor for AD, and women tend to live longer than men.

The incidence of AD is rising quickly because of the aging population, so multiple studies have been undertaken to identify other risk factors, especially those that may explain any sex differences. Prior studies have shown a link between both higher and lower estradiol blood levels and risk of dementia, whereas others have identified no associations. Some studies have shown that hormone therapy after menopause can increase the risk of dementia, but others have documented a decreased risk. Similarly, cognitive decline has been linked with both longer and shorter reproductive periods.

Despite all the conflicting evidence, few, if any, studies have examined the association between estrogen and biomarkers for AD in cerebrospinal fluid, the clear body fluid found within the tissues surrounding the brain and spinal cord. In this new study, a small sampling of women who were free of dementia and underwent natural menopause were followed for 25 years. Based on the results from the cerebrospinal fluid samples, researchers concluded that a longer reproductive life was associated with increased levels of AD biomarkers in the preclinical phase of the disease; however, they suggested that larger studies should be conducted to confirm these findings.

Study results appear in the article "Reproductive period and preclinical cerebrospinal fluid markers for Alzheimer disease: a 25-year study."

"This small population-based study showed an association between duration of the reproductive life span (a surrogate marker for exposure to endogenous estrogen) and biomarkers of Alzheimer disease in the cerebrospinal fluid of women without dementia. This finding needs to be confirmed in larger studies but may be another factor contributing to the increased burden of Alzheimer disease in women that, at least in part, likely relates to aging and the longer life expectancy in women compared with men," says Dr. Stephanie Faubion, NAMS medical director.

A new study in the Journal of the European Economic Association, published by Oxford University Press, finds that electoral districts with a larger gender pay gaps show favoritism toward male political candidates in Parliamentary elections, with fewer female candidates on the ballot.

The researchers here gathered data for seven parliamentary elections in France between 1988 and 2017. Researchers studied candidates from the Left and Right political coalitions, which account for 80% of elected members of Parliament. The researchers consulted administrative and web data on candidates and electoral outcomes, survey data on voters' attitude towards gender, as well as census data on earnings, and voters' demographics across electoral districts.

Analysis found that female candidates made up approximately 15% of all Parliamentary candidates in the 1980s and 1990s. The figure doubled to nearly 30% following the implementation of the Parity Law in 2000, which stipulated that each party should have an equal fraction of male and female candidates across electoral districts in Parliamentary elections. Noncompliance with the parity rule results in a financial penalty to the public funding provided to political parties.

Researchers analyzed local gender pay gaps compared to voting support for male and female candidates in the same electoral districts. Researchers found a positive and strong correlation between gender earnings gaps and electoral gaps across municipalities of the same electoral district: a 150 euros increase in gender monthly earnings gap leads to an increase by 0.6 percentage points in vote shares between male and female candidates. Researchers concluded that female candidates obtain lower votes in areas with less favorable attitudes towards women, including significant gender pay gaps, and thus women are less likely to run for elections in these areas.

Indeed researchers found that voters' attitudes towards gender are strongly associated with the gender distribution of candidates across electoral districts within France. A 10 percentage points increase in survey respondents who thought that men were better political leaders than women correlated with a 2.3 percentage points decrease in the share of female candidates.

Researchers concluded that in districts with strongest electoral competition, the electoral cost of selecting women outweighs the cost of the financial penalty under the Parity Law. When voters are biased against female candidates, electoral competition limits the effectiveness of "soft" quota rules on candidates. In the last Parliamentary election (17 years after the Parity rule was introduced) the two main political parties still selected an average of 40% of female candidates, significantly below the 50% objective of the Parity Law.

"Overall we find that parties allocate female candidates across districts strategically," Thomas Le BarBanchon, Bocconi University, said. "This is very clear after the introduction of the Parity Law. Then parties avoid putting women on the ballot of the most contested districts. In such districts, voters biased against female politicians may lead women to lose the few votes that matter for winning the close race, and parties internalize this competitive disadvantage."