Culture

A healthy heart beats 50 to 100 times a minute and pumps 8,000 litres of blood around our body every day. A precondition for this function is the elasticity of the cardiac walls, which dilate as blood flows in (diastole) and contract again as the blood flows out (systole). Millions of tiny cavities in the heart muscle fibres, the sarcomeres, are responsible for this movement. These contractile units contain the largest protein found in the human body called titin. It has the function of a mechanical spring, which develops a restoring force during the extension of the sarcomeres - just like a rubber band.

Working with researchers from the Universities of Bochum, Würzburg, Cologne, Regensburg, Göttingen and Düsseldorf, a team of researchers at the University of Münster headed by Prof. Wolfgang Linke, Director of the Institute of Physiology II, has now discovered that oxidative stress, in combination with the stretching of the heart walls, triggers a change in cardiac stiffness. The elastic titin in the sarcomeres is more strongly oxidised and, as a result, is modulated in its extensibility. The researchers call this newly discovered mechanism UnDOx ("Unfolded Domain Oxidation"). The study has been published in the journal "PNAS".

Background and method

In the human organism, titin forms the backbone of the sarcomeres, the smallest functional units of the skeletal muscles and the heart. Titin provides both stability and elasticity to muscle cells, due its unique structure. For the first time, the research team has now shown in heart tissue of mice that oxidative stress together with the extension of the heart modulates the spring function of titin. Oxidative stress occurs when too many reactive oxygen species are present in the cell of an organism. These oxygen species, which include so-called free radicals, can cause cell damage. In small quantities, however, they regulate important physiological functions.

The researchers used a mass spectrometer to determine the oxidation status of the proteins in the heart, including titin. Additionally, they isolated heart muscle cells from deep-frozen tissue of a human heart and attached them to a force sensor and a micromotor, in order to stretch the specimens. This enabled them to measure the forces generated upon stretch and observe their increase or decrease during different forms of oxidative stress. In addition, the team produced recombinant titin molecules and also mutated them in a test tube, such that oxidation could no longer occur. "We then used a so-called atomic force microscope to directly measure the effects of stretch and oxidation on the titin spring," Wolfgang Linke explains. "Using this device, we were able to stretch individual titin molecules like a rubber band and record the force upon extension , as well as the changes in force in the presence of an oxidant."

The researchers demonstrated in their experiments that the UnDOx mechanism occurs in hearts under oxidative stress. This is the case, for example, after an acute heart attack or in chronic heart disease associated with altered cardiac filling. "The mechanism regulates the distensibility of the heart," Linke adds. "Extensive wall stiffness is not good for the heart, because less blood flows in. In the case of diastolic heart failure, which is often found in elderly people, the stiffening of the heart is a major problem. We hope that such hearts can be made more distensible through the pharmacological regulation of titin oxidation, i.e. by using medication."

A genetic predisposition to late-onset Alzheimer's disease affects how the brains of young adults cope with certain memory tasks. Researchers from the German Center for Neurodegenerative Diseases (DZNE) and the Ruhr-Universität Bochum report on this in the scientific journal "Current Biology". Their findings are based on studies with magnetic resonance imaging in individuals at the age of about 20 years. The scientists suspect that the observed effects could be related to very early disease processes.

The causes for Alzheimer's in old age are only poorly understood. It is believed that the disease is caused by an unfavorable interaction of lifestyle, external factors and genetic risks. The greatest genetic risk factor for late-onset Alzheimer's disease stems from inherited mutations affecting "Apolipoprotein E" (ApoE), a protein relevant for fat metabolism and neurons. Three variants of the ApoE gene are known. The most common form is associated with an average risk for Alzheimer's. One of the two rarer variants stands for an increased risk, and the other for a reduced risk.

"We were interested in finding out whether and how the different gene variants affect brain function. That is why we examined the brains of young adults in the scanner while they had to solve a task that challenged their memory," explained Dr. Hweeling Lee, who led the current study at the DZNE in Bonn.

Distinguishing similar events

The group of study participants comprised of 82 young men and women. They were on average 20 years old, and all of them were university students considered to be cognitively healthy. According to their genotype for ApoE, 33 of them had an average, 34 an increased and 15 a reduced risk of developing Alzheimer's disease at a late age. During the study in the brain scanner, all individuals were presented with more than 150 successive images displayed on a monitor. These were everyday objects such as a hammer, a pineapple or a cat. Some pictures were repeated after a while, but sometimes the position of the displayed objects on the screen had changed. The study participants had to identify whether an object was "new" or had been shown before - and if so, whether its position had shifted.

"We tested the ability to distinguish similar events from one another. This is called pattern separation," said Hweeling Lee. "In everyday life, for example, it's a matter of remembering whether a key has been placed in the left or right drawer of a dresser, or where the car was parked in a parking garage. We simulated such situations in a simplified way by changing the position of the depicted objects."

High-resolution through modern technology

Simultaneously to this experiment, the brain activity of the volunteers was recorded using a technique called "functional magnetic resonance imaging". Focus was on the hippocampus, an area only a few cubic centimeters in size, which can be found once in each brain hemisphere. The hippocampus is considered the switchboard of memory. It also belongs to those sections of the brain in which first damages occur in Alzheimer's disease.

When measuring brain activity, the scanner was able to show its full potential: It was an "ultra-high field tomograph" with a magnetic field strength of seven Tesla. Such devices can achieve a better resolution than brain scanners usually used in medical examinations. This enabled the researchers to record brain activity in various sub-fields of the hippocampus with high precision. "Up to now, there were no comparable studies with such level of detail in ApoE genotyped participants. This is a unique feature of our research," said Hweeling Lee.

No differences in memory performance

There were no differences between the three groups of subjects with regard to their ability for pattern separation. "All study participants performed similarly well in the memory test. It did not matter whether they had an increased, reduced or average risk for Alzheimer's disease. Such results are certainly to be expected in young healthy people," said Nikolai Axmacher, Professor of Neuropsychology at the Ruhr-Universität Bochum, who was also involved in the current study. "However, there were differences in brain activity. The different groups of study participants activated the various subfields of the hippocampus in different ways and to varying degrees. Their brains thus reacted differently to the memory task. In fact, we saw differences in brain activation not only between people with average and increased risk, but also between individuals with average and reduced risk."

At present, it is uncertain whether these effects are significant for developing Alzheimer's in old age. "Our findings might be related to very early disease processes. Determining this is a task for future studies and could help to devise biomarkers for the early diagnosis of dementia," said Hweeling Lee. "In any case, it is remarkable that a genetic predisposition for Alzheimer's disease is already reflected in the brain at young adulthood."

There are billions of bacteria around us and in our bodies, most of which are harmless or even helpful. But some bacteria such as E. coli and salmonella can cause infections. The ability to swim can help bacteria to seek out nutrients or to colonize parts of the body and cause infection.

Researchers from the Faculty of Health and Medical Sciences, University of Copenhagen, have now provided fundamental insight into how this bacterial movement is powered, solving a yearlong mystery within the field.

'A lot of bacteria can move, or swim, because they have long threads, also known as flagella, which they can use to propel themselves forward. They do this by rotating these threads. The rotation is powered by a rotary motor, which again is powered by a protein complex known as the stator unit. This is all well known within our field. What we now show is how this stator unit powers the motor, which has been a mystery so far', says Associate Professor and Group Leader Nicholas Taylor, Novo Nordisk Foundation Center for Protein Research.

Quite surprisingly, the team shows that the stator unit itself is in fact also a tiny rotary motor. This tiny motor powers the large motor, which makes the threads rotate, causing the bacteria to move. The results contradict existing theories on the mechanism of the stator unit, and this new knowledge might be useful in the fight against bacteria-based diseases.

'Most researchers, including ourselves, actually thought that the technical mechanism and the architecture of the stator unit was quite different to what our study shows. Knowing the actual composition and function of this unit paves the way for therapeutic purposes. When we know what makes bacteria move, we might also be able to inhibit this movement and thereby stop it from spreading', says Nicholas Taylor.

Cryo-electron microscopy reveals the architecture of the motor

The researchers determined the structure of the stator unit complex by using cryo-electron microscopy. Working with this technique, they were able to elucidate its architecture, see how it is activated and provide a detailed model for how it powers rotation of the flagellar motor.

"The motor consists of two proteins: MotA and MotB. The MotB protein is anchored to the cell wall, and is surrounded by MotA proteins, which, upon dispersion of the ion motive force, rotates around MotB. The rotation of MotA in turn powers rotation of the large bacteria motor," says Nicholas Taylor.

"Furthermore, our model shows how the stator unit can power rotation of the bacterial flagellar motor in both directions, which is crucial for the bacteria to change their swimming direction. Without direction change, bacteria would only be able to swim straight in one direction."

Next step for the group is to find out if it is possible to inhibit the stator units using chemical compounds, which could have antibiotic effects.

The cancer called biliary tract cancer (BTC) is not the most widespread form of cancer. In western countries, about 1.6 in 100.000 gets the diagnose every year. It is, however, a very aggressive form of cancer.

The majority of patients with BTC are diagnosed with advanced disease and has an average survival of only 1 year from initiation of chemotherapy. With such narrow survival windows, it is crucial to improve our understanding of the disease.

Now, researchers from Biotech Research & Innovation Centre at the University of Copenhagen and Herlev and Gentofte Hospital along with collaborators from Rigshospitalet and Sygehus Lillebaelt have identified a biomarker that can tell doctors how aggressive a patient's disease may be.

"We have found a biomarker that reliably predicts how aggressive a patients disease will evolve, which in the future could help doctors in the hospitals make the right decisions about chemotherapy for the benefit of each BTC patient," says Jesper Andersen, Associate Professor at BRIC.

Biomarkers can used for more than the diagnose

The researchers measured the levels of two inflammatory proteins and a biomarker commonly used in pancreatic cancer before and during chemotherapy in patients with advanced BTC and found that patients with higher levels of these markers before chemotherapy had a lower survival rate. Especially one protein called IL6 (interleukin-6) proved to be superior to the other markers in predicting those patients at greatest risk of death.

"A common misperception may be that biomarkers are mainly needed to diagnose a specific cancer type, but diverse biomarkers are also needed to guide clinical decision-making throughout each patients' individual journey. These types of prognostic and predictive biomarkers deserve increased attention, in particular as they are playing important roles in the increasingly individualized management of more common cancer types", says Jesper Andersen.

There are several markers to predict patients at greatest risk of death, however it was confirmed that the prognostic information provided by measuring IL-6 is not captured by other inflammatory markers already in routine clinical use. For instance, about 10 percent of the population does not express the marker that is normally measured (CA19-9) to predict the patient clinical outcome. Therefore, the course of disease cannot be predicted for these patients using CA19-9, for which IL-6 may be used instead.

Inhibiting IL-6 may improve response to chemotherapy

By inhibiting signalling of the protein IL-6 in a mouse model of human BTC, researchers discovered that the response of mouse tumours to chemotherapy significantly increased.

"Our data suggests that inhibiting IL-6 signalling may extend therapeutic benefit compared to chemotherapy alone. However, this will require careful evaluation in randomized clinical trial settings. Such a trial is currently ongoing at Herlev and Gentofte Hospital and results from this and potential future trials will contribute to our knowledge in regards to the potential of targeting the IL-6 pathway in patients with BTC", says Jesper Andersen

Large sample size made possible through collaboration

Researchers studying BTC face a data-challenge since only 1.6 per 100,000 of Western populations are diagnosed with BTC annually. This makes it difficult to collect comprehensive amounts of patient data. Therefore, one of the key strengths of this study lies in the patient numbers attained and analysed in this rare cancer demographic, amounting to 1590 serum samples from 452 patients with advanced BTC.

Furthermore, the study explores advanced BTC patients who represent the majority of patients at diagnosis, while the majority of previous BTC studies published to date have focused on early stage disease.

"It is imperative to increase representation of these patients with the worst prognosis in subsequent studies. These studies should also include longitudinal sampling throughout the patient's clinical history, as we have done here", says Jesper Andersen, group leader at BRIC.

The sample size achieved in this study was only made possible through the comprehensive collaboration between Herlev and Gentofte Hospital, Rigshospitalet and Sygehus Lillebaelt in Denmark.

"The number of patients and consecutively collected blood samples is among the largest cohorts presented in BTC and has, despite the small Danish population, been possible to analyze due to a decade of biobank work at the participating hospitals. Our results emphasize further biological and clinical investigation of the complex role of inflammation in BTC. For this, we have a uniquely established foundation due only to the contribution by all the patients" says Dan Høgdall, first-author on the current study and MD at Department of Oncology, Herlev and Gentofte Hospital.

Researchers of the Centro Nacional de Investigaciones Cardiovasculares (CNIC) have discovered a cell-cleaning system that is key to keeping a healthy heart. This mechanism allows the heart's contractile cells (the cardiomyocytes) to release damaged components outside the cell into particles called exophers. These exophers are then taken up by a network of immune cells living inside the heart-the macrophages, which are in charge of removing them before they cause inflammation in the heart.

The study is published in Cell, through collaboration of two groups at CNIC-led by Dr. Andrés Hidalgo and Dr. José Antonio Enríquez- compiles the results of over five years of research, with collaborations with laboratories in Europe, Asia and the US. The insights that this study provides suggests that cardiac dysfunction can emerge in some instances from defects in resident immune cells, rather than from cardiomyocytes. This finding has important implications for the diagnosis and treatment of heart disease.

The assumption so far was that most cells could dispose of, or recycle, their waste products on their own. However, the CNIC teams discovered that in the heart this process requires the close collaboration of two types of cells, such that the material is transferred from cardiomyocytes to neighboring macrophages, which are ultimately responsible for disposing of the waste.

"Macrophages are cells with high phagocytic [gobbling] capacity and their functions have been mostly studied in inflammation and disease. However, we now know that they are also part of most healthy tissues and that they play pivotal tasks in their daily functions," explained Dr. José Ángel Nicolás-Ávila, first author of the article and researcher at CNIC.

These cells were first described in the heart only a decade ago, and we are just beginning to understand what it is that they do. The finding that cardiomyocytes surrogate the removal of their waste to macrophages has many implications. "The fact that the heart requires a population of macrophages to do their cleaning work, among other tasks, suggests that many heart diseases of unknown origin can be explained by failure of these macrophages." Dr. Enriquez says.

Another potential implication pointed out by Dr. Nicolás-Ávila, is that there may be similar processes supporting the fitness of specialized cells in other tissues, including the brain, whose cells share features with cardiomyocytes. "We are currently exploring if phenomena like the ones found in hearts can take place in other organs, and whether they degenerate with age", he says.

Dr. Ana Victoria Lechuga Vieco, co-first author of the article, adds, "cardiomyocytes are cells with extremely high energy demands. The heart needs to beat uninterruptedly to keep the body alive, which explains why cardiomyocytes are full of mitochondria, the organelles that produce energy. Similar to a boiler, the mitochondria suffer wear-and-tear with use and need to be replaced to prevent cell damage. The most striking finding from our study -she notes- is that cardiomyocytes pass this task on to macrophages, possibly because cardiomyocytes are too busy beating and cannot process all this waste material on their own."

Each cardiomyocyte is invaluable, because they cannot proliferate or be replaced once they die. "This is why we believe that this 'surrogation' phenomenon has evolved to allow cardiomyocytes to beat in optimal conditions for many years, with macrophages helping with their maintenance," says Dr. Hidalgo. "In a way, this is like the cleaning system of a city. It lacks glamour, but is essential for the whole city to function." he sums up.

The combined effects of the body's microbiota working together with COVID-19 in the lungs could explain the severity of the disease in people with obesity and diabetes, according to a new article published today in eLife.

The review offers important mechanistic insights into why people with obesity and diabetes seem to be at increased risk of developing severe acute respiratory syndrome (SARS) after infection with the COVID-19 virus, and more often require hospitalisation and ventilation.

"There is rapidly emerging evidence highlighting obesity and type 2 diabetes as key risk factors linked to severity of COVID-19 infections in all ethnic groups, but the detailed underlying connections with these risk factors remain largely unknown," says author Philipp Scherer, Professor at the Department of Internal Medicine, and Director of the Touchstone Diabetes Center, at the University of Texas Southwestern Medical Center, Dallas, US. "There is a paradox that people with obesity and diabetes are generally known to recover better from lung conditions than others. So, what is it about COVID-19 that makes this group of people more susceptible?"

In their article, Scherer and his coauthors revisit the factors and disease pathways that connect obesity and diabetes to the severity of COVID-19 infection. The mechanisms can be roughly divided into two groups: those connected with the ACE2 receptor, and those providing an interaction between COVID-19 and pre-existing bacterial conditions.

ACE2 resides on the surface of many cells in the human body and is involved in regulating fluid volumes, blood pressure and the function of blood vessels. It is also used by COVID-19 to enter human cells. One theory is that increased amounts of ACE2 in people with obesity or diabetes makes it easier for the virus to enter cells and increases the viral load - an important factor in determining disease severity. Alternatively, increased shedding of ACE2 in people with obesity causes it to move to the lungs, where the virus can use it.

Another factor known to be influential in the progression of lung diseases is our body's microbiota. We carry more than 100 trillion bacteria in our body - outnumbering the number of our own cells. People with obesity and diabetes are thought to suffer from a body-wide dissemination of bacteria and the substances they produce, which in turn causes low-level continuous inflammation in different tissues.

The team considered how host bacteria might influence COVID-19 severity. One potential culprit is the lipopolysaccharides (LPS) that bacteria produce, which have been shown to cooperate with other coronaviruses to induce SARS in pigs. It is possible that these LPS molecules join forces with COVID-19 in humans and trigger a chain of events that causes healthy tissue to transform into scarred tissue - as COVID-19 does in the lungs.

"While all of these potential mechanisms can contribute to the severity of COVID-19, we believe that one of them plays the predominant role, and that this must be present not only in obese and diabetic patients, but also in other groups of increased risk in COVID-19," Scherer explains.

The authors propose that a combined deficiency in ACE2 caused by COVID-19, together with obesity or diabetes, leads to impaired gut barrier function, allowing bacteria and their toxins to leak into the circulation. In the lungs, these bacteria and toxins work with the virus to cause more severe lung injury than either would do alone.

"Our theory is supported by experiments showing that the combination of bacterial and viral infection can lead to a 'cytokine storm' - an extreme inflammatory reaction - which is a hallmark of COVID-19", Scherer concludes. "Moreover, the involvement of viral-bacterial interactions can also explain the increased risk of severe COVID-19 seen in older people, those with heart disease and in some ethnic groups."

As the COVID-19 pandemic has swept the world, researchers have published hundreds of papers each week reporting their findings - many of which have not undergone a thorough peer review process to gauge their reliability.

In some cases, poorly validated research has massively influenced public policy, as when a French team reported COVID patients were cured by a combination of hydroxychloroquine and azithromycin. The claim was widely publicized, and soon U.S. patients were prescribed these drugs under an emergency use authorization. Further research involving larger numbers of patients has cast serious doubts on these claims, however.

With so much COVID-related information being released each week, how can researchers, clinicians and policymakers keep up?

In a commentary published this week in Nature Biotechnology, University of New Mexico scientist Tudor Oprea, MD, PhD, and his colleagues, many of whom work at artificial intelligence (AI) companies, make the case that AI and machine learning have the potential to help researchers separate the wheat from the chaff.

Oprea, professor of Medicine and Pharmaceutical Sciences and chief of the UNM Division of Translational Informatics, notes that the sense of urgency to develop a vaccine and devise effective treatments for the coronavirus has led many scientists to bypass the traditional peer review process by publishing "preprints" - preliminary versions of their work - online.

While that enables rapid dissemination of new findings, "The problem comes when claims about certain drugs that have not been experimentally validated appear in the preprint world," Oprea says. Among other things, bad information may lead scientists and clinicians to waste time and money chasing blind leads.

AI and machine learning can harness massive computing power to check many of the claims that are being made in a research paper, the suggest the authors, a group of public and private-sector researchers from the U.S., Sweden, Denmark, Israel, France, the United Kingdom, Hong Kong, Italy and China led by Jeremy Levin, chair of the Biotechnology Innovation Organization, and Alex Zhavoronkov, CEO of InSilico Medicine.

"I think there is tremendous potential there," Oprea says. "I think we are on the cusp of developing tools that will assist with the peer review process."

Although the tools are not fully developed, "We're getting really, really close to enabling automated systems to digest tons of publications and look for discrepancies," he says. "I am not aware of any such system that is currently in place, but we're suggesting with adequate funding this can become available."

Text mining, in which a computer combs through millions of pages of text looking for specified patterns, has already been "tremendously helpful," Oprea says. "We're making progress in that."

Since the COVID epidemic took hold, Oprea himself has used advanced computational methods to help identify existing drugs with potential antiviral activity, culled from a library of thousands of candidates.

"We're not saying we have a cure for peer review deficiency, but we are saying that that a cure is within reach, and we can improve the way the system is currently implemented," he says. "As soon as next year we may be able to process a lot of these data and serve as additional resources to support the peer review process."

A recent study found strong associations between the financial holdings of legislators in the U.S. House of Representatives and how those lawmakers voted on key financial legislation. The study suggests that many lawmakers voted in ways that benefited their personal finances, regardless of whether those votes were consistent with their espoused politics.

"Broadly speaking, we found that House members who owned stocks in firms that would benefit from financial deregulation voted for financial deregulation," says study co-author Jordan Carr Peterson, an assistant professor of political science at North Carolina State University. "And House members who had invested in financial and automotive stocks supported legislation aimed at bailing out the financial and auto sectors.

"Honestly, we were surprised that nobody had done this analysis before, given that all this data was publicly available," Peterson says. "It required a fair amount of tedious work, which may explain it."

Specifically, the researchers did a detailed examination of the financial holdings of all House members who voted on five key pieces of economic legislation between 1999 and 2008: the Gramm-Leach-Bliley bill in 1999 (which repealed Glass-Steagall); the Commodity Futures Modernization Act of 2000 (which involved substantial deregulation to the financial industry); the two 2008 votes on the Troubled Assets Relief Program (which bailed out major banks); and the Auto Industry Financing and Restructuring Act in 2008 (which bailed out the auto industry).

"We chose those five roll-call votes because, unlike many other roll-call votes, the legislation had immediate and direct impacts on the stock market in general - and in particular on the stock prices of individual firms that were regulated by the relevant bills," Peterson says.

In four of the five instances, legislators largely voted in line with what was most beneficial to their financial interests. The sole exception was the Commodity Futures Modernization Act of 2000 - though that may be due to the fact that the bill was bundled into a much larger omnibus legislation package at the tail end of a lame-duck congressional session.

"Our findings indicate that many legislators are more likely to vote in support of their own financial holdings, rather than in line with the political positions they espouse on the campaign trail," Peterson says. "That's clearly problematic - and we don't have to do things this way. For example, an easy fix would be to require that members of Congress not own individual stocks, instead moving their investments into mutual funds or a blind trust.

"And the finding also raises some interesting questions about similar potential conflicts in other governmental institutions," Peterson says.

The spectacular and complex visual patterns created by animal groups moving together have fascinated humans since the beginning of time. Think of the highly synchronized movements of a flock of starlings, or the circular motion of a school of barracudas. Using state-of-the-art robotics, a research team from the University of Konstanz, Science of Intelligence, and the Leibniz Institute of Freshwater Ecology and Inland Fisheries (IGB) shows that animals' speed is fundamental for collective behavioral patterns, and that ultimately it is the faster individuals that have the strongest influence on group-level behavior. The study, published in Biology Letters of the Royal Society, gives new insights on complex collective behavioral patterns in nature, and provides knowledge that could help develop robotic systems that move collectively, such as robot swarms, driverless cars, and drones.

Researchers have long focused on identifying the emergence of collective patterns. Thanks to a combination of behavioral experiments, computer simulations, and field observations, it is clear that many seemingly complex patterns can actually be explained by relatively simple rules: move away from others if they get too near, speed up towards others if they get too far away, and otherwise move at the same speed and align with your group mates.

"Besides understanding the rules that individuals follow when interacting with others, we need to consider the behaviors and characteristics of those individuals that make up the group and determine their influence for collective outcomes"says Dr. Jolle Jolles, scientist at the Zukunftskolleg, University of Konstanz, and lead author of the study. "Across the animal kingdom, it has been found again and again that animals tend to differ considerably from one another in their behavior such as in terms of their activity, risk-taking, and social behavior". What are the consequences of this behavioral heterogeneity when it comes to collective behavior? And how can one test for its social consequences?

The Robofish is recognized as a conspecific

To disentangle the role of individual differences in collective behavior and the mechanisms underlying this type of behavior, the research team built "Robofish", a robotic fish that not only realistically looks and behaves like a guppy - a small tropical freshwater fish - , but also interacts with the live fish in a natural way. The experimenters paired the robotic fish with a guppy and programmed it to always follow its partner and copy its movements, lacking however any movement preferences of its own. The team then used high-definition video tracking and a closed-loop feedback system to let the robotic fish respond to the live fish's actions in real-time.

"One of Robofish's simple interaction rules was to keep a constant distance to its shoal mate" explains Dr. David Bierbach, who works within the Berlin-based Excellence Cluster 'Science of Intelligence' at the HU Berlin and the IGB, and is senior author on the paper. "Using this rule, our Robofish tried to keep the same distance to the live fish by accelerating and decelerating whenever the live fish did. Also, programming the robotic fish without any own movement preferences gave us the unique opportunity to investigate how individual differences in the behavior of the live fish led to group-level differences. In short, with our unique approach, we could isolate the effect of the fish's movement speed on the pair's collective behavior".

Fast guppies become stronger leaders

The researchers first quantified the guppies' natural movement speed by observing their movements when alone in an open environment, and found that there were large individual differences in how fast guppies tended to move. When the fish were subsequently tested with Robofish, the fish and Robofish tended to swim naturally together as a pair. However, the researchers observed that there were large differences in the social behaviors between the pairs: pairs in which the guppy had a faster movement speed tended to be much more aligned, more coordinated, and less cohesive, and the guppy emerged as a clearer leader. As Robofish behaved according to the same identical rules with each and every guppy, it is the individual speed of the guppies that must have led to these differences in group-level properties.

By involving state-of-the-art robotics, this research shows that individual speed is a fundamental factor in the emergence of collective behavioral patterns. As individual differences in speed are associated with a broad range of phenotypic traits among grouping animals, such as their size, age, and hunger level, the results of this study may help understand the role of such heterogeneity in animal groups.

Future studies using the interactive Robofish will focus on other aspects of collective behavior: For example, how can animals act in synchrony if they just respond to the actions of their neighbors? "We want to improve Robofish's software so that it can predict and anticipate the live fish's next steps, which is assumed to be how animals do it." says David Bierbach.

Understanding these mechanisms is not only fundamentally important as it reveals information about the mechanisms that underlie collective behavior and decisions, but also because this knowledge can be applied to artificial systems and used to develop machines that move collectively, such as robot swarms, driverless cars, and drones.

NASA's Aqua satellite captured a visible image of Tropical Depression Rene as it was dissipating in the central North Atlantic Ocean.

The Moderate Resolution Imaging Spectroradiometer or MODIS instrument that flies aboard NASA's Aqua satellite captured a visible image of Rene on Sept. 15 at 12:30 p.m. EDT. Rene appeared elongated from wind shear (outside winds blowing at different levels of the atmosphere) battering the storm. Over the next couple of hours, visible satellite imagery showed that Rene opened into a trough (elongated area) of low pressure and was no longer a tropical cyclone. Several hours later, Rene dissipated into a remnant low-pressure area.

Satellite imagery was created using NASA's Worldview product at NASA's Goddard Space Flight Center in Greenbelt, Md.

Rene's Curtain Call

At 5 p.m. EDT (2100 UTC) on Sept. 15, NOAA's National Hurricane Center (NHC) issued the final advisory on Rene, citing that the storm had dissipated. The remnants of Rene were located near latitude 26.9 degrees north and longitude 49.3 degrees west. Rene was located about 1,045 miles (1,685 km) northeast of the Leeward Islands. The remnants were moving toward the west-southwest near 7 mph (11 kph) and this general motion will likely continue for another day or two. Maximum sustained winds were near 30 mph (45 kph) with higher gusts.

The remnants of Rene are expected to move generally southwestward for the next day or two while the associated winds slowly subside.

About NASA's Worldview and Aqua Satellite

NASA's Earth Observing System Data and Information System (EOSDIS) Worldview application provides the capability to interactively browse over 700 global, full-resolution satellite imagery layers and then download the underlying data. Many of the available imagery layers are updated within three hours of observation, essentially showing the entire Earth as it looks "right now."

NASA's Aqua satellite is one in a fleet of NASA satellites that provide data for hurricane research.

Tropical cyclones/hurricanes are the most powerful weather events on Earth. NASA's expertise in space and scientific exploration contributes to essential services provided to the American people by other federal agencies, such as hurricane weather forecasting.

For updated forecasts, visit: http://www.nhc.noaa.gov

By Rob Gutro
NASA's Goddard Space Flight Center

Published in the journal Diabetologia (the journal of the European Association for the Study of Diabetes [EASD]), the study shows that it is the absence of quality connections with people and not the lack of contact that predicts the onset of type 2 diabetes, suggesting that helping people form and experience positive relationships could be a useful tool in prevention strategies for type 2 diabetes.

The results have implications in light of recent findings that people with diabetes are at greater risk of dying from COVID-19. The study indicates that prolonged loneliness may influence the development of diabetes, suggesting the experience of lockdown could potentially compound people's vulnerability in this pandemic if the loneliness continues for some time.

Loneliness occurs when an individual perceives that their social needs are not being met and reflects an imbalance between desired and actual social relationships. A fifth of adults in the UK and a third of adults in the USA report feeling lonely sometimes.

There is a growing interest in the role of loneliness in health and previous research has associated loneliness with increased risk of death and heart disease. This is the first study to investigate the experience of loneliness with later onset of type 2 diabetes.

The study analysed data from the English Longitudinal Study Ageing on 4112 adults aged 50 years and over which was collected at several times from 2002 to 2017. At the start of data collection all participants were free of diabetes and had normal levels of blood glucose.

The study showed that over a period of 12 years 264 people developed type 2 diabetes. and the level of loneliness measured at the start of data collection was a significant predictor of the onset of type 2 diabetes later on in life. This relationship remained intact when accounting for smoking, alcohol, weight, level of blood glucose, high blood pressure and cardiovascular disease. The association was also independent of depression, living alone and social isolation.

Lead author Dr Ruth Hackett from the Institute of Psychiatry, Psychology & Neuroscience (IoPPN) King's College London said: 'The study shows a strong relationship between loneliness and the later onset of type 2 diabetes. What is particularly striking is that this relationship is robust even when factors that are important in diabetes development are taken into account such as smoking, alcohol intake and blood glucose as well as mental health factors such as depression. The study also demonstrates a clear distinction between loneliness and social isolation in that isolation or living alone does not predict type 2 diabetes whereas loneliness, which is defined by a person's quality of relationships, does.

She continued: 'I came up with the idea for the research during UK lockdown for the COVID-19 pandemic as I became increasingly aware and interested in how loneliness may affect our health, especially as it is likely that many more people were experiencing this difficult emotion during this period.'

According to the study a possible biological reason behind the association between loneliness and type 2 diabetes could be the impact of constant loneliness on the biological system responsible for stress, which, over time affects the body and increases the risk for diabetes.

'If the feeling of loneliness becomes chronic,' explained Dr Hackett. 'Then everyday you're stimulating the stress system and over time that leads to wear and tear on your body and those negative changes in stress-related biology may be linked to type 2 diabetes development.'

Another explanation for the findings could be biases in our thinking that may perpetuate the association between loneliness and diabetes as when people feel lonely, they expect people will react to them negatively which makes it more difficult to form good relationships.

New research provides a global analysis of the footprint of storm surges, providing a first step toward helping decision-makers coordinate flood management and emergency response plans across borders.

When Category 4 Hurricane Laura made landfall, the biggest cause of alarm was a projected "un-survivable" 20-foot storm surge. A storm surge is the sudden rise in sea level generated by a storm that can produce powerful currents, flood roads and destroy infrastructure.

Hurricane Laura's storm surge wound up being just half as high as feared, but storm-associated coastal flooding is expected to become more frequent with sea level rise. Better understanding storm surges and their spatial distribution can help coastal communities prepare for these dangerous flooding events.

New research in AGU's Journal of Geophysical Research: Oceans suggests the footprints of storm surges are more dependent on storm track direction than the intensity of the storm, and that both contiguous and unconnected stretches of coast can be simultaneously impacted by the same event. To reach their conclusion, the authors statistically analyzed both observed surge data from tide gauges and simulated storm surge data to understand how storm surges would simultaneously impact different coastline stretches around the world.

The authors provide a new framework to identify the patterns of coastal hazards. They demonstrate that simulated storm surge data can broadly reproduce the spatial footprints of storm surges obtained from observations, allowing them to analyze storm surge footprints in areas with limited tide gauge data and produce a global picture of storm surge footprints.

This information can be used to improve global coastal risk analysis, emergency plans and adaptation measures, according to the authors. They also conclude that their results, which show that storm surges can impact coastlines across state and national boundaries, highlight the importance of inter-state and international collaboration for disaster preparedness and response plans.

DETROIT - A recent study from the Henry Ford Sports Medicine Research team suggests that high school athletes competing, not only in football, but in soccer, hockey, basketball, swimming, cheerleading and other sports are not only at risk for concussions, but may need a longer recovery than first thought.

The study's results published by Orthopedics, a nationally recognized, peer-reviewed journal for orthopedic surgeons found that the most common sports for brain injuries were indeed football, hockey and soccer.

"We thought that concussion issues would be very short-lived," said Vasilios (Bill) Moutzouros, M.D., chief of Sports Medicine at Henry Ford and a study co-author, "That they wouldn't have as many attention issues, that they'd be able to recover for their sport much more quickly. Our study found just the opposite."

"The two sports, other than football, where concussions are common are soccer and hockey, although brain injuries can happen in any sport," said Meaghan Rourke, one of more than 30 Henry Ford athletic trainers who support sports programs at over 20 high schools, colleges and universities and professional teams in the tri-county area.

Michigan Gov. Gretchen Whitmer's latest executive order allows the high school football season to begin September 18. Football was reinstated by the Michigan High School Athletic Association (MHSAA) after initially being postponed until spring 2021. With football back in action with an adjusted six-game season, athletic trainers will once again be patrolling the sidelines and be on the lookout for signs of concussions. Other sports given the green light to compete this fall include soccer, volleyball, swimming and diving. These competitions will also present the potential for brain injuries from collisions, falls and impacts with the field of play.

"I went through a four-year period as an athletic trainer where I had at least one swimmer suffer a concussion. That's a sport you don't really think about in terms of concussions," said Rourke. She explained that in one instance a swimmer miscalculated her distance to the pool wall while doing the backstroke and bumped her head against the wall. As a result, the swimmer was out for more than a month with a concussion. Diving is another sport susceptible to brain injuries as the divers' heads impact the surface of the water at high speeds generated from their dives. In reality, all sports have the potential for concussions since athletics involve physical activity and competition.

"Competitive cheerleading is another sport where I've seen concussions happen. The kids get very high in the air, and if they slip and fall when they are coming down, they can suffer serious head injuries," said Rourke, "We usually have one or two athletes in that sport suffer concussions. Overall, I've probably had to deal with a concussion in every sport, including golf."

The retrospective study looked at Immediate Post-Concussion Assessment and Cognitive Testing (ImPACT) scores at baseline testing and following concussions performed by neuropsychologists. The study found that memory ImPACT scores increased as players suffered repeated concussions.

ImPACT is the brain injury testing protocol developed in the late 1990s at the University of Pittsburgh and released in the early 2000s. The testing protocol is the only FDA-approved tool for concussion assessment and is the national testing used by healthcare, educational and sports organizations to help assess and manage concussions. The protocol defines a concussion as "a disturbance in brain function that occurs following either a blow to the head or as a result of the violent shaking of the head." Symptoms of a concussion can include a combination of headaches, nausea, vomiting, balance problems, dizziness, fatigue, visual problems and a host of other brain-associated symptoms.

The study examined the records of 357 high school athletes who were treated for concussions at Henry Ford from 2013 to 2016. The athletes age averaged between 14-18 with nearly 62% being males. Football yielded the most concussions (27.7%), followed by hockey (21.8%), soccer (17%), basketball (9 %) and cheerleading (4.2%). From the study's participants, 72 played in "Other" sports and accounted for 20.3% of the total number of concussions. Overall, 14 % reported suffering from amnesia and 33 % reported a history of concussions.

Henry Ford athletic trainers use internationally approved guidelines to accurately diagnose concussions, appropriately manage the recovery process, and safely return athletes back to their game. They use sideline tools such as the Sports Concussion Assessment Tool 5 (SCAT5) to immediately evaluate cognitive function and, if needed, additional neuropsychological tests may be administered by a physician to track progression through the recovery process. SCAT5 is a standardized concussion assessment used by licensed healthcare providers when a concussion is suspected in athletes ages 12 and older.

Current MHSAA protocols call for a player showing concussion symptoms to be sidelined for at least 24 hours. Athletes at high schools staffed with a Henry Ford athletic trainer are sidelined for at least five days and follow a strict return to play protocol, "We're going to slowly bring them back," said Rourke. "We don't want to just throw them out there where they're going to get hit again, and then they're dealing with prolonged symptoms."

The Henry Ford research team found that athletes with only one concussion required at least 30 days of recovery prior to returning to their sport while others who reported a second or more concussions required more recovery time. They also learned that visual motor speed and reaction time scores decreased with recurrent concussions, and that male and female athletes with a previous history of concussion, and those with delayed diagnosis, required more time before returning to competition.

The study team hopes that the results help start the conversation on how to more safely return student athletes to their sport after a brain injury. "When you recognize that it can be up to 30 days to get a young student athlete back, you're going to change your mind-set on how you advance them, in terms of how you push them, in terms of how you test them," said Dr. Moutzouros.

Previously, it was believed that brain injuries were related to a player's age. The younger the player, the shorter the recovery time. "We need more studies on the younger athletes," said Dr. Moutzouros, "Many of us have children. We're all worried about them and we want them to be safe. So, we need to recognize that this is a problem for the youth athlete."

Rural Counties With Access to Obstetrics Have Healthier Infant Birth Outcomes

Rural areas with local access to obstetrical care report better infant health outcomes, including lower infant mortality rates and fewer babies delivered underweight. The retrospective cohort study compared the birth outcomes of rural counties in Alabama with in-county obstetrical care to those without over a 12-year span from 2003 to 2017. Across all four outcome measures--including infant, perinatal, and neonatal mortality rates as well as low birthrate deliveries--counties with access to obstetrical care had significantly better infant birth outcomes. The authors were not able to control for race or other social factors and report that areas with no obstetrical care access were also more likely to have a higher percentage of underrepresented minority residents. This study does not prove a causal link between access to obstetrical care and infant health outcomes, but it does suggest that obstetrical access may play a role in these disparities. These findings have broader implications for the more than half of all rural counties in the United States that do not have access to hospital-based obstetrical care.

Effect of Access to Obstetrical Care in Rural Alabama on Perinatal, Neonatal, and Infant Outcomes: 2003-2017
John B. Waits, MD, et al
Cahaba Medical Care, Centreville, Alabama
https://www.annfammed.org/content/18/5/446

Freezing of gait, one of the most incapacitating symptoms of Parkinson’s disease, manifests as sudden, short episodes of an inability to move the feet forward despite the intention to walk. Researchers at the University of São Paulo (USP) in Brazil have shown that the disorder can be mitigated by means of a complex physical exercise protocol designed to stimulate different motor and cognitive skills simultaneously. An article on the study is published in the journal Movement Disorders.

The study, supported by FAPESP, also showed that resistance training with instability modified brain regions associated with the physiological alterations typical of gait freezing, boosted neuron activation, and enhanced brain plasticity in the affected regions.

“In addition to positive reports from the patients who took the training, clinical trials also evidenced significant improvements, especially a 60% reduction in gait freezing and a 70% reduction in motor symptoms of the disease. Another important outcome concerned the restoration of brain regions directly linked to the problem. Brain plasticity in these areas is a predictor of gait freezing mitigation,” Carla da Silva Batista, a researcher in USP’s School of Physical Education and Sports and first author of the article, told Agência FAPESP.

Reactivation of brain regions was verified by functional magnetic resonance imaging (fMRI). The protocol is the first to reduce symptoms of gait freezing, clinically assessed in an objective manner, and to record the associated pathophysiologic alterations in the brain.

The study was part of Batista’s postdoctoral research, and some of it was conducted at Oregon Health and Science University (OHSU) in the United States with support from FAPESP via a scholarship for a research internship abroad.

According to Batista, activation of the cerebellar area, associated with gait automaticity, and the mesencephalic locomotor region, associated with gait initiation and postural control, explains the reversal of gait freezing after adapted resistance training.

Common cause of falls

There are no specific treatments for gait freezing, which is one of the most common causes of falls among Parkinson’s patients and, alongside tremor and cognitive impairment, responsible for loss of quality of life.

Gait freezing is estimated to affect some 26% of moderate patients and 80% of advanced-stage patients. It usually occurs while the patient is walking: feet appear to be “stuck” but the upper body continues to move, and fractures, as well as falls, may result, leading to premature hospitalization. It also occurs when the patient is rising from a seated position and stumbles. “We don’t know the exact cause but we know of several key predictors, such as heavy use of medications for Parkinson’s, progress of the disease, severe cognitive decline, stress, and anxiety,” Batista said, adding that patients may have all or several of the predictors without suffering from freezing of the gait.

Adapted resistance training with instability

The study conducted by the USP research group had 32 participants in stages 3 and 4 of the disease (deemed to have five stages). They were randomly divided into two groups. One comprised 15 patients and received conventional rehabilitation physical therapy, serving as a control group. The other, with 17 patients, took the complex training program designed by the researchers. The program consisted of 36 sessions spread over a 12-week period and involving exercises that combined instability, weight lifting, motor coordination, and cognitive demands.

“The exercises are intense and must be performed concurrently to cause complexity. This demands considerable effort from the patient and confidence on the part of the trainer, who will invariably have to give patients some support so they don’t fall,” Batista said.

Complexity is necessary to achieve the desired result. “Exercises involving motor complexity are known to be more effective when performed together. Studies in animal models confirm this, enhancing neuroplasticity by forming neurons and synapses in certain brain regions. This is exactly what we wanted to achieve,” she explained.

The degree to which the disorder was mitigated and brain plasticity enhanced was assessed using a fMRI analysis model developed previously by researchers affiliated with USP in partnership with colleagues in the UK and US, including one at OHSU, and published in Scientific Reports in 2017.

“Using this model they measured activity in the brain regions involved in freezing of gait before and after 12 weeks of training,” Batista said. “The methodology proved reversal of the disorder and enhanced plasticity in the brain regions concerned.”

In the study no improvement was observed in the control group. “It’s important to stress that the traditional exercises were unable to mitigate the severity of gait freezing or bring about positive alterations to brain regions,” Batista said.

Combined exercises

Although the causes of gait freezing are poorly understood, the researchers designed the training program to address the difficulties typically experienced by patients with the disorder, and hence to include sensorimotor, weightlifting, motor coordination and cognitive demand exercises simultaneously.

Most patients who suffer from gait freezing experience difficulties with proprioception (how the body senses its position in space), motor coordination, muscular strength, and cognitive function. “This is why we use exercises that involve strength and coordination while trying to maintain balance [on a half-ball or disk],” Batista said. “Cognitive impairment is also a predictor of gait freezing, so we include cognitive tasks and dual-task exercises that require simultaneous attention to two activities or mental flexibility to switch from one task to another as necessary.”

Strength training is also important for Parkinson’s patients, as muscle weakness is another symptom of the disease. “Weights are part of most exercises in our program, which isn’t easy. It demands quite a lot of the patient. Many volunteers in our study said they enjoyed the challenge and felt stronger as time passed, which motivated them to continue,” Batista said.