Culture

The aquatic larvae of the net-winged midge have the unique ability to move around at ease on rocks in torrential rivers using super-strong suction organs. Powerful modern imaging techniques have now revealed the structure of these organs in intricate detail, providing an insight into how they work so reliably. The findings, reported in the journal BMC Zoology, may inform the development of better man-made suction cups that perform well on a variety of surfaces.

The larvae have the ability to quickly detach and reattach to underwater rocks in torrential alpine rivers that can flow as fast as three metres per second. Their highly specialised suction organs are so strong that only forces over 600 times their body weight can detach them. Being in such fast flowing water puts them out of harm's way, since competitors or predators are unlikely to survive in this challenging environment.

"The force of the river water where the larvae live is absolutely enormous, and they use their suction organs to attach themselves with incredible strength. If they let go they're instantly swept away," said Victor Kang, a PhD student in the University of Cambridge's Department of Zoology and first author of the paper. "They aren't bothered at all by the extreme water speeds - we see them feeding and moving around in all directions."

The researchers found that a central piston, controlled by specific muscles, is used to create the suction and enable each larva to form a very tight seal with the surface of the rock. A dense array of tiny hairs come into contact with the rock surface, helping to keep the larva in place. When it needs to move, other muscles control a tiny slit on the suction disc, pulling the disc open to allow the suction organ to detach. This is the first time such an active detachment mechanism has been seen in any biological system.

The work focused on two species of the larvae - Liponeura cinerascens and Liponeura cordata - found in the fastest flowing parts of alpine rivers near Innsbruck, Austria. Despite only wading into the river up to their knees, the researchers found it difficult to stay upright. The larvae they found there were grazing on the underwater rocks, apparently oblivious to the torrents bearing down on them.

"These natural structures have been optimised through millions of years of evolution. We want to learn from them to create better engineered products," said Dr Walter Federle, an expert in Comparative Biomechanics at the University of Cambridge who led the study.

By collaborating with colleagues at the Institute of New Materials, Saarbrücken, Germany, the researchers are using their findings to develop 'bio-inspired' suction cups. Current artificial suction cups only work well on smooth, clean surfaces, like a car windscreen or inside a clean-room facility. The aquatic net-winged midge larvae live on rough, dirty surfaces yet can walk around with ease. Such highly reliable controlled attachment and detachment has many potential industrial applications.

"By understanding how the larvae's suction organs work, we now envisage a whole host of exciting uses for engineered suction cups," said Federle. "There could be medical applications, for example allowing surgeons to move around delicate tissues, or industrial applications like berry picking machines, where suction cups could pick the fruit without crushing them."

The aquatic larvae of net-winged midges have fascinated insect specialists for over a century. Their suction organs have the highest attachment strength ever recorded in insects. Using scanning electron microscopy, confocal laser scanning microscopy, and X-ray computed micro-tomography (micro-CT), this study has revealed the internal structure of the suction organs in three dimensions and provided new insights into their function.

The causes of rare diseases could be uncovered using an approach created to identify genetic mutations that trigger a muscle-wasting condition, a study suggests.

Researchers have devised a way to pinpoint defective genes that are linked to a rare form of muscular dystrophy, which causes muscle weakening and heart problems.

The approach could help doctors perform a faster and cheaper diagnosis of the condition - called Emery-Dreifuss muscular dystrophy, or EDMD.

It could also be adapted to screen for gene mutations involved in other rare diseases, researchers say.

Discovering the cause of rare conditions can be challenging. Robust genetic screening tests are difficult when only a relatively small number of people are affected.

Previous research has shown that mutations in six different genes cause EDMD, which affects around one in 100,000 people worldwide.

However, these mutations are found in less than half of people diagnosed with the disease, indicating that other genes can also trigger it, researchers say.

Researchers from the University of Edinburgh designed a new multi-stage sequencing approach to discover other genetic mutations that might lead to EDMD.

They initially identified more than 300 genes that could be involved, including ones linked to other forms of muscular dystrophy and those that perform a similar function to the genes known to cause EDMD.

By analysing these alongside the genetic code of 56 people from the UK and Germany diagnosed with EDMD, the team identified more than 20 new mutations that appear to cause the condition. These are likely most of the remaining genes linked to EDMD, researchers say.

The study, published in the journal EBioMedicine, was funded by Wellcome, Muscular Dystrophy UK, the Medical Research Council, and the European Union's Seventh Framework Programme.

Professor Eric Schirmer, of the University of Edinburgh's School of Biological Sciences, who led the study, said: "As well as helping to identify mutations in rare diseases, using our approach in initial NHS screening would also save money and help spot misdiagnoses. This is particularly important as it can take many years to get a clear diagnosis of EDMD."

Dr Kate Adcock, Director of Research and Innovation at Muscular Dystrophy UK, said: "We know that many people with neuromuscular conditions are living without a genetic diagnosis. This research could pave the way to help people to get a diagnosis earlier. This will help people to manage their condition thereby helping to provide a better quality of life."

Soil moisture is easy to see when your favorite Little Leaguer slides into second base the day after a big summer storm. The mud splattered on that little hustler's uniform tells the story.

Trying to gauge soil moisture across large areas -- regions, nations, continents -- is a whole 'nother challenge, and a critical one. Knowledge of this dimension of our ecosystem is extremely important for farmers, planners, scientists, insurance companies and anyone concerned about preparing for global environmental change.

"Understanding these patterns is critical to national and international security," said Rodrigo Vargas, associate professor of ecosystem ecology and environmental change in the Department of Plant and Soil Sciences at the University of Delaware. "We cannot measure everything everywhere all the time.... So we are using alternative approaches, such as machine learning that helps us get insight from complex sets of data."

Now Vargas and doctoral student Mario Guevara have developed a new approach that sharpens our ability to predict soil moisture, even in large areas where no data have been available. Compared to standard estimates produced by satellite-based sensors, the new approach increases the accuracy of these estimates by more than 20 percent. It also makes it possible to predict soil moisture conditions in much smaller areas and in greater detail than standard models have been able to show. They described their work in a recent issue of PLOS ONE, a peer-reviewed journal published by the Public Library of Science.

The best data on soil moisture now is collected using satellite-based sensors that deliver predictions in grids of about 27 kilometers per pixel. That's a space almost 17 miles square, about the distance from Main Street in Newark, Delaware, to historic New Castle on the Delaware River.

That's helpful for analyzing regional or global patterns, but such a large scale can provide only limited information on local conditions.

The method Guevara and Vargas have developed provides much higher definition, improving resolution from 27 kilometers to 1 kilometer per pixel -- or from about 17 miles to just over half a mile. That's roughly the distance from UD's Trabant Student Center on one end of East Main Street to the Newark Shopping Center on the other. Much tighter and much more useful for statewide applications.

The new approach combines data science and machine learning with the emerging science of geomorphometry -- quantitative analysis of land surface using topographic information, image analysis and spatial statistics.

Because soil moisture varies by location and changes over time, reliable measurement and predictive methods are essential. Topography -- defining the physical parameters of the Earth's surface -- is a critical factor for soil moisture estimates. Elevation, slope and other land-surface characteristics are strong predictors of how water -- from rain, irrigation and other sources -- will move, drain and affect an area.

"We need to understand water dynamics," Guevara said. "We understand a lot of components of the water cycle, but there is a lot we don't know. We want to protect water resources and know how they are distributed, their geography. Soil moisture is an important indicator of water resources."

Using satellite-based sensors, soil moisture can be measured to a depth of about 5 centimeters (just under 2 inches).

"Satellites cannot easily see soil moisture at deeper soil layers," Guevara said.

But that thin layer of soil holds crucial information.

"Superficial soil moisture is a key indicator of soil dryness. It influences soil productivity and ultimately soil health," Guevara said, "as the water in the first few centimeters of soil is some of the water used by crops or by the soil biodiversity (cycling nutrients) controlling the capacity of soil to produce food, fiber and store water."

In developing the new predictive model, Guevara used satellite data on soil moisture gathered for more than a decade (1991-2016) across the continental United States by the European Space Agency's Climate Change Initiative.

He and Vargas worked in collaboration with UD Information Technologies, used the muscle of UD's Farber high-performance computing cluster and drew upon the resources of the new Data Science Institute.

Guevara developed prediction factors using automated digital terrain analysis and defined 15 types of terrain parameters (such as slope and aspect, among others). He analyzed spatial structure and distribution of these parameters in relation to soil moisture and used an algorithm to select the best models.

The resulting predictions were validated by comparison to "ground truth," field data on soil moisture from the North American Soil Moisture Dataset. This dataset, developed by UD alum Steven Quiring, who was a doctoral student of UD Professor and State Climatologist Dan Leathers, draws strictly curated data from more than 2,000 meteorological stations across the continental United States.

The next chapter of the research is extending the work to the global scale, Vargas said. More discussion on that is available in the journal Earth System Science Data.

Many microbes wear beautifully patterned crystalline shells, which protect them from a harsh world and can even help them reel in food. Studies at the Department of Energy's SLAC National Accelerator Laboratory and Stanford University have revealed this food-reeling process and shown how shells assemble themselves from protein building blocks.

Now the same team has zoomed in on the very first step in microbial shell-building: nucleation, where squiggly proteins crystallize into sturdy building blocks, much like rock candy crystallizes around a string dipped into sugar syrup.

The results, published today in the Proceedings of the National Academy of Sciences, could shed light on how the shells help microbes interact with other organisms and with their environments, and also help scientists design self-assembling nanostructures for various tasks.

Jonathan Herrmann, a graduate student in Professor Soichi Wakatsuki's group at SLAC and Stanford, collaborated with the structural molecular biology team at SLAC's Stanford Synchrotron Radiation Lightsource (SSRL) on the study. They scattered a powerful beam of X-rays off protein molecules that were floating in a solution to see how the atomic structures of the molecules changed as they nucleated into crystals. Meanwhile, other researchers made a series of cryogenic electron microscope (cryo-EM) images at various points in the nucleation process to show what happened over time.

They found out that crystal formation takes place in two steps: One end of the protein molecule nucleates into crystal while the other end, called the N-terminus, continues to wiggle around. Then the N-terminus joins in, and the crystallization is complete. Far from being a laggard, the N-terminus actually speeds up the initial nucleation step ­- although exactly how it does this is still unknown, the researchers said - and this helps explain why microbial shells can form so quickly and efficiently.

A newly discovered retinal structure in the eyes of certain kinds of songbirds might help the animals find and track insect prey more easily.

The foundation of avian vision rests on cells called cone and rod photoreceptors. Most birds have four cone photoreceptors for color vision, a fifth cone for non-color-related tasks, and a rod for night vision. Each cone photoreceptor cell contains a spherical structure called an "oil droplet," which filters light before it is converted to electrical signals by the visual pigments, enhancing color discrimination.

However, the researchers have discovered a never-before-seen type of cone structure in the retina of a group of small songbirds, called flycatchers. Instead of an oil droplet, it contains a high- energy-producing cellular structure called "megamitochondria" surrounded by hundreds of small, orange-colored droplets. The researchers named this novel cellular structure a megamitochondria-small oil droplet complex, or MMOD-complex.

The discovery, made at Purdue University, is detailed in a paper that appeared in the journal Scientific Reports, as part of a collaboration with the State University of New York at Plattsburgh, the University of Wisconsin-Madison, and the University of California, Davis.

The researchers studied this retinal structure using light microscopy, transmission electron microscopy and a technique called microspectrophotometry, which measures the wavelengths of light that these structures absorb the most. The MMOD-complex works as long-pass filters, letting light with wavelengths longer the 565 nanometers - or yellow, orange and red - pass through, and absorbing the shorter wavelengths of green, blue and violet.

Traditional cones were present throughout the retina of these flycatchers, and their density decreased moving away from the center toward the periphery. However, the MMOD-complex photoreceptors were present only in the central region of the retina, an arrangement that could help birds detect flying insects, said Esteban Fernandez-Juricic, a professor of biological sciences at Purdue.

"The retina of flycatchers, which are sit-and-wait predatory birds, evolved a novel cellular structure in a photoreceptor that may allow them to detect, track and capture fast-moving prey, like insects," he said.

The paper's lead author was Luke Tyrrell, a former Purdue doctoral student and now an assistant professor of biological science at SUNY Plattsburgh.

"This new cone organelle has not been reported before in this form in any other vertebrate retina and may allow these birds to see their world in a different way from other animals," Tyrrell said.

A complete listing of the paper's authors is available in the abstract, and the paper is available online here. The research was funded by the National Science Foundation. Future research will be aimed at establishing the function of this structure and assess the ability of flycatchers to catch prey under different ambient light conditions.

ITHACA, N.Y. - In blind tests conducted by Cornell University researchers, consumers rated a California broccoli tastier and better-looking than a pair of varieties grown in New York.

But the New York broccoli fared much better in a subsequent series of tests. It earned the highest marks for flavor and consumers were willing to pay more for it - on par with the California variety.

What changed?

The second group was told the New York broccoli was "locally grown" in New York state, where the tests were conducted. That information improved consumers' perceptions of the broccoli and its value compared with the California alternative.

"If you don't tell the consumers anything, they will penalize the looks and they will even penalize the taste," said Miguel Gómez, associate professor at the Charles H. Dyson School of Applied Economics and Management in the Cornell SC Johnson College of Business. "But as soon as you tell them it's local, it's the other way around. They like it better - not only how it looks, but also how it tastes."

The findings have implications for the marketing of an emerging East Coast broccoli industry, and potentially for other seasonal vegetables regarded as household staples, including carrots, celery, endive and lettuce.

Buyers for grocery stores and restaurants have been reluctant to stock broccoli that looks even slightly different from what consumers are used to, most of which is grown in California. But the study suggests consumers value veggies marketed as local even if they don't look more appealing than non-local options, and even for products where local varieties aren't already expected to be superior, as with tomatoes, the researchers said.

The experiments asked ordinary consumers in upstate New York to inspect and sample three varieties of parboiled broccoli side by side, then submit bids by computer for how much they would pay per pound of each.

When consumers didn't know where the broccoli came from, they bid significantly more for the California product. Their average bid of $1.62 per pound was 18 cents more than the first New York variety and 10 cents more than the second.

But the results were "substantially different" when the broccolis were labeled as grown in New York or California. Bids for both New York broccolis climbed to about $1.70 - slightly more than their California counterpart.

For the food retail and service industries, Gómez said, the results highlight the importance of communicating to consumers that a product is locally grown.

"Not only are they willing to pay more," he said, "but the product tastes better and they look at it in a different way."

Cold Spring Harbor Laboratory (CSHL) scientists are figuring out how to pack more kernels onto a corn cob. One way to boost the productivity of a plant, they say, is to redirect some of its resources away from maintaining an overprepared immune system and into enhanced seed production. Now, a team led by CSHL Professor David Jackson has found a gene that could help them tweak that balance.

To flourish in the wild, plants must be constantly on guard. With an unpredictable array of bacteria, fungi, and viruses lurking in the soil and air, a plant must maintain a robust immune system that is ready to counter any attack. This vigilance comes at a cost: Energy spent on pathogen defense cannot be used to grow taller or produce seeds. But the trade-off is crucial.

For crop plants, however, the situation is different. Corn growing in a farmer's carefully tended field faces fewer threats than the same plant might encounter on an untamed prairie. In this controlled environment, plants could probably ease up on their anti-pathogen protections--but getting them to do so will require some genetic tinkering.

"If we can convince the plants that they don't have to spend a lot of energy on defense, they can put more energy into making seeds," Jackson says.

In work reported in the Proceedings of the National Academy of Sciences, Jackson and his team have identified a gene in corn that contributes to both the plant's development and to the control of its immune system. Manipulating this gene, they say, could be a way to increase crop yields by reprogramming how a plant balances its investments in growth and defense.

Corn plants cannot survive without the gene, which is called Gß (pronounced GEE beta) and encodes part of an essential signaling complex. Seedlings engineered to lack Gß quickly turn brown and die, which postdoctoral fellows Qingyu Wu and Fang Xu determined was because the plant needs the gene to keep its immune system in check. Without it, an overactive immune system attacks the plant's own cells.

By experimenting with dozens of genetically diverse lines of corn, Wu and Xu found that within the right genetic context, plants can grow without Gß. By studying these plants, they discovered that Gß also impacts the size of a plant's meristems, reservoirs of stem cells from which new growth originates. What's more, the team linked naturally occurring variations in the Gß gene to the production of corn ears with unusually abundant kernels.

Jackson says his team's findings indicate not only that Gß is involved in both growth and immunity, but that it likely mediates crosstalk between the cellular pathways that control these competing functions. The researchers are already digging deeper into those interactions, with the hope that they will be key to developing higher-yield crops.

CHICAGO (December 16, 2019): When an error or complication happens during an operation, the surgeon performing the procedure can become a "second victim" due to the psychological and emotional trauma experienced after a major adverse event. While many medical centers offer support to surgeons who may be experiencing self-doubt, guilt, and anxiety after such an event, a new program at Massachusetts General Hospital (MGH), Boston, goes a step further by providing opportunities for surgeons to offer and receive support from fellow surgeons who directly understand their experience. Researchers from MGH report on the success of the program in an "article in press" published on the website of the Journal of the American College of Surgeons ahead of print.

A formal surgery-specific peer support program was developed at MGH with the goal of helping surgeons and surgical trainees deal with not only adverse events that happen during an operation, but also catastrophic patient outcomes and long-term litigation cases. The idea for the program stemmed from results of the Boston Intraoperative Adverse Events Surgeons' Attitudes (BISA) study,* which revealed, confidentially and anonymously, how surgeons felt after an injury happened to a patient during an operation.

"This is an issue that has been swept under the carpet for too many years in the surgical world under the pretext that surgeons can deal with anything," said Haytham Kaafarani, MD, MPH, FACS, a study coauthor and Director of the Center for Outcomes and Patient Safety in Surgery (COMPASS), MGH. "A lot of times surgeons suffer alone. We have a perception that surgeons can deal with anything, that we're made of steel. We continue on without taking time to reflect on our own emotions."

The researchers selected and trained peer supporters who were well respected and trusted by their peers. The training included a four-hour session during which time the peer supporters reviewed literature on physician health and the second victim phenomenon, participated in interactive role-playing exercises, and learned about resources available to second victims.

After identifying a major adverse event and the members of the surgical team who might benefit from the peer support program, peer supporters would reach out to an affected peer and follow a four-step strategy:

1. Introduce the peer support process, emphasizing the confidentiality of the conversation and stressing that he or she does not know the details of the adverse event and that his or her role is to listen and help, not to investigate.

2. Listen in a non-judgmental fashion, acknowledging the second victim's difficult experience rather than trying to resolve any issues. Efforts to trivialize an event or feeling are avoided. Peer supporters are encouraged to offer empathy and to share personal experiences when appropriate.

3. Review common symptoms and feelings clinicians experience after an adverse event and ask if the affected peer is experiencing any of these emotions.

4. Create a plan with the affected peer by reinforcing useful coping strategies and inquiring about existing support systems. The potential need for continued support is discussed.

Efforts were made to match a surgeon with a peer supporter based on availability, absence of hierarchy, gender, and personal/cultural background, when feasible.

"When I sit with a fellow surgeon who is telling me how they felt when they were operating and injured a major structure in a patient, I can tell him or her, with credibility, that I know how it feels," Dr. Kaafarani said. "That simple identification of, 'I know how it feels,' and 'I'm willing to listen to you,' is very powerful."

Throughout the first year of the program, 47 outreach interventions occurred. In a survey administered to evaluate the program, most participants expressed satisfaction and 81 percent suggested the program had a positive impact on the department's safety and support culture by raising awareness of the need to support colleagues going through difficult patient situations.

The researchers identified areas for improvement, including enhancing the process for identifying events requiring outreach, increasing departmental awareness of the program, and providing opportunities for affected individuals to reach out to the program even when an adverse event was not identified.

Dr. Kaafarani believes this program can be implemented in medical centers of any size. The most important aspect for the program to work, he said, is for surgeons to believe in the program and be committed to participating.

"A second victim peer support program for surgeons is a good investment in any hospital," Dr. Kaafarani said. "If we take care of each other as surgeons, I believe that improves our overall well-being and decreases burnout over the long term, which in turn brings better quality of care to our patients."

Surgeon well-being is also an area of focus for the American College of Surgeons (ACS). The ACS Board of Governors Physician Competency and Health Workgroup has developed a repository of online resources for members along with resources included in the Physician Well-Being Index tool. This private validated tool for surgeons at all phases of their careers provides an opportunity for surgeons and trainees to better understand their overall well-being and identify areas of risk compared with physicians and residents across the nation.

Contrary to common belief, blue light may not be as disruptive to our sleep patterns as originally thought - according to University of Manchester scientists.

According to the team, using dim, cooler, lights in the evening and bright warmer lights in the day may be more beneficial to our health.

Twilight is both dimmer and bluer than daylight, they say, and the body clock uses both of those features to determine the appropriate times to be asleep and awake.

Current technologies designed to limit our evening exposure to blue light, for example by changing the screen colour on mobile devices, may therefore send us mixed messages, they argue.

This is because the small changes in brightness they produce are accompanied by colours that more resemble day.

The research, which was carried out on mice, used specially designed lighting that allowed the team to adjust colour without changing brightness.

That showed blue colours produced weaker effects on the mouse body clock than equally bright yellow colours.

The findings, say the team, have important implications for the design of lighting and visual displays intended to ensure healthy patterns of sleep and alertness.

The study is published in Current Biology and funded by the Biotechnology and Biological Sciences Research Council.

The body clock uses a specialised light sensitive protein in the eye to measure brightness, called melanopsin, which is better at detecting shorter wavelength photons.

This is why, say the team, researchers originally suggested blue light might have a stronger effect.

However, our perception of colour comes from the retinal cone cells and the new research shows that the blue colour signals they supply reduce the impact on light on the clock.

Dr Tim Brown, from The University of Manchester, said: "We show the common view that blue light has the strongest effect on the clock is misguided; in fact, the blue colours that are associated with twilight have a weaker effect than white or yellow light of equivalent brightness.

"There is lots of interest in altering the impact of light on the clock by adjusting the brightness signals detected by melanopsin but current approaches usually do this by changing the ratio of short and long wavelength light; this provides a small difference in brightness at the expense of perceptible changes in colour."

He added: "We argue that this is not the best approach, since the changes in colour may oppose any benefits obtained from reducing the brightness signals detected by melanopsin.

"Our findings suggest that using dim, cooler, lights in the evening and bright warmer lights in the day may be more beneficial.

"Research has already provided evidence that aligning our body clocks with our social and work schedules can be good for our health. Using colour appropriately could be a way to help us better achieve that."

A team of researchers at CHU Sainte-Justine and Université de Montréal has discovered a new mechanism involved in a common congenital disease of the aortic valve. The findings of the study, conducted in collaboration with the Hadassa Hebrew University Medical Center, were published in the prestigious journal Nature Genetics.

Valve disease affects two percent of the population, which is a significant proportion. Despite this high incidence and many signs that point to the role played by genetics in aortic diseases, only a few genes have been identified to date. In this case, a gene known as ADAMTS19 was shown to be involved in an aortic valve disease.

"Valve diseases can affect one of the heart's four valves - the tricuspid, pulmonary, mitral or aortic valve. We looked at patients with a bicuspid aortic valve, which is an aortic valve that has only two functional leaflets instead of the usual three," explained Dr. Gregor Andelfinger, a pediatric cardiologist and researcher at CHU Sainte-Justine and at Universite de Montreal. Most patients affected by this valve disease are asymptomatic in early life. But in adulthood, this bicuspid valve can leak or cause premature aortic narrowing, resulting in shortness of breath or abnormal fatigue on exertion.

This discovery was made in the course of following a family at CHU Sainte-Justine; two of the three siblings in this family have this congenital variation, which helped to identify the culprit ADAMTS19 gene. Up to now, this gene had virtually never been characterized by a medical team, not to mention associated with this disease.

"To understand the role of this gene, we had to use a preclinical model that presented the same pathological features as our young patients. This helped us to analyze the function of this gene in great detail and to define the mechanisms of the disease," explained Florian Wünnemann, PhD and the lead author of the study.

"By using single cell sequencing, a new technology that establishes the genetic profile of a single cell - in heart tissue, for example - we can very precisely define the type of cell behind the pathology. This really helped us demonstrate the molecular consequences of the mutation," he added.

Indeed, the data shows that the mutation in patients changes the regulatory mechanism in the valves. One thing leading to another, an Israeli team of researchers at the Hadassa Hebrew University Medical Center that had identified exactly the same gene contacted Dr. Andelfinger and his team, lending support to their hypothesis.

An estimated 4,000 valve surgeries are performed in Canada each year, and this figure is constantly rising due to ageing of the population. On top of the pain and suffering of patients and their families, the economic burden is close to $1 billion a year.

CHU Sainte-Justine is a leading provincial centre of expertise in rare genetic diseases in terms of the quality and number of its research projects, its clinical management and knowledge transfer. The discovery of the genetic causes of some 40 rare diseases by the teams at CHU Sainte-Justine in recent years is a shining example of this expertise.

Antibiotic-resistant bacteria are increasingly the source of deadly infections. A team of scientists from the Technical University of Munich (TUM) and the Helmholtz Center for Infection Research (HZI) in Braunschweig have now modified an approved cancer drug to develop an active agent against multidrug-resistant pathogens.

The methicillin-resistant Staphylococcus aureus (MRSA) is the source of severe and persistent infections. Some strains are even resistant to multiple antibiotics. There is consequently an urgent need for new drugs effective against MRSA infections.

"The industrial development of new antibiotics is stalling and not keeping pace with the spread of antibiotic resistance. We urgently need innovative approaches to meet the need for new infection therapies that do not lead directly to renewed resistance," says Prof. Eva Medina, director of the HZI Infection Immunology Research Group.

New antibiotic development strategies

One promising strategy is to test the potential effect of approved drugs on bacteria. "Our focus was on a class of human proteins, called kinases, which have many inhibitors to begin with," explains study leader Stephan Sieber, professor of organic chemistry at TUM.

In this vein, the researchers chemically modified the active ingredient sorafenib, a cancer drug that is effective against MRSA, to achieve a stronger antibiotic effect. This led to the development of PK150, a molecule ten times more effective against MRSA than the original substance.

Multiple attacks prevent the development of resistance

The potent new agent targets various unconventional structures within the bacteria. Two targets were investigated in greater detail: For one, PK150 inhibits an essential protein involved in bacterial energy metabolism. For another, it acts on the cell wall.

In contrast to previously known antibiotics such as penicillin and methicillin, which interfere with cell wall formation, PK150 acts indirectly. It knocks the protein production in bacteria off kilter. As a result, the bacteria release more proteins that control the cell wall thickness to the outside, causing the cells to burst.

In mice, PK150 has proven to be effective against MRSA in a variety of tissues. While staphylococci rapidly develop resistance to other antibiotics, the researchers did not observe the development of any resistance to PK150.

Effectiveness against biofilms and persisters

Eva Medina and Dr. Katharina Rox, a pharmacologist from the Department of Chemical Biology at HZI, showed that PK150 has favorable pharmacological properties. It can be administered as a tablet, for example, and remains stable in the body for several hours. "As a result of the chemical changes to the molecule, PK150 no longer binds to human kinases, but acts very specifically against bacterial targets," says Sieber.

And PK 150 has another benefit: "MRSA infections are very often chronic, as the bacteria can become dormant. PK150 even kills these, as well as germs protected in biofilms," says Prof. Dietmar Pieper, head of the HZI research group "Microbial Interactions and Processes".

In the context of the aBACTER project, Prof. Sieber's team is now further optimizing PK150 to enter the clinical development phase.

In the last century, French sociologist Maurice Halbwachs declared that personal memories are influenced by their social contexts. From this perspective, the memory function of individuals cannot be understood without taking into account the group to which they belong and the social contexts related to collective memory.

Until now, these theories had never been tested by neuroscientists. Inserm researchers Pierre Gagnepain and Francis Eustache (Inserm/Université de Caen-Normandie/Ecole Pratique des Hautes Etudes/Caen University Hospital/Cyceron Public Interest Group), in association with their colleagues from the Matrice project (involving several French teams), led by historian CNRS Denis Peschanski, decided to take a closer look, using brain imaging techniques. For the first time, they have shown in the brain the link between collective memory and personal memories. Their innovative research has been published in Nature Human Behaviour.

Collective memory is comprised of symbols, accounts, narratives and images that help to construct a community identity. To investigate this concept further, the researchers began by analyzing the media coverage of WWII in order to identify the shared collective representations associated with it. They studied the content of 30 years of WWII reports and documentaries, broadcast on French television between 1980 and 2010, and transcribed.

Using an algorithm, they analyzed this unprecedented corpus and identified groups of words regularly used when discussing major themes associated with our collective memory of WWII, such as the D-Day Landings. "Our algorithm automatically identified the central themes and the words repeatedly associated with them, thereby revealing our collective representations of this crucial period in our history", states Gagnepain.

Visiting the Caen Memorial Museum

But what is the link between these collective representations of the war and individual memory? To answer that question, the researchers recruited 24 volunteers to visit the Caen Memorial Museum and asked them to view photos from that period, which were accompanied by captions.

Based on the words contained in the captions, the team was able to define the degree of association between the photos and the various themes identified previously.

If words which had previously been associated with the theme of the D-Day Landings were found in the caption, for example, the photo was then considered to be linked to this theme as well. In this way, the researchers were able to establish proximity between each of the images: when two photos were linked to the same themes, they were considered to be "close" in collective memory.

Gagnepain and his colleagues then turned their attention to the perception of these photos in the memory of the individuals. They tried to find out whether the same degree of proximity between the photos was perceived in individual memories. The volunteers underwent an MRI examination during which they were asked to recall the images seen at the Memorial Museum the day before. The researchers were especially interested in the activity of their median prefrontal cortex, a brain region linked to social cognition.

The researchers thus compared the level of proximity between the photos by looking at the collective representations of WWII in the media and, via brain imaging, by looking at the individual memories that people had of these images following a visit to the Memorial Museum. The team showed that when photo A was considered close to photo B - because it was linked in the same way to the same collective theme - it also had a higher probability of triggering brain activity similar to photo B in the brains of the subjects.

This novel approach enabled indirect comparison between collective memory and individual memory. "Our data demonstrate that collective memory, which exists beyond the individual level, organizes and shapes personal memory. It constitutes a shared mental model making it possible to link the memories of individuals across time and space", emphasizes Gagnepain.

Other research is ongoing in order to deepen our understanding of the interaction between collective and individual memory. Nevertheless, one lesson can already be learned from this study: the functioning of our memories cannot be researched without taking into account the social and cultural context within which we evolve as individuals.

Researchers at Karolinska Institutet and from the Netherlands have developed a simple tool that shows the survival probability of a person with dementia disease over three years. This, they hope, will facilitate dialogue with the most seriously affected and help doctors and others plan the necessary care. The study is published today in the scientific journal Neurology.

Dementia diseases are currently incurable. There are, however, many kinds of dementia, which develop differently from person to person. Some people can live for many years with their disease, while others have a disease that progresses more aggressively. This means that doctors need a simple tool to indicate the severity of the disease at the point of diagnosis. This can help in planning care and help these patients understand how their disease is likely to develop.

For their study, the researchers monitored patients over the age of 65 who were diagnosed with dementia and registered in the Swedish Dementia Registry between 2007 and 2015. The study included over 50,000 individuals, who were monitored via various health-data registries up to 2016, by which time 20,000 of them had died, on average after a median time of 4.8 years after diagnosis. The researchers examined the effect on post-diagnosis life-expectancy of a number of easily identifiable factors, producing two clear, schematic tables.

The first one is for primary care physicians that produces a prognosis based on sex, age, cognitive ability (measured using the MMSE, Mini-Mental State Examination) and comorbidity (measured using the Charlson Comorbidity Index).

The second table is for specialist clinics, such as memory clinics, that also factors in the specific subtype of dementia (Alzheimer's disease, for instance, is often less aggressive). Equipped with these parameters, doctors can place an individual case in the schematic table to show how likely it is that the patient will die within three years of diagnosis.

The tool is intended for use by people who care for or treat dementia patients in primary care or at specialist clinics. One aim is to give doctors and care providers a better understanding of which patients are in urgent need of a care plan and who may benefit from additional monitoring. Another goal is to help doctors and other care providers to engage in a dialogue with their patients about their disease and the risk of death.

The study's corresponding author Sara Garcia-Ptacek, a neurologist at Stockholm South General Hospital, says that many patients ask about how their disease will progress, and that a tool like this can be useful to help answer those questions.

"It can also be used in conversations about future care with patients who don’t raise the issue themselves,” says Garcia-Ptacek, who is also a researcher at the Department of Neurobiology, Care Sciences and Society (NVS) at Karolinska Institutet. “In those cases, a tool like this can be an incentive to start such a conversation, which should be held before there are too many cognitive obstacles. This conversation could be about where someone would prefer to live, at home or in other accommodation, or anything else that needs planning."

ESO's Very Large Telescope (VLT) has observed the central part of the Milky Way with spectacular resolution and uncovered new details about the history of star birth in our galaxy. Thanks to the new observations, astronomers have found evidence for a dramatic event in the life of the Milky Way: a burst of star formation so intense that it resulted in over a hundred thousand supernova explosions.

"Our unprecedented survey of a large part of the Galactic centre has given us detailed insights into the formation process of stars in this region of the Milky Way," says Rainer Schödel from the Institute of Astrophysics of Andalusia in Granada, Spain, who led the observations. "Contrary to what had been accepted up to now, we found that the formation of stars has not been continuous," adds Francisco Nogueras-Lara, who led two new studies of the Milky Way central region while at the same institute in Granada.

In the study, published today in Nature Astronomy, the team found that about 80% of the stars in the Milky Way central region formed in the earliest years of our galaxy, between eight and 13.5 billion years ago. This initial period of star formation was followed by about six billion years during which very few stars were born. This was brought to an end by an intense burst of star formation around one billion years ago when, over a period of less than 100 million years, stars with a combined mass possibly as high as a few tens of million Suns formed in this central region.

"The conditions in the studied region during this burst of activity must have resembled those in 'starburst' galaxies, which form stars at rates of more than 100 solar masses per year," says Nogueras-Lara, who is now based at the Max Planck Institute for Astronomy in Heidelberg, Germany. At present, the whole Milky Way is forming stars at a rate of about one or two solar masses per year.

"This burst of activity, which must have resulted in the explosion of more than a hundred thousand supernovae, was probably one of the most energetic events in the whole history of the Milky Way," he adds. During a starburst, many massive stars are created; since they have shorter lifespans than lower-mass stars, they reach the end of their lives much faster, dying in violent supernova explosions.

This research was possible thanks to observations of the Galactic central region done with ESO's HAWK-I instrument on the VLT in the Chilean Atacama Desert. This infrared-sensitive camera peered through the dust to give us a remarkably detailed image of the Milky Way's central region, published in October in Astronomy & Astrophysics by Nogueras-Lara and a team of astronomers from Spain, the US, Japan and Germany. The stunning image shows the galaxy's densest region of stars, gas and dust, which also hosts a supermassive black hole, with an angular resolution of 0.2 arcseconds. This means the level of detail picked up by HAWK-I is roughly equivalent to seeing a football (soccer ball) in Zurich from Munich, where ESO's headquarters are located.

This image is the first release of the GALACTICNUCLEUS survey. This programme relied on the large field of view and high angular resolution of HAWK-I on ESO's VLT to produce a beautifully sharp image of the central region of our galaxy. The survey studied over three million stars, covering an area corresponding to more than 60 000 square light-years at the distance of the Galactic centre (one light-year is about 9.5 trillion kilometres).