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850 million people worldwide are affected by chronic kidney disease (CKD) - a worrying figure, and one that continues to rise. Treatment options for patients with CKD are multiple and often determined by the aetiology of CKD. So far, RAAS blockade (ACE inhibitors or angiotensin receptor blockers) was one of the most effective therapeutic intervention which has been shown to affect CKD disease progression. Now, SGLT2 inhibitors add significantly to the armentarium and provided another breakthrough in the management of CKD.

The first to realize this potential of SGLT2 inhibitors was Professor Christoph Wanner, co-author of the EMPA-REG OUTCOME trial and President of the ERA-EDTA. Wanner and his colleagues conducted the EMPA-REG OUTCOME trial [4], the aim of which was to investigate whether the SGLT2 inhibitor Empagliflozin could lower the rate of cardiovascular events in patients with T2D. "It could, but the much more exciting result for me as a nephrologist was an incidental finding of the study, which we analysed and published in a second paper [5]. It seemed that the medication could also slow progression of CKD. At that moment the effect was 'too good to be true' Wanner remembers, but this effect was confirmed in subsequent cardiovascular outcome trials (CVOTs) with other SGLT2 inhibitors [6, 7]. However, the proportion of patients with CKD in these CVOTs, which were conducted among patients with T2D, was relatively low.

At that point, the kidney study program with Canagliflozin was already underway. It was not until 2019 that the CREDENCE trial provided evidence that the SGLT2 inhibitor Canagliflozin could slow CKD progression in patients with T2D and CKD with albuminuria who were already on standard RAAS blockade and baseline glucose lowering therapy [3].

An important link was still missing, however. In about one third of all CKD patients, diabetes is the cause of kidney failure, but what about the other two thirds? Can SGLT2 inhibitors really help these patients, too, and prevent them from reaching end stage kidney disease in need of regular dialysis treatments or renal transplantation?

A new study (DAPA-CKD) was initiated to answer these questions and the results were presented at the virtual ESC Congress. Cardiologists welcomed the prominent treatment originating its effects in the kidney and extending to the heart. The rationale and protocol of the study had been published in Nephrology Dialysis Transplantation, the premier kidney journal in Europe [8], earlier this year. The results were groundbreaking: 4304 patients (67.5% had diabetes) were randomized 1:1 to dapagliflozin or placebo. The primary outcome of worsening of kidney function was a composite of sustained ?50% eGFR decline, occurrence of end stage kidney disease, or renal or CV death. There were 197 events in the dapagliflozin group and 312 in the placebo group; the HR for the primary endpoint was 0.61 (95% CI, 0.51-0.72; P=0.000000028) resulting in a number needed to treat of 19. The benefit of dapagliflozin on the primary endpoint was consistent in patients with and without T2D. No concerning safety signals were observed.

A study on the SGLT2 inhibitor Empagliflozin in 3730 heart failure patients (EMPEROR-Reduced) with and without T2D was already published the day before, saturday morning 8:30 am Eastern US-Time in "The New England Journal of Medicine" [2]. Although kidney parameters were analyzed as secondary endpoints, the results point in the same direction: The annual rate of decline in the estimated glomerular filtration rate was significantly slower in the empagliflozin group than in the placebo group (-0.55 vs. -2.28 ml/min/1.73 m2 per year, P

"All in all, this is great news for patients with CKD. For years, no new treatment option has proved to be safe and effective, which meant that no new drug could be introduced into clinical practice. We now have a whole new substance class that is obviously very effective. It is quite amazing how often important medical innovations derive from incidental discoveries. We wanted to find a therapy to improve cardiovascular outcomes in individuals with type 2 diabetes and found a long-awaited treatment to slow progression of chronic kidney disease, even in those who do not suffer from type 2 diabetes. It's a bit 'Flemingesque', at the beginning we did not realize the significance of our findings, now we have a kidney drug in hands" Wanner concludes.

Pancreatic islet transplants, which revive insulin production to treat type 1 diabetes, only last an average of three years.

By learning from a groundbreaking cancer treatment strategy based on a recent Nobel Prize-winning discovery, researchers at the Georgia Institute of Technology and University of Missouri developed a new microgel drug delivery method that could extend the effectiveness of pancreatic islet transplantations -- from several years to possibly the entire lifespan of a recipient.

Working across multidisciplinary teams using an animal model, the labs of Professors Andrés García at Georgia Tech and Haval Shirwan at the University of Missouri have developed a new biomaterial microgel that could deliver safer, smaller, and more cost-effective dosages of an immune-suppressing protein that could lead to better long-term acceptance of islet transplantations within the body.

The study was published August 28, 2020, in the journal Science Advances. The research was led by Maria Coronel, a postdoctoral fellow in the lab of García, the Parker H. Petit Chair and executive director of the Petit Institute for Bioengineering and Bioscience. García is also a Regents Professor in the George W. Woodruff School of Mechanical Engineering.

In 2018, the Nobel Prize for medicine was awarded for discovering how cancer cells send molecular signals to suppress immune response, thus hiding and protecting those cancer cells from the body's immune system. Researchers soon developed pioneering treatment methods to signal and "turn on" the immune system (such as T cells) so the invading cancer would once again be recognized, allowing a patient's own immune system to more effectively eliminate their cancer cells.

"The work we are doing is taking a page from that discovery and using immunotherapy in the opposite sense used by cancer treatments to control and 'turn off' an immune response to transplant a graft," Coronel said. "When you get a transplant, like an islet transplant or organ transplant, even if it's matched, you will have an immune response to that graft, and your immune system will recognize it as non-self and will try to reject and attack the site of the graft."

After islet transplant surgery, traditional postoperative treatments use immune-suppressing systemic drugs that affect the entire body, and can be toxic -- creating numerous, unwelcome side effects, whose severity often limits the number of candidates for islet and other organ transplants.

"A unique aspect of our method is that we have greatly reduced the dosage needed, which will significantly reduce or eliminate side effects currently caused by today's systemic drug treatments," said Coronel.

The research team developed a new "immune-acceptance" method, which inserts an engineered biomaterial -- in this case a microgel -- with the islets at the time of the transplantation. The microgels, which resemble clusters of micro-sized fish eggs, held and delivered a protein (SA-PD-L1) to a specific transplant area that successfully signaled the immune system to hold back an immune response, protecting a transplanted islet graft from being rejected. This locally delivered molecular signal, using SA-PD-L1, was designed to quietly suppress any immune response and was effective for up to 100 days with no additional systemic immune-suppressing drug intervention.

"We wanted to use PD-L1 for the prevention of allogeneic islet graft rejection by simulating the way tumor cells use this molecule to evade the immune system, but without resorting to gene therapy," said Shirwan, professor of child health and molecular microbiology and immunology at the University of Missouri School of Medicine.

To achieve this goal, Shirwan worked with Esma Yolcu, professor of child health, also at the University of Missouri School of Medicine. Both were previously at the University of Louisville, where they generated the SA-PD-L1, a novel form of the molecule that can be positionally displayed on the surface of islet grafts or microgels for delivery to the graft site.

"Microgels presenting SA-PD-L1 represent an important technological development that has potential not only for the treatment of type 1 diabetes, but also other autoimmune diseases and various transplant types," Shirwan said.

In addition to engineering this specific biomaterial microgel, the team tested its lifespan durability and dosage release possibilities. They also looked at its longer-term effects on both the graft and the immune response and function of the recipient -- evaluating its long-term biocompatibility potential.

"One of the major goals in the diabetes field over the past two decades has been to allow the immune-acceptance of grafts and avoid the toxic drugs used to induce immune suppression, which affect the entire body," García said.

"Generally speaking, organ transplantation is very successful at dealing with a variety of chronic conditions. These are very exciting results as proof of principle that demonstrate this engineered biomaterial and procedure may provide a platform technology that is applicable to other transplantation settings and may enlarge the pool of candidates who can safely receive transplants."

This is the result of the current risk assessment by the German Federal Institute for Risk Assessment (BfR). BfR President Professor Dr. Dr. Andreas Hensel: "Significantly less aluminium is absorbed through skin than previously calculated on the basis of the limited data available at the time." BfR assessed absorption via the skin, i.e. dermal absorption, of aluminium salts for the first time in 2014. "At that time, we pointed out the substantial scientific uncertainty surrounding the data and drew attention to the urgent need for research," continued Hensel. In the meantime, two human studies addressing those data gaps were conducted in 2016 and 2019. Only the latter was able to produce findings to support reassessment. Therefore, reliable data became only available five years after the BfR's request for a scientifically reliable skin absorption study. Hensel: "In this case, our current risk assessment also shows just how dynamic the scientific process can be on certain issues, and that it remains a matter of continuously reducing existing uncertainties by closing data gaps."

To the BfR-Opinion:

https://www.bfr.bund.de/cm/349/new-studies-on-antiperspirants-containing-aluminium-impairments-to-health-unlikely-as-a-result-of-aluminium-uptake-via-the-skin.pdf

Aluminium salts are being used in antiperspirants to block sweating and inhibit malodour. Just how much of the aluminium from antiperspirants is being absorbed through the skin has long been uncertain. There are currently three human studies from 2001, 2016 and 2019 on aluminium absorption via the skin (dermal absorption or bioavailability) from antiperspirants. All three studies are based on measuring the aluminium concentration in blood and/or urine. The scientific conclusion and scientific relevance of the three studies differ considerably.

Only the study from 2019 provides reliable data on which to conclude on the absorption rate/ bioavailability. The BfR used this data as the basis for its risk assessment and from this derived the absorption via the skin in a model calculation. The result was that a significant contribution by antiperspirants to the total aluminium exposure is unlikely based on current data.

Those who wish to protect themselves from excessive aluminium absorption, should make sure that acidic and salty foods and beverages do not come into contact with aluminium, e.g. via bottles, baking trays, grill pans.

According to current scientific knowledge, excessive aluminium levels in the body can have negative effects on the nervous system, the kidneys and bone.

Typhoon Maysak continued to move through the Northwestern Pacific and was closing in on Japan's Okinawa Island when NASA's Terra satellite obtained a visible image of the storm. Maysak's eye is not expected to go over the island, but pass just west of it.

The Moderate Resolution Imaging Spectroradiometer or MODIS instrument that flies aboard NASA's Terra satellite captured a visible image of Typhoon Maysak. Imagery showed the eye of the storm appeared filled with high clouds, as powerful bands of thunderstorm circled it. Bands of thunderstorms from the south were spiraling into the low-level center.

On Aug. 31 at 5 a.m. EDT (0900 UTC), Typhoon Maysak was located about 144 nautical miles south of Kadena Air Base, Okinawa Island, Japan. It was moving to the north-northwest and had maximum sustained winds near 100 knots (115 mph/185 kph).

Maysak's center is expected to pass just west of Okinawa within 24 hours. The storm is expected to make landfall in southern South Korea and will start to become extra-tropical.

About NASA's Worldview and Terra 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 Terra 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.

By Rob Gutro
NASA's Goddard Space Flight Center

CLEMSON, South Carolina - Electrifying research by Clemson University scientists could lead to the creation of lighter, faster-charging batteries suitable for powering a spacesuit, or even a Mars rover.

The research, which was funded by NASA, was recently reported in an article titled "Three-Dimensional Si Anodes with Fast Diffusion, High Capacity, High Rate Capability, and Long Cycle Life" that appeared in the American Chemical Society journal Applied Materials and Interfaces. Its authors include Shailendra Chiluwal, Nawraj Sapkota, Apparao M. Rao and Ramakrishna Podila, all of whom are part of the Clemson Nanomaterials Institute (CNI).

Podila, an assistant professor in the College of Science's department of physics and astronomy, said the revolutionary new batteries could soon be used in U.S. satellites.

"Most satellites mainly get their power from the sun," Podila said. "But the satellites have to be able to store energy for when they are in the Earth's shadow. We have to make the batteries as light as possible, because the more the satellite weighs, the more its mission costs."

Podila said that to understand the group's breakthroughs, you could visualize the graphite anode in a lithium-ion battery as a deck of cards, wherein each card represents a layer of graphite that is used to store the charge until electricity is needed. The problem, Podila said, is that "graphite cannot store much charge."

The Clemson team opted to work with silicon, which can pack more charge, meaning more energy can be stored in lighter cells. While scientists have long valued the high capacity of silicon for electrical storage, this material breaks apart into smaller pieces as it charges and discharges. The solution the team came up with involves the use of tiny silicon "nanosized" particles, which increase stability and provide longer cycle life. Rather than a deck of cards made of graphite, the new batteries uses layers of a carbon nanotube material called Buckypaper, with the silicon nanoparticles sandwiched in between.

With that kind of internal packaging, even if the silicon particles break up, they are "still in the sandwich," Podila said.

"The freestanding sheets of carbon nanotubes keep the silicon nanoparticles electrically connected with each other," said Shailendra Chiluwal, a graduate student at CNI and the first author on the study. "These nanotubes form a quasi-three-dimensional structure, hold silicon nanoparticles together even after 500 cycles, and mitigate electrical resistance arising from the breaking of nanoparticles."

Using batteries made of silicon and other nanomaterials not only increases capacity, it also allows for charging batteries at a higher current, which translates to faster charging times. As anyone whose cellphone has ever died in the middle of a phone call knows, this is an important feature for battery technology.

The faster charging is possible because the new batteries also use nanotubes as a buffer mechanism that allows for charging at a rate four times faster than is currently possible.

Lighter batteries that charge faster and offer greatly increased efficiency will not only be a boon to astronauts wearing battery-powered suits, but also to the scientists and engineers who have to get the astronauts to their destinations.

"Silicon as the anode in a lithium-ion battery represents the 'holy grail' for researchers in this field," said Rao, CNI's director and the principal investigator on the NASA grant. Rao also said the new batteries will soon find their way into electric vehicles.

"Our next goal is to collaborate with industrial partners to translate this lab-based technology to the marketplace," said Podila, corresponding author of the study and a co-investigator on the NASA grant. "We are thankful to the NASA and South Carolina EPSCoR for granting an award to undertake such projects which will have lasting impact on space missions and the global energy landscape."

In a review of existing scientific studies on trendy ketogenic and intermittent fasting diets, researchers at National Jewish Health concluded that these diets do seem to help people lose weight in the short-term, and modest evidence suggests they may contribute to cardiovascular health. However, these diets also allow consumption of foods that are known to increase cardiovascular risk and are unlikely to be as effective at preventing heart disease as well-established nutritional guidelines currently recommended by health experts.

"With diets like keto and intermittent fasting, social and popular media has been flooded with claims, promises and warnings that are at best unverified and at worst harmful to your health," said Andrew Freeman, MD, director of cardiovascular prevention and wellness at National Jewish Health and co-author of the study. "Diets recommended by health experts, such as plant-based and Mediterranean diets, have been extensively studied for safety and efficacy, and demonstrated conclusively to improve cardiovascular health."

Keto is a very low carbohydrate dietary approach that sends the body into ketosis, a metabolic state in which it has reduced access to glucose and is instead mostly fueled by fat. While the limited study of the keto diet shows those who follow it initially lose weight, it tends not to be sustainable according to 12-month data. It is also unclear whether the weight loss is caused by ketosis or simply by calorie restriction.

Researchers also have concerns about the type and amount of fat consumed by those following a keto diet. While existing studies strictly controlled the type of fat and foods participants consumed, many who try keto consume high amounts of unhealthy saturated fat, which is associated with an increased risk of heart disease and high lipid levels in the blood. There is also evidence that eating a keto diet for an extended period of time may lead to stiffening of the arteries, and several studies found that those who eat a keto diet have a greater risk of death.

Keto does, however, show promise as a potential treatment for diabetes, with studies showing improved glucose levels as well as lower fasting glucose and insulin levels in mice fed a keto diet. Further research is needed to confirm these benefits and assess risk before keto is clinically recommended.

Researchers are also optimistic about potential health benefits of intermittent fasting, but are concerned about possible pitfalls. There are a wide range of practices being called "intermittent fasting", with some fasting without food an entire day and others restricting meals to certain hours of the day. Experts also worry that the hunger induced by fasting causes many people to overeat when it is time for meals, or make unhealthy choices that have adverse effects on their cardiovascular health.

A majority of the current evidence regarding the potential benefits of intermittent fasting come from animal studies, which have shown increased longevity, weight loss, decreased blood pressure, improved glucose tolerance and controlled lipid levels.

"The potential risks of intermittent fasting that require further study include effects of starvation and how it may impact organ function," Dr. Freeman said. "It is particularly important for diabetics to speak with their doctor before trying intermittent fasting to discuss how to control their disease and the risk of hypoglycemia that may come with skipping regular meals."

While there is modest evidence regarding favorable effects of both dietary approaches, neither the keto nor intermittent fasting is recommended for the treatment or prevention of any condition until large, long-term studies can more definitively examine their impact. Instead, experts recommend diets that have been extensively studied and scientifically proven to prevent or even reverse cardiovascular issues, which include the mediterranean diet, a whole food plant-based diet and the National Institutes of Health's Dietary Approaches to Stop Hypertension (DASH). All of these share a common foundation that includes fruits, vegetables, legumes, nuts and whole grains.

One common invasive species is so widespread that you can see it from space.

The University of Cincinnati found that satellite imagery can identify nonnative and invasive Amur honeysuckle, an ornamental shrub introduced from Asia that has spread in forests across much of the United States.

UC graduate Bridget Taylor, UC biology professor Denis Conover and UC geography professor Richard Beck used satellite imagery to find nonnative invasive Amur honeysuckle in several urban parks and cemeteries from space.

Using one of the satellites in a series of Earth-observing missions jointly managed by NASA and the U.S. Geological Survey, the Landsat-8 satellite can measure the reflection of wavelength energy in the red and near-infrared bands. The ratio of the two wavelengths helps scientists identify foliage of different plants from orbit.

UC found that the method was effective in detecting Amur honeysuckle, according to a study published in the journal Ecological Restoration.

Amur honeysuckle bushes grow in thick patches, often crowding out and outcompeting other plants in a forest's understory. It has an extended growing season, leafing out earlier and staying green far later in the year than many native trees and shrubs.

UC used Landsat-8 images to examine five urban forests in Greater Cincinnati. The goal: to develop an inexpensive and efficient remote mapping approach for ecological restoration in urban forests. They used global-positioning satellites to corroborate their mapping observations on the ground. They found that their maps were 82% accurate.

"The fact that it was possible to use the satellite imagery in an urban setting was pretty unique," said Taylor, the study's lead author.

"Urban areas have a lot of noise in satellite imagery. So it's harder to identify specific details," she said.

Taylor has participated in efforts to eradicate the nonnative Amur honeysuckle in places like Burnet Woods, the park adjacent to UC's Uptown campus.

"It's very bushy. Birds like to eat the berries and spread the seeds," she said. "It has a chance to green up and leaf out sooner than native plants, so native wildflowers often get killed off when they're growing under honeysuckle."

The study shows that satellite images can provide an effective, inexpensive alternative to using drones or ground surveys to identify larger patches of the invasive bushes for ecological restoration, Taylor said.

A research group led by Prof. WANG Jian from the University of Science and Technology of China (USTC) of the Chinese Academy of Sciences (CAS) proposed a continuous-scanning near-infrared sky brightness monitor (CNISBM). It can measure 2.5 to 5 μm infrared sky brightness based on an InSb detector and a linear variable filter.

This study was published on Jouranl of Astronomical Telescopes, Instruments, and Systems on August 13.

Infrared observation is an important method for astronomical research. The level of sky brightness, measured by numerous major astronomical observatory sites in the world, limits the potential of infrared astronomical telescopes and instruments. Thus it is necessary to measure the infrared sky brightness level at an observatory site to evaluate the feasibility of infrared telescopes and instruments.

Due to the absorption of the Earth's atmosphere, ground-based infrared astronomical observations can only be conducted through several observing windows. 2.5 to 5 μm is the beginning of the infrared wavelength and there are two observing windows in the 2.5 to 5 μm band: L and M.

Because the level of sky brightness is extremely weak, output signal of the InSb detector is lower than nA order and the lock-in amplification technology is used to extract the signal submerged in the noise.

In order to reduce the influence of dark current, the detector is cooled to below -150?. The chopper and optical system adapted to low temperature were designed to overcome the background thermal noise caused by the instrument.

CNISBM can detect weak signal of infrared sky brightness and provide valuable information for the design and construction of infrared telescopes and instruments in the future.

University of Guam research has revealed that younger cycad seeds pose a greater risk for toxicity when consumed than more mature seeds, bringing the scientific community one step closer to understanding the origins of a neurodegenerative disease prevalent on Guam in World War II and closer to understanding related neurological disorders elsewhere. The research was the cover story of the June 2020 issue of Horticulturae, a peer-reviewed journal published by MDPI.

Of interest in recent decades has been the role of cycads as a possible toxin source that influenced one of only two known clusters of a rare neurological disease called sporadic amyotrophic lateral sclerosis, or ALS.

Residents of Guam emerged from World War II exhibiting the neurodegenerative disease with an incidence that was 50 to 100 times more prevalent than in North America. The unprecedented spike in Guam's incidence was described in the early 1950s, and the epidemiology strongly suggested an environmental cause. The island's residents suffered through a war-time occupation from 1941--1944 that led to widespread malnutrition and increased reliance on non-farm food sources, such as seeds from Guam's native cycad, known as Cycas micronesica by botanists and "fadang" in the local language.

"The increased reliance on cycad seeds as a source of dietary starch during the years of the occupation has been one of the proposals for what appears to be an ephemeral increase in exposure to an environmental factor," said Neuroscientist Christopher A. Shaw, professor of ophthalmology at the University of British Columbia and one of the authors of the study.

Shaw has been actively studying the phenomenon for more than 20 years.

The 70-year history of medical research has identified numerous toxins in the cycad tissues that were used for human consumption on the island. But no single toxin or combination of toxins has emerged as the clear-cut culprit of neurodegeneration.

"We became interested in determining the co-varying environmental and human factors that interacted with the toxin exposure as a means of developing a greater understanding of the etiology," Shaw said.

Some of the ambiguity that defines the history of research on the topic has resulted from inadequate control over plant and environmental factors that may have directly influenced cycad toxin concentrations.

"We felt that part of that was because a plant scientist was missing from the decades of research teams," said Adrian Ares, associate director of the Western Pacific Tropical Research Center at the University of Guam. "Our plant physiology laboratory partnered with the Shaw Laboratory to identify some of these co-varying factors to better refine the interpretations of past and contemporary research results."

The team has been publishing their research results since 2005, and the latest addition to the established literature sheds light on the seed sampling problems associated with an inability to determine the age of harvested seeds. All seeds that exhibit a dark brown external color are harvested for human consumption. The onset of this seed color occurs as early as 17 months in age, but seeds may persist on the trees for periods longer than 30 months. Therefore, harvested brown seeds may contrast more than one year in age.

The Guam-Canada team has shown that several secondary metabolites that serve as neurotoxins decline with seed age, so younger seeds appear to pose a greater risk of toxin exposure than older seeds. The authors contend that past research has overlooked this source of variation by not reporting seed age in the methods.

Their current publication defined two derived measurements based on fresh or dry weight of the seed components that created models useful for estimating seed age. These models can be used in future research to add clarity to and validity of the methods.

"Results from this research inform the ongoing attempts to identify environmental toxicants that pose a risk through chronic low-level exposures in many regions of the globe rather than acute high-level exposures in one location," Ares said.

An international research team headed by Anne Bierbrauer, Dr. Lukas Kunz, Dr. Carlos Gomez and Professor Nikolai Axmacher from Ruhr-Universität Bochum and Universitätsklinikum Freiburg now reports that problems in spatial navigation can also be detected in people with a genetic risk for Alzheimer's. Their article was published in the journal Science Advances, released online on 28 August 2020. The team from Bochum, Freiburg, Dortmund, Sevilla, Madrid, Parma and Brussels explored the ability of path integration.

Finding paths without external cues

Animals and humans have the ability to follow their own position in space through self-motion cues, even in the absence of any other sensory information. "If you get up at night and want to find your way to the bathroom in the dark, you need - in addition to knowing the arrangement of your own home - a mechanism that tracks your own position in the room without using external cues," illustrates Anne Bierbrauer. This ability is known as path integration.

Researchers assume that the activity of so-called grid cells in the entorhinal cortex is responsible for this ability. When navigating a spatial environment, these cells display a unique, regular activity pattern. It has long been known that the entorhinal cortex is crucial for spatial navigation. It is also one of the first regions of the brain affected by Alzheimer's disease.

Previous study showed changes in grid cell activity

In a previous study, the researchers had shown that grid cells exhibit altered functioning in people at genetic risk for developing Alzheimer's disease. However, the test persons did not show any obvious navigation problems. "We assume that they used compensatory mechanisms to find their way," explains Nikolai Axmacher, "presumably via external cues in their surroundings. In Bochum, for example, the winding tower of the Bergbau-Museum can be seen in many places, as it is often visible over the rooftops of other buildings."

Alzheimer's risk and navigation problems go hand in hand

In the current study, the team therefore used a computerized navigation task in which the participants couldn't use external landmarks to find their way. The researchers compared the navigation performance of 202 volunteers without genetic Alzheimer's risk and 65 volunteers with increased genetic risk. The latter had a specific expression of the gene for apolipoprotein E, the APOE-ε4 allele.

Participants with a genetic risk of Alzheimer's disease didn't perform as well as the control group.

Insights into grid cell activity

An additional group of test persons performed the same task while the researchers recorded their brain activity with functional magnetic resonance imaging. The objective of this experiment was to find out which brain processes play a role in path integration. The team found grid cell representations in the entorhinal cortex to be specifically associated with navigation without external cues, which highlights the role of this brain region for path integration.

"In this study, we demonstrated a very specific deficit in healthy people with a genetically increased risk for Alzheimer's," concludes Lukas Kunz. "In the future, such behavioural changes might perhaps help diagnose Alzheimer's disease earlier, before any serious symptoms appear." Researchers believe that drug therapies for Alzheimer's disease have so far failed, because the diagnosis is made too late.

Imagine working on a jigsaw puzzle with so many pieces that even the edges seem indistinguishable from others at the puzzle's centre. The solution seems nearly impossible. And, to make matters worse, this puzzle is in a futuristic setting where the pieces are not only numerous, but ever-changing. In fact, you not only must solve the puzzle, but "un-solve" it to parse out how each piece brings the picture wholly into focus.

That's the challenge molecular and cellular biologists face in sorting through cells to study an organism's structural origin and the way it develops, known as morphogenesis. If only there was a tool that could help. An eLife paper out this week shows there now is.

An EMBL research group led by Anna Kreshuk, a computer scientist and expert in machine learning, joined the DFG-funded FOR2581 consortium of plant biologists and computer scientists to develop a tool that could solve this cellular jigsaw puzzle. Starting with computer code and moving on to a more user-friendly graphical interface called PlantSeg, the team built a simple open-access method to provide the most accurate and versatile analysis of plant tissue development to date. The group included expertise from EMBL, Heidelberg University, the Technical University of Munich, and the Max Planck Institute for Plant Breeding Research in Cologne.

"Building something like PlantSeg that can take a 3D perspective of cells and actually separate them all is surprisingly hard to do, considering how easy it is for humans," Kreshuk says. "Computers aren't as good as humans when it comes to most vision-related tasks, as a rule. With all the recent development in deep learning and artificial intelligence at large, we are closer to solving this now, but it's still not solved - not for all conditions. This paper is the presentation of our current approach, which took some years to build."

If researchers want to look at morphogenesis of tissues at the cellular level, they need to image individual cells. Lots of cells means they also have to separate or "segment" them to see each cell individually and analyse the changes over time.

"In plants, you have cells that look extremely regular that in a cross-section looks like rectangles or cylinders," Kreshuk says. "But you also have cells with so-called 'high lobeness' that have protrusions, making them look more like puzzle pieces. These are more difficult to segment because of their irregularity."

Kreshuk's team trained PlantSeg on 3D microscope images of reproductive organs and developing lateral roots of a common plant model, Arabidopsis thaliana, also known as thale cress. The algorithm needed to factor in the inconsistencies in cell size and shape. Sometimes cells were more regular, sometimes less. As Kreshuk points out, this is the nature of tissue.

A beautiful side of this research came from the microscopy and images it provided to the algorithm. The results manifested themselves in colourful renderings that delineated the cellular structures, making it easier to truly "see" segmentation.

"We have giant puzzle boards with thousands of cells and then we're essentially colouring each one of these puzzle pieces with a different colour," Kreshuk says.

Plant biologists have long needed this kind of tool, as morphogenesis is at the crux of many developmental biology questions. This kind of algorithm allows for all kinds of shape-related analysis, for example, analysis of shape changes through development or under a change in environmental conditions, or between species. The paper gives some examples, such as characterising developmental changes in ovules, studying the first asymmetric cell division which initiates the formation of the lateral root, and comparing and contrasting the shape of leaf cells between two different plant species.

While this tool currently targets plants specifically, Kreshuk points out that it could be tweaked to be used for other living organisms as well.

Machine learning-based algorithms, like the ones used at the core of PlantSeg, are trained from correct segmentation examples. The group has trained PlantSeg on many plant tissue volumes, so that now it generalises quite well to unseen plant data. The underlying method is, however, applicable to any tissue with cell boundary staining and one could easily retrain it for animal tissue.

"If you have tissue where you have a boundary staining, like cell walls in plants or cell membranes in animals, this tool can be used," Kreshuk says. "With this staining and at high enough resolution, plant cells look very similar to our cells, but they are not quite the same. The tool right now is really optimised for plants. For animals, we would probably have to retrain parts of it, but it would work."

Currently, PlantSeg is an independent tool but one that Kreshuk's team will eventually merge into another tool her lab is working on, ilastik Multicut workflow.

A study of nearly 1200 UK adults, being presented at this year's European and International Conference on Obesity (ECOICO 2020), held online this year (1-4 September), suggests that there is a link between eating a larger proportion of one's daily energy intake during the evening, and having a higher total energy intake and lower quality of diet.

In recent decades there has been a growing interest in how the timing of our food consumption can influence metabolism and other physiological processes. Sensations of hunger follow a strong daily rhythmic pattern and are often most intense later in the day. This phenomenon could influence both the type and amount of food we eat.

The research was conducted by Judith Baird, Nutrition Innovation Centre for Food and Health (NICHE), Ulster University, Northern Ireland, UK, and colleagues. It aimed to investigate the association of energy intake (EI) during the evening on total EI and diet quality.

The team selected a group of 1177 adults aged 19-64 years from the UK National Diet and Nutrition Survey, using data covering the years 2012-2017. The Survey, which began in 2008, collects detailed information on the food consumption, nutrient intake and nutritional status of the general UK population aged 18 months and over by canvassing a representative sample of around 1000 participants each year.

Subjects were grouped into quartiles (4 equal groups of 25%) based on the proportion of their daily EI consumed after 6pm, from the lowest with under 31.4%, through to the highest whose evening consumption accounted for more than 48.6% of their EI. Diet quality was assessed by scoring the food diaries kept by participants using the Nutrient Rich Food Index, which classifies and ranks foods according to the ratio of important nutrients they contain relative to their energy content.

Across the whole sample group, eating during the evening provided an average of almost 40% (39.8%) of daily EI. The authors found a significant variation in total EI across the different quartiles, with individuals in the lowest quartile of evening EI consuming fewer calories in total over the day than those in the other three quartiles.

Quality of diet also differed across the quartiles with participants who consumed the largest proportion of their EI in the evening having a significantly worse score on the Nutrient Rich Food Index than those in the rest of the sample groups.

The authors say: "Our results suggest that consuming a lower proportion of EI in the evening may be associated with a lower daily energy intake, while consuming a greater proportion of energy intake in the evening may be associated with a lower diet quality score."

They conclude: "Timing of energy intake may be an important modifiable behaviour to consider in future nutritional interventions. Further analysis is now needed to examine whether the distribution of energy intake and/or the types of food consumed in the evening are associated with measures of body composition and cardiometabolic health."

Miniaturized lasers capable of emitting over the full visible spectrum have been demonstrated to be an essential tool for versatile photonic devices ranging from sensors to full-color laser display panels. For most of these devices, multicolor microlasers with high spectral purity are of great importance because the laser emission at multiple frequencies can lead to temporal fluctuations and false signaling. Single-mode microlasers, due to the advantages of low noise and good monochromaticity, hold a promising potential in promoting the advancement of functional photonic devices. Up to now, several strategies have been developed to achieve single-mode lasers. However, most of these strategies allow us to achieve single-mode lasers operate in only one gain region because of the intrinsic difficulties in simultaneously fabricating distinct materials. As a key requirement of the fields of photonics and optoelectronics, multicolor single-mode microlasers capable of emitting over the full visible spectrum, particularly the red, green and blue (RGB) color regions, still remains a big challenge.

In a new paper published in Light Science & Application, a team of scientists, led by Professor Yong Sheng Zhao from Key Laboratory of Photochemistry, Institute of Chemistry, Chinese Academy of Sciences and co-workers have demonstrated tunable red, green and blue single-mode laser in an optimized heterogeneously coupled cavities constructed with three spherical microcavities incorporated with distinct gain media. The microcavities with perfect circle boundary and smooth surface were applied as high-quality WGM resonators. Benefiting from the outstanding flexibilities, RGB lasing was obtained by doping the corresponding dyes into different WGM microcavities. Different color-emissive spherical cavities were integrated to form a heterogeneously coupled system by using a strategy of nanoarchitectonics. In such a heterogeneously coupled system, each individual microsphere serves as not only the laser source but also the filter for the other resonator, which would enable the output of single-mode laser from individual microcavities. Furthermore, we fabricated heterogeneously coupled system, which permits optical coupling between multiple resonators, thereby realizing tunable RGB single-mode microlasers. The results demonstrate a unique approach for the modulation of lasing modes in heterogeneously coupled cavities and shed new light on the generation of microlasers capable of emitting over the full visible spectrum with high spectral purity for optoelectronic integrated system.

"Benefiting from the doping flexibility of organic materials, the color of the single-mode lasers output from the heterogeneously coupled structure can be freely designed by doping different gain media into the spherical microcavities" they added.

"We believe that the reported work will provide insights into the achievements of heterogeneous microstructures with advanced functionalities, which will not only inspire people to reunderstand the connection between photonic functions and nanoarchitectonics, but also lead to innovation of concepts and structure design of functional elements for photonic integrated circuits." the scientists forecast.

An international study reveals how future climate change could affect malaria transmission in Africa over the next century.

Malaria is a climate sensitive disease; it thrives where it is warm and wet enough to provide surface water suitable for breeding by the mosquitoes that transmit it.

For more than two decades now, scientists have suggested that climate change may alter the distribution and length of transmission seasons due to new patterns of temperature and rainfall.

The burden of this disease falls primarily on Africa. In 2018, out of an estimated 228 million cases of malaria worldwide, 93% were in the African continent.

Detailed mapping of malaria transmission is vital for the distribution of public health resources and targeted control measures.

In the past, rainfall and temperature observations have been used in malaria climatic suitability models to estimate the distribution and duration of annual transmission, including future projections.

But factors affecting how rainfall results in water for mosquito breeding are highly complex, for example how it is absorbed into soil and vegetation, as well as rates of runoff and evaporation.

A new study, led by the Universities of Leeds and Lincoln in the UK, for the first time combined a malaria climatic suitability model with a continental-scale hydrological model that represents real-world processes of evaporation, infiltration and flow through rivers.

This process-focused approach gives a more in-depth picture of malaria-friendly conditions across Africa.

When run using future climate scenarios up to the end of this century, a different pattern of future changes in malaria suitability emerges compared to previous estimates.

While the findings show only very minor future changes in the total area suitable for malaria transmission, the geographical location of many of those areas shifts substantially.

When a hydrological model is used, aridity-driven decreases in suitability are no longer observed across southern Africa, particularly Botswana and Mozambique.

Conversely, projected decreases in malaria suitable areas across West Africa are more pronounced. The largest difference is in South Sudan, where the study estimates substantial decreases in malaria suitability in the future.

The study, published today in Nature Communications, highlights river corridors as year-round hot spots of malaria transmission.

While flowing water in large rivers is not a suitable habitat for malaria-carrying mosquitoes, nearby smaller water bodies, such as bankside ponds and floodplains can make for ideal larvae breeding grounds, as do associated irrigation schemes.

The Niger and Senegal rivers in Mali and Senegal, and the Webi Juba and Webi Shabeelie rivers in Somalia, are all identified in the study as suitable for malaria transmission despite currently extending beyond the geographical ranges hitherto predicted to be climatically suitable.

This is especially important since human populations tend to concentrate close to rivers.

Study lead author Dr Mark Smith, from the School of Geography at Leeds, said: "Since the huge efforts to eradicate malaria from parts of the world, the areas where we observe malaria today are only a part of the total area that would otherwise be suitable for malaria transmission.

"But if we are to project the impact of climate change on the geography of malaria transmission, we need to develop more sophisticated ways of representing that envelope of malaria suitability both today and in the future.

"Our approach aims to lay out the environmental risks of malaria more clearly, so that projections of climate change impacts can help inform public health interventions and support vulnerable communities.

"But this is only a first step, there is a lot more we can do to embed state-of-the-art hydrological and flood models into estimates of malaria environmental suitability and, potentially, even early warning systems of local malaria epidemics."

Co-author, Professor Chris Thomas from Lincoln Centre for Water and Planetary Health, at the University of Lincoln added: "The shrinking map of malaria in Africa over that last 20 years is primarily due to huge public health efforts underway to tackle this disease, not climate change.

"But malaria elimination is made much more difficult where the climate is highly suitable for transmission, so it is key to know where these areas are now and are projected to be in the future.

"In this study we show that linking physical geographic processes to the biology helps us get to grips with some of that complexity. The exciting challenge now is to develop this approach at local scales."

Hamilton, ON (August 28, 2020) - Brain cancer in children is always a devastating diagnosis, but McMaster University researchers may have found a way to have the most serious types of pediatric brain cancer respond better to therapies.

Medulloblastoma (MB) is the most common malignant childhood brain tumour and it has recently been categorized into four molecular subtypes. Group 1 tumors have excellent outcomes, rarely spread, and are rarely lethal. But Groups 2, 3 and 4 are still aggressive, have metastatic spread and are lethal in 20-30% of patients despite full treatment.

Group 1 MB is also called the Wnt subtype, because it is characterized by apparent activation of the Wnt signaling pathway, a signaling pathway important in multiple tissues and organs during normal development.

Research conducted in Dr. Sheila Singh's laboratory at McMaster University published today in the journal Nature Communications, has identified a small molecule compound that can activate the Wnt pathway in non-Wnt subtypes of medulloblastoma, making these aggressive forms of cancer more responsive to therapies.

The work also found the Wnt pathway, which has historically been considered cancer-promoting, to function as a cancer inhibitor in certain contexts.

Branavan Manoranjan did the research as part of his PhD thesis in McMaster's Michael G. DeGroote School of Medicine MD/PhD program.

He investigated several different ways to see if activating Wnt in a Group 3 or 4 MB made the tumour less aggressive, decreased the cancer stem cell fraction and self-renewal ability, and decreased the ability of the tumour to grow and spread.

Through performing genetic sequencing of individual brain tumour stem cells, he found that a rare fraction of cells in the Group 2, 3 and 4 cancers were Wnt active and when those cells were sorted, they generated smaller, more benign-looking tumours, while the Wnt inactive cells generate the aggressive, metastatic tumours.

The team then tested a small molecule that turned on the Wnt pathway in mice with non-Wnt medulloblastoma subtype tumors, which resulted in a reduction in tumor growth and improved survival.

"Our work shows the Wnt pathway, which has historically been considered cancer-promoting, may function as a tumour suppressor in certain contexts," said Manoranjan, now a neurosurgery resident at the University of Calgary. "We also found all different subtypes do have a minority fraction of Wnt active cells, and this is promising."

Singh, the senior author for the study, added that a drug currently in use for other conditions has been found to selectively and specifically activate Wnt signaling.

"In the end, Wnt activation could present an innovative targeted therapeutic strategy for treatment-resistant medulloblastoma," she said.

The research was funded by several agencies, notably Canadian Institutes of Health Research, Cancer Research Society, and Brain Tumour Foundation of Canada.