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Within the intricate network of cells that make up the brain, chandelier cells stand out for their elaborate, branching structure. With an elegant shape similar to that of its namesake, a single chandelier cell reaches out to connect and communicate with more than 100 other neurons. Abnormalities in chandelier cells have been linked to epilepsy, autism, and schizophrenia, underscoring their critical role in keeping brain signaling in balance. However, these cells have been notoriously difficult to study as their numbers are few, so until recently, chandelier cells remained largely enigmatic.

Chandelier cells are influential regulators of signaling in the brain, according to Cold Spring Harbor Laboratory (CSHL) Professor Linda Van Aelst, CSHL/Stony Brook University graduate student Nicholas Gallo, and Penn State Assistant Professor Anirban Paul. They note in a review article published online June 18, 2020 in the journal Trends in Neurosciences (TINS) that in addition to the sheer abundance of their connections, chandelier cells have an unusually direct method of communication. Most neurons contact their target neurons in places that don't directly generate electrical "spikes," but chandelier cells connect directly to the part of a target neuron that initiates a spike. Spikes facilitate both short and long distance communication in the brain. Van Aelst explains, "In principle, the chandelier cell is ideally suited to exert powerful control over the output or spiking of neighboring neurons."

In recent years scientists have been able to apply new tools to understanding these previously poorly understood cells. In particular, a genetically engineered mouse from CSHL Professor Z. Josh Huang and a labeling method developed in Van Aelst's laboratory give researchers the ability to find and manipulate the cells.

The TINS article details important discoveries about when and how chandelier cells form and establish their connections, as well as the accumulating evidence linking the cells to neurodevelopmental disorders. Gallo describes how epilepsy could be caused by having too many or too few chandelier cells:

"The main take-home point is that there's this imbalance in the excitation and inhibition in the brain. So I was thinking it's like a Seesaw, you know, to keep it level, so stuff functions properly. But if you have an increase in inhibition or an increase in excitation, either way, it's going to cause epilepsy. If you cause too much excitation you'd get a seizure."

Priorities for future research include looking at how chandelier cells differ in different parts of the brain, as well as determining how other cell types influence chandelier cell development and wiring. Importantly, Van Aelst, Gallo, and Paul say such studies will allow them to tease out the cells' functional roles and their contributions to disease. Van Aelst thinks chandelier cell research is lighting up:

"Over the past few years, there's several new technologies that have emerged that allowed us to address a little better--it's still challenging--uh, to gain more insight on chandelier cells. There's so much cool stuff to be done. Does it have different impact on behavior? Are there different molecules involved? The cool thing is if you have a molecule, you can manipulate a molecule and see where it affects those physiological properties, right? So that's the reason why the excitement over the last few years."

Molecular switches - they are the molecular counterparts of electrical switches and play an important role in many processes in nature. Such molecules can reversibly interconvert between two or more states and thereby control molecular processes. In living organisms, for example, they play a role in muscle contraction but also our visual perception is based on the dynamics of a molecular switch in the eye. Scientists are working intensively to develop novel molecular components that enable switching between different states, so that molecular processes can be specifically controlled.

A European research team led by nanotechnologist Dr. Saeed Amirjalayer from the University of Münster (Germany) now gained a deeper insight into the processes of a molecular switch: Using molecular dynamics simulations, the scientists produced a photographic film at the atomic level and thus tracked the motion of a molecular building block. The result was a light-controlled "pedalo-type motion", going forward and backward. Although it had already been predicted in this context in earlier work, it could not be directly proven so far.

In the future, the results may help to control the properties of materials with the help of molecular switches - for example, in order to release drugs specifically from nano-capsules. "For efficient embedding in novel responsive materials, detailed elucidation of the switching process and thus the way they function at the molecular and atomic level is crucial," emphasizes Dr. Saeed Amirjalayer, group leader at the Institute of Physics at Münster University and the Center for Nanotechnology (CeNTech). The study has been published in the "The Journal of Physical Chemistry Letters".

Background and methods:

Molecular dynamics simulations enable, by calculating the interactions between atoms and molecules, to describe their motion in the computer. In their current study, the scientists investigated an azodicarboxamide-based molecular switch in this way, using a so-called combined quantum mechanical/molecular mechanical method in the simulations. "Previous experimental and theoretical studies provided only an indirect insight into the operation mechanism of such a switch in solution. With the help of our theoretical approach, we could now follow the light-induced dynamics while taking the molecular environment into account," explains Saeed Amirjalayer.

The pedalo-type motion of the switch, triggered by light, moves backward and forward - like a bicycle pedal. Detailed understanding of the operation mechanism of a photo-responsive switch forms an important basis for the application of these molecular building blocks in novel "intelligent" functional materials.

In addition to the University of Münster, the Universities of Bologna (Italy) and Amsterdam (Netherlands) were involved in the study. "Despite the current circumstances in the wake of the Corona crisis, the cross-border exchange with colleagues from Europe could take place - virtually, but still very intensively. Together we achieved interesting and valuable results," says Saeed Amirjalayer summing up the cooperation.

June 18, 2020 (Toronto) - The suicide rate for people with schizophrenia spectrum disorders (SSD) is 170 times higher than the general population according a study just published in the journal Schizophrenia Research, a figure the authors call "tragically high."

The study of 20-years of population data, believed to be the largest of its kind ever done, examined statistics on over 75,000 patients who received a first diagnosis of SSD. On average, each patient was followed for almost ten years. The study found several key factors that were predictors of suicide including:

During the first five years after an individual has been diagnosed with SSD

If there was evidence of a mood disorder or hospitalization prior to diagnosis

If the individual was diagnosed with SSD at a later age

"What this study teaches is us that although people with SSD are at higher risk for suicide, we can target those at the highest risk with changes in policy and treatment," said lead author Dr. Juveria Zaheer, Clinician Scientist at the CAMH Institute for Mental Health Policy Research.

"In the past clinicians have focused on treating the psychosis itself when it first appears," said senior author Dr. Paul Kurdyak, Director, Health Outcomes and Performance Evaluation, CAMH Institute for Mental Health Policy Research and Clinician Scientist at ICES. "This study shows that treatment has to include suicide prevention safety planning as well from the very beginning."

The authors suggest increasing the age limit for admission to first episode psychosis programs (most are closed to people over 30) and increasing the length of clinical follow-up care after a first episode of psychosis.

"Now that we know what is happening, we need to better understand why," said Dr. Zaheer. "Our next step will be to study the lived experience of people with SSD who have had suicidal ideation."

Researchers at Children's Cancer Institute have discovered what could prove a new and improved way to treat the poor-prognosis blood cancer, acute myeloid leukaemia or AML.

Unlike acute lymphoblastic leukaemia (ALL), the most common childhood cancer, AML is notoriously difficult to cure, often proving resistant to standard treatments. The researchers have been investigating what they believe to be the root cause of treatment resistance, leukaemia stem cells, and have now hit upon a new therapeutic approach that works by targeting these cells.

Stem cells are special cells that are not only capable of giving rise to different types of cells, but also of copying themselves indefinitely in a process known as self-renewal. If stem cells in the blood becomes cancerous, they can multiply out of control, causing leukaemia. And while ever leukaemia stem cells remain in a child's body, that child remains at risk of relapse.

"Leukaemia stem cells have their own protective mechanisms that make them resistant to anticancer drugs", explains lead researcher Dr Jenny Wang, head of the Cancer and Stem Cell Biology Group. "After chemotherapy, if even one leukaemic stem cell is left alive, it can regenerate and the disease can come back."

The new treatment approach, published this month in one of the world's leading cancer research journals, Cancer Cell, works by disrupting the ability of leukaemia stem cells to self-renew. Specifically, it uses an antibody treatment (anti-RSPO3) to interfere with the interaction between two key molecules thought to drive the self-renewal process.

Using highly specialised laboratory models ? mice growing cancer cells taken directly from patients with AML ? the researchers found that the treatment not only markedly reduced the amount of leukaemia, but also prevented new leukaemia cells from growing. Importantly, it did not harm healthy stem cells, which children treated for AML need to reconstitute their blood system after treatment.

Best of all, the new targeted therapy has the potential to replace intensive chemotherapy - the cause of serious long-term side effects. Following more preclinical studies, the researchers hope to see the therapy progress to clinical trial and prove effective in children with AML.

"This disease is very tough, and the survival rate is low," says Dr Wang. "We really need to find a cure."

For researchers looking to understand and someday treat certain neuropsychological ailments, one place to start is a molecule known as GABA, which binds to receptor molecules in neurons and helps regulate neuron firing rates in the brain. Now, researchers have produced a detailed map of one such GABA receptor, revealing not just the receptor's structure but new details of how it moves from its inactive to active state, a team writes June 17 in Nature.

Scientists have never seen such details before in a human receptor, said Cornelius Gati, a structural biologist at the Department of Energy's SLAC National Accelerator Laboratory and a senior author of the new paper. Information about the structure of the molecule and its transitions between states could help scientists better understand GABA receptors and may help chemists design better drugs to treat addiction, psychosis and other conditions.

GABA, short for gamma aminobutyric acid, is central to our brains' proper functioning. When released, it binds to neurons at one of two receptors, GABAA and GABAB, and slows their firing rates. Drugs that mimic GABA generally have a calming effect - the tranquilizer benzodiazepine, for example, works by binding to GABAA and activating the receptor.

In the new study, Gati and colleagues focused their attention on GABAB, using cryo-electron microscopy to take detailed pictures of the molecule. The technique involves freezing a sample to better preserve it under the harsh conditions in an electron microscope, and its chief advantage is that it can catch molecules in a more natural state than other methods.

In this case, the scientists hoped to map the structure of GABAB in both inactive and active, GABA-bound states. But when they reviewed data from their experiments, they found they had also caught more detail than they had anticipated. Those new findings include the existence and rough maps of two intermediate states that, Gati said, "we didn't even know existed."

But perhaps, more important than the intermediate states themselves, was observing, for the first time, the active form of GABAB, said Vadim Cherezov, a structural biologist at the University of Southern California and the new paper's other senior author.

To capture the active state, the team added two molecules into the mix with GABAB and took additional cryo-EM images. Adding those molecules - a GABA-like molecule and another, called a positive allosteric modulator or PAM, that fine-tunes GABAB function - stabilized GABAB receptor in its active state.

Being able to see each of those steps along with new details, such as the site where the PAM binds to GABAB, Cherezov said, could help researchers design better drugs to treat neuropsychological disease.

The giant sequoia (Sequoiadendron giganteum) has developed effective strategies to protect itself against external influences in its natural environment in the Sierra Nevada. Its bark ensures that the tree survives wild fires and rock fall almost unscathed. Prof. Dr. Thomas Speck from the Cluster of Excellence Living, Adaptive and Energy-autonomous Materials Systems (livMatS), working with Dr. Georg Bold and Max Langer of the Institute of Biology, have examined the structural properties of its bark in detail for the first time. The University of Freiburg team has shown that the bark fibers form a three-dimensional network with cavities. This network distributes energy acting on the bark across the entire tissue. The results of their study have been published in the International Journal of Molecular Sciences.

The outer bark of the sequoia tree contains many fibers, which are organized in fiber bundles. These cross over each other and are also layered on top of each other, creating a three-dimensional netted structure. In between the fiber bundles are air-filled cavities. When a rock strikes the bark, these cavities are compressed. Compressing the hollow spaces and stretching the fiber network has the effect of distributing the energy evenly over the bark and protecting the inside of the tree with the sensitive cambium that forms wood and bark. The bark later returns almost completely to its original state. The cavities also insulate the tree so that it is resistant to the heat generated during wild fires.

Due to this structure, the bark of the sequoia tree behaves like an open-pored foam similar to the foam used in the construction of cars and houses, for example. On the basis of their findings, the researchers are, among others, to develop with colleagues from the University of Stuttgart a new type of light weight concrete with bundles of hollow fibers, which could be used to insulate and to better protect buildings against earthquakes, for example.

Scientists have discovered that the summer sea ice in the Weddell Sea sector of Antarctica has decreased by one million square kilometres - an area twice the size of Spain - in the last five years, with implications for the marine ecosystem. The findings are published this month (June 2020) in the journal Geophysical Research Letters.

Sea ice surrounding Antarctica provides an important habitat for many species including penguins and seals, which rely on it to access food and to breed.

An international team of researchers studied satellite records of sea ice extent and weather analyses starting in the late 1970s to understand why summer sea ice in the Weddell Sea area of Antarctica has reduced by a third over the last five years. They found that ice loss occurred due to a series of severe storms in the Antarctic summer of 2016/17, along with the re-appearance of an area of open water in the middle of the 'pack ice' (known as a polynya), which had not occurred since the mid-1970s.

Lead author Professor John Turner, a climate scientist at British Antarctic Survey, says:

"Antarctic sea ice continues to surprise us. In contrast to the Arctic, sea ice around the Antarctic had been increasing in extent since the 1970s, but then rapidly decreased to record low levels, with the greatest decline in the Weddell Sea. In summer, this area now has a third less sea ice, which will have implications for ocean circulation and the marine wildlife of the region that depend on it for their survival."

The ocean around Antarctica freezes and doubles the size of the continent in the austral winter, with the sea ice extent reaching over 18 million square kilometres by late September. Through the spring and summer, the sea ice almost completely melts in most parts of the Antarctic, with only the Weddell Sea retaining a significant amount of sea ice.

There are few storms around the Antarctic in the austral summer, but in December 2016, a number of intense and unseasonal storms developed in the Weddell Sea and drew warm air towards the Antarctic, melting a large amount of sea ice. The ice-free ocean absorbed energy from the Sun and then created a warm ocean temperature anomaly that still persists today.

The winter of 2016 also saw the development of a polynya in the Weddell Sea, a large area of open water within the sea ice, which also contributed to the overall decline in sea ice extent. This polynya was created by the strong winds associated with the storms and unprecedented warm ocean conditions.

This recent rapid sea ice loss is affecting both the Weddell Sea ecosystem and the wider Antarctic wildlife/plants and animals. Many species, ranging from tiny ice algae and shrimp-like crustaceans called krill to seabirds, seals and whales, are highly adapted to the presence of sea ice. If the drastic changes observed continue, they will have repercussions throughout the food chain, from affecting nutrients to the reduction of essential habitat for breeding and feeding for vast numbers of animals, such as ice seals and some species of penguins.

Author and ecologist Professor Eugene Murphy from British Antarctic Survey says:

"The dramatic decline in sea ice observed in the Weddell Sea is likely to have significant impacts on the way the entire marine ecosystem functions. Understanding these wider consequences is of paramount importance, especially if the decline in ice extent continues."

Because of the large year-to-year variability in Antarctic sea ice extent the scientists cannot be sure if the ice in the Weddell Sea will in the short-term recover to the values seen before 2016 or whether they are seeing the start of the expected long-term decline of sea ice.

The particular kind of waves that the brain produces during sleep, which repeatedly sweep the surface of the cerebral cortex, travel through the anatomical "highways" that connect distant areas of the cortical mantle, a new study in The Journal of Neuroscience shows.

Contrary to what is commonly believed, sleep is not a uniform, unitary state of the whole brain. In fact, each area of the brain may produce its own "sleep rhythms". Among these, the so-called "slow waves" are regarded as the most typical hallmark of deep sleep. While coordination of slow waves across distant areas of the brain is essential for sleep functions, how this process takes place remains partially unknown.

The new study by researchers at the Molecular Mind Laboratory (MoMiLab) of the IMT School for Advanced Studies Lucca investigated how sleep slow waves propagate across the two halves of the brain, the right and left hemispheres. To this aim, researchers at the IMT School studied an extremely rare group of neurological patients, the so-called "split brain" patients, who underwent a complete resection of the corpus callosum, the most important white matter fiber bundle that connects the two brain hemispheres, as a treatment for drug-resistant epilepsy. These patients and a group of adults with an intact corpus callosum were studied during their sleep using a particular electroencephalographic (EEG) technique with high spatial resolution, called high density-EEG. Results showed that, in patients without the corpus callosum, slow waves remained confined to the brain hemisphere in which they originated. "Our findings clearly indicate that sleep slow waves propagate through anatomical pathways connecting the origin site to distant brain areas", said Giulia Avvenuti, first author of the study and PhD student at the IMT School.

The study, conducted within an international collaboration led by the IMT School which included the Marche Polytechnic University, the University of Wisconsin (USA), the University Hospital of Lausanne (Switzerland) and the University of Bristol (UK), is the first to demonstrate what had only been hypothesized for some time, namely that slow waves propagate in the brain through anatomical cortical connections, and that a damage to such pathways significantly alters their propagation.

This study also has important implications for our understanding of how sleep is regulated and exerts its essential functions. "The slow waves of sleep are known to have a key role in the restorative functions of sleep, but they also seem to be important for the consolidation of recently acquired memories", explained Giulio Bernardi, co-senior author of the paper, together with Michele Bellesi, and Assistant Professor at the IMT School. "Their synchronization within particular connected networks of brain areas could be especially important for the processing of novel memories". The results also have important implications for our understanding of what happens in some pathological conditions. In particular, they indicate that studying the propagation of sleep slow waves could inform regarding the status of brain connections and may thus allow to identify functional or structural alterations caused by traumatic or neurodegenerative disorders.

Furthermore, this study demonstrates that the loss of connections between the two hemispheres in adult life is not sufficient, per se, to allow the appearance of uni-hemispheric sleep in humans, a behavioral state that is present in other animals, including dolphins. Such an observation indicates that other specific features that are absent in the human brain are necessary for this particular asymmetric state to manifest. "Disruption of sleep integrity is central in most psychiatric conditions and affects millions of individuals worldwide. Understanding the basic regulatory mechanisms in the brain is essential to develop innovative therapeutic strategies," added Pietro Pietrini, a psychiatrist coauthor of the study and Director of MoMiLab and the IMT School in Lucca.

Each year, the U.S. Coast Guard performs thousands of search and rescue missions at sea. In situations where every minute matters, it is critical to have the most efficient ocean modeling data and algorithms at hand.

Researchers at Virginia Tech are part of a multi-institutional group using mathematical techniques with ocean models and experiments to better understand near-surface flow patterns and hidden flow structures. With more accurate modeling data, response teams can better predict the search area grid from the air, and reduce emergency response time when lives are on the line.

Throughout this study, published in Nature Communications on May 26, the research team has uncovered hidden transient attracting profiles - or TRAPs - in ocean-surface velocity data. These transient attracting profiles act as short-term collection zones for all floating objects, debris as well as persons in the water. When incorporated into search and rescue algorithms, the locations of the TRAPs give a more accurate prediction on regions to focus search efforts.

"From the moment they are alerted that someone is lost, search and rescue teams use sophisticated software to try to pinpoint the last known location in the water, factor in how much time has passed, and make their best prediction on how far they have drifted," said Shane Ross, professor in the Kevin T. Crofton Department of Aerospace and Ocean Engineering. "By improving the modeling of drifting objects in unsteady currents, search teams will have more efficient probability computations that enable them to set a tighter search grid and make faster, safer rescues."

Current flow models used in search and rescue operations factor in ocean dynamics, weather prediction, and in-situ observations, such as self-locating datum marker buoys deployed from air. According to the research team, even with high-resolution ocean models and improved weather prediction, search and rescue planning is still based on conventional practices, and rescuers rely on their hunches as much as sophisticated prediction tools.

Computational tools can predict how particles or objects are transported and reveal areas of the flow where drifting objects are likely to converge. In engineering terms, these patterns are called Lagrangian coherent structures. Unfortunately, calculating Lagrangian structures can often be time-consuming and computationally expensive.

For use in disaster response scenarios, transient attracting profiles are easily interpreted and can be computed and updated instantaneously from snapshots of ocean velocity data. This eliminates very expensive and timely computation, especially when short-time predictions are critically important in search and rescue. After six hours, the likelihood of rescuing people alive drops significantly.

These attracting profiles, where persons in the water are likely to collect, provide continuously updated and highly specific search paths. The inset shows a migrant boat that capsized on April 12, 2015 in the Mediterranean Sea.

In order to prove the predictive influence of transient attracting profiles in coastal waters ?-- or identify the regions where objects or people are most likely to accumulate over a two- to three-hour period of time ?-- the research team conducted multiple field experiments off the coast of Martha's Vineyard in Massachusetts.

Using both Coastal Ocean Dynamics Experiment drifters and 180-pound OSCAR Water Rescue Training manikins, targets were released around areas of predicted transient attracting profiles with GPS tracking devices that reported location every five minutes. Even without accounting for wind-drag or inertial effects, the researchers observed that the TRAPs invariably attracted the floating drifters and manikins in the water over a two- to three-hour period.

Identifying transient attracting profiles on ocean surface velocity data can also have significant impact on the containment of environmental disasters, such as catastrophic oil spills. TRAPs provide critical information for environmental hazard response teams and have the potential to limit the spread of toxic materials and reduce damaging impact on the surrounding ecological systems.

June 17, 2020 - Older adults who suffer a hip fracture requiring surgery are at a higher risk of suicide, suggests a study in the June 17, 2020 issue of The Journal of Bone & Joint Surgery. The journal is published in the Lippincott portfolio in partnership with Wolters Kluwer.

In the first six months following hip fracture, the risk of suicide was nearly 3 times greater among patients who had sustained a hip fracture compared with a matched cohort of those who had not, according to the South Korean nationwide study by Yong-Han Cha, MD, of Eulji University Hospital, Daejeon, and colleagues. Dr. Cha comments, "So far, we have focused on the treatment of comorbidity and hip fracture itself in the management of elderly patients with hip fracture, but evaluation and management of their mental stress and emotional status are also important."

Suicide Risk Remains Elevated Through One Year After Hip Fracture

With use of a national health-insurance database, the researchers identified 11,477 patients who underwent surgical repair of a hip fracture. Each patient was matched with two controls with similar demographic and health characteristics but without hip fracture. The average age was 75 years, and nearly three-fourths of patients were women.

The researchers compared the suicide rates of the injured and uninjured cohorts over an average follow-up of about 4.5 years (total 158,139 person-years), identifying a total of 170 patients who died by suicide.

Through the first six months, there were 14 suicides among nearly 11,500 patients with a hip fracture compared with 10 suicides among nearly 23,000 matched controls. The cumulative rate of suicide was 0.13 percent among those with a hip fracture (incidence rate: 266.1 per 100,000 person-years) and 0.04 percent among the matched controls (incidence rate: 89.2 per 100,000 person-years). Thus, older adults with hip fracture were about three times more likely to die by suicide within the first six months following surgical treatment.

The difference in suicide rates persisted through the first year but was not significant at longer follow-up intervals. This may reflect the high risk of death and poor health among patients with a hip fracture, the researchers speculate: patients who survive beyond the first year may represent a cohort with higher levels of health and functioning.

The suicide rate during the first six months following surgical treatment was "remarkably high," Dr. Cha and coauthors write - even compared with studies of older adults with cancer and other serious diseases. The findings are also consistent with data showing the "steadily increasing number of elderly suicides in South Korea."

Hip fracture is a common and often catastrophic event in older adults, with a major impact on physical and mental health and functioning. The authors note some limitations of their study, including a lack of data on fracture severity and on the causative factors leading to suicide. However, because it was based on a large national database, the findings "could be generalized to other populations."

Meanwhile, the high suicide rate underscores the need to target mental health issues in older adults after surgical repair of a hip fracture. Dr. Cha and colleagues conclude: "These results imply the need for a new approach to psychiatric evaluation and management among elderly patients with hip fracture."

Although global climate models vary in many ways, they agree on this: The Mediterranean region will be significantly drier in coming decades, potentially seeing 40 percent less precipitation during the winter rainy season.

An analysis by researchers at MIT has now found the underlying mechanisms that explain the anomalous effects in this region, especially in the Middle East and in northwest Africa. The analysis could help refine the models and add certainty to their projections, which have significant implications for the management of water resources and agriculture in the region.

The study, published last week in the Journal of Climate, was carried out by MIT graduate student Alexandre Tuel and professor of civil and environmental engineering Elfatih Eltahir.

The different global circulation models of the Earth's changing climate agree that temperatures virtually everywhere will increase, and in most places so will rainfall, in part because warmer air can carry more water vapor. However, "There is one major exception, and that is the Mediterranean area," Eltahir says, which shows the greatest decline of projected rainfall of any landmass on Earth.

"With all their differences, the models all seem to agree that this is going to happen," he says, although they differ on the amount of the decline, ranging from 10 percent to 60 percent. But nobody had previously been able to explain why.

Tuel and Eltahir found that this projected drying of the Mediterranean region is a result of the confluence of two different effects of a warming climate: a change in the dynamics of upper atmosphere circulation and a reduction in the temperature difference between land and sea. Neither factor by itself would be sufficient to account for the anomalous reduction in rainfall, but in combination the two phenomena can fully account for the unique drying trend seen in the models.

The first effect is a large-scale phenomenon, related to powerful high-altitude winds called the midlatitude jet stream, which drive a strong, steady west-to-east weather pattern across Europe, Asia, and North America. Tuel says the models show that "one of the robust things that happens with climate change is that as you increase the global temperature, you're going to increase the strength of these midlatitude jets."

But in the Northern Hemisphere, those winds run into obstacles, with mountain ranges including the Rockies, Alps, and Himalayas, and these collectively impart a kind of wave pattern onto this steady circulation, resulting in alternating zones of higher and lower air pressure. High pressure is associated with clear, dry air, and low pressure with wetter air and storm systems. But as the air gets warmer, this wave pattern gets altered.

"It just happened that the geography of where the Mediterranean is, and where the mountains are, impacts the pattern of air flow high in the atmosphere in a way that creates a high pressure area over the Mediterranean," Tuel explains. That high-pressure area creates a dry zone with little precipitation.

However, that effect alone can't account for the projected Mediterranean drying. That requires the addition of a second mechanism, the reduction of the temperature difference between land and sea. That difference, which helps to drive winds, will also be greatly reduced by climate change, because the land is warming up much faster than the seas.

"What's really different about the Mediterranean compared to other regions is the geography," Tuel says. "Basically, you have a big sea enclosed by continents, which doesn't really occur anywhere else in the world." While models show the surrounding landmasses warming by 3 to 4 degrees Celsius over the coming century, the sea itself will only warm by about 2 degrees or so. "Basically, the difference between the water and the land becomes a smaller with time," he says.

That, in turn, amplifies the pressure differential, adding to the high-pressure area that drives a clockwise circulation pattern of winds surrounding the Mediterranean basin. And because of the specifics of local topography, projections show the two areas hardest hit by the drying trend will be the northwest Africa, including Morocco, and the eastern Mediterranean region, including Turkey and the Levant.

That trend is not just a projection, but has already become apparent in recent climate trends across the Middle East and western North Africa, the researchers say. "These are areas where we already detect declines in precipitation," Eltahir says. It's possible that these rainfall declines in an already parched region may even have contributed to the political unrest in the region, he says.

"We document from the observed record of precipitation that this eastern part has already experienced a significant decline of precipitation," Eltahir says. The fact that the underlying physical processes are now understood will help to ensure that these projections should be taken seriously by planners in the region, he says. It will provide much greater confidence, he says, by enabling them "to understand the exact mechanisms by which that change is going to happen."

Eltahir has been working with government agencies in Morocco to help them translate this information into concrete planning. "We are trying to take these projections and see what would be the impacts on availability of water," he says. "That potentially will have a lot of impact on how Morocco plans its water resources, and also how they could develop technologies that could help them alleviate those impacts through better management of water at the field scale, or maybe through precision agriculture using higher technology."

Physicochemical cargo-switching nanoparticles (CSNP) designed by KAIST can help significantly reduce cholesterol and macrophage foam cells in arteries, which are the two main triggers for atherosclerotic plaque and inflammation.

The CSNP-based combination drug delivery therapy was proved to exert cholesterol-lowering, anti-inflammatory, and anti-proliferative functions of two common medications for treating and preventing atherosclerosis that are cyclodextrin and statin. Professor Ji-Ho Park and Dr. Heegon Kim from KAIST's Department of Bio and Brain Engineering said their study has shown great potential for future applications with reduced side effects.

Atherosclerosis is a chronic inflammatory vascular disease that is characterized by the accumulation of cholesterol and cholesterol-loaded macrophage foam cells in the intima. When this atherosclerotic plaque clogs and narrows the artery walls, they restrict blood flow and cause various cardiovascular conditions such as heart attacks and strokes. Heart attacks and strokes are the world's first and fifth causes of death respectively.

Oral statin administration has been used in clinics as a standard care for atherosclerosis, which is prescribed to lower blood cholesterol and inhibit its accumulation within the plaque. Although statins can effectively prevent the progression of plaque growth, they have only shown modest efficacy in eliminating the already-established plaque. Therefore, patients are required to take statin drugs for the rest of their lives and will always carry the risk of plaque ruptures that can trigger a blood clot.

To address these issues, Professor Park and Dr. Kim exploited another antiatherogenic agent called cyclodextrin. In their paper published in the Journal of Controlled Release on March 10, Professor Park and Dr. Kim reported that the polymeric formulation of cyclodextrin with a diameter of approximately 10 nanometers(nm) can accumulate within the atherosclerotic plaque 14 times more and effectively reduce the plaque even at lower doses, compared to cyclodextrin in a non-polymer structure.

Moreover, although cyclodextrin is known to have a cytotoxic effect on hair cells in the cochlea, which can lead to hearing loss, cyclodextrin polymers developed by Professor Park's research group exhibited a varying biodistribution profile and did not have this side effect.

In the follow-up study reported in ACS Nano on April 28, the researchers exploited both cyclodextrin and statin and form the cyclodextrin-statin self-assembly drug complex, based on previous findings that each drug can exert local anti-atherosclerosis effect within the plaque. The complex formation processes were optimized to obtain homogeneous and stable nanoparticles with a diameter of about 100 nm for systematic injection.

The therapeutic synergy of cyclodextrin and statin could reportedly enhance plaque-targeted drug delivery and anti-inflammation. Cyclodextrin led to the regression of cholesterol in the established plaque, and the statins were shown to inhibit the proliferation of macrophage foam cells. The study suggested that combination therapy is required to resolve the complex inflammatory cholesterol-rich microenvironment within the plaque.

Professor Park said, "While nanomedicine has been mainly developed for the treatment of cancers, our studies show that nanomedicine can also play a significant role in treating and preventing atherosclerosis, which causes various cardiovascular diseases that are the leading causes of death worldwide."

Nestled in the constellation Taurus, a spectacle of swirling cosmic gases measuring half a dozen lightyears across glows in shades of emerald and auburn. The Crab Nebula was born of a supernova, the explosion of a giant star, and now, a lab machine the size of a double door replicates how the immense blasts paint the astronomical swirls into existence.

"It's six feet tall and looks like a big slice of pizza that's about four feet wide at the top," said Ben Musci of the supernova machine he built for a study at the Georgia Institute of Technology.

The machine is also about as thin as a door and stands vertically with the point of the "slice of pizza" at the bottom. A concise detonation in that tip thrusts a blast wave toward the top, and in the middle of the machine, the wave passes through two layers of gas, making them mix turbulently into swirls like those left by supernovas.

Laser light illuminates the swirls, and through a window, a high-speed camera with a close-up lens captures the beauty along with data on a centimeter scale that can be extrapolated to astronomical scales using well-established physics math. Getting the machine to produce results useful for studying nature took two and a half years of engineering adjustments.

Matching up swirls

"We suddenly go from a perfectly still chamber to a little supernova. There was a lot of engineering done to contain the blast and at the same time make it realistic where it hits the gas interface in the visualization window," said Devesh Ranjan, the study's principal investigator and a professor in Georgia Tech's George W. Woodruff School of Mechanical Engineering.

"The hard part was troubleshooting the artifacts that were not part of supernova physics. I spent a year getting rid of things like an extra shock wave bouncing around in the chamber or air leaking in from the room," said Musci, the study's first author and a graduate research assistant in Ranjan's lab. "I also had to make sure that gravity, background radiation, and temperature did not throw off the physics."

The researchers publish their results in The Astrophysical Journal on June 17, 2020. The research was funded by the U.S. Department of Energy's Fusion Energy Science program. Musci plans to collaborate with Lawrence Livermore National Laboratory to compare the machine's gas patterns with actual data on supernova remnants.

Supernova's special blast

Not all nebulas are remnants of supernovas, but many are. They and other supernova remnants start out with a massive star. Stars are balls of gases, which are arranged in layers, and when a star explodes in a supernova, those layers enable the formation of the beautiful swirls.

"On the outside, the gasses have low density and on the inside high density, and very deep in the star, the density begins to force the gases together to make iron in the star's core," Ranjan said.

"After this point, the star runs out of nuclear fuel, so the outward force caused by nuclear fusion stops balancing the inward gravitational force. The extreme gravitation collapses the star," Musci said.

In the center of the star, there is a point explosion, which is the supernova. It sends a blast wave traveling at about a tenth of the speed of light ripping through the gases, jamming their layers together.

Heavier gas in inner layers stabs turbulent outcrops into lighter gas in the outer layers. Then behind the blast wave, pressure drops, stretching the gases back out for a different kind of turbulent mixing.

"It's a hard push followed by a prolonged pull or stretch," Musci said.

Explosive mimics supernova

The researchers used small amounts of a commercially available detonator (containing RDX, or Research Department eXplosive, and PETN, or pentaerythritol tetranitrate) to make the concise miniature blast that sent a clean wave through the interface between the heavier and lighter gases in the machine.

In nature, the blast wave goes out spherically in all directions, and Musci achieved a partial representation of its curvature in the machine's blast wave. In nature and in the machine, interfaces between the gases are full of small, uneven twists and turns called perturbations, and the blast wave whacks them at skewed angles.

"That is important to growing the initial perturbation that leads to turbulence because that unevenness puts a torque on the interface between the gas layers," Musci said.

Convolutions and curlicues ensue to make supernova remnants, which expand for thousands of years to become softer and smoother forms that stir our hearts with their splendor. To physicists, those initial twists are highly recognizable structures interesting for study: Turbulent spikes of heavy gas protruding into light gas, "bubbles" of light gas isolated in areas of heavy gas, and curls typical of early turbulent flow.

"One of the most interesting things we saw related to a mystery about supernovas - they shoot high-density gas called ejecta way out, which may help create new stars. We saw some of this gas propulsion in the device where heavy gas was propagated way out into the light gas," Musci said.

Supernova remnants perpetually expand at speeds of hundreds of miles per second, and the new machine could help refine calculations of those speeds and help characterize remnants' changing forms. The Crab Nebula's supernova was recorded in the year 1054 by Chinese astronomers, but for many other remnants, the machine could also help calculate their moment of birth.

Inertial confinement fusion

The machine's insights would apply in reverse to help with the development of nuclear fusion energy. The process called inertial confinement fusion applies extreme force and heat from the outside inward evenly onto a tiny area where two isotopes of hydrogen gas are layered upon each other, one denser than the other.

The layers are forced together until the atoms' nuclei fuse, unleashing energy. Fusion researchers are striving to eliminate turbulent mixing. What is beautiful in the supernova makes nuclear fusion less efficient.

A new film made of gold nanoparticles changes color in response to any type of movement. Its unprecedented qualities could allow robots to mimic chameleons and octopi -- among other futuristic applications.

Unlike other materials that try to emulate nature's color changers, this one can respond to any type of movement, like bending or twisting. Robots coated in it could enter spaces that might be dangerous or impossible for humans, and offer information just based on the way they look.

For example, a camouflaged robot could enter tough-to-access underwater crevices. If the robot changes color, biologists could learn about the pressures facing animals that live in these environments.

Although some other color-changing materials can also respond to motion, this one can be printed and programmed to display different, complex patterns that are difficult to replicate. The UC Riverside scientists who created this nanomaterial documented their process in a Nature Communications paper published this past week.

Nanomaterials are simply materials that have been reduced to an extremely small scale -- tens of nanometers in width and length, or, about the size of a virus. When materials like silver or gold become smaller, their colors will change depending on their size, shape, and the direction they face.

"In our case, we reduced gold to nano-sized rods. We knew that if we could make the rods point in a particular direction, we could control their color," said chemistry professor Yadong Yin. "Facing one way, they might appear red. Move them 45 degrees, and they change to green."

The problem facing the research team was how to take millions of gold nanorods floating in a liquid solution and get them all to point in the same direction to display a uniform color.

Their solution was to fuse smaller magnetic nanorods onto the larger gold ones. The two different-sized rods were encapsulated in a polymer shield, so that they would remain side by side. That way, the orientation of both rods could be controlled by magnets.

"Just like if you hold a magnet over a pile of needles, they all point in the same direction. That's how we control the color," Yin said.

Once the nanorods are dried into a thin film, their orientation is fixed in place and they no longer respond to magnets. "But, if the film is flexible, you can bend and rotate it, and will still see different colors as the orientation changes," Yin said.

Other materials, like butterfly wings, are shiny and colorful at certain angles, and can also change color when viewed at other angles. However, those materials rely on precisely ordered microstructures, which are difficult and expensive to make for large areas. But this new film can be made to coat the surface of any sized object just as easily as applying spray paint on a house.

Though futuristic robots are an ultimate application of this film, it can be used in many other ways. UC Riverside chemist Zhiwei Li, the first author on this paper, explained that the film can be incorporated into checks or cash as an authentication feature. Under normal lighting, the film is gray, but when you put on sunglasses and look at it through polarized lenses, elaborate patterns can be seen. In addition, the color contrast of the film may change dramatically if you twist the film.

The applications, in fact, are only limited by the imagination. "Artists could use this technology to create fascinating paintings that are wildly different depending on the angle from which they are viewed," Li said. "It would be wonderful to see how the science in our work could be combined with the beauty of art."

DALLAS – June 17, 2020 – The molecular changes that lead to Fuchs’ endothelial corneal dystrophy (FECD) occur decades before the disease causes blurry vision and other noticeable symptoms in patients, new research by UT Southwestern scientists shows. This insight into this earliest stage of FECD may eventually lead to new ways of screening for and treating the common condition, which affects an estimated 4 percent of U.S. adults over the age of 40.   

“We found changes in the pre-symptomatic tissue that would not be readily apparent to ophthalmologists who are examining patients,” says Vinod Mootha, M.D., a professor of ophthalmology at UTSW and a co-senior author of the study. “This molecular cascade of events is initiated decades before we usually detect disease in the clinic.” 

FECD is an age-related, degenerative disease of the cornea – the clear outer layer of the eye. Patients with FECD, which usually affects both eyes at once, experience swelling of the cornea, leading to discomfort and blurry vision.

Over the last decade, Mootha has helped uncover the genetic and molecular drivers of FECD. In 2015, his laboratory co-discovered that most cases of late-onset FECD, appearing in people in their 50s and 60s, are caused by a repetitive section of DNA that gives rise to toxic accumulations of repeat RNA in corneal tissue. The TCF4 gene harbors a three-nucleotide repeat; the number of times this repeat occurs varies among individuals, and people who have more than 40 of the repeats are at the highest risk of FECD. The mechanism is similar to that of other diseases known as degenerative trinucleotide repeat diseases, which include Huntington’s and some forms of amyotrophic lateral sclerosis (ALS).

“For most trinucleotide repeat diseases, it’s impossible to obtain affected tissue, and very hard to study the early stages of disease,” says David Corey, Ph.D., a professor of pharmacology and biochemistry who holds the Rusty Kelley Professorship in Medical Science at UTSW and a co-senior author of the study. “But with the eye, we can actually look at human tissue samples quite easily.”

In the paper, published in the journal Nucleic Acids Research, Corey, an expert in trinucleotide repeat diseases, teamed up with Mootha to better understand how the repeats in TCF4 lead to corneal degeneration. The researchers compared corneal tissue collected during eye surgery from 10 FECD patients with healthy post-mortem tissue from nine eye bank donors. In addition, while screening eye bank samples for inclusion in the study, the researchers discovered six people who had the genetic predisposition for FECD but no outward signs of disease on their corneas yet.

When the researchers compared the patterns of gene expression in the three groups of eye tissue, they pinpointed a number of molecular changes in the corneas of people diagnosed with FECD. Moreover, many of those same changes were already measurable in the eyes of people with the gene for FECD, even though they hadn’t yet developed symptoms.

On average, the FECD patients in the study were 66.5 years old, and the pre-symptomatic patients from the eye bank samples were 46.8 years old, suggesting that molecular changes occur decades before full-fledged disease.

“It was really a surprise that the seeds of eventual dysfunction are sown in the tissue so long before the symptoms are visible,” says Corey.

Many of the molecular changes the team identified in the cornea were related to fibrosis, the thickening and scarring of tissue. That fits with what ophthalmologists see when they examine the eyes of people with FECD, says Mootha, and points toward fibrosis molecules and pathways as possible ways to target the disease with drugs. If levels of the fibrosis-related molecules are altered in the blood of patients before they develop FECD, for instance, a screening test could be developed. 

“Our ultimate goal is to try to slow down or stop the disease process so that patients don’t need corneal transplants,” says Mootha. “Based on the results of this study, we have a much better idea of what’s happening early in the disease process, which lets us better track whether we can reverse those early changes.”

Corey’s research group has already developed one therapeutic approach for treating trinucleotide repeat diseases by blocking the repetitive genetic material. They hope to eventually test that approach on FECD.

Other UTSW researchers who contributed to this study are Yongjun Chu, Jiaxin Hu, Hanquan Liang, Mohammed Kanchwala, Chao Xing, Walter Beebe, Charles B. Bowman, and Xin Gong.

Mootha holds the Paul T. Stoffel/Centex Professorship in Clinical Care.

This research was supported by funds from the National Institutes of Health (R01EY022161, P30EY030413, and R35GM11810), Research to Prevent Blindness, Harrington Discovery Institute, Alfred and Kathy Gilman Special Opportunities in Pharmacology Fund, and Welch Foundation I-1244.

About UT Southwestern Medical Center

UT Southwestern, one of the premier academic medical centers in the nation, integrates pioneering biomedical research with exceptional clinical care and education. The institution’s faculty has received six Nobel Prizes, and includes 24 members of the National Academy of Sciences, 16 members of the National Academy of Medicine, and 13 Howard Hughes Medical Institute Investigators. The full-time faculty of more than 2,500 is responsible for groundbreaking medical advances and is committed to translating science-driven research quickly to new clinical treatments. UT Southwestern physicians provide care in about 80 specialties to more than 105,000 hospitalized patients, nearly 370,000 emergency room cases, and oversee approximately 3 million outpatient visits a year.

Journal

Nucleic Acids Research