Earth

The human brain's meticulous interface with the bloodstream now on a precision chip

image: The blood-brain barrier on a chip is as small as many organs on chips, but it gives astrocytes lots of room to unfold in 3D.

Image: 
Georgia Tech / YongTae Kim lab

A scrupulous gatekeeper stands between the brain and its circulatory system to let in the good and keep out the bad, but this porter, called the blood-brain barrier, also blocks trial drugs to treat diseases like Alzheimer's or cancer from getting into the brain.

Now a team led by researchers at the Georgia Institute of Technology has engineered a way of studying the barrier more closely with the intent of helping drug developers do the same. In a new study, the researchers cultured the human blood-brain barrier on a chip, recreating its physiology more realistically than predecessor chips.

The new chip devised a healthy environment for the barrier's central component, a brain cell called the astrocyte, which is not a neuron, but which acts as neurons' intercessors with the circulatory system. Astrocytes interface in human brains with cells in the vasculature called endothelial cells to collaborate with them as the blood-brain barrier.

But astrocytes are a particularly fussy partner, which makes them a great part of the gatekeeper system but also challenging to culture in a physiologically accurate manner. The new chip catered to astrocytes' sensibilities by culturing in 3D instead of in a flat manner, or 2D.

The 3D space allowed astrocytes to act more naturally, and this improved the whole barrier model by also allowing cultured endothelial cells to function better. The new chip presented researchers with more healthy blood-brain barrier functions to observe than in previous barrier models.

'Astro' in astrocyte

"You need to be able to closely mimic a tissue on a chip in a healthy status and in homeostasis. If we can't model the healthy state, we can't really model disease either, because we have no accurate control to measure it against," said YongTae Kim, an associate professor in Georgia Tech's George W. Woodruff School of Mechanical Engineering and the study's principal investigator.

In the new chip, the astrocytes even looked more natural in the 3D space, unfolding the star-like shape that gives them their "astro" name. In the 2D cultures, by contrast, astrocytes looked like fried eggs with fringes. With this 3D setting, the chip has added possibilities for reliable research of the human blood-brain barrier, where currently alternatives are few.

"No animal model comes close enough to the intricate function of the human blood-brain barrier. And we need better human models because experimental drugs that have successfully entered animal brains have failed at the human barrier," Kim said.

The team published its results on January 10, 2020, in the journal Nature Communications. The research was funded by the National Institutes of Health. Kim has founded a company with plans to mass-produce the new chip in the future for use in academic and potentially pharmaceutical research.

Choosy, bossy astrocytes

The brain is the only part of the body outfitted with astrocytes, which regulate nourishment uptake and waste removal in their own, unique way.

"Upon the brain's request, astrocytes collaborate with the vasculature in real-time what the brain needs and opens its gates to let in only that bit of water and nutrients. Astrocytes go to get just what the brain needs and don't let much else in," Kim said.

Astrocytes form a protein structure called aquaporin-4 in their membranes that are in contact with vasculature to let in and out water molecules, which also contributes to clearing waste from the brain.

"In previous chips, aquaporin-4 expression was not observed. This chip was the first," Kim said. "This could be important in researching Alzheimer's disease because aquaporin-4 is important to clearing broken-down junk protein out of the brain."

One of the study's co-authors, Dr. Allan Levey from Emory University, a highly cited researcher in neurological medicine, is interested in the chip's potential in tackling Alzheimer's. Another, Dr. Tobey McDonald, also of Emory, researches pediatric brain cancer and is interested in the chip's possibilities in studying the delivery of potential brain cancer treatments.

Barrier acting healthy

Astrocytes also gave signs that they were healthier in the chip's 3D cultures than in 2D cultures by expressing less of a gene triggered by pathology.

"Astrocytes in 2D culture expressed significantly higher levels of LCN2 than those in 3D. When we cultured in 3D, it was only about one fourth as much," Kim said.

The healthier state also made astrocytes better able to show an immune reaction.

"When we purposely confronted the astrocyte with pathological stress in a 3D culture, we got a clearer reaction. In 2D, the ground state was already less healthy, and then the reaction to pathological stresses did not come across so clearly. This difference could make the 3D culture very interesting for pathology studies."

Nanoparticle delivery

In testing related to drug delivery, nanoparticles moved through the blood-brain-barrier after engaging endothelial cell receptors, which caused these cells to engulf the particles then transport them to what would be inside the human brain in a natural setting. This is part of how endothelial cells worked better when connected to astrocytes cultured in 3D.

"When we inhibited the receptor, the majority of nanoparticles wouldn't make it in. That kind of test would not work in animal models because of cross-species inaccuracies between animals and humans," Kim said. "This was an example of how this new chip can let you study the human blood-brain barrier for potential drug delivery the way you can't in animal models."

Credit: 
Georgia Institute of Technology

NASA analyzes ex-Tropical Cyclone Damien's rainfall in Western Australia

image: On Feb. 10 at 5:41 a.m. EST (1041 UTC), GPM passed over Western Australia and measured the rate of rainfall from Damien's remnants. GPM showed heaviest rainfall occurring south of the center and falling at a rate of at least 5 mm/0.2 inches (dark blue) per hour.

Image: 
NASA/JAXA/NRL

Tropical Cyclone Damien made landfall on Feb. 9 along the northern Pilbara coast of Western Australia. On Feb. 10, the GPM or Global Precipitation Measurement mission core satellite analyzed the rainfall generated by the remnants that triggered warnings.

As Damien was making landfall around 1:15 a.m. EST (0615 UTC) on Feb. 9, the MODIS instrument aboard NASA's Aqua satellite captured a visible image of the storm. The MODIS image showed the recently developed eye on the coastline. By 11 a.m. EST, Damien's center had moved inland into Western Australia. Tropical Cyclone Damien has weakened to a Category 2 system, according to the Australian Bureau of Meteorology (ABM).

On Feb. 10 at 5:41 a.m. EST (1041 UTC), GPM passed over Western Australia and measured the rate of rainfall from Damien's remnants. GPM showed heaviest rainfall occurring south of the center and falling at a rate of at least 0.2 inches (5 mm) per hour.

The Australian Bureau of Meteorology posted an update at 3 a.m. EST (4 p.m. AWST), Feb. 10, and noted Ex-Tropical Cyclone Damien was located over the northeast Gascoyne, about 62 miles (100 kilometers) north northeast of Meekatharra, moving towards the south.

ABM said, "Ex-Tropical Cyclone Damien is expected to carry with it an area of heavy rainfall as it moves south southeast through the southeastern Gascoyne and the adjacent Goldfields." That heavy rainfall that may lead to flash flooding.

ABM's update noted, "Heavy rainfall is forecast over the southeastern Gascoyne and adjacent Goldfields, this area will gradually move south overnight Monday (Feb. 10). Strong and squally winds are also possible. Locations which may be affected include Mount Magnet, Cue, Leinster and Sandstone."

Since 9 a.m. AWST Monday (8 p.m. EST on Sunday, Feb 9) the following rainfall amounts have been observed: Wiluna Airport 40 mm (1.57 inches) and at Meekatharra 29.8 (1.17 inches).

For updated warnings, visit: http://www.bom.gov.au/wa/warnings/

Credit: 
NASA/Goddard Space Flight Center

Acid-loving microbe can improve understanding of past climate

image: Strains of acid-loving archaea thrive in extreme environments like the Norris Geyser Basin in Yellowstone National Park.

Image: 
Photo by Wil Leavitt.

HANOVER, N.H. - February 10, 2020- Food and energy availability cause physical changes in acid-loving microorganisms that are used to study Earth's climate history, according to research from Dartmouth College.

The finding that factors other than temperature can influence the membranes of single-celled archaea adds to the complexity of paleoclimate studies which have traditionally used the microbe's fossilized remains to reconstruct past climate conditions.

Archaea are one of three major domains of life alongside bacteria and eukarya, the domain that includes animals and plants.

The research result, published in Environmental Microbiology, can help resolve disagreements in paleoclimate research and can support a more detailed understanding of the planet's climate systems.

"Biomarkers, like the fat molecules that make up the cell membranes in our own bodies, can be powerful recorders of the environment that can last for billions of years," said William Leavitt, an assistant professor of earth sciences at Dartmouth. "The motivation of this research was to better explain how archaea respond to all major types of stress in their environment, and how they record that stress in fat molecules that last over geologic time."

Cell membranes are constructed from lipids that protect cells from changes in their surroundings such as temperature, acidity and the availability of food. Fluctuations in those external conditions can cause the organisms to change their membrane structure to aid in survival.

Common ocean-dwelling archaea respond to shifts in temperature by changing the "packing efficiency" of their lipid membranes. The closeness of this side-to-side packing between the individual lipids can be tuned by adjusting the number of molecular rings in the lipids. Counting the number of rings in these preserved lipids allows researchers to use ancient deposits of the microorganisms to determine past ocean temperatures.

While most research on archaeal membranes has focused on species that live in lakes and oceans, the Dartmouth researchers studied thermoacidophiles - acid and heat-loving relatives that originally evolved in hot springs and thrive in some of Earth's most extreme environments. Instead of studying how the microbe reacted to temperature changes, the research team focused on the effects of varying food and energy availability.

"The idea that access to food stimulates membrane changes has recently been proposed in low-temperature archaea that live in the ocean. This is the first demonstration that this effect occurs in high-temperature, acid-loving microbes as well," said Leavitt, who served as the senior researcher on the study.

The Dartmouth lab used a thermoacidophile called Sulfolobus acidocaldarius for the experiments because of its close evolutionary relationship to ocean-dwelling archaea and because it was common in extreme environments throughout much of the planet's past history, giving researchers a window into previous conditions on the planet. The microbe's rapid growth rate also makes it useful in laboratory experimentation.

Researchers placed the organism in a bioreactor with a constant temperature of a scalding 80 degrees Celsius and a pH level close to that of battery acid. By controlling the amount of sugar available to the microbe, the team demonstrated that food levels are directly linked to the number of rings in the membrane.

"This bioreactor-based approach was unique because it allowed us to fully isolate the effect of limiting sugar to these microbes," said Alice Zhou, who served as first author of the study while she was a graduate student at Dartmouth. "This is different from the vast majority of microbiology experiments that are conducted in closed-system batch cultures, where multiple variables such as solution chemistry and population size change over time and confound results."

The research aims to help geologists and climatologists in their efforts to fine-tune records of past sea surface temperatures as they piece together portraits of Earth's past climate.

"It's critical that we are as careful as possible when we interpret the geological record. It is pretty rare that there is just one factor at play. We need to understand all the parameters before we make big-picture projections," said Leavitt.

According to the research team, the existing proxy that relies on data from archaeal membranes to determine past temperatures - known as TEX86 - is accurate in most sea surface environments. However, there are noticeable anomalies in places such as the polar regions where temperatures predicted by TEX86 can disagree with actual measurements.

Because there are conditions under which the current TEX86 proxy may lead to inconclusive results, it is hoped that the research can help refine climate records where disagreements exist.

According to the research, energy limitation is a common phenomenon that causes these microbes to alter the types and structures of lipids produced. This research suggests that the response in lipids to energy limitation may be universal across archaea, and must therefore always be considered when evaluating what lipids recovered from ancient sediments might be telling the research community.

Credit: 
Dartmouth College

Youth with HIV less likely than adults to achieve viral suppression

Despite similar rates of enrollment into medical care, youth with HIV have much lower rates of viral suppression--reducing HIV to undetectable levels--compared to adults, according to an analysis funded by the National Institutes of Health. Among more than 1,000 youth, most of whom were newly enrolled in care at treatment centers throughout the United States, 12% had attained viral suppression, far lower than the 32% to 63% observed in studies of adults over age 24. The findings suggest that after they enroll in an HIV treatment program, a low proportion of youth adhere to care regimens. The study appears in the Journal of Acquired Immune Deficiency Syndrome.

"Our findings indicate an urgency for research on how best to tailor HIV intervention services to the needs of youth," said the study's first author, Bill G. Kapogiannis, M.D., of the Maternal and Pediatric Infectious Diseases Branch at NIH's Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD). The analysis was funded by NICHD, the National Institute on Drug Abuse and the National Institute of Mental Health.

The researchers analyzed data from the Adolescent Medicine Trials Network for HIV/AIDS Interventions (ATN), an NIH-supported network of 13 sites dedicated to the health and care of youth with and at risk for HIV. The youth were enrolled in care through the SMILE (Strategic Multisite Initiative for the Identification, Linkage and Engagement in Care of Youth) Collaborative, a network of clinics at each ATN site that offers diagnostic services and referral to treatment facilities.

Among the 1,411 youth ages 12 to 24 years who were referred to the ATN sites, 75% were enrolled in care, with 34% remaining in care and beginning anti-HIV (antiretroviral) treatment and 12% achieving viral suppression after a median interval of nearly 5 months. Viral suppression occurs when antiretroviral therapy reduces a person's HIV in the blood to an undetectable level. Maintaining viral suppression for at least 6 months after a person's first test finds no detectable levels of the virus prevents the sexual transmission of HIV and allows people with HIV to remain healthy.

On average, youth who were referred to care within a shorter time frame after an HIV diagnosis were more likely to achieve viral suppression. Compared to youth referred to care after three months, those referred within one to six weeks were 2.5 times more likely to reach viral suppression. Those referred from six weeks to three months were roughly twice as likely to reach viral suppression.

To ensure the shortest possible time to enrollment in care, the study authors stressed the importance of enlisting trained peer counselors and of maintaining frequent contact with youth through text and social media messages. They added that additional strategies to ensure that youth enroll and remain in care are urgently needed.

Credit: 
NIH/Eunice Kennedy Shriver National Institute of Child Health and Human Development

Common medication may lower risk of 'broken heart' during bereavement

image: Man with chest pain

Image: 
Pixabay

The increased risk of heart attack or "a broken heart" in early bereavement could be reduced by using common medication in a novel way, according to a world-first study led by the University of Sydney and funded by Heart Research Australia.

Lead Investigator Professor Geoffrey Tofler said while most people gradually adjust to the loss of a loved one, there is an increase in heart attack and death among bereaved people, particularly those grieving a spouse or child.

"The increased risk of heart attack can last up to six months. It is highest in the first days following bereavement and remains at four times the risk between seven days to one month after the loss."

The study, published in the American Heart Journal, is the first randomised controlled clinical trial to show it is possible to reduce several cardiac risk factors during this time, without adversely affecting the grieving process.

"Bereavement following the death of a loved one is one of the most stressful experiences to which almost every human is exposed," said Professor Tofler, Professor of Preventative Cardiology at the University of Sydney's Faculty of Medicine and Health, and Senior Staff Cardiologist at Royal North Shore Hospital.

"Our study is the first clinical trial to examine how the cardiac risk factors could be mitigated during early bereavement."

About the study

The research team from the University of Sydney, Royal North Shore Hospital and the Kolling Institute enrolled 85 spouses or parents in the study within two weeks of losing their family member.

Forty-two participants received low daily doses of a beta blocker and aspirin for six weeks, while 43 were given placebos. Heart rate and blood pressure were carefully monitored, and blood tests assessed blood clotting changes.

"The main finding was that the active medication, used in a low dose once a day, successfully reduced spikes in blood pressure and heart rate, as well as demonstrating some positive change in blood clotting tendency," said Professor Tofler.

The investigators also carefully monitored the grief reaction of participants.

"We were reassured that the medication had no adverse effect on the psychological responses, and indeed lessened symptoms of anxiety and depression," said Professor Tofler.

"Encouragingly, and to our surprise, reduced levels of anxiety and blood pressure persisted even after stopping the six weeks of daily beta blocker and aspirin."

Co-investigator Associate Professor Tom Buckley said the study builds on the team's novel work in this area with their earlier studies among the first to identify the physiological correlates of bereavement.

"While beta blockers and aspirin have been commonly used long term to reduce cardiovascular risk, they have not previously been used in this way as a short-term preventative therapy during bereavement," said Associate Professor Buckley of the University of Sydney Susan Wakil School of Nursing and Midwifery.

Implications and next steps

The authors acknowledge that larger long-term studies are needed to identify who would benefit most however the findings provide encouragement for health care professionals to consider this preventative strategy among individuals that they consider to be at high risk associated with early bereavement.

"Our finding on the potentially protective benefit of this treatment is also a good reminder for clinicians to consider the well-being of the bereaved," said Associate Professor Buckley.

"Future studies are needed to assess if these medications could be used for other short periods of severe emotional stress such as after natural disasters or mass bereavement where currently there are no guidelines to inform clinicians."

Co-investigator Dr. Holly Prigerson, Co-Director of the Center for Research on End-of-Life Care at Weill Cornell Medicine in New York, said, "This is an important study because it shows ways to improve the physical and mental health of at-risk bereaved people. It is a preventive intervention that is potentially practice-changing, using inexpensive, commonly available medicines."

People experiencing cardiac symptoms should discuss their condition with a health care professional before taking medication as incorrect use could be harmful.

Credit: 
University of Sydney

Tumor vs. immune system: A battle to decide the host's fate

image: Figure

Image: 
University of Tsukuba

Tsukuba, Japan - The goal of most cancers is to grow and take over the host's body. The immune system has long been in the crosshairs of cancer researchers, as it plays a central role in defending the human body from foreign invasion. In a new study, researchers from the University of Tsukuba have revealed that tumors that produce a protein called soluble CD155 accumulate in the lungs of mice by disabling the immune system of the animals.

Soluble CD155 is a protein that is made by many different cells in the body and plays an important role in how cells migrate and develop. Surprisingly, several studies by the group at the University of Tsukuba have shown that higher serum levels of soluble CD155 can be found in patients with various types of cancer.

"Correlation does not imply causation," says the corresponding author of the study and associate professor Kazuko Shibuya. "We wanted to know specifically how soluble CD155 is involved in the growth of cancer."

To function, proteins bind to other proteins. CD155 has been shown to bind to the proteins DNAM-1, TIGIT, and CD96, all of which are expressed by various types of immune cells. To achieve their goal, the researchers changed cancer cells, called B16/BL6 melanoma cells, to produce soluble CD155. When injected into normal mice or mice that are deficient in TIGIT or CD96, the soluble CD155-producing B16/BL6 cancer cells were able to settle and grow in their lungs, more so than compared with B16/BL6 cancer cells that had not been changed. Quite the opposite happened, however, when the same experiment was performed with mice deficient in DNAM-1--the researchers could not find a larger tumor in the lungs of the animals.

"Our results show that DNAM-1 was somehow involved in the tumor-promoting actions of soluble CD155," says lead author of the study Genki Okumura. "Our next goal was to explore further how the two proteins interact to enable the growth of cancer".

The researchers then depleted a certain type of immune cells, called natural killer (NK) cells, in the mice and found that all difference between the mice disappeared. In further experiments, they found that soluble CD155 prevented NK cells from releasing small proteins that are toxic to cancer cells by binding to DNAM-1.

"These are striking results that show how a single protein can drastically change the fate of a tumor. Targeting soluble CD155 could therefore be a new powerful strategy to treat cancer," says Shibuya.

Given that tumor cells have to shield themselves from the immune system to grow, finding and disabling their ways to survive could mean defeating the growth and spread of cancer. Targeting soluble CD155 could mean an improved therapy for various types of cancer.

Credit: 
University of Tsukuba

Experimental measurement of the quantum geometric tensor using coupled qubits in diamond

image: The authors exploit the technique of parametric driving to add external periodic modulations to the corresponding Hamiltonian parameters: (a) and (b) correspond to the linear parameters modulation, while (c) corresponds to the elliptical parameters modulation.

Image: 
©Science China Press

The quantum geometric tensor represents a central and ubiquitous concept in quantum mechanics, by characterizing the geometric structure of the Hilbert space. It is responsible to a number of striking phenomena, such as quantum phase transitions and novel topological matters, and has a wide range of applications in the area of quantum information and quantum metrology. The imaginary part of the quantum geometric tensor is corresponding to the well-known Berry curvature, while the real part is corresponding to Riemannian metric which defines the distance of quantum states in parameter space through the overlap of wavefunctions.

Recently, a team led by Jianming Cai and Shaoliang Zhang at Huazhong University of Science and Technology in collaboration with Tomoki Ozawa (Interdisciplinary Theoretical and Mathematical Sciences Program, RIKEN), Nathan Goldman (Universite? Libre de Bruxelles), Martin B. Plenio and Fedor Jelezko (Ulm University) have made breakthrough in experimentally measuring the complete quantum geometric tensor in solid-state spin system. This work has been published on National Science Review.

The experiment was performed in a two-level system of color center in diamond: Firstly, they make use of the coupling between an engineered microwave field and a nitrogen-vacancy (NV) center in diamond to simulate a monopole in parameter space; Secondly, they exploit the technique of parametric driving to add external periodic modulations to the corresponding Hamiltonian parameters: as shown in the figures below, (a) and (b) correspond to the linear parameters modulation, while (c) corresponds to the elliptical parameters modulation.

Finally, they measure the dynamical processes (i.e. Rabi transitions between the dressed eigenstates) induced by parametric modulation. Since the frequencies of Rabi transitions are related to the transition matrix elements that are dependent on the corresponding matrix elements of the quantum geometric tensor, the team is able to achieve the measurement of the full quantum geometric tensor.

This is the first experimental demonstration of direct measurement of the Riemannian metric in solid-state spin system. The technique can also be used to precisely measure the other matrix elements of the quantum geometric tensor, such as Berry curvature.

Furthermore, the researchers have applied this method to an interacting two-qubit system, which consists of an NV center electron spin coupled to a C13 nuclear spin located in the vicinity of the NV center. And they realize the direct measurement of the full quantum geometric tensor in such an interacting quantum system.

These results demonstrate that coherent dynamical responses can serve as a powerful tool to access the geometric and topological properties of quantum systems and open a way to explore the fundamental role of the QGT in various scenarios, ranging from many-body systems to open quantum systems.

Credit: 
Science China Press

The brain of migraine sufferers is hyper-excitable, new study suggests

Individuals who suffer from migraine headaches appear to have a hyper-excitable visual cortex researchers at the Universities of Birmingham and Lancaster suggest.

Migraines are characterised as debilitating and persistent headaches, often accompanied by an increased sensitivity to visual or other sensory stimuli. The exact causes of these headaches are not well understood, although scientists believe they may be related to temporary changes in the chemicals, nerves, or blood vessels in the brain.

In a new study, published in the journal Neuroimage: Clinical, researchers set out to test a theory that at least part of the answer lies in the visual cortex - the part of our brain that is responsible for vision.

Dr Terence Chun Yuen Fong, lead author on the study, explained: "Most migraineurs also report experiencing abnormal visual sensations in their everyday life, for example, elementary hallucinations, visual discomforts and extra light sensitivity. We believe this hints at a link between migraine experiences and abnormalities in the visual cortex. Our results provide the first evidence for this theory, by discovering a specific brain response pattern among migraineurs."

The study was carried out by researchers based in the Centre for Human Brain Health and School of Psychology at the University of Birmingham, and the Department of Psychology, Lancaster University. The team set up an experiment with a group of 60 volunteers, half of whom were 'migraineurs' - regularly suffering from migraines. Participants were presented with a striped grating pattern, and asked to rate the pattern according to whether it was uncomfortable to look at, or any associated visual phenomena from viewing it.

In a further test, the participants underwent an electroencephalogram (EEG) test, in which the researchers were able to track and record brain wave patterns when the visual stimuli were presented.

In both tests, the researchers found a larger response in the visual cortex among the group of migraine sufferers when participants were presented with the gratings.

The study also took into account results from a subgroup of non-migraineurs - participants who reported additional visual disturbances, a common feature of migraines. Surprisingly, it was found that these participants also showed hyperexcitability in the response of their visual cortex.

Dr Ali Mazaheri, the senior author on the paper, explains: "Our study provides evidence that there are likely specific anomalies present in the way the visual cortex of migraine sufferers processes information from the outside world. However, we suspect that is only part of the picture, since the same patterns of activity can also be seen in non-migraineurs who are sensitive to certain visual stimuli."

The next step in this research will be to monitor the group over time to see if their response to the visual stimuli changes as they get close to having a migraine and to try to map what other physiological changes might be occurring. This will pave the way to being able to forecast migraine headaches and help prevent their onset.

Credit: 
University of Birmingham

New world map of fish genetic diversity

In a population of animals or plants, genetic diversity can decline much more quickly than species diversity in response to various stress factors: disease, changes to habitat or climate, and so on. Yet not much is known about fish genetic diversity around the world.

Help on that front is now on the way from an international team of scientists from French universities and ETH Zurich. They have produced the first global distribution map for genetic diversity among freshwater and marine fish. Furthermore, they identified the environmental factors that are instrumental in determining the distribution of genetic diversity. Their study was recently published in the journal Nature Communications.

Genetic diversity is unevenly distributed

To begin their study, the researchers analysed a database that contained the data of over 50,000 DNA sequences representing 3,815 species of marine fish and 1,611 species of freshwater fish. From this sequence data, the scientists estimated the average genetic diversity in sections of bodies of water, each section measuring 200 square kilometres.

Their analysis revealed that genetic diversity is unevenly distributed throughout marine and freshwater fish. The greatest genetic diversity was found among marine fish in the western Pacific Ocean, the northern Indian Ocean and the Caribbean. Among freshwater fish, genetic diversity was greatest in South America, but comparatively low in Europe.

In addition, the researchers determined that temperature is a key factor influencing genetic diversity among marine fish: as the temperature rises, so does diversity. By contrast, the key determinants of genetic diversity in freshwater fish were the complexity of their habitat structure and how their habitats have changed over time.

Impact on nature conservation strategies

The researchers see their study as a tool in efforts to improve conservation of genetic diversity and in turn biodiversity. Their map makes it easier to detect hotspots of species and genetic diversity and to plan appropriate protective action. Maintaining the genetic diversity is crucial, say the researchers. "The more diverse a population's gene pool is, the higher the potential for adaptation to environmental changes," explains Loïc Pellissier, co-?lead author of the study and Professor at ETH's Institute of Terrestrial Ecosystems.

Based on the findings, Pellissier predicts that fish populations will have potentially differing levels of adaptability in various areas of their range. "When setting up conservation areas, this characteristic has to be taken into account with respect to location, size and ecological connectivity," he says.

Protective measures thus far have concentrated primarily on maintaining species diversity. For example, several years ago Switzerland launched a programme for monitoring species diversity within its borders, but Pellissier believes this is not enough. "If we want to protect our biodiversity, we also have to monitor the genetic diversity of populations. This is the only way to ensure that the pool of varied genetic material is large enough to enable the survival of species under changing environmental conditions," he explains.

The current study was made possible by a large number of local researchers who sequenced DNA samples from fish and shared the data in a publicly accessible database (http://www.barcodinglife.org). "This is a clear demonstration of how important open data is for the global study of natural processes," Pellissier says.

Credit: 
ETH Zurich

Quantum technologies: New insights into superconducting processes

image: This is the measurement setup for the characterization of microbridges in a cryostat.

Image: 
Martin Wolff

The development of a quantum computer that can solve problems, which classical computers can only solve with great effort or not at all - this is the goal currently being pursued by an ever-growing number of research teams worldwide. The reason: Quantum effects, which originate from the world of the smallest particles and structures, enable many new technological applications. So-called superconductors, which allow for processing information and signals according to the laws of quantum mechanics, are considered to be promising components for realizing quantum computers. A sticking point of superconducting nanostructures, however, is that they only function at very low temperatures and are therefore difficult to bring into practical applications.

Researchers at the University of Münster and Forschungszentrum Jülich now, for the first time, demonstrated what is known as energy quantization in nanowires made of high-temperature superconductors - i. e. superconductors, in which the temperature is elevated below which quantum mechanical effects predominate. The superconducting nanowire then assumes only selected energy states that could be used to encode information. In the high-temperature superconductors, the researchers were also able to observe for the first time the absorption of a single photon, a light particle that serves to transmit information.

"On the one hand, our results can contribute to the use of considerably simplified cooling technology in quantum technologies in the future, and on the other hand, they offer us completely new insights into the processes governing superconducting states and their dynamics, which are still not understood," emphasizes study leader Jun. Prof. Carsten Schuck from the Institute of Physics at Münster University. The results may therefore be relevant for the development of new types of computer technology. The study has been published in the journal "Nature Communications".

Background and methods:

The scientists used superconductors made of the elements yttrium, barium, copper oxide and oxygen, or YBCO for short, from which they fabricated a few nanometer thin wires. When these structures conduct electrical current physical dynamics called phase slips occur. In the case of YBCO nanowires fluctuations of the charge carrier density cause variations in the supercurrent. The researchers investigated the processes in the nanowires at temperatures below 20 Kelvin, which corresponds to minus 253 degrees Celsius. In combination with model calculations, they demonstrated a quantization of energy states in the nanowires. The temperature at which the wires entered the quantum state was found at 12 to 13 Kelvin - a temperature several hundred times higher than the temperature required for the materials normally used. This enabled the scientists to produce resonators, i.e. oscillating systems tuned to specific frequencies, with much longer lifetimes and to maintain the quantum mechanical states for longer. This is a prerequisite for the long-term development of ever larger quantum computers.

Absorption of a single photon in high-temperature superconductors

Further important components for the development of quantum technologies, but potentially also for medical diagnostics, are detectors that can register even single-photons. Carsten Schuck's research group at Münster University has been working for several years on developing such single-photon detectors based on superconductors. What already works well at low temperatures, scientists all over the world have been trying to achieve with high-temperature superconductors for more than a decade. In the YBCO nanowires used for the study, this attempt has now succeeded for the first time. "Our new findings pave the way for new experimentally verifiable theoretical descriptions and technological developments," says co-author Martin Wolff from the Schuck research group.

Credit: 
University of Münster

Research uncovers new path for melanoma detection and treatment

image: Lead researcher from Edith Cowan University, Associate Professor Elin Gray.

Image: 
Edith Cowan University

A new way to spot melanoma cells circulating in the blood has the potential to significantly improve the monitoring of cancer patients and guide future treatment.

Edith Cowan University's Melanoma Research Group, in collaboration with Harvard Medical School and clinicians at Western Australian hospitals, has pioneered a new technique to detect circulating tumour cells (CTCs) that could provide a new avenue for cancer diagnosis and therapies.

This work builds on the continued success of the Melanoma Research Group, who developed the world's first blood test capable of detecting melanoma in its early stages.

Lead researcher Associate Professor Elin Gray said this new step was the first study to comprehensively describe the immense diversity found in melanoma CTCs.

"These preliminary findings are a first step towards a new way to stop melanoma from spreading around the body," Professor Gray said.

"Cancer spreads around the body when CTCs shed from the primary tumour and travel through the blood to form secondary tumours (metastases) in other organs.

"If we can find a way to reliably detect these cells, then we have a chance to stop melanoma in its tracks with a powerful diagnostic tool and perhaps opportunities for therapies in the future."

Like a needle in a haystack

Until now Melanoma CTCs have proved to be incredibly elusive, with detection rates wildly varying from 40 to 87 per cent.

Professor Gray said this ECU-led research has explained why CTCs have been so hard to find.

"We now understand that CTC detection cannot be resolved with a one-size-fits-all approach," she said.

"There is a huge amount of variety in the shape and bioactivity of these CTCs and so they all look different and respond differently to assay tests.

"To complicate things further, melanoma CTCs are hidden among thousands of other cells and matter in blood. Within one millilitre of blood, there are often fewer than 10 cancer cells among one billion red cells and one million white blood cells.

"It is much like finding a needle in a haystack."

A new approach

Armed with a better understanding of the complexity of the task, the researchers tried a multifaceted approach to detecting melanoma CTCs.

"By combining three assays together, we raised detection rates to 72 per cent, which was a significantly and consistently higher result than using one test," Dr Gray said.

"We are confident this approach is a move towards the reliable detection of CTCs, but we now need to tweak the assay to include a better combination to capture the broadest range of CTCs."

The ECU Melanoma Research Group is now working with artificial intelligence experts to fast-track the identification of CTCs.

The latest research was published in the British Journal of Cancer.

Credit: 
Edith Cowan University

New research shows that El Niño contributes to insect collapse in the Amazon

image: Dichotomius enceladus, the largest dung-roller beetle species in the study region photographed while rolling a golf ball-sized morsel of dung within an undisturbed forest in the Santarém region of the Brazilian state of Pará, 2017

Image: 
Filipe França

Hotter and drier El Niño events are having an alarming effect on biodiversity in the Amazon Rainforest and further add to a disturbing global insect collapse, scientists show.

A new study focusing on the humble, but ecologically key, dung beetle has revealed for the first time that intense droughts and wildfires during the last El Niño climate phenomenon, combined with human disturbance, led to beetle numbers falling by more than half - with effects lasting for at least two years.

Although the El Niño of 2015-16 captured less attention than the deforestation fires of 2019, it delivered a very significant drought and, in combination with human activities such as agriculture and deforestation, contributed to mega wildfires that burned more than 3 million hectares of Amazon forests, including a million hectares in just one region.

The effects of droughts and wildfires on Amazonia's trees have been studied for decades, but researchers were less clear about the impacts on fauna and the role they have in ecosystem functioning.

Dung beetles are key for spreading nutrients and seeds, and they are important indicator insects used to gauge the overall health of an ecosystem.

An international team of scientists from the UK, Brazil and New Zealand counted more than 14,000 dung beetles from 98 species across 30 forest plots in the Brazilian state of Pará, within the Amazon, through several surveys conducted between 2010 and 2017. They also monitored how much dung was removed and how many seeds were dispersed by dung beetles.

The researchers counted around 8,000 beetles across the plots in 2010. However, in 2016, following the El Niño, numbers had plummeted to around 3,700 and in 2017 they found just 2,600 beetles.

Human disturbance, through activities such as deforestation and predatory logging, significantly increases the flammability of the forests - as forest fires do not occur naturally in the Amazon.

All surveyed forests saw beetle numbers fall, though the results also show that forests that burned had fewer beetles than those areas that had just experienced drought.

"Our investigation provides important insights into how human activities and climate extremes can act together and affect tropical forest biodiversity and ecosystem functioning," said lead researcher Dr Filipe França from the Lancaster Environment Centre at Lancaster University and associate researcher at Embrapa Amazônia Oriental in Brazil.

He also said that "The loss of these hardworking beetles could indicate a wider problem that many mammals living in the forest may have also succumbed to the drought and fires. Dung beetles depend on mammal's poo for nesting and feeding, therefore declining in beetles are likely associated with the loss of mammals due to that El Niño drought and fires."

Previous research has shown that mammal presence has a large influence on dung beetles.

The loss of beetles may indicate other animals were lost, but also raises concerns that forest regeneration will be negatively affected after extreme drought and fire events.

"We found far fewer dung beetles after the El Niño event, and those that survived were struggling to do their work of spreading nutrients and seeds in forests already impacted either by drought alone or in areas that also experienced fires", explained Professor Rodrigo Fadini from the Federal University of Western Pará in Brazil.

Taken together, the research findings suggest that human activities can interact with climate extremes in different ways and that, combined or not, these disturbances can threat the delicate balance of tropical forest fauna, including insects, and their key contribution to ecosystem processes.

Professor Jos Barlow from the Federal University of Lavras in Brazil and Lancaster University, said: "Tropical forests around the globe are increasingly threatened by anthropogenic climate change, local human disturbances and more frequent and severe weather extremes. We need actions to mitigate the ongoing climate and biodiversity crisis if we want to keep the forest biodiversity and its contribution to people for future generations."

Credit: 
Lancaster University

Family dynamics may influence suicidal thoughts in children

Death by suicide in children has reached a 30-year high in the United States. During middle and high school, 10 to 15% of kids have thoughts of suicide, according to the Centers for Disease Control and Prevention.

How early in a child's life do these thoughts begin? New research from Washington University in St. Louis is narrowing the gap in psychology's understanding of suicidal thoughts in young people, the findings show that such thoughts begin as early as 9 and 10 years old.

Further, family conflict and parental monitoring are significant predictors of suicidal thoughts, and the majority of children surveyed had caregivers who either didn't know, or didn't report, the suicidal thoughts of the children in their charge.

"There's already been press about suicidal ideation in teenagers," said Deanna Barch, chair and professor of Psychological & Brain Sciences in Arts & Sciences and professor of radiology in the School of Medicine "But there's almost no data about rates of suicidal ideation in this age range in a large population sample."

The results were published in the JAMA Network Open.

The study, conducted by Barch and Diana Whalen, PhD, psychiatry instructor at the School of Medicine, as well as colleagues at the Laureate Institute for Brain Science, looked at 11,814 9- and 10-year-olds from the Adolescent Brain Cognitive Development (ABCD) study, a national, longitudinal study on adolescent brain health in which caretakers also participate.

Dividing suicidal thoughts and actions into several categories, researchers found that 2.4 to 6.2% of the children reported having thoughts about suicide, from wishing they were dead to devising -- but not carrying out -- a plan.

When it came to actions, they saw 0.9% of these 9- and -10-year-olds said they had tried to commit suicide; 9.1% reported non-suicidal self-injury.

Going into this study, Barch said she did not know what to expect, but she did expect to see nontrivial amounts of suicidal thoughts in this age group.

"There were two reasons I was sure," she said. "When you look at the CDC rate of kids in middle and high school who have these thoughts, it's pretty high. It's clear that they weren't arising out of the blue."

The second reason she was prepared: In previous work, she had already seen suicidal thoughts in preschoolers.

Also of note are some discrepancies seen between males and females. Specifically, males showed more suicidal thoughts and more non-suicidal self-injury than the girls; these trends reverse as people age, studies show.

"We don't really know why ," Barch said. "By the time adolescence hits, the rates go up for everyone, but they go up disproportionately for girls. The discrepancy was completely unexpected."

Another group that may have found the results unexpected: caregivers.

This is the age when kids and their caregivers generally tend to give different reports of internal experiences, Barch said, but still, the disconnect between self-reports of suicidal thoughts and caregivers' reports of their kids' thoughts diverged widely. In more than 75% of cases where children self-reported suicidal thoughts or behaviors, the caregivers did not know about  the child's experience.

The nature of the ABCD study, following the children over time, will allow researchers to tease out this apparent contradiction. "One question is going to be whether one of those reports" -- that of the child or the caregiver -- "is more predictive than the other of how the kids do over time," Barch said.

In fact, caregivers seem to play an important role when it comes to suicidal thoughts and behaviors in this young age group. After adjusting for sex, family history, and other variables, family conflict was a predictor of suicidal thoughts and non-suicidal self-injury. Monitoring by a caretaker was also predictive of those measures, as well as suicide attempts.

Historically, the belief has been that people don't need to ask kids about suicidal thoughts before adolescence, Barch said. "Our data suggests that's absolutely not true. Kids are having these thoughts. They're not at the same rates as adults, but they are nontrivial."

She suggested parents, caregivers and people working with children should be aware of the possibility that a 9-year-old is thinking about suicide.

"If you have kids who are distressed in some way, you should be asking about this," she said. "You can help identify kids that might be in trouble."

Credit: 
Washington University in St. Louis

Understanding unexplained low blood sugar in children: More than normal variation

Lisa is two years old. She often gets uneasy--shaking and sweating--especially in the morning. She vomits and refuses to eat. Her mother, Karoline, knows she has to act before Lisa starts to deteriorate.

To avoid convulsions and loss of consciousness, Karoline desperately tries to give Lisa sugar-rich drinks but has to proceed with energy gel applications on Lisa's chin and today, also an intramuscular glucagon injection. Lisa improves, but it takes hours before she wants to eat and drink normally again.

-It's because of the accelerated fat burn, explains Yazeid Alhaidan, PhD.

Alhaidan has spent three years trying to understand the genetic background of IKH in children like Lisa.

Looking for genetic explanations

-Lisa's sugar deposits are somehow ineffective, so a normal night's fasting after high physical activity the day before can be enough to provoke low blood glucose (sugar) and toxic substances like acetone because of accelerated fat burn, Yazeid Alhaidan explains.

-And then she gets nausea and vomits. This will not stop until she burns sugar again and her fat-burn ketones have been eliminated, and this can take several hours.

Idiopathic ketotic hypoglycemia (IKH) is often relatively mild and may remain undiagnosed. Luckily it often disappears with age. But severe variants, sometimes affecting several family members, have prompted the research team at the Complex Hypoglycemia Center, Odense University Hospital, Denmark, to dive more deeply into potential new genetic explanations for this disease.

Previously unknown causes of low blood sugar

-We have identified four novel genes that appear to explain the IKH in at least four families, Alhaidan continues.

-I searched in all 22,000 genes in the human genome and was lucky to be able to pinpoint mutations in NCOR1, IGF2BP1, SGLT2, and NEK11 in four families with IKH.

These genes are related in different ways to glucose metabolism and may well be previously unknown causes of low blood sugar. Known genetic causes were identified in four other families while no mutations were found in nine families.

First step towards new drugs

-Every gene involved in glucose metabolism and low blood sugar is of high interest for diabetes research, says Henrik Thybo Christesen, professor in pediatric endocrinology and leader of the Complex Hypoglycemia Center.

To understand the genetics in children like Lisa may be the first step in designing a novel drug against diabetes.

-In type 2 diabetes, you want to lower the blood sugar. If you can design a drug that acts like the mutation in patients like Lisa, you may have a successful treatment, provided the blood sugar doesn't get too low and the side effects are acceptable, explains Professor Christesen.

More studies needed

Molecular biologist and associate professor Klaus Brusgaard, who has led the study,calls for caution.

Although the mutations in the four novel genes seem to be severe and potentially disease-causing, more studies are needed to show their exact functional significance.

-If other researchers can find mutations in the same genes in other patients, this will also be helpful. Until then, we can only call them candidate genes. Our study may be the first of many to identify novel genetic explanations for IKH--which may also end up being split into many specific diseases. And each novel disease may have its own treatment. That's what we call precision medicine, Dr Brusgaard explains.

Credit: 
University of Southern Denmark Faculty of Health Sciences

Build it and they will come

image: Convention: Arterial roads, Garden Ring, Third Transport Ring, Moscow Ring Road (MKAD), Moscow Small Ring (MMK), Moscow Ring Railway (MKZhD)/ Zones of the Moscow agglomeration: Centre (TsDR), New Residential-Business Belt, Housing Belt, Belt of Subcentres, Suburban Belt, Peripheral Belt/ Original state of territories used for construction: High-density housing construction, Tear-downs or reconstruction, Industrial zone, Territory free from construction

Image: 
Image courtesy of Nikolay Kurichev

Migration, both domestic and abroad, is playing a major role in transforming the world's largest cities, and Moscow is no exception. Researchers at HSE University, the Institute of Geography of the Russian Academy of Sciences (IGRAN) and Strelka KB identified which cities' residents are buying newly built apartments in the capital and how economic inequality between Russia's regions is changing the face of the city.

Major cities are the backbone of any modern economy and a gateway between national economies and international markets. People move to such cities for the sake of superior education, good jobs, the higher quality of life and personal prospects. But before all else, they need housing.

Moscow and the Moscow region are vivid examples of how a major influx of migrants and the resultant housing boom can transform a city and its environs. Such metamorphoses are apparent to even the untrained eye, but surprisingly little research has been conducted on the subject --with regard to Moscow as well as other cities. There are various theoretical models of spatial equilibrium that describe the relationship between migration, economic stimuli and intangible factors that make this or that territory attractive, but there are practically no studies analysing the empirical data with regard to Russian cities.

The regulatory framework governing the market for land determines what is built, where, and at what price in metropolitan areas. The influx of migrants also drives up prices and the number of new housing starts. Migrants from wealthier regions and those hailing from areas with lower incomes purchase housing in different price categories and in different parts of the city. For this reason, prices along with inter-regional inequality determine how attractive the city is for migration. After all, it is problematic to move to a city that offers no affordable housing.

Six Concentric Belts

The researchers based their work on data on temporary labour migrants, those who took up permanent residence in the Moscow region, information on housing construction in Moscow and the Moscow region, as well as on a depersonalized customer base in the primary housing market.

In analysing the housing data, researchers identified 877 multi-storey residential projects with a total housing area of 37.5 million sq. ft that were at the stage of either construction or sale in 2015. Each is located in one of six concentric belts: three in the core and three in the suburban zone.

At the core of the metropolitan area is a business district within the Garden Ring, a residential and business belt at the site of former industrial zones along the Third Transport Ring and a residential belt within the MKAD. The suburban zone includes a belt of sub-centres within 10 km of the Moscow Ring Road, a suburban belt within the Moscow Small Ring (MMK) and a peripheral belt beyond that.

By analysing these data, the researchers were able to assess the share of non-resident buyers in the Moscow housing market and compare that to migration activity.

It turns out that among the buyers of Moscow region real estate, the residents of cities with a population of 100,000-250,000 are the most active in relation to their numbers. These include residents of such cities as Kovrov, Novomoskovsk, Murom and Novocheboksarsk. It is primarily residents of larger cities who buy apartments in Moscow itself. They hail from oil and gas centres such as Surgut and Nizhnevartovsk or neighbouring regional centres such as Vladimir, Smolensk and Tula. They have both the incentive and the opportunity to relocate. It is very difficult for the residents of small cities and rural areas to save enough money to buy housing in even the outlying Moscow region, and the residents of Russia's megacities see Moscow as offering little advantage over their own locations.

Homebuyers from the poorer regions focus on the zone between the Moscow Ring Road and MMK that lies approximately 30 km from the city centre and where up to 70% of all new housing was built in 2015-2017. (The zone lying 10 km. from the centre saw half as much new housing construction.) From this distance, the commute to jobs in central Moscow takes about 70-80 minutes.

In the nearby Moscow region, where a huge pool of low-cost housing is concentrated, the proportion of buyers from other regions is growing, reaching an average of 24%. That figure is as high as 35%-45% for the buyers of inexpensive housing located 25 km. or more from the city centre.

The nearby suburban zone of the capital is the main 'territory of entry' for migrants, and housing construction in the Moscow suburbs is the most important mechanism for limiting prices on housing in the region and maintaining economic incentives for large-scale migration to the capital region.

How to Manage an Anthill

'There are many studies on how the city or agglomeration develops, on the relationship between migration and economic incentives,' said Nikolay Kurichev, Dean and Associate Professor of the HSE University Faculty of Geography and Geoinformation Technologies and Senior Researcher at the IGRAN. 'However, there are practically no articles examining how people coming from different regions are distributed within the city.'

The researcher said that U.S. studies reveal that strict construction regulation influences how urban agglomerations develop in terms of the dynamics of employment, nominal wages, housing prices, supply volume, migration flow and population. There are also Chinese studies showing the correlation between the affordability of housing and migration from rural areas to the cities. Lithuanian studies have shown that limiting housing construction tends to constrain long-term growth of the population in an agglomeration by forcing housing prices upward. Kurichev notes, however, that in existing studies the spatial structure of the city and its interaction with domestic migrations are considered in isolation.

The geographer says that the results of the new work are important for the spatial development strategy of not only the Moscow region but of the whole country. Regulation of construction of the 30-km zone beyond the Moscow Ring Road -- a tiny sliver compared to the area of the entire country -- is the key to managing migration to Moscow and the Moscow region and, by extension, the national issue of relocation. The Moscow metropolitan area is now undergoing extensive development, diminishing the quality of life for everyone and destroying the ecological underpinnings of the region.

The current urban development policy and the reality of the market for land in the Moscow region are actually stimulating this process. By investing in the construction of roads and metro lines, by funding housing construction -- including through renovation -- Moscow promotes a further influx of migrants and an outflow of skilled personnel from other Russian cities, diminishing their human capital. It thus becomes a vicious circle: by 'luring' people from the regions, the capital becomes even more attractive for the next wave of migrants.

Credit: 
National Research University Higher School of Economics