Earth

While global sea levels are rising due to the climate crisis and threatening near-coastal infrastructures, higher temperatures in other areas are having exactly the opposite effect. The water levels are falling and also causing massive problems. Although the consequences are equally serious, however, declining water levels are receiving less attention according to Matthias Prange, Thomas Wilke of the Justus Liebig University in Gießen, and Frank P. Wesselingh of the University of Utrecht and the Naturalis Biodiversity Center Leiden (the Netherlands).

"The Caspian Sea can be viewed as representative of many other lakes in the world. Many people are not even aware that an inland lake is dramatically shrinking due to climate change, as our models indicate," says Matthias Prange. The report of the Intergovernmental Panel on Climate Change (IPCC) also failed to mention lakes, and disregarded the social, political and economic consequences of global warming on the affected regions. "This has to change. We need more studies and a better understanding of the consequences of global warming in this region." The goal must be to raise awareness of the consequences of climate change for inland seas and lakes so that appropriate strategies can be developed, including approaches for other large lakes and regions facing similar challenges.

Because of its size (it is the largest lake in the world) and because of its relatively high salinity of about one per cent, which is about one-third of the salt concentration in the oceans, the Caspian has been named a 'Sea'. Its largest inflow is the Volga River and it has no natural connection to the ocean. The water level is determined by the proportional influences of inflow, precipitation and evaporation. Global warming is causing increased evaporation, which results in a declining water level.

The Caspian Sea is an important regional water reservoir and, despite its salt content, a biological and commercial center. It is bounded by Kazakhstan, Turkmenistan, Iran, Azerbaijan and Russia. Depending on the degree of global warming in the future, the water level could fall by 9 to 18 meters during this century. "This would affect not only the biodiversity, various species, and habitats that would disappear. The economies of all the bordering countries would be impacted, including harbors, fisheries and fish farming." For this reason, the authors argue that in the future the Caspian Sea should be used as an example in scientific research to assess the vulnerability of certain regions to falling water levels. Because no nation can solve the resulting conflicts alone, they propose a global task force to develop and coordinate strategies. The article suggests that "international climate funds" could offer a possibility for financing projects and adaptation measures if changes in the lake level are attributed to climate change.

MADISON -- The proliferation of face coverings to keep COVID-19 in check isn't keeping kids from understanding facial expressions, according to a new study by University of Wisconsin-Madison psychologists.

It's easiest to understand the emotions of the people around you by taking in all the hints they're dropping, on purpose or otherwise. Yet when people cover some of their facial expressions, they take some of those cues away.

"We now have this situation where adults and kids have to interact all the time with people whose faces are partly covered, and a lot of adults are wondering if that's going to be a problem for children's emotional development," says Ashley Ruba, a postdoctoral researcher in UW-Madison's Child Emotion Lab.

The researchers showed more than 80 children, ages 7 to 13, photos of faces displaying sadness, anger or fear that were unobstructed, covered by a surgical mask, or wearing sunglasses. The kids were asked to assign an emotion to each face from a list of six labels. The faces were revealed slowly, with scrambled pixels of the original image falling into their proper place over 14 stages to better simulate the way real-world interactions may require piecing things together from odd angles or fleeting glimpses.

The kids were correct about the uncovered faces as often as 66 percent of the time, well above the odds (about 17 percent) of guessing one correct emotion from the six options. With a mask in the way, they correctly identified sadness about 28 percent of the time, anger 27 percent of the time, and fear 18 percent of the time.

"Not surprisingly, it was tougher with parts of the faces covered. But even with a mask covering the nose and mouth, the kids were able to identify these emotions at a rate better than chance," says Ruba, who published results today in the journal PLOS ONE with co-author Seth Pollak, a UW-Madison psychology professor.

Variations in the results reflect differences in the way emotional information is conveyed by the face. Sunglasses made anger and fear difficult to identify, suggesting the eyes and eyebrows are important to those facial expressions. Fear, often confused with surprise, was also the trickiest for children to spot behind a mask -- which may have complicated matters by covering clues like surprise's signature mouth shape. :O

If children can do better than guessing at emotions even with a mask in place, they're likely to do even better in real-life situations.

"Emotions aren't conveyed solely through your face," Ruba says. "Vocal inflections, the way that someone positions their body, and what's going on around them, all that other information helps us make better predictions about what someone is feeling."

It all adds up to kids growing in their emotional capabilities, even if some of their interactions with others are happening through face coverings.

"I hope this settles some nerves," Ruba says. "Kids are really resilient. They're able to adjust to the information they're given, and it doesn't look like wearing masks will slow down their development in this case."

How can conifers that are used for example as Christmas trees keep their green needles over the boreal winter when most trees shed their leaves? Science has not provided a good answer to this question but now an international team of scientists, including researchers from Umeå University, has deciphered that a short-cut in the photosynthetic machinery allows the needles of pine trees to stay green. The study was published in the journal Nature Communications.

In winter, light energy is absorbed by the green chlorophyll molecules but cannot be utilized by the downstream reactions in the photosynthetic machinery as freezing temperatures stop most biochemical reactions. This is especially a problem in the early spring when temperatures can still be very low, but sunlight is already strong, and the excess light energy can damage the proteins of the photosynthetic machinery. The researchers showed that the photosynthetic apparatus is wired in a special way which allows pine needles to stay green all year long.

Under normal conditions, the two photosystems, the two functional units where light energy is absorbed and converted into chemical energy, are kept apart from each other to prevent a short-cut and allow efficient photosynthesis. In winter, the structure of the thylakoid membrane, where the two photosystems are located, is reorganized which brings the two photosystems in physical contact. The researchers showed that photosystem II donates energy directly to photosystem I and this short-cut mode protects the green chlorophyll and the needles when conditions become harsh.

"We have followed several pine trees growing in Umeå in northern Sweden over three seasons," says Pushan Bag, PhD student at Umeå University, who has collected samples all around the year and made many of the analyses. "It was essential that we could work on needles "straight from outdoors" to prevent that they adjusted to the higher temperatures in the lab environment before we analysed them for example with electron microscopy which we used to visualize the structure of the thylakoid membrane".

All plants have safety valves to deal with the excess light energy which is either dissipated as heat or as fluorescence light. However, only conifers seem to have such powerful valves that they can keep the photosynthetic apparatus intact over the extreme boreal winter. The research team combined biochemistry and ultrafast fluorescence analysis, a very sophisticated method that can resolve chlorophyll fluorescence light at a picosecond time scale. Like this, they could demonstrate how the pine needles deal with excess light energy to protect their sensitive photosynthetic apparatus from damage.

"We needed to adjust the equipment to study pine needles in cold temperatures in order to trap the unique mechanism," explains Volha Chukhutsina from Vrije Universiteit Amsterdam, who has performed much of the ultrafast fluorescence analysis. "We also tried spruce needles but they were hard to fit in a good way into the equipment."

Alfred Holzwarth, who has developed the time-resolved fluorescence measurements adds: "The pine needles gave us the opportunity to study this shortcut mechanism - also called spill-over - as they really show an extreme adaptation".

The study was done with pine trees, but the researchers believe that the mechanism is probably similar for other conifer species - like the typical Christmas trees spruces and firs - because their photosynthetic apparatus is similar.

"This remarkable adaptation not only enjoys us during Christmas but is in fact extremely important for mankind," says professor Stefan Jansson from Umeå University. "Hadn´t conifers been able to survive in extreme harsh winter climates vast areas in the northern hemisphere may not have been colonized as conifers provided firewood, housing and other necessities. Still today they form the basis of the economy in most of the circumpolar taiga region."

Anyone entering the world of quantum physics must prepare themself for quite a few things unknown in the everyday world: Noble gases form compounds, atoms behave like particles and waves at the same time and events that in the macroscopic world exclude each other occur simultaneously.

In the world of quantum physics, Reinhard Dörner and his team are working with molecules which - in the sense of most textbooks - ought not to exist: Helium compounds with two atoms, known as helium dimers. Helium is called a noble gase precisely because it does not form any compounds. However, if the gas is cooled down to just 10 degrees above absolute zero (minus 273 °C) and then pumped through a small nozzle into a vacuum chamber, which makes it even colder, then - very rarely - such helium dimers form. These are unrivaledly the weakest bound stable molecules in the Universe, and the two atoms in the molecule are correspondingly extremely far apart from each other. While a chemical compound of two atoms commonly measures about 1 angstrom (0.1 nanometres), helium dimers on average measure 50 times as much, i.e. 52 angstrom.

The scientists in Frankfurt irradiated such helium dimers with an extremely powerful laser flash, which slightly twisted the bond between the two helium atoms. This was enough to make the two atoms fly apart. They then saw - for the very first time - the helium atom flying away as a wave and record it on film.

According to quantum physics, objects behave like a particle and a wave at the same time, something that is best known from light particles (photons), which on the one hand superimpose like waves where they can pile upor extinguish each other (interference), but on the other hand as "solar wind" can propel spacecraft via their solar sails, for example.

That the researchers were able to observe and film the helium atom flying away as a wave at all in their laser experiment was due to the fact that the helium atom only flew away with a certain probability: With 98 per cent probability it was still bound to its second helium partner, with 2 per cent probability it flew away. These two helium atom waves - Here it comes! Quantum physics! - superimpose and their interference could be measured.

The measurement of such "quantum waves" can be extended to quantum systems with several partners, such as the helium trimer composed of three helium atoms. The helium trimer is interesting because it can form what is referred to as an "exotic Efimov state", says Maksim Kunitski, first author of the study: "Such three-particle systems were predicted by Russian theorist Vitaly Efimov in 1970 and first corroborated on caesium atoms. Five years ago, we discovered the Efimov state in the helium trimer. The laser pulse irradiation method we've now developed might allow us in future to observe the formation and decay of Efimov systems and thus better understand quantum physical systems that are difficult to access experimentally."

Serotonin is a neurochemical that plays a critical role in the way the brain controls our thoughts and feelings. For example, many antidepressants are designed to alter serotonin signals sent between neurons. In an article in Cell, National Institutes of Health-funded researchers described how they used advanced genetic engineering techniques to transform a bacterial protein into a new research tool that may help monitor serotonin transmission with greater fidelity than current methods. Preclinical experiments, primarily in mice, showed that the sensor could detect subtle, real-time changes in brain serotonin levels during sleep, fear, and social interactions, as well as test the effectiveness of new psychoactive drugs. The study was funded, in part, by the NIH's Brain Research through Advancing Innovative Neurotechnologies (BRAIN) Initiative which aims to revolutionize our understanding of the brain under healthy and disease conditions.

The study was led by researchers in the lab of Lin Tian, Ph.D., principal investigator at the University of California Davis School of Medicine. Current methods can only detect broad changes in serotonin signaling. In this study, the researchers transformed a nutrient-grabbing, Venus flytrap-shaped bacterial protein into a highly sensitive sensor that fluorescently lights up when it captures serotonin. Previously, scientists in the lab of Loren L. Looger, Ph.D., Howard Hughes Medical Institute Janelia Research Campus, Ashburn, Virginia, used traditional genetic engineering techniques to convert the bacterial protein into a sensor of the neurotransmitter acetylcholine. The protein, called OpuBC, normally snags the nutrient choline, which has a similar shape to acetylcholine. For this study, the Tian lab worked with Dr. Looger's team and the lab of Viviana Gradinaru, Ph.D., Caltech, Pasadena, California, to show that they needed the added help of artificial intelligence to completely redesign OpuBC as a serotonin catcher.

The researchers used machine learning algorithms to help a computer 'think up' 250,000 new designs. After three rounds of testing, the scientists settled on one. Initial experiments suggested that the new sensor reliably detected serotonin at different levels in the brain while having little or no reaction to other neurotransmitters or similarly shaped drugs. Experiments in mouse brain slices showed that the sensor responded to serotonin signals sent between neurons at synaptic communications points. Meanwhile, experiments on cells in petri dishes suggested that the sensor could effectively monitor changes in these signals caused by drugs, including cocaine, MDMA (also known as ecstasy) and several commonly used antidepressants.

Finally, experiments in mice showed that the sensor could help scientists study serotonin neurotransmission under more natural conditions. For instance, the researchers witnessed an expected rise in serotonin levels when mice were awake and a fall as mice fell asleep. They also spotted a greater drop when the mice eventually entered the deeper, R.E.M. sleep states. Traditional serotonin monitoring methods would have missed these changes. In addition, the scientists saw serotonin levels rise differently in two separate brain fear circuits when mice were warned of a foot shock by a ringing bell. In one circuit - the medial prefrontal cortex - the bell triggered serotonin levels to rise fast and high whereas in the other - the basolateral amygdala - the transmitter crept up to slightly lower levels. In the spirit of the BRAIN Initiative, the researchers plan to make the sensor readily available to other scientists. They hope that it will help researchers gain a better understanding of the critical role serotonin plays in our daily lives and in many psychiatric conditions.

December 23, 2020 - For patients receiving spinal cord stimulation (SCS) for chronic pain, integration with an immersive virtual reality (VR) system - allowing patients to see as well as feel the effects of electrical stimulation on a virtual image of their own body - can enhance the pain-relieving effectiveness of SCS, reports a study in PAIN®, the official publication of the International Association for the Study of Pain (IASP). The journal is published in the Lippincott portfolio by Wolters Kluwer.

The integrated SCS-VR approach improves pain control over SCS alone, with fast-acting and long-lasting effects that may increase with repeated use, according to the new collaborative research by Olaf Blanke, MD, of Ecole polytechnique fédérale de Lausanne (EPFL), Geneva, Switzerland, Ali Rezai, MD, of West Virginia University Rockefeller Neuroscience Institute, and Vibhor Krishna MD, PhD, of the Ohio State University and their colleagues. "To our knowledge this study shows, for the first time that it is possible to integrate immersive and multisensory VR with spinal neuromodulation and reduce chronic pain," the researchers write.

Integrated SCS-VR puts patients in the picture to help control chronic pain

Drs. Blanke, Rezai, Krishna and their team tested their integrated SCS-VR "digiceutical" method in 15 patients with chronic leg pain. All patients already had SCS implants for chronic leg pain, in most cases related to failed back surgery syndrome.

Spinal cord stimulation uses mild electrical impulses to interrupt pain signals before they reach the brain. While SCS is an effective and increasingly common treatment for chronic pain, it has limitations: stimulation reduces pain in only about half of patients and rarely eliminates pain completely.

Previous studies have shown that immersive and embodied VR - integrating an image of the patient's body or avatar into a 3D scene viewed in a VR headset - may have pain-relieving properties. The new approach integrates SCS with VR for the first time, allowing patients to "see" and "feel" the effect of SCS on a real-time virtual image of their own body or avatar. The stimulated area of the patient's virtual leg as shown in VR "lit up" when the electrical current was on.

For example, if the right thigh tingled during SCS, the same area of the patient's virtual thigh was illuminated in VR. In the new study, pain scores with integrated SCS-VR were compared with VR alone, with SCS turned off; and with "incongruent" SCS-VR, with SCS turned on but a different area of the virtual scene illuminated.

The results showed lower pain ratings when integrated SCS-VR was used. Average pain score (on a continuous visual analog scale) decreased from 6.2 before treatment to 2.72 with "congruent" SCS-VR - when the stimulated area of the leg "lit up" during SCS. Pain scores decreased by an average of 44 percent with congruent SCS-VR, compared to 23 percent with incongruent SCS-VR. Virtual reality alone had little or no effect on pain scores.

All but 1 of the 15 patients had reduced pain scores during SCS-VR. Importantly and in contrast to the control conditions, the effect lasted for at least ten minutes after SCS was turned off; repeated applications of SCS-VR had larger effects on pain scores. VR-SCS also induced changes in "leg embodiment" - when viewing the VR scene, patients had the impression they were looking at their real legs, and that the illuminated area was actually causing the SCS-induced tingling sensation.

The immersive, personalized SCS-VR approach "combines neuromodulation, VR, and the latest research from cognitive neuroscience of multisensory integration into a single therapeutic solution," the researchers write. Integrated VR is a "completely noninvasive" addition to SCS, with the potential to increase its pain-relieving effectiveness with no adverse effects.

It's not entirely clear how immersive VR increases the effect of SCS, but the new results show that it's not just an effect of distraction. The matching visual and tactile signals may result in "enhanced masking" of pain inputs, Dr. Blanke, Rezai, Krishna and colleagues suggest. They conclude: "[T]he strength of the effect, its selectivity, its ease of application, and consistent increase across sessions and long-term analgesia will facilitate the application of prolonged and more frequent therapy doses in future SCS-VR studies, likely further boosting the described effects."

DECEMBER 23, 2020, NEW YORK - Researchers led by Ludwig San Diego Member Don Cleveland and Peter Campbell of the Sanger Center have solved the mystery of how free-floating circular DNA fragments, which are almost exclusively found in cancer cells, drive gene amplification to generate drug resistance in cancer. The research, published on December 23 in the journal Nature, provides new insights into how cancers evolve to adapt to changing environments and suggests ways to reduce drug resistance by combining therapies.

"Drug resistance is the most problematic part of cancer therapy," said Ofer Shoshani, a postdoctoral researcher in Cleveland's lab and the study's first author. "If not for drug resistance, many cancer patients would survive."

Extrachromosomal DNAs (ecDNA) are distinct circular units of DNA that are unassociated with chromosomes, which package genomic DNA in the cell's nucleus. ecDNA can contain many copies of cancer genes that help tumors grow and survive. Understanding the biology and origins of ecDNA took on some urgency after a team led by Ludwig San Diego Member Paul Mischel and his colleague Vineet Bafna at the University of California San Diego School of Medicine first reported in 2017 that it is found in nearly half of all tumor types and that it plays a major role in the growth and diversity of cancer cells.

In the new study, Shoshani, Cleveland, Campbell and colleagues show that chromothripsis, the shattering of chromosomes and their reassembly in shuffled order, initiates the formation of ecDNA.

Chromothripsis was first described in 2011 by a team led by Campbell. Scientists hypothesized at the time that chromosomal shattering could produce DNA snippets that circularize to form ecDNA, but this has not been proven until now. "What we were able to show is the link between chromosomal shattering and the formation of ecDNA," Cleveland said. The team also showed that ecDNA can itself undergo successive rounds of chromothripsis to spawn rearranged ecDNAs that provide even higher drug resistance.

"We've watched these pieces evolve with time as they get shattered and reshattered," Cleveland said. "That means if an ecDNA fragment acquires a gene that encodes for a product that directly counters an anticancer drug, it can make more and more of it, leading to drug resistance. We have now established this in three different cell lines forming resistance to methotrexate and in biopsies from human colorectal cancer patients forming resistance to BRAF therapy."

While chromothripsis occurs naturally in cancer cells, the researchers found that it can also be induced by chemotherapeutic drugs such as methotrexate, which kill dividing cells by damaging their DNA. Moreover, the particular kind of DNA damage these drugs cause--breaking both strands of the DNA double helix--provides an opening for ecDNA to reintegrate back into chromosomes.

"We show that when we break a chromosome, these ecDNAs have a tendency to jump into the break and seal them, serving almost like a 'DNA glue,'" Shoshani said. Thus, some of the very drugs used to treat cancers might also be driving drug resistance by generating double-stranded DNA breaks.

The researchers found that such ecDNA formation can be halted by pairing chemotherapeutic drugs with molecules that prevent the DNA fragments created by chromosomal shattering from closing to form circles. Shoshani showed that when applied together to cancer cells, this strategy inhibited the formation of ecDNA and reduced the emergence of drug resistance.

"This means that an approach in which we combine DNA repair inhibitors with drugs such as methotrexate or vemurafenib could potentially prevent the initiation of drug resistance in cancer patients and improve clinical outcomes," Shoshani said.

Cleveland added, "I think the field has accepted that combination therapy is how we're going to generate better outcomes for cancer patients, but here's a specific example of what kinds of combinations should be tested."

The cells in our body are in motion. Some migrate from A to B to heal wounds or fight pathogens. They do so with the help of small "feet" at the leading edge of migrating cells, so-called lamellipodia. These thin extensions are pushed forward and bind to the surface while the rest of the cell is pulled along. Inside these feet is a dense network of interwoven protein threads, called actin filaments, which form the cell's cytoskeleton. So far, it was unclear how the Arp2/3 complex, an assembly of seven proteins central for cell motility, sprouts off new actin filaments from pre-existing ones and thus generates dense, branched networks providing the required protrusive forces to the cell.

Difficult choices

Until now, scientists had to decide when they wanted to analyze the structure of the Arp2/3 complex: One option was to study it in isolation, where the protein complex is in an inactive conformation and hence does not allow understanding of how the network is formed. In order to become fully activated, however, the Arp2/3 complex needs to be bound to actin filaments. This requires using a method called electron tomography, which comes at the cost of considerably lower resolution. "Previous electron tomography data of Arp2/3 complexes bound to actin filaments in a test-tube environment was too imprecise, making it impossible to unambiguously tell where the individual elements of the complex must be located," explains Florian Fäßler, a postdoc in the group of IST Austria professor Florian Schur.

For more than two years, he has been looking for a way to depict the protein complex in its natural environment in such a way that the individual structures can be analyzed precisely. Now he has succeeded. He imaged the complex within lamellipodia of mouse cells in its active actin-bound conformation. "We said to ourselves: Okay, we are going into the cell, where the environment is much more intricate because there is not only the protein complex and actin filaments but all sorts of other things as well. But this was the only way we were able to maintain this network in such a way that we could determine its structure," says molecular biologist Florian Schur.

Shock-frozen cells

This was made possible by temperatures of minus 196 degrees Celsius. Within milliseconds, the researchers froze the samples - too quickly to allow ice crystals to form that would have destroyed the cell's fine structures. They then used one of the most powerful cryo-electron microscopes available - and the only one of its kind in Austria - to image cells from different angles using cryo-electron tomography. Doing so, the team collected enough data for the 3D reconstruction of over 10,000 Arp2/3 complexes in their active state. Combined with advanced image processing, they then generated a 3D model of the Arp2/3 complex at a resolution of less than one nanometer. For comparison: human hair is about 50,000 nanometers thick. "We are now able to describe relatively precisely the structure of the protein complex and its subunits and how they form the actin filament network inside the lamellipodium of previously living cells," says Florian Fäßler. "Five years ago, probably no one would have thought that this could be done," adds Schur.

To the limit

Due to the advanced methodology, the team could refute an earlier model that had assumed much larger area connections between Arp2/3 complex and actin filaments. However, the scientists confirmed other aspects of how this complex is regulated and forms new actin filaments. With this knowledge, other scientists can now better understand this important protein complex's regulation and activity in its multiple roles beyond cell motility and the development of disease. "What we have done is to go as far as is currently possible with such complex samples in terms of methodology and resolution. With the current resolution, we have gained new biological insights, but it was also a methodological advance to show: It is possible," Schur says enthusiastically. Florian Fäßler now wants to improve the method even further to visualize other proteins and explore how far the method allows us to see inside a cell. "We are just starting to realize the full potential of cryo-electron tomography," says Schur.

Scientists at Trinity College Dublin today announced a significant advance in our understanding of an early onset form of dementia that may also progress our understanding of conditions such as Alzheimer's disease.

Adult onset Leukoencephalopathy with axonal Spheroids and Pigmented glia (ALSP) is an ultra-rare condition characterised by mutations in a gene called Colony stimulating factor-1 receptor (CSF1R). The condition manifests initially with psychiatric and behavioural changes in patients followed by a rapid progression of dementia in the third or fourth decade of life. While the condition is very rare, for affected families it can represent a devastating diagnosis.

As the condition involves the degeneration of white matter in the brain, scientists previously thought that immune cells within the brain termed microglia were the primary culprits in driving pathology observed in this condition.

However, the Trinity team, working with patient samples as well as pre-clinical models, were able to show that dysfunctional circulating white blood cells were the key driver of neurodegeneration.

"This was fundamentally a translational research project, where data obtained from patient samples critically informed the direction of our pre-clinical studies. Our findings have shed light on a novel mechanism of neurodegeneration that may ultimately teach us more about common forms of dementia," said Dr Matthew Campbell, Associate Professor at Trinity.

Importantly, the work has identified that a disruption in CSF1R function in patients, as well as in pre-clinical models, induces damage to the so-called blood-brain barrier (BBB). This damage can subsequently change the integrity of capillaries in the brain, causing them to leak and spark the deterioration of the brain. Intriguingly, dysfunctional white blood cells seem to be the main driver of this BBB breakdown.

Relevance to other dementias

Unfortunately, there are currently no approved therapies for conditions such as Alzheimer's disease, which is in part due to the lack of a robust understanding of the early initiators of disease. If we can better understand what the early hallmarks of Alzheimer's are, we may be able to develop novel forms of therapy that target these newly discovered mechanistic pathways.

Dr Conor Delaney, Irish Research Council scholar, Postdoctoral research fellow and first author of the study, added: "The most exciting aspect of our study is that we have now honed in on a novel pathway that to date has not been explored in great detail. Additionally, our data suggest that modifying white blood cell function may be therapeutically relevant for progressive neurodegenerative conditions."

A multidisciplinary team of geneticists, immunologists, neurologists and neuropathologists from Trinity, the Royal College of Surgeons Ireland (RCSI), University College Cork (UCC), Sligo General Hospital and the University of Ghent undertook the study.

While shedding light on an often-neglected rare disease, the findings could pave the way for a targeted therapeutic approach for other forms of dementia.

Commenting on the clinical significance of the findings, Colin Doherty, Professor of Epilepsy in Trinity, said: "It is absolutely critical that we focus our research endeavours on identifying the underlying cause of neurodegenerative conditions. Studies like these will pave the way for better clinical management of our patients and hopefully new medicines to treat the condition."

Rapid, accurate communication worldwide is possible via fiber optic cables, but as good as they are, they are not perfect. Now, researchers from Penn State and AGC Inc. in Japan suggest that the silica glass used for these cables would have less signal loss if it were manufactured under high pressure.

"Signal loss means that we have to use amplifiers every 80 to 100 kilometers (50 to 62 miles)," said John C. Mauro, professor of materials science and engineering, Penn State. "After that distance, the signal wouldn't be detected properly. Across continents or across oceans that becomes a big deal."

Glass fibers lose signal strength because of Rayleigh scattering -- scattering of light that comes from fluctuations in the glass's atomic structure.

"Glass, on an atomic scale, is heterogeneous," said Mauro. "It has an open porosity on an atomic scale that occurs randomly."

The strands in fiber optical cables are made from ultra-high purity silica glass.

"Historically, the biggest breakthrough was the discovery that led to the original optical fiber -- how to get rid of the water in the glass," said Mauro.

Normally glass has a lot of water that absorbs the signal at the frequencies commonly used for telecommunications. Using a modified form of chemical vapor deposition, the fibers could be made free of water. But, like nearly all glass, optical fibers are manufactured at ambient pressure.

Mauro and his team used molecular simulations to investigate the effects of pressure when making optical fibers. They reported their results in npj Computational Materials. The simulations showed that using pressure quenching of the glass, the Rayleigh scattering loss could be reduced by more than 50%.

Pressure treatment of the glass would make the material more homogeneous and decrease the microscopic holes in the structure. This would create a higher mean density material with less variability.

"We were looking for the independent processes that can control mean and variance," said Mauro. "We realized that the pressure dimension had not been explored previously."

Mauro's work is a molecular simulation, but Madoka Ono of AGC Inc.'s Materials Integration Laboratories, who is an associate professor in the Research Institute for Electronic Science at Hokkaido University in Japan, tested bulk pieces of silica glass and found that the results matched the simulation.

"The optimum pressure we found was 4 gigapascals," said Mauro. "But there is still a process challenge that needs to be addressed."

To manufacture optical fiber under pressure, the glass would need to be formed and cooled under pressure while it is in the glass transition phase -- the temperatures when glass is sticky, not a solid and not truly liquid. To do this would require a pressure chamber capable of 40,000 atmospheres.

Black children are removed from their families at much greater rates than any other race or ethnicity in this country. At the same time the sheer number of all child abuse investigations in the US is staggering: experts estimate that by age 18 one out of three children has been the subject of a child protective services investigation. Yet, many of these investigations and removals are unjustified and stem from a misguided policy shift that began in the late 1960s, says University of Rochester health policy historian and physician Mical Raz.

"These numbers are astounding, particularly as the rates of serious physical injury to children are on the decline," writes Raz in her latest book Abusive Policies: How the American Child Welfare System Lost Its Way (University of North Carolina Press, 2020), which traces the history of child abuse policy in the US over the last half century.

Part of the problem is an overly broad definition of what constitutes child abuse that has become politicized and "weaponized" against vulnerable populations, says Raz, who is an associate professor of history at the University of Rochester, and a physician at the University's Strong Memorial Hospital.

"Biased viewpoints regarding race, class, and gender played a powerful role shaping perceptions of child abuse," says Raz. Coupled with overzealous policies and a belief among the public that serious child abuse was widespread and frequent, "these perceptions are often directly at odds with the available data and disproportionately target poor African American families above others."

This overreporting of alleged child abuse, Raz argues, has caused the child welfare system to get bogged down in unnecessary investigations, seriously undermining its ability to focus on its other roles. Poverty is too often equated with abuse, she says, while at the same time "we're just having investigations at the expense of providing services."

Raz says that most reports of neglect are really about manifestations of poverty. Often children are removed and placed in foster homes where foster parents receive funding from the government.

"Had that funding instead been given to the original family, they would have been able to provide what their child needs at home," says Raz.

Q&A

Why is removing a child who seems at risk a bad thing?

We should think about parenting as an affirmative right--that parents have the right to parent their children, that families have a right to be together, and that children have a right to be with their parents. Children should be removed from their families only as a last resort for severe harm. And yet, we know that in the US, about a quarter of all children who are removed from their homes are returned within 30 days. The problem is not that they are returned too quickly. Rather, what's the point of taking them in the first place if they can be returned so quickly? Removal unnecessarily creates trauma for children and families and makes them less likely to seek help in other circumstances.

How do race and class bias enter into the perception of child abuse?

We know that poor families, particularly poor families of color, are reported to child welfare agencies at higher rates, and child removal happens more often. When a child from a poorer, or Black family is removed--the child is then less likely to come home and stays longer in substitute care--compared to a child from a white family. So, there's a clear overrepresentation of poor families and families of color.

How did we get here?

The evolution of how society views child abuse goes back to an idea from the 1960s that parents who abuse their children are sick and need help. In order to "help" these parents the idea became to better identify them and report more often. Once we started reporting more families, people started reporting more Black and poor families. So, an idea that was designed to provide assistance and social support ended up being co-opted into a way to report and coerce poor families.

What role does poverty play?

Since the 1970s federal law has required the reporting not just of abuse but also of neglect, which is a very amorphous category and is too often confused with manifestations of poverty, particularly in a country where we don't have access to universal health care, or to universal social services. Reporting a family for not having what a child needs to thrive essentially amounts to reporting a family for being poor. Reporting parents, for example, for not pursuing dental care for their child makes little sense because child welfare services are now tied up with chasing up that report, instead of providing the needed services and dealing with the real problem. We know that most reports of neglect are about manifestations of poverty. Often children are removed and placed in foster homes where foster parents get funding from the government. Had that funding instead been given to the original family, they would have been able to provide what their child needs at home. So instead of addressing the underlying poverty, we remove children for other people to raise them.

Isn't the expansion of mandatory reporting a good thing, given what we've learned in recent years about systemic child sexual abuse?

We certainly do want people to report cases of child abuse and I regret the many cases that remain unreported. But we know that most reports to child protective services are not about physical or sexual child abuse, but are, in fact, about poverty. And having social workers sort through all of these reported cases is a huge drain on the system: it doesn't keep families safer, and it doesn't provide services for families. It actually obscures the problem and makes it harder for social workers to identify the children who are in need of intervention.

What should the system be doing instead of conducting these investigations?

It should be providing services to struggling families. In the 1950s and early '60s before the policy shift, for example, child welfare services would send a homemaker to the home of a recently widowed father, or they would send a caregiver to help a mom who was in the hospital for a gall bladder surgery: they would provide services that would help families who are experiencing difficult situations. What these families needed was help at home, they needed food, they needed childcare. We know families need access to health care, food, and shelter to thrive. What they don't need is an investigation for neglect.

You write that the definition of child abuse is too general. What needs changing?

I think the definitions of child abuse and neglect are far too broad, and yet agents of the state are constantly working to expand them. For instance, in the 1980s and '90s many states expanded these definitions to include prenatal drug use as a form of child abuse, rather than working to ensure states could offer pregnant mothers treatment for addiction. We should advocate for a narrow definition of child abuse, focusing on cases of physical abuse, sexual abuse, and severe neglect with risk of imminent harm to the child, and find alternative methods to assist families with other struggles that are often related to poverty.

How do you fix to the problem?

Given that only a small percentage of reported child abuse cases deal with sexual or severe physical abuse--and those should certainly be addressed swiftly--we should think about the bigger picture in which families are swept into investigations and allegations, where parents later are placed on registries and lose their jobs, or can't find jobs--for allegations of neglect. If parents lose custody or their parental rights, it's essentially the destruction of their family. We should instead be thinking of ways to preserve families and offer them services at home. It's more cost effective and also the right thing to do. When we live in a society in which children may not have access to healthcare, childcare, food, shelter--all these basic things--then if anybody should be charged with neglect it should be the state not the parents.

When a person has an infection, the body activates immune responses to fight it. IFNγ is an inflammatory molecule produced by the immune system that helps fight infections. However, long-term exposure to IFNγ has undesirable consequences - it irreversibly exhausts blood stem cells, the progenitors of all blood cells, including immune cells, by triggering their proliferation and excessive terminal differentiation. Lacking immune cells, patients eventually are unable to fight infections.

Baylor College of Medicine researchers investigated the mechanism by which IFNγ mediates depletion of blood stem cells, which are normally quiescent, meaning they are in a dormant state until activated when stimulated. They showed in the journal Cell Reports that IFNγ stimulates the production of protein BST2 on these cells, which resulted in their emergence from the quiescent state, persistent proliferation and finally exhaustion. The findings suggest that modulating BST2 expression on blood stem cells may provide a means to regulate these cells' activation and/or persistence during chronic infections.

"We began our investigation by asking, 'What is changing about blood stem cells when they interact with IFNγ, and how does that influence their reproduction or depletion?'" said co-corresponding author Dr. Katherine King, associate professor of pediatrics-infectious diseases and member of the Dan L Duncan Comprehensive Cancer Center at Baylor.

Blood stem cells reside in the bone marrow, normally in contact with CAR cells that form a sort of a nest. CAR are nurse cells that support stem cell health.

"To investigate the real-time interaction of blood stem cells and CAR cells in live animals, we developed new mouse models designed to express different fluorescent proteins in blood stem cells (red) and CAR cells (green) in the same animals. This model enabled us to visualize and track both cell types individually and simultaneously within intact bones of living animals," said co-corresponding author Dr. Dongsu Park, assistant professor of molecular and human genetics and pathology and immunology at Baylor.

Combining this approach with advanced live-animal imaging technology, the team discovered a tight interaction between blood stem cells and CAR cells in normal bone marrow, but when exposed to IFNγ, the stem cells unexpectedly moved away from CAR cells.

"We think IFNγ is disrupting the quiescent state of stem cells and promoting cell activity," King said. "Our next experiments looked at how that was happening."

The researchers looked for proteins on the surface of stem cells that were expressed after exposure to IFNγ. They hypothesized that probably a surface protein induced by IFNγ was promoting the separation of stem cells from CAR cells.

"Think of it as a sticky tag that is on the outside of the stem cells that is pulling them to some other place. That's how we identified this protein called BST2," King said. "In fact, in mice in which we knocked out BST2, the relocalization of stem cells away from the nest and their excessive proliferation and exhaustion did not happen, supporting the role of BST2 in these functions."

Homing

The researchers also found that BST2 helps cells bind to E-selectin, a protein on the surface of endothelial cells, such as those lining blood vessels. These findings are relevant to homing, a process by which blood stem cells from a bone marrow transplant find their way to their home in the recipient's bone marrow.

"Homing of stem cells improved when we exposed them to IFNγ. We propose that having more BST2 may help stem cells stick to E-selectin on endothelial cells, facilitating crossing through blood vessels to reach the bone marrow," King said.

"BST2 is a fascinating protein that has been mostly studied for its ability to both protect our body from viral infections and its role in cancer. I am most excited that we are the first group to report that BST2 plays an important role in blood stem cells, which are at the top of immune system hierarchy," said first author Marcus A. Florez, a student in Baylor's Medical Scientist Training Program (M.D./Ph.D.) in the King lab. "This project has important implications in a wide variety of diseases including chronic infections, bone marrow failure and transplant recipients."

A research team from the University of Helsinki has discovered a tree hyrax in the Taita Hills, Kenya, which may belong to a species previously unknown to science.

The discovery, which was part of a study of the vocalisations of nocturnal animals in the Taita Hills, was published in mid-December in the scientific journal Discovery.

Very little is known about the diversity and ecology of tree hyraxes because these animals, which look like large guinea pigs but are distant relatives of elephants, are mainly active at night in the tree canopies in Africa's tropical forests. These animals are known to be able to scream with the strength of more than one hundred decibels, but the 'strangled thwack' calls that have been recorded in Taita's forests have not been described anywhere else.

The re­cord­ings re­veal that the Taita tree hyraxes sing

The tree hyrax song may continue for more than twelve minutes, and it consists of different syllables that are combined and repeated in various ways.

"The singing animals are probably males attempting to attract females that are willing to mate," postulates Hanna Rosti, who spent three months in Taita's forests, following the nocturnal mammals and recording their vocalisations.

The results suggest that the two populations of dwarf galago in the Taita Hills may belong to different species. The calls of the animals of the smaller population are very similar to those of the Kenya coast dwarf galago, a species that has previously been thought to live only in coastal, low elevation forests. The peculiar calls of the second population cannot yet be linked with certainty to any known species.

"The taxonomy of many nocturnal mammals remains poorly known, and many populations have not been studied at all yet," says researcher Henry Pihlström, who reviewed the complex taxonomy of tree hyraxes and galagos for the published study.

Protein synthesis is a finely tuned process in the cell by macromolecules known as ribosomes. Which regulators are responsible for controlling protein synthesis in the brain, and how do they exert their control on the ribosome? To address this question, a team of researchers from Charité - Universitätsmedizin Berlin studied the structure of the brain's ribosomal complexes in great detail. The team was able to identify a new factor which is also involved in controlling brain development. Details of this research have been published in Molecular Cell*.

Proteostasis refers to maintaining a delicate balance of protein levels in the cell, which is of particularly crucial importance to neurons. Abnormal protein production is a characteristic feature of many brain disorders. High precision protein production is of immense importance during the early development of a complex part of the cerebral cortex known as the neocortex. It is particularly important in the production of membrane proteins, which play an important role in cell-to-cell sites of synaptic contact between nerve cells. As the cell's 'molecular protein factories', ribosomes are at the heart of the regulatory processes involved in proteostasis. A range of molecules can influence ribosome function, and are responsible for controlling the production of specific proteins in different tissues and at different developmental stages. The way in which these various factors interact with the ribosome during development remains widely unknown. However, a group of Charité researchers has successfully observed protein production by ribosomes in the developing brain.

"It is the first time the ribosomal complex has been visualized in action inside the brain at near atomic-level resolution," says Prof. Dr. Christian Spahn, Director of Charité's Institute of Medical Physics and Biophysics. "While the structure of the ribosomal complex has been mapped in other tissues and organisms, our approach enabled us to identify Ebp1 as the new key factor responsible for controlling both ribosome function and the synthesis of specific proteins during brain development." The interaction between the regulatory protein Ebp1 (short for ErbB3 binding protein 1) and the ribosome takes place at the ribosome's exit tunnel, through which the newly formed protein chain emerges from the ribosome. Through this interaction, Ebp1 influences the production of membrane proteins that play an important role in neuronal interactions, thus maintaining neuronal proteostasis.

As part of a multidisciplinary project linking aspects of structural biology and neuroscience, the researchers used cryo-electron microscopy (cryo-EM) as their main investigative tool, combining it with mass spectrometry, RNA sequencing and genetic techniques. The cryo-EM imaging technique enables scientists to determine protein structures - particularly larger complexes comprising multiple molecules - at extremely low temperatures and near-physiological conditions. The study's first author, Dr. Dr. Matthew L. Kraushar (a neuroscientist at the Max Planck Institute for Molecular Genetics (MPIMG) in Berlin and previously a member of Prof. Spahn's laboratory), explains: "We could therefore visualize the molecular architecture of the ribosome at high resolution, as it would be found inside brain cells. We were able to capture snapshots of the ribosome in action."

"Protein production in various types of brain cells is subject to finely tuned control mechanisms. Small changes can lead to big consequences, such as neurodegenerative diseases or disrupted development. Our findings on the role of ribosomes during normal brain development will help us to better understand pathological changes affecting the brain," says Prof. Spahn. As a next step, the researchers are conducting a large-scale study to understand the way ribosomes translate messages from the genetic code (mRNA) into numerous essential proteins throughout brain development.

Ann Arbor, December 22, 2020 - There has been continual progress in expanding immunization programs over time, but even before the COVID-19 pandemic, tens of millions of children worldwide were not receiving basic doses of vaccines. New research finds that there continue to be significant disparities in childhood vaccination, and poorer children from under-represented and minority groups in most countries are more likely to be less fully vaccinated with all the recommended immunizations. A special supplement to the American Journal of Preventive Medicine, published by Elsevier, looks at the barriers and challenges that limit or prevent access to vaccines in vulnerable children.

"Improving access and receipt of immunizations for all children everywhere are key to achieving the World Health Organization's (WHO's) Sustainable Development Goal of realizing continued progress in reducing global mortality in children under five," explain Guest Editors Matthew L. Boulton, MD, MPH, and Abram Wagner, PhD, MPH, both of the Department of Epidemiology, School of Public Health, and Global Institute for Vaccine Equity, University of Michigan, Ann Arbor, MI, USA. "It's going to require a more sustained effort and investment on the part of governments worldwide to close the inequalities gap in childhood vaccination."

Dr. Boulton and Dr. Wagner observe that understanding who gets vaccinated can help us plan targeted programs to prevent future outbreaks of preventable disease like COVID-19. However, it is not just who gets vaccinated; vaccine timeliness also matters. Delays in vaccination leave children vulnerable to disease. An analysis of children in Sub-Saharan Africa looked at on-time vaccination and inequalities by household wealth, maternal education, and place of residence. Researchers report that over half the children received one or more vaccinations over a month late. On-time vaccination was consistently higher in children of educated mothers, in the richest households, and in urban areas.

"Our findings suggest that to reduce inequality in on-time vaccination coverage, health providers and policy makers should design health interventions that include an equality lens," says lead investigator Martin K. Mutua, PhD, African Population and Health Research Center, Nairobi, Kenya. "There should be more awareness campaigns in areas where the poorest live and in rural areas. Mobile health clinics with flexible hours targeting these populations may help reduce the inequality gap."

Health interventions generally have a "pro-rich" pattern: they are more commonly adapted among wealthy than among poor individuals. However, loss of public confidence in vaccines and the rising attention to antivaccination movements are more commonly associated with higher-income countries. "Vaccine hesitancy" is one of the top 10 health threats identified by the WHO and may play a larger role in the future. Investigators sought to determine if vaccine hesitancy may be emerging among the wealthy in low and middle income countries, and what the impact might be on immunization coverage.

"We found that the classical pro-rich inequality pattern, in which the wealthy present better coverage than the poor, appears to be changing, especially in upper-middle income countries. The number of countries exhibiting the classical pro-rich inequality pattern declined as national income increased. This shift may be due to vaccine hesitancy among wealthy families," suggests lead investigator Cesar G. Victora, MD, International Center for Equity in Health, Federal University of Pelotas, Pelotas, Brazil. "Every vaccine demands a minimum level of coverage to secure community immunity. Special attention to prevent vaccine hesitancy in low and middle income countries is needed." Vaccine hesitancy is not limited to the wealthy; elsewhere in the supplement, studies address vaccine hesitancy based on religious beliefs and among lower income migrants to an urban area.

Dr. Boulton and Dr. Wagner note that insuring access to COVID-19 vaccines for historically marginalized groups, including persons of color, will be important to ensure the universal coverage needed to eradicate the pandemic. "Inequitable distribution of a COVID-19 vaccine will further reinforce and entrench existing disparities and contribute to the substantial gaps we currently see globally in pandemic-related illness and death," says Dr. Wagner.

The Guest Editors suggest that the research published in this supplement can inform current and future discussions about global vaccine equity and contribute to the achievement of the WHO's vision of a world in which everyone can benefit from vaccines to improve health and well-being.