Brain

In the summer of 2011, visitors to the University of California, Davis, Arboretum may have witnessed an unusual site: small teams of students wielding large nets, leaping into the arboretum's waterway to snag basking turtles.

The students weren't in search of new pets -- quite the opposite, in fact. The teams were part of a massive project to remove hundreds of invasive red-eared slider turtles from the arboretum in an effort to observe how California's native western pond turtles fair in the absence of competitors.

Red-eared sliders are the most commonly traded pet turtles in the world, but are often released into the wild by disgruntled owners when they get too big to handle. Thanks to illegal dumping, the sliders, which are native to the Central United States and Northeastern Mexico, can now be found all over the world. Their new stomping grounds include California, where they vie for food and sunny basking sites with western pond turtles, whose populations are in rapid decline due to agriculture and urbanization.

The results of the removal study, published recently in the journal PeerJ, showed that western pond turtles get a lot fatter and healthier without competition from their invasive brethren -- and the remaining sliders likely fair better, too. The study is the first to quantify competition between these two species in the wild.

"I think, finally, we have some good evidence in the United States that it's time to critically think about not having pet slider turtles, and likely other aquatic turtles, and mitigating this pet trade because it's not great for the pets, and it's not great for these wild species either," said Max Lambert, a postdoctoral researcher at the University of California, Berkeley, and lead author of the study.

It's not hard to see why red-eared sliders are the most popular pet turtle in the United States: As hatchlings, sliders are small, friendly and sport striking red stripes on either side of their heads.

But give it a few years, and the once-cute reptiles grow snappy, smelly and can expand to the size of a dinner plate.

"They are so cheap, they are in every single pet store, and they seem like a great pet until they get to be a few years old, and then they get big, mean, smelly and are a pain to take care of," Lambert said. "So, people just take them to a nearby pond and let them go."

As an undergraduate studying ecology and conservation at UC Davis, Lambert was curious to know what effect these invasive turtles might be having on western pond turtles, which are currently listed as vulnerable on IUCN's Red List of Threatened Species. While experiments in laboratory settings have hinted that sliders will compete for food with pond turtles, he couldn't find any data looking at how the two species interact in the wild.

Lambert and five other UC Davis undergraduates teamed up with their faculty adviser, H. Bradley Shaffer, who is a professor of ecology and evolutionary biology at UCLA, and Gregory Pauly, curator of herpetology at the Natural History Museum of Los Angeles County and senior author of the study, to design the removal experiment.

With the help of volunteers and other UC Davis undergraduates, including Jennifer McKenzie and Robyn Screen, who are co-first authors of the recent publication, the team used turtle traps, nets and, when necessary, their own hands, to remove and euthanize 177 red-eared sliders living in the UC Davis Arboretum waterway during the summer of 2011. Lambert estimates they caught about 90 percent of the total red-eared slider population in the arboretum.

They also tracked the weight of the western pond turtles and observed the turtles' basking habits. Time spent basking in the sun is critical for cold-blooded turtles; they need the heat to power digestion and their immune systems, Lambert said.

The researchers found that, in the year after the slider removal, the pond turtles gained an average of about 40 grams, representing about 5 to 10% of their body weight -- quite a lot for a turtle. This weight gain is especially important for female turtles, whose egg clutch size is related to their overall size, Pauly said.

"If these females are much healthier and much more likely to have larger clutch sizes, that increases the likelihood that we are then going to get more juvenile turtles cruising around these urban waterways," said Pauly, who was a postdoctoral researcher studying reptile and amphibian conservation at UC Davis at the start of the experiment.

While the slider removal didn't have much of an impact on the western pond turtles' basking behavior, the researchers did find that the remaining sliders spread out to a few select basking sites, indicating that they were actually crowding each other out before the removal.

"The reality is, in many of these urban ponds, there are so many red-eared sliders that there are high levels of competition amongst those sliders for basking sites and also probably for food," Pauly said. "It's not just that red-eared sliders are having negative impacts on the western pond turtles, but the red-eared sliders are themselves facing this huge series of challenges."

As a postdoctoral researcher at UC Berkeley, Lambert says he has plans to study western pond turtles and red-eared sliders in the Bay Area. He is initiating partnerships with the East Bay Regional Park District to first observe western pond turtles in ponds and lakes in the system, and then conduct another intensive removal of red-eared sliders in and around places like Jewel Lake.

"What we found with our slider removal at Davis was that it was just so human-intensive and would cost any agency a ton of money to do what we did at that scale," Lambert said. "And so, while it seems that slider removal has an effect, the question is, 'How much of an effect is it having, relative to western pond turtles living in an urban place, where they get run over by cars, eaten by raccoons and coyotes and dogs and sometimes taken home as pets by people not realizing the negative impacts they are having?' We're hoping to parse out a bit better the degree to which sliders are having an impact relative to every other challenge we throw at these turtles."

AMHERST, Mass. - Polymer chemists and materials scientists have achieved some notable advances that mimic Nature, but one of the most common and practical features of cells has so far been out of reach - intracellular compartmentalization. It refers to the way many different organelles, vesicles and other "water-in-water" soft structures in the cell, contain and isolate chemical reactions and processes. It also lets reaction products be selectively shared with end users inside the cell.

Now a research team led by Thomas Russell at the University of Massachusetts Amherst and the Lawrence Berkeley National Laboratory, with postdoctoral researcher Ganhua Xie and others, describe in a new paper how they take advantage of differences in electrical charge to create an "all aqueous," water-in-water construct that achieves compartmentalization in a synthetic system.

"Our results point to new opportunities for manipulating and improving continuous separation and compartmentalized reactions. I feel we have developed a strategy to mimic the behavior of living cells," Russell notes. "People have tried before to build synthetic systems that mimic nature and haven't done it, but we have. I think this is the first time this has been demonstrated." Details appear in the current issue of Chem.

Evan Runnerstrom, program manager in materials design at the Army Research Office, which supported this work with the U.S. Department of Energy, says, "This ability to program stable structure and chemical functionality in all-aqueous systems that are environmentally friendly and bio-compatible will potentially provide unprecedented future capabilities for the Army. The knowledge generated by this project could be applicable to future technologies for all-liquid batteries, water purification or wound treatment and drug delivery in the field."

Russell and colleagues have been interested in liquid interfaces for several years and earlier conducted many oil-and-water experiments to observe results under various conditions. "This led us to start looking at water-in-water liquid interfaces," he notes.

For this work, Xie used two polymer aqueous solutions, one of polyethylene glycol (PEG) and water, the other dextran and water, with different electrical charges; they can be combined but do not mix. It's a "classic example" of coacervation, they suggest - the solution undergoes liquid-liquid phase separation and forms two separate domains, like the non-mixing wax-and-water in a lava lamp.

Next, Xie used a needle to send a high velocity jet of the dextran-plus-water solution into the PEG-plus-water solution, something Russell calls "3D printing water-in-water." This operation creates a coacervate-membrane-stabilized aqueous or water-filled tubule where the path-length of the tube can be kilometers long, he says. This 3D water-on-water printing forms a membranous layer of a coacervate that separates the two solutions.

Another feature of the water tube formed this way is that electrical charge regulates whether and in which direction a material can pass through the coacervate membrane, the authors explain. A negatively charged dye or other molecule can only pass through a negatively charged wall of the asymmetrical membrane, and likewise for positively charged materials. Xie says, "It effectively forms a diode, a one-sided gate. We can do a reaction inside this tube or sac that will generate a positively charged molecule that can only diffuse into the positive phase through the coacervate."

He adds, "If we design the system right, we can separate things out easily by charge, so it can be used for separations media in all-aqueous compartmentalized reaction systems. We can also trigger one reaction that will allow a coordinated reaction cascade, just as it happens in our bodies."

Xie explains that the 3D water-on-water printing allows them to direct where they put these domains. "We can build multi-layered structures with positive/negative/positive layers. We can use the sac-shaped ones as reaction chambers," he says. Advantages of separating functions and materials in cells by compartmentalization include allowing many processes to occur at once, many different chemical environments to coexist and otherwise incompatible components to work side by side.

Among other tests and experiments, the researchers report on how they designed an all-aqueous tubular system and attached needles and syringe pumps at each end to allow water to pump through the entire structure without leakage, creating a flow-through coordinated reaction system.

"Once we'd done it, we looked at the biological mimicry" Russell says. "There have been lots of efforts to mimic biological systems, and a biologist might object and say this is too simple. But I do think that even though it involves simple materials, it works. It's treading very close to vasculature, and it mimics any place where chemicals flow through a membrane. Is it in the body? No, but it does mimic a real metabolic process, a compartmental reaction."

If you've never seen a horseshoe bat, you're missing out. Their comically large ears are only rivaled for wackiest feature by their nose leaves, little flaps of skin that spread outward from their faces like petals. If you grew up with siblings who would say, "That's you," when they saw an ugly creature on TV, they'd have a field day with horseshoe bats.

But while they have faces only a biologist could love, horseshoe bats have caught the interest of scientists studying the bat family tree. There are more than 100 recognized species of horseshoe bats, and researchers now believe that number could be still higher. In a study published in BMC Evolutionary Biology, researchers from the Field Museum, National Museums of Kenya, and Maasai Mara University used gene sequencing to identify up to 12 new species of horseshoe bats. They also cast doubt on the validity of several recognized species.

MacArthur Curator of Mammals and senior author of the study Bruce Patterson says, to put it simply, "We found a lot more species than we thought were there."

"Horseshoe bats are defined by the broad flap of skin on their upper lip. It serves as a radar dish for their echolocation calls," says Patterson. "I think they're totally bizarre and for students of biology that bizarreness is what makes them so fascinating."

Terry Demos, post-doctoral researcher and lead author of the paper, also agrees that horseshoe bats are unique looking-- "You could say there's beauty in the elaborateness of the nose, I mean it is so intricate."

The researchers wanted to study the bats because, despite being so rich in different species, little is known about their evolutionary history. East Africa has remained understudied, even though it's one of the most diverse regions in the world. For centuries, colonialism meant that European researchers were the only people with access to the land. Patterson and Demos hope that studies like this one will help equip local scientists with the tools they need to research their own land. "We're trying to understand evolutionary history in an understudied area," says Demos, "while also building in-country resources."

The research team examined hundreds of bat specimens from the collections at the Field Museum and National Museums of Kenya. Using small samples of tissue, they sequenced the bats' DNA to see how closely related they were to each other, like 23AndMe testing on a species level.

The genetic similarities and differences between the bats suggested that some distinctive groupings could be new species. Some of these new species may be what scientists call "cryptic"-- visually, they look very similar to species we already know about, but genetically, they're different enough to be considered their own separate species. These cryptic species were hiding in plain sight in the museums' collections, waiting to be discovered.

While the study did suggest that there are more species of horseshoe bat than previously imagined, new species will not be officially named until the team carries out the next part of their research.To designate a new species, researchers will need to examine the bats' teeth and skulls to see how their physical traits differ. They'll also need to compare the bats' echolocation calls, since different bat species that live near each other often make their calls at different frequencies, like different channels on a walkie-talkie.

The researchers are excited by the possibilities that come with rewriting the horseshoe bat family tree. "The implications of this study are really countless," says Patterson. "Bats eat insects that carry diseases, what are the implications of that? We can also use this to designate areas for conservation."

A team led by Texas A&M University's College of Veterinary Medicine & Biomedical Sciences' (CVM) researcher Dr. Stephen Safe has discovered a new pathway that may help suppress the development of glioblastoma tumors, one of the deadliest forms of cancer.

The Texas A&M team's research focuses on the AH receptor, which controls expression of a diverse set of genes, essentially contradicts what was previously understood in glioblastoma research. The Texas A&M study was published in July in the Journal of Biological Chemistry.

"We found the AH receptor--which was previously reported in the literature to be a pro-invasion gene--actually blocked invasion of glioblastoma cells," said Safe, who is a Distinguished Professor of Veterinary Physiology & Pharmacology (VTPP) in the CVM.

"When we add certain AH receptor ligands (molecules that bonds to another molecule), we observed a potent inhibition of glioblastoma cell invasion. Basically, we've shown that it's a good gene that can be targeted by drugs to make it even more effective."

Glioblastomas, the most common and aggressive malignant brain tumor in adults, are comprised of tumor cells that rapidly reproduce and divide, which allow the tumor to grow into nearby normal brain tissue. Currently, these brain tumors are incurable -- a patient's median life expectancy after diagnosis is 11-15 months with standard treatments.

According to the American Brain Tumor Association, glioblastomas also form new blood vessels so they can maintain their rapid growth and may use connection fibers to spread to the opposite side of the brain.

Safe said that the tumors are difficult to treat. Because glioblastomas often have finger-like tentacles that spread through the brain, they may not be completely removed through surgery. The tumor's individual cells also respond differently to various therapies.

The Texas A&M study used patient glioblastoma cells in collaboration with colleagues at the Detroit Medical Center, as well as cells that were used in previously published glioblastoma studies. The researchers analyzed the AH receptor and several receptor ligands, including Kynurenine.

Previous published studies in the journal Nature found that the AH receptor and Kynurenine were involved in glioblastoma cells' invasion of the brain.

However, the Texas A&M researchers refuted these findings by showing that AH receptors actually serve a protective function and do not promote the invasion of glioblastoma cells. In addition, when researchers added AH receptor ligands but Kynurenine was not active, the level of protection to the brain was enhanced.

These findings suggest that the AH receptor could be a target for the development of drugs to inhibit glioblastoma. The Texas A&M team is now studying the use of the AH receptor as a target for inhibiting glioblastoma and identifying compounds that bind to the AH receptor to provide additional protection to the brain.

"This study opens up a new way for developing potential clinical applications," Safe said. "Whether this line of inquiry will be successful remains to be seen, but our work may offer hope for a disease which has such a poor prognosis."

A team of scientists from Weill Cornell Medicine and The Rockefeller University has illuminated the basic mechanism of Piezo proteins, which function as sensors in the body for mechanical stimuli such as touch, bladder fullness, and blood pressure. The discovery is a feat of basic science that also opens up many new paths of investigation into the roles of Piezo proteins in human diseases and potential new therapeutic strategies.

In the study, published Aug. 21 in Nature, the scientists used advanced microscopy techniques to image the Piezo1 protein at rest and during the application of mechanical forces. They confirmed this complex protein's structure and showed essentially how it can convert mechanical stimuli into an electrical signal.

"Our analysis shows that tension on the cell membrane in which Piezo1 is embedded can flatten and widen the protein's structure," said co-senior author Dr. Simon Scheuring, a professor of physiology and biophysics in anesthesiology at Weill Cornell Medicine. Dr. Scheuring and his laboratory collaborated on the study with the laboratory of Dr. Roderick MacKinnon, a professor of molecular neurobiology and biophysics at The Rockefeller University. Dr. MacKinnon was co-recipient of the Nobel Prize in Chemistry in 2003 for his work determining the structures and mechanisms of ion channel proteins.

Piezo1 and Piezo2 are very large and complex proteins with unique structures. They are embedded within the membranes of certain cell types, and their function is to transduce mechanical force on cells into electrical signals that alter cell activity. Piezo1 proteins work for example in bladder cells to detect when the bladder is full, and in blood vessel-lining cells to detect and help regulate changes in blood pressure. Piezo2 proteins work in sensory nerve endings in the skin and joints, helping to mediate the senses of touch, pain, and proprioception--the sense of how one's limbs are arranged.

Advances in imaging techniques have enabled scientists in recent years to determine the basic structure of Piezo1--a structure that Piezo2 is thought to mostly share. From above this structure has a three-armed, propeller or "triskelion" appearance.

From the side it looks like a shallow bowl embedded in the cell membrane, with an ion channel at its center. The latter, when opened, allows a flow of calcium and other positively charged ions into the cell.

The basic mechanism by which mechanical force opens the ion channel has remained mysterious. But in the new study Dr. Scheuring and Dr. MacKinnon and their colleagues, including lead author Dr. Yi-Chih Lin, a postdoctoral associate in anesthesiology, were able to get a clearer picture of how it works.

They combined cryo-electron microscopy with a less well-known technique called high-speed atomic force microscopy, which produces an image of an object essentially by feeling its surface with a super-sensitive mechanical probe. They showed with these methods that Piezo1 is a springy structure that normally bends the cell membrane where it sits, but will flatten out when, for example, a mechanical force is applied to the cell membrane.

"As the membrane tension increases, the structure of Piezo1 flattens and stretches out to occupy a larger area, which in turn opens the ion channel," Dr. Scheuring said.

He noted the possibility that other stimuli that stretch and flatten the Piezo1 structure, such as a pulling force on its arms from the inside or on an external domain called the CED from the outside the cell, in principle could open the ion channel--making it a suitably versatile mechanism for the wide range of cell types and physiological functions in which it works.

Moreover, given this wide range of cell types--in organs including the lungs, bladder, intestines, and pancreas, as well as in blood vessels and the sensory nervous system--the discovery of the basic Piezo-protein mechanism could lead to new ways of understanding and treating many human diseases. To take one example, Dr. Scheuring said, if the membranes of cells lining blood vessels contain excess cholesterol they would become stiffer, increasing the background tension on embedded Piezo 1 proteins and potentially disrupting these proteins' normal ability to detect and help regulate blood pressure.

"Our finding leads to a great many predictions about Piezo proteins' roles in disease that we and others can now go and investigate," he said.

GALVESTON, Texas - Researchers have unlocked mysteries surrounding how a pregnant mother's cells and her fetus' cells communicate throughout pregnancy. With this new information, The University of Texas Medical Branch at Galveston team and their colleagues in South Korea can develop new non-invasive methods of monitoring and improving the health of the fetus using this mode of communication. The findings are now available in the American Journal of Obstetrics and Gynecology.

"During pregnancy, there is constant communication between maternal and fetal cells using sacs filled with chemicals called exosomes," said senior author Ramkumar Menon, UTMB associate professor in the department of obstetrics and gynecology. "Our prior studies have shown that the fetal exosomes signal to the mother's body that her/his organs have fully matured, which triggers the labor and delivery process. Given this, we sought out to learn more about the extent and capabilities of this communication system in order to develop new ways to monitor and support the fetus during pregnancy."

To test exosome trafficking and function, the research team used mice that were genetically engineered to have certain exosome proteins glow florescent red and green when blood and tissue samples are stained and viewed under a microscope in order to distinguish between the fetal and maternal exosomes.

The researchers learned that isolating and tracking fetal exosomes travelling to the maternal side is a useful indicator of the fetus's health and development that can be measured in minimally invasive maternal blood samples. Likewise, they now know that trafficking of exosomes from the maternal side to the fetus produces functional changes.

"We've just received a $ 1.5 million three-year contract to test a novel approach in treating preterm birth," said Menon. "We will test the usefulness of drugs enclosed in exosomes that can potentially cross the placenta barrier, reach the fetus and prevent fetal inflammation, a major cause of preterm birth for which there is currently no drug treatment. Fetal inflammatory response is primarily responsible for preterm delivery, which impacts 15 million pregnancies yearly and responsible for 1 million neonatal deaths."

Macrocyclic compounds are ring-shaped molecules made by connecting two ends of linear molecules. One of their unique and exciting properties is that their cyclical configuration reduces their flexibility, which means that macrocycles need less energy to bind targets than conventional small molecules.

In fact, macrocycles show a great ability to bind difficult targets that have flat, featureless surfaces. This has raised tremendous interest in the pharmaceutical industry, which is particularly interested in macrocyclic compounds with a molecular weight below 1 KDa, which would be small enough to cross the cell membrane and reach intracellular disease targets, e.g. proteins or even genes in the cell.

Still, there is a hurdle: there aren't enough suitable macrocycle libraries or methods to generate such small macrocycles. The compound libraries that pharmaceutical companies use today in high-throughput screens do contain 1-2 million different molecules, but those are mostly classical small molecules and only a handful are actual macrocyclics - at most, only a few hundred. This is too small a number for the screens to yield good hits when searching for possible drug candidates against challenging disease targets.

Now, scientists at EPFL have found a way to generate libraries of more than 9,000 of macrocyclic molecules below 1 KDa, all with high structural diversity. "Initially, what we wanted to do is generate orally available or cell-permeable macrocyclic drugs," says Professor Christian Heinis, whose lab led the study.

The libraries were generated by "cyclizing" short linear peptides in combination with diverse linker reagents, which promote chemical bonding. The yields of the macrocyclization reactions turned out to be so efficient that there was no need for purification. And in a key breakthrough, the new method also led to the discovery of surprisingly efficient macrocyclization reactions based on the ligation of thiol and amino groups of short peptides.

The work was supported by EPFL's Biomolecular Screening Facility (BSF), headed by Gerardo Turcatti. "EPFL has already developed the liquid handling processes to perform the combinatorial synthesis and to screen the macrocyclic compound libraries," he says. Screening identified binders of different disease targets, including inhibitors of thrombin, an important target of coagulation disorders. X-ray structure analysis of a thrombin inhibitor by partners in Italy showed a snug fit of the macrocycle to its target.

Heinis's lab is now further developing the macrocycle synthesis approach in order to screen even larger combinatorial libraries. Working closely with the BSF with the support of NCCR Chemical Biology, the next step is to generate macrocyclic inhibitors of intracellular protein-protein interactions, for which we currently have no good inhibitors.

Researchers from the Harvard John A. Paulson School of Engineering and Applied Sciences (SEAS) have developed a mathematical framework that can turn any sheet of material into any prescribed shape, inspired by the paper craft termed kirigami (from the Japanese, kiri, meaning to cut and kami, meaning paper).

Unlike its better-known cousin origami, which uses folds to shape paper, kirigami relies on a pattern of cuts in a flat paper sheet to change its flexibility and allow it to morph into 3D shapes. Artists have long used this artform to create everything from pop-up cards to castles and dragons.

"We asked if it is possible to uncover the basic mathematical principles underlying kirigami and use them to create algorithms that would allow us to design the number, size and orientation of the cuts in a flat sheet so that it can morph into any given shape," said L. Mahadevan, de Valpine Professor of Applied Mathematics, Physics, and Organismic and Evolutionary Biology, the senior author on the paper.

"Specifically, if we are given a general shape in two-or-three dimensions, how should we design the cut patterns in a reference shape so that we can get it to deploy to the final shape in one motion?" said Gary P. T. Choi, a graduate student at SEAS and first author of the paper. "In this work, we solve that problem by identifying the constraints that have to be satisfied in order to achieve this cut pattern, use a numerical optimization approach to determine the patterns, and then verify this experimentally."

The research is published in Nature Materials.

This research follows previous work by the Mahadevan lab that characterized how origami-based patterns could be used as building blocks to create almost any three-dimensional curved shape.

"We were actually able to do a little more with kirigami than we were able to do with origami," said Levi Dudte, graduate student in the Mahadevan lab and co-author of the paper. "The presence of cuts and holes in the interior of the material gives kirigami the ability to change its shape significantly."

"Our work draws on inspiration from art, tempered by the rigor of mathematics, and the challenges of engineering shape. Finding kirigami tessellations that can convert a square to a circle, or a flat sheet into a poncho is just the start. We think that this is just the beginning of a class of new ways to engineer shape in the digital age using geometry, topology, and computation," said Mahadevan.

Next the researchers aim to explore how to combine cuts and folds to achieve any shape with a given set of properties, thus linking origami and kirigami.

Researchers are increasingly studying the effects of environmental insults on psychiatric and neurological conditions, motivated by emerging evidence from environmental events like the record-breaking smog that choked New Delhi two years ago. The results of a new study publishing August 20 in the open-access journal PLOS Biology by an international group of researchers using large data sets from the US and Denmark suggests a possible link between exposure to environmental pollution and an increase in the prevalence of psychiatric disorders.

The team found that poor air quality was associated with higher rates of bipolar disorder and major depression in both US and Danish populations. The trend appeared even stronger in Denmark, where exposure to polluted air during the first ten years of a person's life also predicted a more than two-fold increase in schizophrenia and personality disorders.

"Our study shows that living in polluted areas, especially early on in life, is predictive of mental disorders in both the United States and Denmark," said computational biologist Atif Khan, the first author of the new study. "The physical environment - in particular air quality - warrants more research to better understand how our environment is contributing to neurological and psychiatric disorders."

Although mental illnesses like schizophrenia develop due to a complex interplay of genetic predispositions and life experiences or exposures, genetics alone do not account entirely for variations in mental health and disease. Researchers have long suspected that genetic, neurochemical and environmental factors interact at different levels to affect the onset, severity and progression of these illnesses.

Growing evidence is beginning to provide insight into how components of air pollution can be toxic to the brain: Recent studies on rodents suggest that environmental agents like ambient small particulate matter (fine dust) travel to the brain through the nose and lungs, while animals exposed to pollution have also shown signs of cognitive impairment and depression-like behavioral symptoms. "We hypothesized that pollutants might affect our brains through neuroinflammatory pathways that have also been shown to cause depression-like signs in animal studies," said Andrey Rzhetsky, who led the new study.

To quantify air pollution exposure among individuals in the United States, the University of Chicago team relied on the US Environmental Protection Agency's measurements of 87 air quality measurements. For individuals in Denmark, they used a national pollution register that tracked a smaller number of pollutants with much higher spatial resolution.

The researchers then examined two population data sets, the first being a U.S. health insurance claims database that included 11 years of claims for 151 million individuals. The second dataset consisted of all 1.4 million individuals born in Denmark from 1979 through 2002 who were alive and residing in Denmark at their tenth birthday. Because Danes are assigned unique identification numbers that can link information from various national registries, the researchers were able to estimate exposure to air pollution at the individual level during the first ten years of their life. In the US study, exposure measurements were limited to the county level. "We strived to provide validation of association results in independent large datasets," said Rzhetsky.

The findings have not been without controversy. "This study on psychiatric disorders is counterintuitive and generated considerable resistance from reviewers," said Rzhetsky. Indeed, the divided opinions of the expert reviewers prompted PLOS Biology to commission a special companion article from Prof. John Ioannidis of Stanford University (Ioannidis is unconnected with the study, but assisted the journal with the editorial process).

"A causal association of air pollution with mental diseases is an intriguing possibility. Despite analyses involving large datasets, the available evidence has substantial shortcomings and a long series of potential biases may invalidate the observed associations," says Ioannidis in his commentary. "More analyses by multiple investigators, including contrarians, are necessary."

Rzhetsky also cautioned that the significant associations between air pollution and psychiatric disorders discovered in the study do not necessarily mean causation, and said that further research is needed to assess whether any neuroinflammatory impacts of air pollution share common pathways with other stress-induced conditions.

Bioengineers and dentists from the UCLA School of Dentistry have developed a new hydrogel that is more porous and effective in promoting tissue repair and regeneration compared to hydrogels that are currently available. Once injected in a mouse model, the new hydrogel is shown to induce migration of naturally occurring stem cells to better promote bone healing. Current experimental applications using hydrogels and stem cells introduced into the body or expensive biological agents can come with negative side effects.

The findings, published online in the journal Nature Communications, suggest that in the near future the next generation of hydrogel systems could greatly improve current biomaterial-based therapeutics to repair bone defects.

Hydrogels are biomaterials that are made up of a 3D network of polymer chains. Due to the network's ability to absorb water and its structural similarities to living tissue, it can be used to deliver cells to defective areas to regenerate lost tissue. However, the small pore size of hydrogels limits the survival of transplanted cells, their expansion and new tissue formation, making this less than ideal for regenerating tissue.

One material that has caught on in the field of biomaterials is the naturally occurring mineral, clay. Clay has become an ideal additive to medical products with no reported negative effects. It has been shown to be biocompatible and is readily available.

The clay is structured in layers, with the surface having a negative charge. The unique layered structure and charge were important to researchers as their hydrogels had a positive or opposite charge. When the hydrogel was inserted into the clay layers, through a process called intercalation chemistry, the end result was a clay-enhanced hydrogel with a much more porous structure that could better facilitate bone formation.

Once they had their clay-enhanced hydrogel, the researchers used a process called photo-induction, or the introduction of light, to turn their new biomaterial into a gel, which would make it easier to be injected into their mouse model.

The mouse model had a non-healing skull defect, which the researchers injected with their clay-enhanced hydrogel. After six weeks, they found that the model showed significant bone healing through its own naturally occurring stem cell migration and growth.

"This research will help us develop the next generation of hydrogel systems with high porosity and could greatly improve current bone graft materials," said lead author Min Lee, professor of biomaterials science at the UCLA School of Dentistry and a member of the Jonsson Comprehensive Cancer Center. "Our nanocomposite hydrogel system will be useful for many applications, including therapeutic delivery, cell carriers and tissue engineering."

Injectable combinations of living cells and bioactive molecules using hydrogels would be a preferred medical application to treat unhealthy or damaged areas of the body rather than more invasive surgery.

Future research is planned to learn how the physical properties of nanocomposite hydrogels affect the migration of cells and their function, as well as the formation of blood vessels.

First study to demonstrate relationship between green space and mental wellbeing at an individual level published

Using data from 25,518 people, the researchers show that Londoners who live within 300m of green space have significantly better mental wellbeing

Proximity to green space was more important than lifestyle factors such as employment, income, and general health.

It is hoped that planners will use the results to help create a healthier, happier and more productive urban landscape.

Living within 300m of urban green space such as parks, nature reserves or play areas is associated with greater happiness, sense of worth, and life satisfaction - according to a new study by researchers at the University of Warwick, Newcastle University and the University of Sheffield.

It has long been understood that individuals feel positive emotions when exposed to natural environments, and successive Governments have enshrined this in planning guidance - but how much green space is needed and how close does it need to be to people's homes to make a difference?

Dr Victoria Houlden, Professor Joao Porto de Albuquerque, Professor Scott Weich and Professor Stephen Jarvis set out to apply new geospatial research techniques to create an accurate measure of the relationship between green space and 3 different aspects of mental wellbeing.

Most previous studies have only been able to take into account the overall amount of green space within a specific area, rather than the exact amount of green space that surrounds an individual's home, and have found mixed results.

By combining survey responses from 25,518 participants in the UK government's Annual Population Survey (APS) with data on the shape, size and location of London's 20,000 public green spaces, the team were able to more accurately model greenspace distribution in relation to where each of the 25,518 survey participants lived, and explore how that influenced their mental wellbeing as revealed in their survey answers.

The study, published in the August issue of Applied Geography, found:-

Overall there is a very strong relationship between the amount of green space around a person's home and their feelings of life satisfaction, happiness and self-worth

Green space within 300m of home had the greatest influence on mental wellbeing

An increase of 1 hectare - about the size of an international Rugby Union pitch - within 300m of residents was associated with an increase of 8 percentage points in a life satisfaction, 7 in worth and 5 in happiness.

Green space was less important for mental wellbeing in Central London and East London

Dr Houlden said: "We believe this it is the first study to demonstrate how urban greenspaces may improve a broader definition of mental wellbeing.

"A lot of research focuses on poor mental health, or single aspects of wellbeing like life satisfaction. What makes our work different is the way we consider multi-dimensional mental wellbeing, in terms of happiness, life satisfaction and worth."

"While government guidelines recommend minimum amounts of greenspace in residential developments, our study was able to establish more specifically where greenspace may be most valuable."

Scott Weich, Professor of Mental Health at the University of Sheffield, said:

"Contrary to popular opinion, up until now the evidence for the link between green space and mental wellbeing has been pretty circumstantial. By combining advanced statistical and mapping methods, we've shown that the effect is real and substantial. Basically we've proven what everyone has always assumed was true."

Professor Stephen A. Jarvis, Director of the EPSRC Centre for Doctoral Training in Urban Science at the University of Warwick, said:

"The EPSRC-funded Centre for Doctoral Training in Urban Science, hosted at the University of Warwick, has been tackling difficult urban questions for several years. Much of this research has been to provide evidence, resulting from the application of data-analytic methods, to support decision making by local councils and government agencies.

"This is the first study to provide concrete evidence of how urban greenspaces may improve mental wellbeing in the broadest sense, and should therefore lead to healthier, happier and more productive urban landscapes in the future."

Professor João Porto de Albuquerque, Director of the University of Warwick's Institute of Global Sustainable Development, added:

"As part of the Sustainable Development Goals, the United Nation Members States committed to provide every access to green and public spaces for every citizen by 2030, which is usually measured based on the area of cities that is open space for public use.

"However, our study makes clear that it is not only the area of public greenspace in the whole city that matters when it comes to maximising benefits for mental wellbeing. We provide evidence that the proximity of greenspace to an individual's home is important for detecting significant associations with improved mental wellbeing, and that the strength of this association may vary in different areas of the city.

"This result has important implications for urban planning and decision making related to how we measure access to urban green spaces and how to design more sustainable and liveable cities."

Stomata are plant-specific epidermal structures that consist of paired guard cells surrounding a pore. The opening and closing of these micro-valves facilitate carbon dioxide uptake for photosynthesis and reduce excessive water loss in plants.

Recently, a research group led by Prof. LE Jie at the Institute of Botany of the Chinese Academy of Sciences (IBCAS) found a genetic suppressor of flp stomatal defects. They found that RPA2a, a core subunit of Replication Protein A (RPA) complexes, acted downstream from the core cell cycle genes of CDKB1 to ensure terminal division during stomatal development and the formation of paired guard cells to create functional stomata units.

RPA is a heterotrimeric single-stranded DNA (ssDNA)-binding protein complex that is required for multiple aspects of DNA metabolism, including DNA replication, recombination, and repair. The homologues of each of the three RPA subunits (RPA1-3) are well conserved in eukaryotes, including humans.

LE's group demonstrated that CDK-mediated phosphorylation at the N-terminus of RPA2a was essential for RPA functioning and localization. The scientists also showed that Serine-11 and Serine-21 are evolutionarily conserved CDK-phosphorylation sites. Furthermore, their results revealed that being phosphorylated by CDK was required for RPA2a to respond to DNA damage.

The study, entitled "A conserved but plant specific CDK-mediated regulation of DNA replication protein A2 in the precise control of stomatal terminal division," was published online in PNAS on August 20, 2019. YANG Kezhen is the first author and LE Jie is the corresponding author.

In 2006, scientists discovered a way to "reprogram" mature cells -- adult skin cells, for example -- into stem cells that could, in principle, give rise to any tissue or organ in the body. Many assumed it was only a matter of time until this groundbreaking technique found its way into the clinic and ushered in a regenerative medicine revolution.

Because the same patient would be both the donor and the recipient of cells derived from these so-called induced pluripotent stem cells (iPSCs), these cells would be seen as "self" by the immune system, the thinking went, and not subject to the problems of rejection that plague conventional transplants.

But iPSCs haven't emerged as the cure-all that was originally envisioned, due to unforeseen setbacks, including the surprising preclinical finding that iPSC-derived cell transplants are often rejected, even after being reintroduced into the organism the cells were sourced from.

Scientists have struggled to understand why this rejection occurs. But a new study from the UC San Francisco Transplant and Stem Cell Immunobiology (TSI) Lab, in collaboration with the Laboratory of Transplantation Genomics at the National Heart, Lung, and Blood Institute (NHLBI) and Stanford University, shows that the adult-to-iPSC conversion process can mutate DNA found in tiny cellular structures called mitochondria. These mutations can then trigger an immune response that causes mice and humans to reject iPSCs, and stem cell transplants more generally.

"The role of mitochondria has been largely ignored in the field of regenerative medicine, but earlier efforts in our lab suggested that they may affect the outcome of stem cell transplants, said Tobias Deuse, MD, the Julien I.E. Hoffman Chair in Cardiac Surgery at UCSF and lead author of the new study, published August 19 in Nature Biotechnology. "It's important that we understand their role so that we're able to reliably quality-control our engineered cells and make sure stem cell products can be transplanted into patients without rejection."

Often referred to as the cell's powerhouses, mitochondria produce the energy that fuels nearly every biological process on Earth (bacteria, which don't have mitochondria, are the exception). But mitochondria are special for another reason: they contain their own genome.

The "nuclear" human genome, so called because it resides in the cell's nucleus, contains more than 20,000 protein-coding genes and 3 billion DNA bases -- the four-letter chemical alphabet that constitutes the genetic code. The human mitochondrial genome, by contrast, contains only 13 protein-coding genes and fewer than 17,000 bases. However, in tissues with high energy demands, the tiny mitochondrial genome can contribute disproportionately to cells' total protein content.

"In cells that do a lot of work, like heart muscle cells, up to a third of the cell's protein-producing mRNA molecules are mitochondrial in origin. This means that the burden of a single mitochondrial mutation may be tremendous. You don't end up with just a few proteins that can potentially provoke an immune response -- you end up with thousands," said Sonja Schrepfer, MD, PhD, professor of surgery and senior author of the new study.

To show that such mitochondrial mutations can trigger an immune response, the scientists created hybrid stem cells with nuclear DNA from one mouse strain and mitochondrial DNA from another. They transplanted these cells into mice with identical nuclear DNA, but whose mitochondrial DNA differed by a single base in two protein-coding genes. A few days post-transplant, they harvested immune cells from the mice and exposed the cells to various mitochondrial protein fragments. The only proteins that triggered a response were those produced by the two "foreign" mitochondrial genes.

Though similar experiments can't be performed in humans, the scientists were able to devise a clever workaround. "We recruited liver and kidney transplant patients and designed experiments that took advantage of naturally occurring sequence differences in the mitochondrial DNA of donors and recipients," Deuse said.

As in the mouse experiments, the researchers isolated immune cells from each transplant recipient -- three and six months later in this case -- and exposed the cells to mitochondrial protein fragments. The results were identical: the recipient's immune cells were only triggered by the "foreign" mitochondrial proteins that originated from the organ donor.

"In both mouse and human, even one mitochondrial mutation is enough to have a recognizable immune response," Schrepfer said.

But an important question remained: would iPSC-derived cells behave the same way as the liver and kidney cells?

It turns out that the iPSC conversion process is highly mutagenic, and gives rise to many new, immune-activating mitochondrial mutations, said Deuse. "Under normal physiological conditions, mitochondrial DNA is 10 to 20 times more susceptible to mutation than nuclear DNA. Transforming adult cells into stem cells is a harsh process, so we expected mutation rates to be just as high or higher."

Moreover, unlike the nucleus, mitochondria lack the molecular machinery that repairs DNA. Instead, the body relies on the immune system to find and destroy cells that produce unfamiliar mitochondrial proteins -- a clear sign that the mitochondrial DNA has mutated.

But cells that become iPSCs are reprogrammed and grown outside of the body, and do not undergo this weeding out process by the immune system, Shrepfer said. "We don't make iPSCs in an organism, we make them in a petri dish in the absence of immune surveillance. The longer we culture these cells, the greater the chance that new mutations will be introduced, or that very rare mutations that are already present will be amplified. This makes iPSCs more likely to be rejected when transplanted."

Study co-author Hannah Valantine, MD, whose lab performed the genetic sequencing to identify these mitochondrial DNA mutations, said that the findings could have a significant impact on the field of transplantation.

"This study uncovers a possible new mechanism by which transplants are rejected, and which might be leveraged in the future to develop better diagnostic and immunosuppressive agents," said Valantine, lead investigator of the Laboratory of Organ Transplant Genomics in the Cardiovascular Branch at NHLBI, part of the National Institutes of Health.

But iPSC transplants aren't doomed, say Deuse and Schrepfer, who previously discovered a way to make iPSCs "invisible" to the immune system -- a technique that could ensure that iPSCs and other stem cells with mitochondrial mutations aren't rejected. But without this sort of invisibility cloak, the new study suggests that clinicians may need to perform careful screenings for mitochondrial mutations before administering stem cell therapies.

"The bottom line is that we want to make people aware of this phenomenon. Just because iPSCs are derived from your own cells doesn't necessarily mean they won't induce an immune response," Schrepfer said. "It's very easy to introduce mutations during iPSC production, so it's critical that iPSC and stem cell products used therapeutically are screened for mitochondrial mutations prior to transplant."

Bottom Line: An observational study of 601 mother-child pairs from six cities in Canada hints at an apparent association between maternal exposure to fluoride during pregnancy and lower IQ scores measured in children ages 3 to 4. Community water has been fluoridated for decades to prevent tooth decay; a majority of U.S. residents are supplied with fluoridated water, as are more than one-third of Canadian residents and about 3% of European residents. This study analyzed two measures of fluoride exposure during pregnancy. Data on maternal urinary fluoride concentrations and children's IQ were available for 512 mother-child pairs, and self-reported consumption of tap water and other water-based drinks (tea and coffee) and IQ scores were available for 400 of the 601 mother-child pairs. After accounting for factors associated with fluoride metabolism and children's intellectual abilities, a 1-mg/L increase in maternal urinary fluoride was associated with a 4.5-point lower IQ score in boys without a statistically significant association with IQ score in girls. A 1-mg higher intake of fluoride was associated with a 3.7 lower IQ score among boys and girls. The study's conclusions are limited by its observational design, which can't account for unmeasured factors that could explain the results, and there was no assessment of children's fluoride exposure during infancy. An accompanying podcast discusses the meaning and implications of the findings.

Author: Christine Till, Ph.D., of York University, Toronto, Canada, is the corresponding author.

(doi:10.1001/jamapediatrics.2019.1729)

Editor's Note: The article contains conflict of interest and funding/support disclosures. Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.

Researchers at Purdue University have created a quantum spin wave for light. This can be a carrier of information for future nanotechnologies but with a unique twist: they only flow in one direction.

The article "Unidirectional Maxwellian spin waves", by Todd Van Mechelen and Zubin Jacob has been published in the open access journal Nanophotonics on degruyter.com.

Information technologies at the nanoscale rely on manipulating particles such as electrons and photons. The electron, which is the carrier of charge (electricity), is a fermion while the photon, which is the long-distance transmitter of information, is a boson.

The most important difference between a fermion and a boson is literally how they "spin". Even though electron spin is widely utilized in commercial nanotechnologies such as magnetic memories, optical spin has only recently become a fundamental degree of freedom in nanophotonics with possible applications in fiber optics, plasmonics, resonators and even quantum metrology. This explosion of research into optical spin is due to the remarkable features of strongly confined electromagnetic waves. At the nanoscale, spin and direction of motion of light are intrinsically locked to one another.

The researchers used many designs to achieve this behavior, in particular, an interface of mirror symmetric gyrotropic media, illustrated in the accompanying figure. Gyrotropy is a form of material response to light waves that transfer spinning behavior of electrons to photons (shown by circular arrows).

"Our research opens up the possibility of new applications where devices communicate information in one direction but block it completely in the reverse. This is important for the safe functioning of high power devices as well as for reducing interference between transmitted/received electromagnetic signals from cellphone antennas," said Zubin Jacob.