Brain

BUFFALO, N.Y. -- University at Buffalo chemists have shown that self-assembling molecular traps can be used to capture PFAS -- dangerous pollutants that have contaminated drinking water supplies around the world.

The traps are made from iron-based and organic building blocks that connect, like Legos, to form a tetrahedral cage. Experiments showed that these structures bind to certain PFAS (short for per- and polyfluoroalkyl substances), and a lab analysis revealed how this happens. As it turns out, the PFAS stick strongly to the outside of the cages instead of getting caught inside, researchers say.

These insights were detailed in a study released this month and could help scientists fine-tune the traps in favorable ways -- for example, by enlarging the openings of the cages to potentially catch other types of PFAS. The eventual goal is to use such cages -- known as metallacages -- in systems that isolate PFAS from water, which could lead to better water treatment, or improved techniques for detecting the pollutants in water.

IMAGES: http://www.buffalo.edu/news/releases/2020/05/033.html

"PFAS are highly stable and toxic chemicals that can cause adverse human health effects," says Diana Aga, PhD, Henry M. Woodburn Professor of Chemistry in the UB College of Arts and Sciences. "There is increasing evidence to suggest links between exposure to PFAS and adverse health outcomes in humans and animals, with potential effects including decreased birth weight, decreased fertility, and increased risk of diabetes and certain cancers, to name a few. The findings in our new paper are exciting because they provide evidence that the molecular traps are effective sorbents for some PFAS."

"We're very excited about a few ways this work may evolve, from enabling the detection of PFAS that current analyses may miss, to altering the cages such that in addition to binding the PFAS, they also destroy them," says Timothy Cook, PhD, assistant professor of chemistry in the UB College of Arts and Sciences.

Cook and Aga led the study, along with Cressa Ria P. Fulong, PhD, a recent Cook lab graduate, and Mary Grace E. Guardian, a PhD candidate in Aga's lab. All team members made important contributions, with Fulong and Guardian spearheading experimental and analytical work that took place in the lab.

The research was featured on the cover of the May 18 issue of the journal Inorganic Chemistry. Cook created the cover art, which he drew by hand with a fountain pen on paper, then digitized and colored. The illustration depicts molecular building blocks self-assembling to form tetrahedral structures that converge on a PFAS molecule.

The traps capture a subset of PFAS

PFAS are not a single compound; they are a group of manmade chemicals that are used in food packaging, nonstick coatings, firefighting foams and other goods. Because the compounds don't break down easily, they persist in the environment for a long time.

Numerous studies have detected PFAS in drinking water supplies worldwide, including a paper that Aga and colleagues published on May 19 in the journal Chemosphere. That project searched for the pollutants in the Philippines and Thailand and found them in surface waters, bottled water and water from re-fill stations. Other studies have shown that PFAS accumulate in people's blood.

With these concerns in mind, Cook, Aga, Fulong and Guardian set out to learn whether molecular cages could help trap PFAS.

The scientists screened about a dozen different types of self-assembling cages that contain metals. Fulong synthesized the cages in Cook's lab, and Guardian used advanced analytical techniques in Aga's lab to study whether each structure was binding to PFAS.

This process led the team to the iron-based cages, which captured a subset of PFAS with chains of six or more fluorinated carbon atoms, including perfluorocarboxylic acids, sulfonic acids and fluorotelomers.

Next up? Tweaking the cages to trap more PFAS -- and maybe destroy them

The study gives scientists new knowledge that could help them make experimental improvements to the cages. By tweaking the cages' building blocks, researchers could potentially create structures that bind more strongly with PFAS, sponge up additional varieties of the pollutants, or even destroy the chemicals, Cook says.

"I've been reading reports in the popular media that people are trying to incinerate these PFAS, and it might be making the problem even worse," Cook says. "It basically just sends them up into the air and disperses them even more. I'm wondering if we can develop cages with electro- or photochemical properties that will enable them to break up the bonds in PFAS."

"I'm hopeful that the molecular traps can be designed to potentially capture the most highly water soluble PFAS that typically escape conventional water treatment technologies," Aga says. "There are already many sorbents in use, such as activated carbon, that interact with PFAS. However, activated carbon does not have building blocks or pores that can be easily tuned -- and this is the beauty of the metallacages."

PHILADELPHIA - The normal functioning of our hearts is maintained by our body's control center - the brain - via an intricate network of nerves. When this communication is disrupted, it results in heart disease, including heart attacks, sudden cardiac death and problems in blood supply. As an added layer of safety, the heart has its own 'little brain', called the intracardiac nervous system (ICN) to monitor and correct any local disturbances in communication. The ICN is essential in supporting heart health and can even protect cardiac muscle during a heart attack. But it's not clear how exactly the ICN carries out these roles, because the organization of the neurons that make up the ICN are poorly understood; we don't know where they are located in the heart, how they are connected to each other, and what their molecular properties are.

In a groundbreaking study published in iScience on May 26th, researchers at Thomas Jefferson University and their collaborators have been able to answer these questions in unprecedented detail.

"The ICN represents a big void in our understanding that falls between neurology and cardiology," says co-senior author James Schwaber, PhD, director of the Daniel Baugh Institute for Functional Genomics and Computational Biology (DBI) and co-senior author of the study. "Our goal was to bridge that gap by providing an anatomical framework of the ICN."

"The only other organ for which such a detailed high-resolution 3D map exists is the brain," says co-senior author Raj Vadigepalli, PhD, Professor of Pathology, Cell Biology and Anatomy. "In effect what we have created is the first comprehensive roadmap of the heart's nervous system that can be referenced by other researchers for a range of questions about the function, physiology, and connectivity of different neurons in the ICN."

The study drew on technologies and expertise from different research groups (from Jefferson and University of Central Florida) and industry partners (Strateos and MBF Bioscience), eventually creating a dual-approach pipeline. One approach involved a novel imaging technique called Knife-Edge Scanning Microscopy (KSEM) that allowed the researchers to build a precise 3D model of the entire rodent heart; it is the first use of this technology for cardiac research. The second approach used a technique called laser capture microdissection to sample single neurons for gene expression analysis, as well as to map their individual positions within the 3D structure of the heart.

"Because this hasn't been done before, we were trouble-shooting the protocol as we went along," says co-author Sirisha Achanta, Lab Manager at the DBI. "The heart, unlike the brain, is not symmetrical, so we had to figure out ways to maintain consistency across each heart that we imaged."

The 3D map revealed hitherto unknown complexity of the ICN. The researchers found that the neurons that make up the ICN are found in a coherent band of clusters on the base (top) of the heart, where the heart's veins and arteries enter and leave, but also extend down the length of the left atrium on the back of the heart. They're positioned close to certain key heart structures like the sinoatrial node.

"We know the sinoatrial atrial node is important in creating the heart rate or pace," says co-author Jonathan Gorky, a recently graduated MD/PhD student and now a resident at the Massachusetts General Hospital. "Seeing the clustering of neurons around it was something we had always suspected but had never known for sure. It was really interesting to see the physical evidence of the ICN's function and the precise distribution of the neurons in relationship to the anatomical structures of the heart."

The gene expression analysis of individual neurons also pointed to previously unknown diversity of molecular identities or phenotypes. "We found that there are several different types of neuromodulators and receptors present," explains Dr. Vadigepalli. "This means that we don't just have neurons in the heart that shut on and off activity, but also those that can fine-tune the activity of the ICN."

When comparing male and female rat hearts, the researchers also found sex-specific differences in the way neurons were organized, both spatially and by their gene expression. Co-authors Alison Moss, PhD Candidate in Biochemistry and Molecular Pharmacology, and Shaina Robbins, a senior research assistant, are pursuing further analyses based on these findings. "It could help us explain some of the differences in heart disease in men and women," says Moss. "We're now trying to create a 3D model of the intrinsic nervous system of the pig heart, which is even more anatomically comparable to the human heart, to explore those questions further."

This project is part of a NIH research program called 'Stimulating Peripheral Activity to Relieve Conditions', or SPARC, which aims to promote development of therapeutic devices that modulate electrical activity in nerves to improve organ function. "Around thirty years ago, there were studies showing peripheral nerves like the vagus nerve were critical for the health of organs like the heart and stimulating them could even remediate disease" explains Dr. Schwaber. "But those studies were not able to tell us what amount, frequency and location of stimulation is beneficial or harmful."

"Now that we know where neurons are located in relation to heart structures, we can ask questions like - does stimulating in one location, or even selectively stimulating specific neurons make a difference?" says Dr. Vadigepalli.

The researchers are delighted that the pipeline they've created is now being used by other groups in the SPARC research program. "Our protocol uses everyday lab materials and techniques," says Achanta. "It is highly reproducible and is available now for other organ systems to map not just neurons, but other micro-structures."

"Eventually the hope is to create a 3D map for the human heart, both in health and disease," says Dr. Schwaber. "We've created the foundation for an endless possibility of future studies."

Plant products ingested by pregnant women through their diet are broken down by the intestinal microbiota into chemical substances, some of which can cross the placental barrier and reach the fetus. These foreign substances can harm the unborn child, even if they are of "natural origin". Researchers at the Department for BioMedical Research (DBMR) at the University of Bern and Inselspital, University Hospital Bern, therefore warn against underestimating the effects of such substances.

All mammals, including humans are colonized by billions of microbes. These mainly live in our intestines, but which can also be found in the respiratory tract, on the skin and in the urogenital tract. In the gastroenterology research group of the Department for BioMedical Reserarch (DBMR) at the University of Bern and at the University Hospital Bern, Inselspital, Stephanie Ganal-Vonarburg and Andrew Macpherson investigate the interaction of these benign intestinal microbes with the host organism. The positive influence of the intestinal flora on our immune system has been recognized for a long time. Interestingly, even the maternal intestinal microbiota already has an efect on the development of the child's immune system during pregnancy as well as immediately after birth. In a review article published in the journal Science, Stephanie Ganal-Vonarburg and Andrew Macpherson compiled the latest knowledge of the extent to which the maternal intestinal flora is involved in the development of the child's immune system. They also found evidence that the effects of plant-based substances that pregnant women ingest through diet have so far been underestimated in research and may pose a potential risk to the unborn.

The placenta only offers partial protection

Scientists have always assumed that the developing embryo and fetus grow in a completely sterile environment in the womb, i.e. in the absence of colonizing microbes, and that colonization with micorbes only takes place at the time of birth. "However, the fetus is not protected against microbial metabolites that originate from the maternal intestinal flora," says Ganal-Vonarburg. The placenta offers only partial protection and transfer of microbial substances leads to the maturation of the offspring innate immune system already during pregnancy. Previous studies by the group around Ganal-Vonarburg and Macpherson have shown this. "It is common for pregnant women to take medication with great caution and only after consulting their doctor, since many medications can cross the placenta and interfere with the child's development. However, much less is known about which naturally occurring substances present in the diet can pass on to the unborn child and to what extent this can be beneficial or harmful for the development of the child's immune system", explains Ganal-Vonarburg.

Even plant substances need to be handled with caution

Together with Andrew Macpherson, she has now summarized published research results and found evidence that metabolic products from the diet cannot only directly reach the the maternal organism and thus into the developing fetus, but that this often only occurs after metabolism through the intestinal flora. This also applies to the intake of herbal products, such as superfoods that are considered particularly healthy during pregnancy, such as goji berries or chia seeds: "Although plants products are 'natural' substances, they are always so-called xenobiotic substances that are foreign to the body and should be handled very carefully", says Macpherson. "Especially when pregnant women take plant-based products in large quantities".

Ganal-Vonarburg and Macpherson recommend that future studies should investigate which natural substances could have a beneficial or negative effect on the development of the unborn child and what influence differences in the maternal intestinal flora can have on this process.

How our immune system develops

As soon as the newborn crosses the mother's birth canal, the colonization of its body surfaces with the benign flora begins. Over the first few years, it matures into a complex community of microbes. External influences, such as childbirth (spontaneous delivery, caesarean section), as well as nutrition (breastfeeding or formula feeding) have a long-term influence on this process. In parallel, the child's immune system develops. It is now proven that certain microbial stimuli during this early period shape the immune system lifelong.

Retinal damage due to diabetes is now considered the most common cause of blindness in working-age adults. In low- and middle-income countries, an eye examination via smartphone could help to detect changes at an early stage. This is shown by a new study carried out by scientists from the University of Bonn together with colleagues from Sankara Eye Hospital Bangalore (India). The results are published in the journal Ophthalmology.

One of the most dangerous long-term complications of diabetes is vascular damage. In the eye's photosensitive layer, the retina, this also impacts the capillaries. This network of small vessels supplies the sensory cells with oxygen and nutrients. If it deteriorates, abnormal new vessels form instead and further harm the damaged retina. Left untreated, this often result in loss of vision and ultimately blindness.

"If such a retinopathy is recognized and treated in time, vision loss can often be prevented," emphasizes Dr. Maximilian Wintergerst from the Department of Ophthalmology at the University Hospital Bonn. "An important aspect of therapy is better control of the diabetes; in addition, it is also possible to treat the undersupplied retina with laser light before further problems occur." Laser treatment destroys the undersupplied retina so that it can no longer cause problems by releasing growth factors. These can otherwise cause the formation of abnormal vessels and fluid accumulation in the retina.

Screening alternative with potential

A lack of exercise and an increasingly high-calorie diet mean that diabetes is currently on the rise globally. It is estimated that 8 out of 10 people with diabetes worldwide live in developing and emerging countries, which often have a poorly resourced health system. Systematic retinal screening of diabetics is therefore usually not possible in these countries.

This could be overcome by using devices that were actually designed for a completely different purpose - smartphones. The increasingly affordable devices nowadays usually come with high-quality cameras. And these are surprisingly useful for diagnosing diseases of the retina. The current study conducted by Wintergerst together with colleagues from Bonn and Bangalore in southern India points in this direction.

In the study, the researchers compared four different approaches aimed at enabling ophthalmoscopy with a standard mid-range smartphone. Not all of them fulfilled this promise equally well. "The best result in our test was achieved by an adapter with an additional lens that is attached to the smartphone," Wintergerst concludes. "It allowed almost 80 percent of eyes with any retinal changes to be detected, even in the early stages. Advanced damage could even be diagnosed 100 percent of the time."

The scientists had trained optometrists (ophthalmic assistants) from the Sankara Eye Hospital in Bangalore for their study. On average, they needed one to two minutes per examination. This involved documenting changes in the retina by filming the back of the eye with a smartphone camera. The co-author of the study, Prof. Dr. Robert Finger from the Department of Ophthalmology at the University Hospital Bonn, considers these capabilities to be what makes the method so appealing: "This means that the examination can also be enabled by trained laypersons," he says. "The images are then sent via the Internet to the ophthalmologist for diagnosis."

"COVID-19 has further necessitated the need for us to explore methods of reducing patients visiting hospital. This modality is promising in increasing efficiency of screening for retinal changes in diabetics", added co-author Dr. Mahesh P. Shanmugam, Head VitreoRetina & Ocular Oncology, Sankara Eye Foundation India.

Next step: artificial intelligence supports diagnostics

The researchers are currently developing an app in collaboration with their colleagues from the Sankara Eye Foundation in India. This app will make it possible to create an encrypted electronic patient file for each patient on the smartphones used for the examination. It not only stores the images, but also the findings of the doctor who ultimately reviewed them. Furthermore, the researchers are working on an automatic pre-evaluation of the images using artificial intelligence. In such methods, a software "learns" to recognize pathological changes independently on the basis of thousands of retinal images.

The researchers hope that their work will improve eye care in developing and emerging countries. The project is funded by the German Federal Ministry for Economic Cooperation and Development and the Else Kröner-Fresenius Foundation. Recently, it was also presented with the special award of the "bytes4diabetes Award" for innovative digital approaches in the fight against diabetes.

ITHACA, N.Y. - Cornell researchers have sequenced and analyzed the genome of a single-celled alga that belongs to the closest lineage to terrestrial plants and provides many clues to how aquatic plants first colonized land.

The report, "The Penium margaritaceum Genome: Hallmarks of the Origins of Land Plants," was published May 21 in the journal Cell.

Penium margaritaceum belongs to a group of freshwater algae called charophytes, and specifically to a subgroup called the Zygnematophyceae, which had a common ancestor with the first land plants some 600 million years ago. In order to shift from water to land - a transition that still puzzles scientists - plants had to protect themselves from drying out and from ultraviolet (UV) radiation, and they had to develop structures to support themselves without the buoyancy provided by water.

The researchers found footprints of all these adaptations in the Penium genome, providing insight into the mechanisms and genetics that early terrestrial plants required.

"We knew almost nothing about the genomes of the immediate ancestors of land plants," said senior author Jocelyn Rose, professor of plant biology in the College of Agriculture and Life Sciences.

"We now have exciting insights into the last common ancestor of algae and land plants," Rose said, "and that allows plant biologists to infer the origins of land plant molecular pathways, developmental systems and biological processes, and to place them in the context of land colonization in ways that have not previously been possible."

Though some algae of the charophyte group are branched and look like early land plants, molecular data reveals that the common ancestor had a simpler filament-like shape.

"We are very interested in why it is that the simple body plan might have been evolutionarily advantageous," Rose said. "Penium lives in the margins of fresh water and land, in habitats that expose it to periods of drying and rehydration and this was likely a key factor."

The Penium genome contains a great deal of repetitive and "junk" (non-coding) DNA, which created challenges for the researchers. They ended up extracting a clean set of DNA from purified nuclei and integrating many kinds of DNA sequencing techniques and assembly programs to cover the entire genome. They also conducted cutting-edge transcriptome (RNA) sequencing to complement the genome sequencing and to understand which genes were turned on and off by different stresses.

"We found out that the genome is huge," said Zhangjun Fei, professor of bioinformatics at Boyce Thompson Institute and an adjunct associate professor in the Plant Pathology and Plant-Microbe Biology Section. Fei is a co-leading author of the study and handled the computational and sequencing work.

The genome of this tiny single-celled alga is even larger than the notoriously large maize genome and the human genome.

"One big result is that we found flavonoids, chemicals that can protect from UV light radiation," Fei said.

"Previously it was thought that these compounds only existed in land plants," Rose said. "We detected not only the flavonoids themselves, but also parts of the pathway for their biosynthesis."

The researchers also identified genes involved in regulatory systems and hormone signaling that have previously only been found in land plants, as well as mechanisms that keep plants from drying out, including the production of mucilage.

They also found a large number of genes that contribute to cell wall biosynthesis and reorganization, which are necessary for structural support.

"Again, it's a single cell, but it has enormous families of cell wall modifying proteins," Rose said. "This suggests highly complex control of wall structure, dynamics and biomechanical properties that may be every bit as elaborate as in multicellular lands."

The researchers believe the Penium genome will open up investigations into many areas of plant biology, including possible applications for modern crops. The team plans to investigate the genomes of other species of charophytes.

A group of Skoltech scientists, in collaboration with colleagues from the University of Southampton (UK), developed a fully optical approach to control the couplings between polariton condensates in optical lattices. This study is an important step towards the practical application of optical polariton condensate lattices as a platform for simulating condensed matter phases.
Over its three years of existence, the Laboratory of Hybrid Photonics of the Skoltech Center for Photonics and Quantum Materials and its team of young researchers, working under the guidance of Professor Pavlos Lagoudakis, has been pushing the state of the art in the field of exciton polaritonics. Their recent demonstration of coherently coupled polariton condensates has notably been proposed as a new simulator platform [1,2]. This technology uses an elaborate laser excitation pattern to generate high-complexity polariton graphs in a highly scalable manner, with up to a thousand condensates currently achievable. No matter which technological platform is used, and whether its nodes are polariton condensates, cold trapped atoms or superconducting qubits, the ability to tune the couplings between nearest and next-nearest neighboring nodes is an essential step to simulate condensed matter phases. As the coupling between polariton condensates was predefined by the laser excitation geometry and the polariton wave vector, controlling the coupling between the nodes of a fixed latticed geometry remained elusive.

To tackle this technological challenge, the researchers suggested using another weaker laser pattern to form incoherent exciton reservoirs that would act as optically imprinted potential barriers. In an experiment, they demonstrated that introducing such a barrier of variable height between nodes changes the phase of the transmitted condensate signal in a precise and controlled manner, ultimately changing the sign of the complex coupling. In this work, Skoltech researchers demonstrated ferromagnetic, antiferromagnetic and paired ferromagnetic phases in polariton cluster up 4×4 condensates.

Skoltech researcher and first author, Dr. Sergey Alyatkin, notes: "These results were achieved due to the hard and coordinated work of our team, which allowed us to first create a unique experimental setup and to use it to achieve these exciting results. Together with our colleagues from Southampton, we have developed a way to very precisely control the excitation spatial profile, which allows us to imprint optical lattices of polariton condensates in almost any arbitrary geometry. We also implemented a homodyne interferometry technique for in-situ readout of the relative phases of the lattice nodes, which allows us to project a classical spin (from +1 to -1) for each corresponding node."

Alexis Askitopoulos, senior researcher of the Hybrid Photonics Labs and co-author, adds: "Our results showcase that we can tune the nearest neighbor and next nearest neighbor interactions in our polariton lattice. Effectively this gives us control of some of the non-diagonal elements of the Hamiltonian of our system, greatly increasing the number of configurations that could be simulated with our platform, as well as opening up possibilities for implementing machine learning processes and algorithms."

The result of a constant back-and-forth of people, samples and ideas between Skoltech and Southampton University, this high-impact article also serves as a reminder of the importance of international collaborations in academia. In these current days of self-isolation, the Russian and UK groups remain in close contact through a weekly online seminar, where they discuss current progress and propose news ways to push their research further.

The authors are confident that the results of their research will be of great interest not only to the specialists working in the field of polaritonics, but also to the wider global photonics and optical computing community. The extreme precision of the control over the relative phase between nodes, along with the ease, scalability and tunability of its fully optical implementation, is believed to makes this development a critical step in the development of high-performance polariton simulators, which could one day unlock the full power of optical computing.

As dentists and their teams across America get back to their regular schedules after a sharp COVID-19-related reduction, a new study shows a key opportunity to reduce the use of opioid painkillers by their patients.

The analysis of four years' worth of data from two million patients show that those who had dental procedures on a Friday or a day before a holiday were much more likely to fill a prescription for an opioid than other patients.

Teens and young adults were the most likely to get opioids, which were likely prescribed in order to get them through the weekend or holiday break without needing to contact the dentist for pain care.

One in five of the patients, all between the ages of 13 and 64, filled a prescription for an opioid, even though non-opioid pain medications are equally effective at controlling pain and have lower risks.

Those who had pre-weekend or pre-holiday procedures were 27% more likely to pick up an opioid prescription. If they were teens or young adults, they were 43% more likely than older patients to do so.

The new findings, reported in the Journal of the American Dental Association by a team from the University of Michigan, build on prior work showing overprescribing of opioids by dentists with no increase in pain relief or patient satisfaction .

The rate of weekend and holiday opioid prescription-filling by young people is especially troubling because of previous work showing that those who get opioids after getting their wisdom teeth out are nearly three times as likely to keep refilling the prescription long after their mouths should have healed.

"Variation in opioid prescription fills may put some patients at increased risk," says Caitlin Priest, the U-M Medical School student who led the analysis as part of the Michigan Opioid Prescribing Engagement Network team. "Now that we understand that dental opioid prescription fills were increased on Fridays and before holidays, we can create and disseminate best practices to avoid unnecessary prescribing."

Just over half of the patients whose records were analyzed had their dental procedure on an emergency basis. But the rest were scheduled - one-fifth of them on Fridays and the days before holidays.

Half of the patients who filled an opioid prescription had had scheduled surgical tooth extractions, but the pre-weekend and pre-holiday increase was seen across all 11 dental procedures studied.

This suggests multiple opportunities to reduce unneeded opioid prescribing, says Romesh Nalliah, M.H.C.M., D.D.S., the associate dean for patient services at the U-M School of Dentistry and a member of the study team. He notes that patients may seek Friday and pre-holiday appointments for their scheduled procedures to avoid missing work as they recover.

"The significance of our study is that, with the help of big data, it begins to unpack potentially harmful opioid prescribing trends that were not previously understood," he says. "In the event that we have particular concerns about a given case or patient, we can more deliberately book surgeries when we are available to follow-up."

The senior author of the paper, Chad Brummett, M.D., co-directs Michigan OPEN, which has published evidence-based guidelines for opioid prescribing for acute pain caused by many types of procedures and operations. He is also director of pain research in the Department of Anesthesiology at Michigan Medicine, U-M's academic medical center.

The guidelines say that for dental extractions, non-steroidal anti-inflammatory medications and over-the-counter pain relievers should be sufficient for pain control.

Highlight

In an analysis of blood and urine samples from 46,748 US adults, elevated levels of 7 environmental chemicals were associated with markers of kidney disease.

Washington, DC (May 21, 2020) -- Researchers have found links between various chemicals in the environment and a higher risk of kidney disease. The findings appear in an upcoming issue of CJASN.

Exposure to certain chemicals may contribute to the development of chronic kidney disease (CKD), but the growing number of chemicals being introduced into the environment has made it difficult to understand the extent of the problem and to decipher which compounds are especially toxic to kidney health.

To investigate, Jeonghwan Lee, MD, PhD (Seoul National University Boramae Medical Center) and his colleagues tested hundreds of chemicals for potential links to CKD, through what is known as an environmental-wide association study. "Recently, people have been exposed to more environmental chemicals than before. Of these chemicals, only a few are known for their effects on diseases such as CKD," said Dr. Lee. "Moreover, the impact of newly introduced chemicals is not known at all."

The researchers analyzed information on 46,748 US adults who participated in the National Health and Nutrition Examination Survey from 1999 to 2016, and they looked for associations between 262 chemicals measured in urine or blood with signs of kidney disease--specifically, albuminuria (excess urinary excretion of the protein albumin) and low estimated glomerular filtration rate (eGFR), a measure of kidney function.

Among the 262 environmental chemicals, 7 (3%) showed significant associations with higher risk of albuminuria, lower eGFR, or a composite of both albuminuria and lower eGFR. These chemicals included metals and other chemicals that have not previously been associated with CKD.

Specific findings include:

High blood and urine levels of cotinine (found in tobacco) and high blood levels of 2,5-dimethylfuran (a volatile organic compound) and cadmium (a heavy metal) were associated with albuminuria.

High blood levels of lead and cadmium were associated with lower eGFR.

High blood levels of cadmium and lead and 3 volatile compounds (blood 2,5-dimethylfuran, blood furan, and urinary phenylglyoxylic acid) were associated with the composite of both albuminuria and lower eGFR.

A total of 23 chemicals--including serum perfluorooctanoic acid, 7 urinary metals, 3 urinary arsenics, urinary nitrate and thiocyanate, 3 urinary polycyclic aromatic hydrocarbons, and 7 volatile organic compounds--were associated with lower risks of one or more manifestations of CKD.

Additional studies that investigate the mechanisms by which these different chemicals in the environment can affect the kidneys are warranted. An accompanying editorial by James Kaufman, MD (New York University School of Medicine and VA New York Harbor Healthcare System) notes that this is a daunting task. "Meanwhile, we need to make sure that workers have appropriate protective equipment when exposed to toxic chemicals and that we all have access to clean, safe water," he wrote.

Researchers at the National Institute of Standards and Technology (NIST) have used state-of-the-art atomic clocks, advanced light detectors, and a measurement tool called a frequency comb to boost the stability of microwave signals 100-fold. This marks a giant step toward better electronics to enable more accurate time dissemination, improved navigation, more reliable communications and higher-resolution imaging for radar and astronomy. Improving the microwave signal's consistency over a specific time period helps ensure reliable operation of a device or system.

The work transfers the already superb stability of the cutting-edge laboratory atomic clocks operating at optical frequencies to microwave frequencies, which are currently used to calibrate electronics. Electronic systems are unable to directly count optical signals, so the NIST technology and techniques indirectly transfer the signal stability of optical clocks to the microwave domain. The demonstration is described in the May 22, 2020, issue of Science.

In their setup, the researchers used the "ticking" of two of NIST's ytterbium lattice clocks to generate light pulses, as well as frequency combs serving as gears to translate the higher-frequency optical pulses accurately into lower-frequency microwave signals. Advanced photodiodes converted light pulses into electrical currents, which in turn generated a 10 gigahertz (GHz, or a billion cycles per second) microwave signal that tracked the clocks' ticking exactly, with an error of just one part in a quintillion (1 followed by 18 zeros).This performance level is on par with that of both optical clocks and 100 times more stable than the best microwave sources.

"Years of research, including important contributions from NIST, have resulted in high-speed photodetectors that can now transfer optical clock stability to the microwave domain," lead researcher Frank Quinlan said. "The second major technical improvement was in the direct tracking of the microwaves with high precision, combined with lots of knowhow in signal amplification."

Optical waves have shorter, faster cycles than microwaves do, so they have different shapes. In converting stable optical waves to microwaves, the researchers tracked the phase--the exact timing of the waves--to ensure they were identical, and not shifted relative to one another. The experiment tracked phase changes with a resolution corresponding to just one millionth of a cycle.

"This is a field where just doubling microwave stability can take years or decades to achieve," group leader Chris Oates said. "A hundred times better is almost unfathomable."

Some components of the NIST system, such as the frequency combs and detectors, are ready to be used in field applications now, Quinlan said. But NIST researchers are still working on transferring state-of-the-art optical clocks to mobile platforms. The ytterbium clocks, which operate at frequencies of 518 terahertz (trillion cycles per second), currently occupy large tables in highly controlled laboratory settings.

Ultra-stable electronic signals could support widespread applications, including future calibration of electronic clocks, such as electric devices powered by oscillating quartz crystals. This is an important consideration for the redefinition of the international time standard, the SI second, now based on the microwave frequencies absorbed by the cesium atoms in conventional clocks. In the coming years, the international scientific community is expected to select a new time standard based on optical frequencies that other atoms, such as ytterbium, absorb. Super-stable signals could also make wireless communications systems more reliable.

Optically derived electronic signals could make imaging systems more sensitive. Radar sensitivity, particularly for slow-moving objects, is now limited by microwave noise and could be greatly enhanced. New photodiodes, produced in a collaboration between NIST and the University of Virginia, convert the optical signals to microwave signals more predictably and with lower noise than earlier designs. In addition, microwaves could carry signals from distant optical clocks for applications in navigation and fundamental physics research.

Astronomical imaging and relativistic geodesy, which measures the Earth's gravitational shape, are now based on detecting microwave signals at receivers around the world and combining them to form images of objects. Remote calibration of these receivers could make it possible to move the network from Earth into space, which would enhance image resolution and avoid atmospheric distortions that limit observation time. With hours of observing time instead of seconds, researchers could image many more objects.

Researchers from the Muñiz group have published a paper in Angewandte Chemie - International Edition presenting a new metal-free methodology for the photo-catalysed nucleophilic fluorination of aliphatic hydrocarbon bonds. Daniel Bafaluy, first author of the paper shares the story behind it:

What have you done?

The paper describes a new metal-free method to selectively introduce Fluor in aliphatic C-H bonds that can be applied to late-stage functionalisation. The current methodologies used to this purpose employ electrophilic Fluor reagents, but they present economic as well as environmental drawbacks. So, we decided to take a page from the group's strategies to carry out aminations using an iodine oxidant and applied the know-how to develop nucleophilic fluorinations.

By using an iodine oxidant, we create in situ a nitrogen-iodine bond which we then photochemically break to create the nitrogen radical. Breaking that bond is quite easy because it's a very labile species and doesn't require much energy - a regular lightbulb is enough for this. The new strategy works under mild conditions and uses a (nucleophilic) ammonium fluoride as fluorine source and molecular Iodine as a catalyst to address position-selectivity and produce fewer by-products than the current electrophilic Fluor methods.

Since we employed the nitrogen functionality as the directing group, the strategy can be used on different amine derivatives. In general, we can control the position selectivity by means of the directing group choice and specifically insert the Fluor atom on tertiary positions. This way we gain access to two different kinds of compounds: 1,3 or 1,4 fluoroamines with the same protocol. For example, the reaction works in the presence of benzylic positions, heteroatoms in phenyl groups, etc.

Why is this important?

From a basic-research viewpoint, this work demonstrates that Iodine catalysis has a big potential to be further explored. We present a novel nucleophilic Fluor and metal-free strategy that combines the power of an Iodonium III oxidiser and photochemistry, which is unprecedented in the literature. Also, with our strategy, we selectively control the position where we will introduce the Fluor.

Finally, fluorinated compounds are important from a biological and pharmacological point of view, the presence Fluor enhances the bio-utility of these compounds as drugs or pesticides, among other applications. Unfortunately, their synthesis is quite complex. So, our new method can be quite useful for the late-stage functionalisation of organic molecules.

What's next?

Aside from its use for late-stage-functionalisation, we would have liked to further optimise the process and apply it to radio-labelling for medical applications, like PET scans for instance. Some of the most common compounds used as radiotracers are molecules containing Fluor-18 isotope, which is generated in synchrotrons and has a 20-minute half-life time. This means the isotope must be rapidly inserted into the radiotracers before injecting it to the patient and doing the scan. Therefore, that needs to be a fast-paced procedure. Current methods use electrophilic Fluor but synchrotrons generate nucleophilic Fluor-18, so our new methodology could be easily adapted to fulfil these medical applications.

Nearly half of parents of children under age 18 say their stress levels related to the coronavirus pandemic are high, with managing their kids' online learning a significant source of stress for many, according to a new survey by the American Psychological Association.

As the global pandemic continues and parents juggle child care, work and schooling demands, the mental health toll on parents is growing, warns APA. At the same time, the proportion of Americans saying that the economy or work is a significant source of stress in their life has risen significantly.

"For many parents, it can feel overwhelming to face competing demands at home and work along with possible financial challenges during this unprecedented crisis," said Arthur C. Evans Jr., PhD, APA's chief executive officer. "Children are keen observers and often notice and react to stress or anxiety in their parents, caregivers, peers and community. Parents should prioritize their self-care and try their best to model healthy ways of coping with stress and anxiety."

Stress in America 2020 Stress in the Time of Coronavirus, Volume 1, was conducted by The Harris Poll from April 24 to May 4, 2020, and surveyed online 3,013 adults age 18+ who reside in the United States. This is the first of at least three monthly surveys APA and The Harris Poll plan to gauge the impact of the pandemic on stress.

The survey found that 46% of parents say their average stress level related to the coronavirus pandemic is high (between 8 and 10 on a 10-point scale where 1 means "little or no stress" and 10 means "a great deal of stress"). Only 28% of adults who don't have children under the age of 18 report similar levels of stress.

With schools closed and many parents working from home while coordinating their children's schedules, 71% of parents say managing distance/online learning for their children is a significant source of stress.

Parents are more likely than those without children to say basic needs--such as access to food and housing--are a significant source of stress (70% compared with 44%). Other significant stressors for parents include access to health care services (66% vs. 44%) and missing major milestones, such as weddings and graduation ceremonies (63% vs. 43%).

As unemployment numbers have reached record highs, the economy and work have increased as stressors for Americans. The current survey found that the economy is a significant source of stress for 70% of adults, compared with 46% in APA's 2019 Stress in America poll. Current stress levels are similar to the levels seen in the 2008 Stress in America poll during the Great Recession. Similarly, 7 in 10 employed adults say work is a significant source of stress in their lives, compared with 64% in the 2019 survey.

Pandemic-related stress is having a disproportionate impact on communities of color. People of color are more likely than white adults to report significant stressors in their life as a result of the coronavirus pandemic, namely getting coronavirus (71% vs. 59%, respectively), basic needs (61% vs. 47%), and access to health care services (59% vs. 46%). Slightly more than 2 in 5 Hispanic adults (41%) say their average level of stress related to the coronavirus pandemic during the past month was between 8 and 10. Hispanic adults are also most likely to say they constantly or often feel stress as a result of the pandemic (37%), as compared with white (32%), black (32%), Native American (31%), and Asian (28%) adults.

"The mental health ramifications of the coronavirus pandemic are immense and growing," Evans warned. "We need to prepare for the long-term implications of the collective trauma facing the population. On an individual level, this means looking out for one another, staying connected, keeping active and seeking help when necessary."

It is increasingly clear that male and female humans and rodents process pain in different ways. And that there are important differences in the underlying mechanisms involved at genetic, molecular, cellular, and physiological levels. Despite this fact, according to a review paper from McGill University published today in Nature Reviews Neuroscience, most pain research remains overwhelmingly based on the study of male rodents, continuing to test hypotheses derived from earlier experiments on males. This points to an important blind spot in pain research, particularly as it relates to advancing research into new pain medications. This is especially troublesome given that it is well-documented that most chronic pain sufferers are female.

"The pain literature is biased such that, because of the overwhelming use of male animals in experiments, we are increasingly learning about the biology of pain in males. And wrongly concluding that this is the biology of pain. It's only the biology of pain in males," says Jeffrey Mogil, the author of the paper, a professor in McGill's Departments of Psychology and Anesthesia, the E. P. Taylor Chair in Pain Studies and the Canada Research Chair in the Genetics of Pain.

Persistent male bias in pain research ... despite recent inclusion of females

Canadian funding agencies began recognizing sex as a biological variable and asking pain researchers to include female rodents in their experiments in 2006. In the US, a similar shift took place in 2016. Indeed, of the more than 1000 scholarly articles that Mogil reviewed published between January 2015 and December 2019 in Pain, the leading journal in the field, starting in 2016 more and more papers featured testing of both female and male rodents, with male-only studies dropping from 80% of the total in 2015 to only 50% of the total in 2019.

At first glance, the presence of these articles may represent a promising shift in research design. But when Mogil looked more closely at the existing sex differences in pain literature, he found clear evidence of a persistent male bias.

"The very ideas we come up with for experiments, are based on experiments in males and therefore they work in males and not in females. I discovered that in those papers where both sexes were actually tested and results reported on the differences by sex, the experiments "worked out", meaning the scientific hypothesis being tested was found to be true, in males 72.4% of the time and in females only 27.6%," said Mogil. "If there were no bias in the literature and there were a number of papers were the experiment worked in one sex and not the other, it should work in females just as often as in males. Why has this happened? Because the hypothesis that that experiment tested out was generated based on prior data from experiments on only males. So, of course, it only worked in males."

Developing analgesics that will work for women

According to Mogil, the conclusion that can be reached from this overview is that researchers are still some way away from developing analgesics that will work in women.

"This research suggests that lots of what's in the pipeline right now, if it works in anyone at all, will largely be men. Whereas the clear majority of chronic pain patients have been and continue to be women."

Children of parents with a degree are almost a year of schooling ahead in maths by the age 11 than peers whose parents have just GCSEs, a new study by the University of Sussex has discovered.

Greater parental education is the strongest predictor of maths attainment and faster future growth for children moving into secondary school even after adjusting for their intelligence (IQ), research by University of Sussex psychologists published today by the Royal Society reveals

The study also showed that:

Boys achieve significantly higher grades in maths at age 11 but this gap did not grow through secondary school. Academics believe the gap at 11 could be explained by girls' increasing maths anxiety and decreasing enjoyment of the subject at this age.

Statistically significant but very weak evidence that pupils with higher emotional symptoms in early childhood had lower maths attainment when they were older.

The study's authors recommend that strategies focusing on improving parental education could be a very effective method of increasing attainment in children.

Danielle Evans, researcher in achievement in mathematics at the University of Sussex, said:

"Our study shows that increased maths growth was significantly predicted by higher IQ, higher socioeconomic status and greater parental education, suggesting that children with greater intelligence and higher socioeconomic status progress at a quicker rate across the transition to secondary education compared with their peers. While this finding is not unexpected, it demonstrates the importance of parents within their child's education and suggests that having higher-educated parents may potentially 'buffer' the negative impacts of the transition to secondary education on children's attainment."

Dr Darya Garsina, senior lecturer in psychology at the University of Sussex, said:

"Recent campaigns launched by the BBC in collaboration with the National Numeracy Charity focusing on promoting adult education and maths training is a step in the right direction but much more work is needed to overcome the extent of poor numeracy in the UK and the negative effects associated with underachievement in maths."

The study examined working memory and internalizing symptoms as predictors of children's maths attainment trajectories across the transition to secondary education through analysis of the Avon Longitudinal Study of Parents and Children (ALSPAC) involving almost 9,000 children born between 1 April 1991 and 31 December 1992.

The study focuses on the transition from primary to secondary education because of the reported declines in academic achievement and maths specifically during the move from primary to secondary schools - it is reported that more than a third of children do not show any progress in maths during the transition year.

The study's authors believe higher-educated parents support the transition to secondary education in different ways that lessen the negative impact of the transition on maths attainment including their own positive attitudes towards education, involvement with school activities or helping with homework in a supportive environment.

The authors had hypothesised that emotional temperament in early childhood could be a very early indicator of poor maths attainment later on in adolescence but later concluded that it was not possible to predict later problems with underattainment in maths using emotional difficulties early on in childhood.

The study's authors say additional research is needed to further uncover the relationship of memory during a task (working memory) and internalizing symptoms such as anxiety on attainment, using more time-appropriate measures.

Andy Field, Professor of Quantitative Methods at the University of Sussex, said:

"The current state of maths attainment and performance of children and adults in the UK is particularly alarming with almost half of all working-age adults in the UK having the maths skills expected of primary-school children. Poor maths attainment in childhood persist well into adulthood and can be associated with several negative outcomes such as poorer employment prospects, greater likelihood of homelessness, poorer health outcomes and mental health difficulties such as depression. The ability to identify predictors of maths attainment as early as possible in childhood could have life-changing consequences."

A study by a team of researchers from Canada and Italy recently published in Nature Materials could usher in a revolutionary development in materials science, leading to big changes in the way companies create modern electronics.

The goal was to develop two-dimensional materials, which are a single atomic layer thick, with added functionality to extend the revolutionary developments in materials science that started with the discovery of graphene in 2004.

In total, 19 authors worked on this paper from INRS, McGill, Lakehead, and Consiglio Nazionale delle Ricerche, the national research council in Italy.

This work opens exciting new directions, both theoretical and experimental. The integration of this system into a device (e.g. transistors) may lead to outstanding performances. In addition, these results will foster more studies on a wide range of two-dimensional conjugated polymers with different lattice symmetries, thereby gaining further insights into the structure vs. properties of these systems.

The Italian/Canadian team demonstrated the synthesis of large-scale two-dimensional conjugated polymers, also thoroughly characterizing their electronic properties. They achieved success by combining the complementary expertise of organic chemists and surface scientists.

"This work represents an exciting development in the realization of functional two-dimensional materials beyond graphene," said Mark Gallagher, a Physics professor at Lakehead University.

"I found it particularly rewarding to participate in this collaboration, which allowed us to combine our expertise in organic chemistry, condensed matter physics, and materials science to achieve our goals."

Dmytro Perepichka, a professor and chair of Chemistry at McGill University, said they have been working on this research for a long time.

"Structurally reconfigurable two-dimensional conjugated polymers can give a new breadth to applications of two-dimensional materials in electronics," Perepichka said.

"We started dreaming of them more than 15 years ago. It's only through this four-way collaboration, across the country and between the continents, that this dream has become the reality."

Federico Rosei, a professor at the Énergie Matériaux Télécommunications Research Centre of the Institut National de la Recherche Scientifique (INRS) in Varennes who holds the Canada Research Chair in Nanostructured Materials since 2016, said they are excited about the results of this collaboration.

"These results provide new insights into mechanisms of surface reactions at a fundamental level and simultaneously yield a novel material with outstanding properties, whose existence had only been predicted theoretically until now," he said.

Millions of the world's poorest children are leaving school without mastering even basic levels of reading or maths because of an overlooked pattern of widespread, wealth-based inequalities in their countries' education systems, new research suggests.

The University of Cambridge-led study shows that children from the very poorest families, in what are already some of the lowest-income countries in the world, consistently perform worse in basic literacy and numeracy tests than those from more affluent backgrounds.

The overwhelming reason, the study found, is that poorer children are disproportionately clustered in the lowest-quality schools, which often lack even basic resources - such as textbooks, electricity, or toilets.

The researchers say that there is an urgent need to 'raise the floor' in global education, by focusing both national-level efforts and international aid on students from the most disadvantaged communities.

Institutions like the United Nations Educational, Scientific and Cultural Organisation (UNESCO) and the World Bank have long referred to a 'learning crisis' in the Global South. While growing numbers of children in low-income countries now attend school compared with previous generations, many still lack basic literacy or numeracy skills.

Until now, most analyses have looked at the factors that explain low learning outcomes in general, rather than differentiating between groups of children. But the new study suggests that there is a huge gulf between the quality of education that children from the poorest families receive compared with wealthier children, and that this is directly linked to their ability to read, write, add, or subtract, by Grade 6.

Dr Rob Gruijters, from the Faculty of Education, University of Cambridge, who led the research, said: "There is a high level of social segregation in many of these countries' education systems. The pattern is similar to the UK, where rich children tend to go to better-resourced schools. But the differences in school quality are much more pronounced, and they are strongly linked to family background"

"Global reporting on the learning crisis often pays little attention to these inequalities, focusing instead on average differences between countries. But if we really want to fix things, there needs to be a commitment not only to investing in education, but to raising the floor: to ensuring that every school has a minimum level of support, in staffing, training, and resources."

The study analysed data from the Programme for the Analysis of Education Systems (PASEC), a survey managed by the association of education ministries in francophone Africa. The survey assessed more than 30,000 Grade 6 students in more than 1,800 schools in 10 countries: Benin, Burundi, Burkina Faso, Cameroon, Chad, Congo (Brazzaville), Ivory Coast, Niger, Senegal and Togo. All 10 have 'received scant attention' in previous analyses of the learning crisis, the study says.

The data provides the pupils' scores in basic maths and reading tests. The researchers cross-referred this with additional information about their socio-economic backgrounds, their health, and the quality of their schools; dividing each country's sample group into fifths based on their families' relative wealth.

Overall, pupils from the poorest 20% of families consistently performed worst in the tests, while those children who - although often poor by international standards - fell into the wealthiest 20%, consistently had the highest test scores.

Poorer students also tended to fail to reach PASEC's Grade 6 'proficiency threshold', meaning that by the time they leave primary school, many still struggle with basic sums and reading.

The researchers then explored possible reasons why this link between household wealth and performance exists. They found that differences in the quality of schooling explained almost the entire learning gap between poor and wealthier children.

Children from disadvantaged backgrounds were consistently found to be clustered in educational settings that scored low for school quality in the dataset - meaning that teachers' own education levels were often poor, classrooms overcrowded, and critical resources and facilities, from textbooks to running water, often unavailable. Wealthier children, on the other hand, were much more likely to attend better-resourced private schools.

Importantly, in cases where children from the wealthiest 20% and poorest 20% of families attended the same school, there was almost no difference in their test results.

"The problem is that most of them are not attending the same schools, and that's why we are seeing these learning gaps" said Dr Julia Behrman of Northwestern University, who co-authored the study. "Wealthier children learn more largely because they are going to better schools, with better resources."

The researchers say that their assessment of the impact of socioeconomic status on learning outcomes is almost certainly conservative, as the PASEC data only covers children who reach Grade 6. In countries like Burkina Faso, Niger and Chad, where fewer than half of all children finish primary school and many never attend, the poorest children face a 'double hurdle': first, getting to school; and second, finding a school that is sufficiently equipped to give them a basic education.

The study therefore argues that policy initiatives and aid efforts aimed at solving the global learning crisis should focus on equalising access to learning opportunities for all children.

"One silver lining is that our research emphasises there is nothing inherent in being poor that stops children from learning," Gruijters added. "Give them a better place to learn, with better resources, and they can do just as well as children from the wealthiest end of the scale."