Culture

Eating high fibre foods may reduce the effects of stress on our gut and behaviour, according to new research published in The Journal of Physiology.

Stress is a significant health concern and can cause major changes in the gut and in the brain, which can cause changes in behaviour. In recent years there has been growing interest in the link between gut bacteria and stress-related disorders including anxiety, depression and irritable bowel syndrome.

Bacteria in the gut produce short-chain fatty acids (SCFAs), which are the main source of nutrition for cells in this region of the body1. Foods such as grains, legumes and vegetables, contain high levels of fibres and will stimulate the production of these SCFAs.

The study conducted by scientists at APC Microbiome Ireland at University College Cork and Teagasc Food Research Centre found that there was decreased levels of stress and anxiety-like behaviour when SCFAs were introduced.

Moreover, stress experienced over a prolonged period of time can affect the bowel by making the barrier between the inside of the gut and the rest of the body less effective and "leaky". This means undigested food particles, bacteria and germs will pass through the leaky gut wall into the blood and cause persistent inflammation. Treating with the SCFAs can also reverse this "leakiness".

These results provide new insights into mechanisms related to the impact of the gut bacteria on the brain and behaviour as well as gut health. Developing dietary treatments which target these bacteria will be important for treating stress-related disorders.

The study involved feeding mice the main SCFAs normally produced by the gut bacteria and then subjecting them to stress. Using behavioural tests the mice were assessed for anxiety and depressive-like behaviour, stress-responsiveness, cognition and sociability as well as how easily material passes through the gut.

The exact mechanisms by which SCFAs facilitate their effect remain undetermined. SCFAs had no effect on an increase in body weight caused by stress therefore understanding why SCFAs only affect certain stress-induced effects will be important.

Professor John F. Cryan, the corresponding author on the research, commented on the findings 'There is a growing recognition of the role of gut bacteria and the chemicals they make in the regulation of physiology and behaviour. The role of short-chain fatty acids in this process is poorly understood up until now. It will be crucial that we look at whether short-chain fatty acids can ameliorate symptoms of stress-related disorders in humans.'

Up until quite recently, the animal phylum Placozoa enjoyed a unique position in animal systematics. It was the only phylum to which only a single species had ever been assigned: Trichoplax adhaerens. Now, however, at team led by Professor Gert Wörheide of LMU's Department of Earth and Environmental Sciences and GeoBio-Center has discovered that placozoan specimens collected from coastal waters off Hong Kong clearly differ from T. adhaerens in their genetic make-up. Indeed, the differences between the two are so striking that the Hong Kong population not only represents a new species but also has been assigned to a new genus - even though the two genera are morphologically indistinguishable. The definition of a new species and genus solely on the basis of comparative genomic data constitutes a new departure in the systematic classification of animals. The findings appear in PLOS Biology.

Placozoa are among the simplest known multicellular animals, lacking both muscles and nerve cells. They are only a few millimeters long and their cells are organized into two flat layers. They have been found in tropical and subtropical waters around the world. But, regardless of locality of origin, all placozoans have the same gross morphology and same basic cellular architecture. Since conventional approaches to the definition and differentiation of animal species rely on differences in overall body plans and detailed morphology, all placozoan specimens so far collected have been attributed to the species T. adhaerens, which was first described in 1883. "However, genetic data based on short DNA signature sequences that serve to distinguish species from one another had already suggested that placozoans exhibit a great deal of genetic diversity. And that in turn indicates that the phylum actually includes many different species," says Wörheide.

For this reason, he and his colleagues decided to sequence the genome of a placozoan line derived from specimens collected in Hong Kong. Their signature sequences indicated that this line was distantly related to T. adhaerens, whose genome was published in 2008. "Based on comparative genomic analysis, we then developed a novel method for the description of a new species based exclusively on genomic data," says Michael Eitel, first author of the new study. The researchers refer to this approach as 'taxogenomics', which takes into account factors such as structural differences between chromosomes, differences in the total number of genes, and sequence differences between selected protein-coding genes.

The genetic and genomic data for the placozoans from Hong Kong revealed such large differences between them and T. adhaerens that they were ultimately assigned not only to a new species, but to a new genus, which represents a higher rank in the hierarchy of biological taxonomy. "This is a completely new departure. It is the first time that a new genus has been erected purely on the basis of genomic data," Wörheide explains. The new species bears the name Hoilungia hongkongensis. This translates as 'Hong Kong Sea Dragon' - which refers to the fact that, just like the Dragon King in Chinese mythology, placozoans can readily alter their shapes.

The authors of the new study believe that the placozoans may have undergone a very peculiar mode of evolution, in which speciation has occurred exclusively at the genetic level without notable morphological diversification. "We have some indications that point to the operation of negative selection, so it is possible that the development of morphological novelties may be repressed. But we are still very much at the beginning of the search for an explanation of this unique evolutionary trajectory," says Eitel.

The authors also suggest that the taxogenomic approach could also be used for detailed studies of the process of speciation in other animal phyla. This holds in particular for animal groups that consist of minuscule individuals, such as nematodes and mites, in which it is often difficult to discriminate between species by optical inspection alone.

Despite high hopes and high investment in CRISPR-Cas9 gene editing, scientists still have a lot to learn about how it works in humans.

In the latest example, University of California, Berkeley, scientists found that people's assumptions about how cells repair the genome after the Cas9 enzyme snips DNA are wrong.

The discovery gives insight into why CRISPR-Cas9 gene editing works remarkably well in nearly every cell attempted, though not with equal success in all cells. And it could help researchers boost the efficiency with which cells insert new DNA into the genome - to replace a harmful mutation with the correct DNA sequence, for example - and generally tweak CRISPR-Cas9 editing to get the desired outcome.

"If you want to treat sickle cell anemia, your chances of success are inextricably tied to the efficiency with which you can replace the mutated sickle cell gene with the correct one," said UC Berkeley postdoctoral fellow Chris Richardson, first author of a paper describing the findings. "If you harvest a million cells from a patient and you have 10 percent insertion rate, that is not as good as if you have 30 to 40 percent. Being able to manipulate those cells to increase the frequency of this process, called homology-directed repair, is exciting."

"Gene editing is super-powerful, with a lot of promise, but, so far, a lot of trial and error. The way it works in human cells has been a black box with a lot of assumptions," said lead author Jacob Corn, a UC Berkeley adjunct professor of molecular and cell biology. "We are finally starting to get a picture of what's going on."

Corn, Richardson and their colleagues will publish their findings in the August issue of the journal Nature Genetics, available online now.

Corn was until recently the scientific director of biomedicine in the Innovative Genomics Institute, a joint CRISPR research program between UC Berkeley and UC San Francisco. This fall, he will join the faculty of ETH in Zurich, Switzerland.

CRISPR relies on DNA repair

CRISPR-Cas9 is revolutionary because of the precision with which it homes in on a specific DNA sequence out of billions in the genome and cleaves the double-stranded DNA molecule. But after that, it's up to the cell to repair the damage.

Repair can happen in two ways. Enzymes can stitch the dangling ends back together, which often results in one or more bases - the building blocks of DNA - being added or deleted, disrupting the function of the gene. Alternatively, other enzymes can patch the break with a single strand of DNA that matches the DNA sequence upstream and downstream of the cut. A complementary DNA strand is created to complete the double-strand repair.

The former, called non-homologous end-joining, appears to be the most common outcome after CRISPR cutting. The latter, homology-directed repair, happens more frequently in some types of cells than others, and requires the presence of a piece of DNA that can be used to patch the break. Researchers often supply a single-stranded piece of DNA and hope that the cell uses it to replace the faulty sequence with the new one.

Both processes are a bit mysterious, however, and no one knows why some cells readily patch in DNA while others do so infrequently.

"The enthusiasm for using CRISPR-Cas9 for medical or synthetic biology applications is great, but no one really knows what happens after you put it into cells," Richardson said. "It goes and creates these breaks and you count on the cells to fix them. But people don't really understand how that process works."

To find out which DNA repair enzymes are critical to homology-directed repair after CRISPR cutting, Richardson and Corn employed a technique called CRISPR interference (CRISPRi) to knock out, one at a time, more than 2,000 genes known or suspected to be involved in DNA repair, a function critical to a healthy cell.

Surprisingly, many of the genes that proved to be important - homology-directed repair dropped dramatically when they were silenced - were involved in an important repair system not thought to be involved in CRISPR repair.

Fanconi anemia

The pathway involves 21 separate proteins and is called the Fanconi anemia pathway because, if any of the genes for these proteins is damaged, people develop Fanconi anemia, a rare but serious hereditary disease in which the bone marrow cannot make enough new blood cells. It is associated with birth defects and a high risk of cancer, including a 10 percent chance of developing leukemia in childhood. Few patients live beyond 30 years of age.

The pathway has been known and studied for decades, but it was largely understood to repair one specific kind of DNA damage: DNA interstrand crosslinks, where a nucleotide on one strand of DNA bonds tightly with a nucleotide on the adjacent strand, interfering with DNA replication and often killing the cell. Researchers in the 1980s had reported a connection between homology-directed repair and the Fanconi anemia pathway, but it had been ignored or misunderstood, Corn noted.

"Based on our work, we believe that the Fanconi anemia pathway plays a major role in fixing other types of lesions as well, but is best understood as the pathway that repairs double-strand breaks," Richardson said. "After Cas9 editing, the Fanconi anemia pathway is required if you want to insert new DNA."

The importance of the Fanconi anemia pathway in repairing CRISPR breaks throws into doubt some planned CRISPR treatments for the disease itself, however. Without an active Fanconi anemia pathway, cells may not be able to replace their mutated genes with normal genes after Cas9 makes a cut.

In fact, the level of activity of the Fanconi anemia pathway may affect how efficiently CRISPR can insert DNA in a specific cell. The researchers concluded that, while end-joining is the default repair mechanism after a double-strand break, the Fanconi anemia pathway competes with it, and that higher activity results in more homology-directed repair and less end-joining.

Cancer treatments

While the findings help scientists better understand the DNA repair mechanisms in human cells, they could also help researchers developing anti-cancer therapies that target DNA repair in cancer cells. Because other factors now appear to be involved in the repair of double-strand breaks, this research expands the list of proteins that could be misregulated in order to screw up DNA repair in cancer cells and make them more susceptible to death.

Richardson also found that one of the 21 proteins in the pathway, FANCD2, always homes in on the site of the double-strand break created by CRISPR-Cas9, indicating it plays an important role in regulating the insertion of new DNA into the genome at the cut site. FANCD2 could be tweaked to boost the frequency with which a cell inserts DNA via homology-directed repair.

"Also, since FANCD2 localizes to the site of Cas9 breaks, you can use FANCD2 to map where Cas9 is cutting in any cell type," Richardson said. "If you edit a population of cells and you want to know where the on- and off-target cuts are, you can just map where FANCD2 was found in the genome and you can find the cuts."

"The whole Fanconi anemia pathway affects the balance between end-joining and homology-directed repair; it acts like a traffic cop," Corn said. "So a patient's genotype will affect how you do gene editing."

AUGUSTA, Ga. (July 30, 2018) - Using a manmade version of a human antibody to directly deliver a drug that inhibits a powerful driver of inflammation, can reverse a disease course that often leads to kidney failure and dialysis, investigators report.

They have additionally found that it's the powerhouses of kidney cells, called mitochondria, that are particularly impacted by the acute or chronic inflammation called nephritis, and that, at least in their animal model and cell cultures, the treatment restores their function.

Things like a serious infection or injury, and diseases like uncontrolled hypertension and diabetes, can cause acute or chronic nephritis, which affects both kidneys and the million filtering units in each. Particularly when it's chronic, patients often wind up in kidney failure on dialysis.

"That is why we are looking at promoting recovery," says Dr. Michael P. Madaio, nephrologist and chair of the Department of Medicine at the Medical College of Georgia at Augusta University.

"We are delivering something to the kidney that is reducing inflammation and restoring mitochondrial function. We are helping the mitochondria be a little healthier and the kidney cells function better," says Madaio, corresponding author of the study in the journal Kidney International.

For their studies, they used a model of immune-mediated nephritis in mice that develops rapidly and progressively over seven to 10 days.

But a few days after the disease was established, when they also gave a single dose of the protein kinase C-alpha inhibitor - delivered directly to the kidney via their manmade antibody - those mice instead recovered kidney function and survived.

Parallel studies that enabled the investigators to look directly at the impact of both toxicity and treatment on the endothelial cells that line the filtering units, also showed the inhibitor reduced cell death and improved cell recovery.

A proteomic analysis determined that 157 proteins were significantly altered by nephritis - either up- or down-regulated by disease and restored by treatment - and that it was the mitochondria, the cell powerhouses, most affected.

Collectively, their studies show protein kinase C-alpha's crucial role in the damage done by nephritis as they provide some of the first evidence that inhibiting it - and restoring mitochondrial function - could be helpful in reversing the inflammatory disease, Madaio says.

Nephritis therapy today incudes approaches like systemic high-dose steroids to battle inflammation and systemic immunosuppressive drugs, like those taken by transplant patients. Side effects include increased risk of infections, even cancer, but Madaio is hopeful that a targeted approach, like the one they are developing, could better fight the problem with fewer side effects.

Right now, they are using just a small dose of the whole human antibody but eventually they hope to use a physically smaller, non-inflammatory version of their manmade antibody, called a minibody, to simultaneously deliver multiple drugs that can arrest the disease and protect the kidneys.

The human monoclonal antibody they are using is good at finding the kidneys because it targets a collagen that is unique in the connective tissue found in the kidneys' filtering units.

The antibody is produced in a rare kidney disease called Goodpasture syndrome, a rapidly progressing, difficult-to-treat condition that inflames and scars the kidneys and can quickly destroy the organs. The antibody's usual job at its usual level is actually promoting inflammation, but the investigators in this case are taking advantage of its skill at reaching the kidneys to use it as a mechanism for drug delivery that instead blocks inflammation.

Madaio's group found that the antibody's natural target, or antigen, is normally sequestered in the kidneys, however it is highly expressed during inflammation, which further enhances its role as a targeted delivery system in this scenario, Madaio says.

While the protein kinase C-alpha inhibitor it delivers clearly worked in their animal and cell models, the investigators also are already exploring other drugs for potential delivery. They reported five years ago in the American Journal of Physiology-Renal Physiology that delivery of prostaglandin E2, one of few prostaglandins known for its anti-inflammatory impact, to the filtering units also was effective at treating nephritis, and the two drugs appear to have similar pathways of recovery.

Madaio thinks the targeted therapy approach could one day also work well for common kidney diseases like diabetic nephropathy, which can accompany type 1 and 2 diabetes and is the leading cause of chronic kidney disease and end-stage renal disease.

Their discovery that mitochondria play a role in recovery was of particular interest, Madaio says. Mitochondria primarily produce energy and the proteins inside these powerhouses most affected by nephritis were those associated with using oxygen to turn food into fuel and generating waste products like carbon dioxide and water. These essential proteins were downregulated by kidney inflammation and inhibiting protein kinase C-alpha restored normal expression.

Looking at the endothelial cells that line the millions of kidney filtering units, the toxin that produced nephritis in the mice also dramatically affected the cell powerhouses, even changing their shape, changes that were normalized with protein kinase C-alpha inhibition.

Using both an animal model and cell culture for their studies enabled these detailed assessments. "Using the whole animal approach, we can look at both inflammation and recovery as they happen, however we can more precisely hone in on the mechanisms with kidney cell culture," Madaio says. "Then when you dig out a mechanism in the cell, you can go back to the animal model to test to see how relevant that is to the disease."

Additive manufacturing, otherwise known as 3-D printing, can be used to manufacture porous electrodes for lithium-ion batteries--but because of the nature of the manufacturing process, the design of these 3-D printed electrodes is limited to just a few possible architectures. Until now, the internal geometry that produced the best porous electrodes through additive manufacturing was what's known as an interdigitated geometry--metal prongs interlocked like the fingers of two clasped hands, with the lithium shuttling between the two sides.

Lithium-ion battery capacity can be vastly improved if, on the microscale, their electrodes have pores and channels. An interdigitated geometry, though it does allow lithium to transport through the battery efficiently during charging and discharging, is not optimal.

Rahul Panat, an associate professor of mechanical engineering at Carnegie Mellon University, and a team of researchers from Carnegie Mellon in collaboration with Missouri University of Science and Technology have developed a revolutionary new method of 3-D printing battery electrodes that creates a 3-D microlattice structure with controlled porosity. 3-D printing this microlattice structure, the researchers show in a paper published in the journal Additive Manufacturing, vastly improves the capacity and charge-discharge rates for lithium-ion batteries.

"In the case of lithium-ion batteries, the electrodes with porous architectures can lead to higher charge capacities," says Panat. "This is because such architectures allow the lithium to penetrate through the electrode volume leading to very high electrode utilization, and thereby higher energy storage capacity. In normal batteries, 30-50% of the total electrode volume is unutilized. Our method overcomes this issue by using 3D printing where we create a microlattice electrode architecture that allows the efficient transport of lithium through the entire electrode, which also increases the battery charging rates."

The additive manufacturing method presented in Panat's paper represents a major advance in printing complex geometries for 3-D battery architectures, as well as an important step toward geometrically optimizing 3-D configurations for electrochemical energy storage. The researchers estimate that this technology will be ready to translate to industrial applications in about 2-3 years.

The microlattice structure (Ag) used as lithium-ion batteries' electrodes was shown to improve battery performance in several ways such as a fourfold increase in specific capacity and a twofold increase in areal capacity when compared to a solid block (Ag) electrode. Furthermore, the electrodes retained their complex 3D lattice structures after forty electrochemical cycles demonstrating their mechanical robustness. The batteries can thus have high capacity for the same weight or alternately, for the same capacity, a vastly reduced weight--which is an important attribute for transportation applications.

The Carnegie Mellon researchers developed their own 3-D printing method to create the porous microlattice architectures while leveraging the existing capabilities of an Aerosol Jet 3-D printing system. The Aerosol Jet system also allows the researchers to print planar sensors and other electronics on a micro-scale, which was deployed at Carnegie Mellon University's College of Engineering earlier this year.

Until now, 3-D printed battery efforts were limited to extrusion-based printing, where a wire of material is extruded from a nozzle, creating continuous structures. Interdigitated structures were possible using this method. With the method developed in Panat's lab, the researchers are able to 3-D print the battery electrodes by rapidly assembling individual droplets one-by-one into three-dimensional structures. The resulting structures have complex geometries impossible to fabricate using typical extrusion methods.

"Because these droplets are separated from each other, we can create these new complex geometries," says Panat. "If this was a single stream of material, as is in the case of extrusion printing, we wouldn't be able to make them. This is a new thing. I don't believe anybody until now has used 3-D printing to create these kinds of complex structures."

This revolutionary method will be very important for consumer electronics, medical devices industry, as well as aerospace applications. This research will integrate well with the biomedical electronic devices, where miniaturized batteries are required. Non-biological electronic micro-devices will also benefit from this work. And on a bigger scale, electronic devices, small drones, and aerospace applications themselves can use this technology as well, due to the low weight and high capacity of the batteries printed using this method.

Researchers at Vanderbilt University Medical Center and their colleagues are a step closer to developing a broadly effective antibody treatment against the three major Ebola viruses that cause lethal disease in humans.

Reporting July 17 in the journal Immunity, they describe the isolation of two potent monoclonal antibodies from human survivors of Ebola virus disease that, in cell culture studies, efficiently neutralized the Zaire, Sudan and Bundibugyo ebolaviruses.

The antibodies, EBOV-515 and EBOV-520, also showed the capacity to protect against infection by these viruses in animal models.

While further study is needed, these antibodies could lead to development of injectable antibody "cocktails" for people at high risk of being infected by Ebola viruses. The hope is that the antibodies -- like heat-seeking missiles -- would seek out and destroy the viruses before they can wreak havoc in the body.

"Our team was very excited to discover these new antibodies that have the capacity to treat all ebolaviruses," said the paper's senior author, James Crowe Jr., MD, director of the Vanderbilt Vaccine Center. "They appear very promising for development as a treatment and prevention for Ebola virus disease."

Crowe is the Ann Scott Carell Professor in the Departments of Pediatrics and Pathology, Microbiology and Immunology in the Vanderbilt University School of Medicine. The paper's first author, Pavlo Gilchuk, PhD, is a senior staff scientist in Crowe's lab.

Ebola virus disease, which was first reported in Central Africa in 1976, can cause massive bleeding. The death rate is about 50 percent. The virus is spread by contact with contaminated body fluids, including blood and semen.

A major outbreak in West Africa claimed more than 11,000 lives between 2014 and 2016. Earlier this month the World Health Organization reported 29 deaths from a smaller outbreak that began in April in the Democratic Republic of the Congo.

For several years Crowe and his colleagues have been studying the immune responses of people who have survived Ebola virus disease.

His lab has developed high-efficiency methods that can quickly isolate antibody-producing white blood cells from survivor blood samples and then fuse them to fast-growing myeloma (cancer) cells. In this way the researchers can produce large quantities of antibodies that target specific viruses.

In the current study, plasma was obtained from survivors of Ebola virus disease outbreaks in the Congo and West Africa. Monoclonal antibodies were generated from the white blood cells of two survivors that showed the highest activity against the three Ebola viruses.

The strategy used by the Oropouche virus to replicate in human cells has been described for the first time by researchers at the University of São Paulo (USP) in Brazil and international collaborators in an article published in the journal PLOS Pathogens.

According to the study, shortly after invading the cell, the pathogen "hijacks" an organelle called the Golgi complex, which becomes a veritable virus factory. The virus does this by recruiting host cell protein complexes known as ESCRT (pronounced "escort"), which are capable of deforming the organelle's membrane and allowing the viral genome to penetrate it.

"This method of hijacking the Golgi complex via the use of ESCRT proteins had never been demonstrated for any other virus. It's a discovery that points to novel targets for exploration in the effort to prevent infection," said Natalia Barbosa, a PhD researcher affiliated with USP's Ribeirão Preto Medical School (FMRP-USP) and the first author of the article.

The study was supported by the São Paulo Research Foundation - FAPESP and supervised by Luis Lamberti Pinto da Silva, a professor at FMRP-USP. Scientists at Tübingen University Hospital in Germany collaborated.

According to Silva, very little is known about the replication mechanisms of viruses in the family Peribunyaviridae, to which Oropouche virus belongs.

"They're important pathogens from the public health standpoint," he said. "In Brazil, only Oropouche virus causes disease, but La Crosse encephalitis virus and Crimean Congo virus, which causes hemorrhagic fever, are endemic in other parts of the world. There are also members of the family that cause disease in cattle."

The symptoms of Oropouche virus infection are similar to those of dengue, consisting mainly of joint pain, headache, pain behind the eyes, and high fever. The difference is that in approximately half of all cases, a relapse of the disease occurs after the symptoms improve.

The virus is transmitted by Culicoides paraenses, a biting midge with urban habits. Outbreaks in villages and towns in the Brazilian Amazon are estimated to have caused half a million cases, but Oropouche has also cropped up in other parts of the country and is considered an emerging virus by experts.

"The disease is certainly underreported, as it's often confused with other arboviruses," said the FAPESP scholarship supervisor. "It's rated as low severity, but the concern is that we don't yet know whether and how much the infection harms the nervous system in the long run."

In vitro experiments performed by the FMRP-USP group showed that the virus can infect neurons in mice and hamsters. The researchers are now trying to reproduce the experiments using human nerve cells. The principal investigator for this study is Eurico Arruda, a member of FMRP-USP's Virus Research Center and a coauthor of the article.

"Oropouche appears to be capable of infecting various types of cell. In other words, it succeeds in interacting with different receptors located on the surface of human cells. However, we don't yet know which receptors are used by any member of the family Peribunyaviridae," Silva said.

Methodology

To investigate Oropouche's replication mechanisms, the FMRP-USP group performed in vitro experiments with HeLa cells, the oldest and most widely used line in laboratories, derived from a human patient's cervical cancer cells.

"As soon as the cells are infected, the virus starts producing proteins that attract the host's ESCRT complexes to the external membrane of the Golgi complex. These ESCRT proteins then push on the organelle's membrane, rupture it and sweep into the Golgi complex, taking the viral genome with them. So the virus replicates inside the complex. What probably happens then is that some time later, the modified organelle full of viruses merges with the plasma membrane and releases the pathogens into the extracellular medium," Silva said.

Other viruses are known to recruit the ESCRT machinery in order to replicate. For example, HIV, the pathogen that causes AIDS, uses ESCRT proteins to cross the plasma membrane that separates the intracellular and extracellular mediums.

"However, this mechanism had never been described for invasion of the Golgi complex by viruses," Silva said.

The Golgi complex is a series of stacked membranes and vesicles whose main function is to process, store and distribute proteins produced in ribosomes.

"We don't know exactly how this hijacking of the Golgi complex affects the host cell, but the HeLa cells die some 36 hours after being infected," Silva said.

In a previous study led by Arruda, the group showed that Oropouche produces a protein called NSs that induces apoptosis, a process of programmed death, in the host cell.

"This protein isn't part of the virus's structure, and we don't know how killing the host cell by apoptosis benefits the pathogen, but it could be the result of a defense mechanism," Arruda said. "The NSs protein in isolation can cause apoptosis, and its use could be explored to kill tumor cells, for example."

Possible targets

In one of the experiments described in the PLOS Pathogens article, the researchers manipulated HeLa cells so that they no longer expressed Tsg101, an important ESCRT protein. To do this, they used RNA interference, a method of blocking gene expression by inserting short RNA sequences into cells.

"This intervention made HeLa cells more resistant to infection by Oropouche. They took longer to die and had a much smaller viral load. There are experimental drugs that inhibit Tsg101, and we're now going to test them against Oropouche," Silva said.

Because Tsg101 is a key protein in normal human cell function, he added, it may not be possible to use drugs that inhibit it or other ESCRT proteins to treat patients. The risk of adverse side effects would be considerable.

"However, there may be a molecule that inhibits interaction between the virus and human proteins without impeding the activity of Tsg101 in cells. This deserves to be studied," he said.

The FAPESP-funded research also plans to determine which proteins are produced by Oropouche to recruit the ESCRT complex. "They would also be potential targets worth exploring to halt the infection," Silva said.

ANN ARBOR, MI - Nearly a third of older adults have received a prescription for an opioid pain medicine in the past two years, but many of them didn't get enough counseling about the risks that come with the potent painkillers, how to reduce their use, when to switch to a non-opioid option, or what to do with leftover pills, a new poll finds.

But the poll also finds that nearly three-quarters of older adults would support limits on how many opioid pills a doctor could prescribe at once. Even more supported other efforts to limit exposure to these medications, and potentially combat the national epidemic of opioid misuse due to medication diversion.

The new findings, from the National Poll on Healthy Aging, suggest a major opportunity for providers and community organizations to focus on safe opioid use and safe disposal among older Americans. These findings also could help state and federal policymakers understand the views of a key demographic group at a critical time.

The poll of 2,013 adults between the ages of 50 and 80 was conducted by the University of Michigan Institute for Healthcare Policy and Innovation, and sponsored by AARP and Michigan Medicine, U-M's academic medical center.

"We know that unused opioid medications that linger in homes are one of the primary pathways to diversion, misuse, abuse, and dependence. As prescribers, we must find opportunities to discuss safe opioid use, storage, and disposal with our patients," says Jennifer Waljee, M.D., M.P.H., M.S., the co-director of the Michigan Opioid Prescribing Engagement Network (Michigan OPEN) and an associate professor of surgery at Michigan Medicine. "It is critically important to provide a detailed plan for patients who get opioids for pain management and resources for disposal."

Waljee worked with NPHA director and U-M professor Preeti Malani, M.D., and IHPI National Clinician Scholar Calista Harbaugh, M.D., to design the poll.

They focused not only on older adults' own opioid use but also their storage and disposal habits, as well as their perceptions of recent policy measures around opioid prescribing.

Common prescribing, inadequate counseling

Most of the 589 older adults who said they'd received an opioid prescription in the previous two years said it related to arthritis pain, back pain, surgery and/or an injury. While the majority remembered their doctor, pharmacist or other health care provider talking with them about how often to take the medication, the percentage who said they'd talked with any provider about other opioid issues was much lower.

For instance, less than half said their doctor or other provider had counseled them about the risk of addiction or overdose. Just over a quarter said their pharmacist had provided counseling. Slightly more individuals reported that doctors and pharmacists discussed options to reduce the amount of opioids they were taking.

Only 37 percent said their doctor had talked with them about what to do with leftover opioid pills, while 25 percent said their pharmacist had done so. Half of those who had been prescribed an opioid said they had had pills left over, and 86 percent said they kept them for later potential use.

"The fact that so many older adults report having leftover opioid pills is a big problem, given the risk of abuse and addiction with these medications," says Alison Bryant, Ph.D., senior vice president of research for AARP. "Having unused opioids in the house, often stored in unlocked medicine cabinets, is a big risk to other family members as well. These findings highlight the importance of improving older adults' awareness and access to services that will help them safely dispose of unused opioid medications."

Disposal vs. keeping unused pills

The poll also asked those who didn't have leftover medication, and those who had not been prescribed an opioid in the past two years, what they would have done with leftover pain pills. Two-thirds said they would save them for future use, 27 percent said they would dispose of them at home, and 36 percent said they would take them to an approved disposal facility.

Disposing of leftover medications may require travel to a facility such as a police station, authorized pharmacy, or community "takeback" event that can sometimes be logistically difficult for patients.

The poll asked all respondents to think about what they would do if there were a safe-disposal product that they could pick up along with their prescription. Such products are already on the market and include powders that can be poured into the bottle with extra pills, mixed with water, and safely disposed of in the trash. In all, 39 percent said they would definitely use it, but the majority of the rest said they'd save the medication for future use. And if the safe-disposal product cost $5 or $10, only 9 percent said they would be very likely to buy it.

Opioid policy opinions

The researchers suspect that older adults may fear that they will not be able to obtain pain medications when needed as new state opioid-related policies and laws target reduced prescribing.

Current and proposed laws in some states require providers to look at patients' prescription records before prescribing opioids, and some require patients to tell their provider if they have been taking pain medications. Other states have proposed special provider education, prescribing restrictions, and required return of unused medications.

The poll shows that nearly all older adults support policies such as required review of prescription records and disclosure of prior opioid medication use, despite concerns that these policies may be perceived as invading patients' privacy. A slightly lower percentage supported requiring providers to get special training before they can prescribe opioids. But the poll team was surprised to find that 74 percent supported restrictions on the number of opioid pills, or the number of days' supply, for which prescribers could write a single prescription. On the other hand, just under half of older adults said they'd support required return of unused medications.

Taken together, Malani says, the poll results suggest that healthcare providers who prescribe or dispense opioids should do more to help patients understand how to safely use and dispose of them, in language that patients understand. This should include a disposal plan that helps patients understand why they should dispose of extra medications, and how best to do so.

"When a patient is prescribed an opioid, there are often many other aspects of care at the forefront of patient's minds, such as their diagnosis, social stressors, work-related concerns, and caring for loved ones, and it can result in education fatigue," says Waljee. "But we spend a lot of time educating our patients on when they can drive, return to work, and take care of their painful condition or surgical incision sites. Similarly, we need to educate our patients on what to expect following pain, the role and risks of opioids, and important alternatives such as over-the-counter analgesics, breathing, exercise, and sleep."

The poll results are based on answers from a nationally representative sample of 2,013 people ages 50 to 80. The poll respondents answered a wide range of questions online. Questions were written, and data interpreted and compiled, by the IHPI team. Laptops and Internet access were provided to poll respondents who did not already have it.

Alexandria, Va., USA - At the 96th General Session of the International Association for Dental Research (IADR), held in conjunction with the IADR Pan European Regional (PER) Congress, Benjamin Chaffee, University of California, San Francisco, USA gave a poster presentation "Nicotine and Carcinogen Exposure by Tobacco Product Type and Dual-Use." The IADR/PER General Session & Exhibition is in London, England at the ExCeL London Convention Center from July 25-28, 2018.

Tobacco use remains a leading cause of oral cancer but the tobacco landscape is evolving with increasing use of non-cigarette tobacco products and dual-use of multiple product types. Chaffee and co-author Neal Benowitz, also from the University of California, San Francisco, evaluated exposure to known carcinogens according to recent use of different tobacco product types, alone or in combination.

Data was analyzed from the Population Assessment of Tobacco and Health which includes a sample of U.S. adults who provided urine specimens for analysis of tobacco-specific nitrosamines (TSNAs) N'-nitrosonornicotine (NNN), a known oral and esophageal carcinogen, 4-(methynitrosamino)-1-(3)-pyridyle-1-butanol (NNAL), a metabolite of lung carcinogen (NNK) and total nicotine equivalents.

Participants were categorized according to use of combustible -- which includes cigarettes, cigars, water pipe, pipes, blunts (marijuana-containing cigars), smokeless -- which includes moist snuff, chewing tobacco and snus, e-cigarettes and nicotine replacement products. For each product, recent use was defined as within the prior 3-days and non-use defined as none within 30-days.

All tobacco use categories demonstrated elevated nicotine and TSNA concentrations relative to non-users. TSNA exposures were highest among smokeless tobacco users, whether used or together with other product types. Exclusive e-cigarette users were exposed to lower NNN and NNAL levels than other product users, despite comparable nicotine exposure. However, most e-cigarette users concurrently used combustible tobacco resulting in TSNA exposure similar to exclusive cigarette smokers.

The analysis shows that the vast majority of non-cigarette tobacco users are exposed to carcinogen levels comparable to or exceeding exposure among exclusive cigarette smokers -- levels that are likely to place users at substantial risk.

Alexandria, Va., USA - At the 96th General Session of the International Association for Dental Research (IADR), held in conjunction with the IADR Pan European Regional (PER) Congress, David Wong, University of California, Los Angeles, USA presented his research "Saliva Diagnostics and Salivaomics" as part of the symposium "Will Saliva Translate to a Real Diagnostic Tool?" on Saturday, July 28, 2018. The IADR/PER General Session & Exhibition is in London, England at the ExCeL London Convention Center from July 25-28, 2018.

In the era of new diagnostic methods and treatment options, patient care is rapidly changing. Early detection is an emerging paradigm which seeks to decrease patient morbidity and mortality by detecting disease at a phase where it is easily treatable. Wong spoke about the exciting new opportunities to use saliva liquid biopsy for early assessment of lung cancer because of the clinical performance of cancer detection, non-invasive collection process and the ease of collecting, transporting and storing saliva.

Studies have been conducted on using saliva to measure stress hormones, enzyme levels, developmental disease biomarkers and even cancer mutations.
"There are a variety of scenarios with which saliva can be used," said Wong. "One of the most exciting emerging frontiers of saliva is liquid biopsy, which is a non-invasive means to assess the presence and characteristics of cancer in a patient with an indeterminate pulmonary nodule detected by low dose computerized tomography (LDCT)." Saliva liquid biopsy delivers the best performance in the detection of circulating tumor DNA of lung cancer.
This research was presented as part of the symposium "Will Saliva Translate to a Real Diagnostic Tool?" that took place on Saturday, July 28, 2018 from 8 a.m. - 9:30 a.m. at the ExCeL London Convention Center in London, England.

If validated biomarkers were combined with high-quality detection tools,

saliva would open up a new frontier in high-quality healthcare allowing physicians, dentists and patients to work

together for real-time health monitoring and high-impact personalized preventative medicine.

Alexandria, Va., USA - At the 96th General Session of the International Association for Dental Research (IADR), held in conjunction with the IADR Pan European Regional (PER) Congress, John Estrada-Montoya, Universidad Nacional de Colombia, Bogotá, gave a poster presentation titled "Does a Country's Political Regime Influence Its DMTF Index." The IADR/PER General Session & Exhibition is in London, England at the ExCeL London Convention Center from July 25-28, 2018.

Estrada-Montoya and co-author Jesús Erazo Estrada, also from the Universidad Nacional de Colombia, Bogotá, sought to determine whether prolonged exposure to a given political regime affected the decay-missing-filled (DMF) Index in various countries according to the political typologies of Social Democratic, Conservative, Liberal and Dictatorial regimes.

This ecological epidemiological was study based on secondary sources from the World Health Organization, the Pan American Health Organization, the World Bank and various websites from countries that met the inclusion criteria. A country's assignment to a political typology was determined by the political orientation of its ruling party.

The results from the 62 countries showed that countries categorized as Social Democratic and Liberal had better results in decreasing the DMTF Index (Social Democratic with a decrease of -65.72% and Liberal with a decrease of -53.97%) than did Conservative (with a decrease of -37.62%) and especially Dictatorial regimes (with an increase of +14.53%).

The authors note that the typology they used did not adapt well for Third World politics. They suggest the creation of new interdisciplinary typologies better suited to Third World political realities in order to further characterize and study the relationship between political regimes and oral healthcare indicators.

NASA's Transiting Exoplanet Survey Satellite has started its search for planets around nearby stars, officially beginning science operations on July 25, 2018. TESS is expected to transmit its first series of science data back to Earth in August, and thereafter periodically every 13.5 days, once per orbit, as the spacecraft makes it closest approach to Earth. The TESS Science Team will begin searching the data for new planets immediately after the first series arrives.

"I'm thrilled that our new planet hunter mission is ready to start scouring our solar system's neighborhood for new worlds," said Paul Hertz, NASA Astrophysics division director at Headquarters, Washington. "Now that we know there are more planets than stars in our universe, I look forward to the strange, fantastic worlds we're bound to discover."

TESS is NASA's latest satellite to search for planets outside our solar system, known as exoplanets. The mission will spend the next two years monitoring the nearest and brightest stars for periodic dips in their light. These events, called transits, suggest that a planet may be passing in front of its star. TESS is expected to find thousands of planets using this method, some of which could potentially support life.

TESS is a NASA Astrophysics Explorer mission led and operated by MIT in Cambridge, Massachusetts, and managed by NASA's Goddard Space Flight Center in Greenbelt, Maryland. Dr. George Ricker of MIT's Kavli Institute for Astrophysics and Space Research serves as principal investigator for the mission. Additional partners include Northrop Grumman, based in Falls Church, Virginia; NASA's Ames Research Center in California's Silicon Valley; the Harvard-Smithsonian Center for Astrophysics in Cambridge, Massachusetts; MIT's Lincoln Laboratory in Lexington, Massachusetts; and the Space Telescope Science Institute in Baltimore. More than a dozen universities, research institutes and observatories worldwide are participants in the mission.

Fruit fly larvae can taste ribonucleosides, the building blocks of gene transcripts, according to a new study publishing on August 7 in the open-access journal PLOS Biology by Hubert Amrein and Dushyant Mishra of Texas A&M Health Science Center and their colleagues. Moreover, the ability to detect ribonucleosides in the environment helps promote the rapid growth needed by developing larvae and dramatically increases their survival.

Fats, proteins, and carbohydrates make up the bulk of calorically rich macronutrients sought out by animals of all kinds. Taste receptors are generally thought to be attuned to identifying these compounds in the environment, allowing organisms to distinguish them from unpalatable and harmful compounds, which by contrast are usually bitter. Animals also need a fourth major macronutrient class, the ribonucleosides and deoxyribonucleosides, which are used to make RNA and DNA, but because animals can build their own ribonucleosides from carbohydrates and proteins, they had not previously been thought to be sensed by taste receptors.

While testing the ability of fruit fly larvae to detect a variety of sugars, the authors discovered their strong interest in consuming ribose, a sugar component of RNA, as well as RNA itself. The larvae were found to detect these compounds using previously uncharacterized members of the Gustatory Receptor (Gr) protein receptor family, a subfamily called Gr28. Laval taste neurons expressing members of Gr28 were activated by ribose and RNA (but not deoxyribose), and when Gr28 genes were transferred to sugar sensing taste neurons that don't normally express them, these neurons were also activated by ribose and RNA.

This taste for RNA is not just a luxury; the authors found that larvae given food from which ribonucleosides were excluded fared worse than those grown on whole medium, and larvae lacking Gr28 receptors grew slower and had poor survival rates than those with them.

Even though the body can synthesize them, the ability to detect these compounds in the environment provides an advantage to a rapidly growing organism such as the fruit fly larva, the authors argue, since the larva must increase its body weight by 200-fold in only a few days. "We hypothesize that the ability to taste RNA evolved because ingestion, rather than de novo synthesis, provides a survival advantage during this period of extreme growth," Amrein said.

Something mysterious is going on at the Sun. In defiance of all logic, its atmosphere gets much, much hotter the farther it stretches from the Sun's blazing surface.

Temperatures in the corona -- the tenuous, outermost layer of the solar atmosphere -- spike upwards of 2 million degrees Fahrenheit, while just 1,000 miles below, the underlying surface simmers at a balmy 10,000 F. How the Sun manages this feat remains one of the greatest unanswered questions in astrophysics; scientists call it the coronal heating problem. A new, landmark mission, NASA's Parker Solar Probe -- scheduled to launch no earlier than Aug. 11, 2018 -- will fly through the corona itself, seeking clues to its behavior and offering the chance for scientists to solve this mystery.

From Earth, as we see it in visible light, the Sun's appearance -- quiet, unchanging -- belies the life and drama of our nearest star. Its turbulent surface is rocked by eruptions and intense bursts of radiation, which hurl solar material at incredible speeds to every corner of the solar system. This solar activity can trigger space weather events that have the potential to disrupt radio communications, harm satellites and astronauts, and at their most severe, interfere with power grids.

Above the surface, the corona extends for millions of miles and roils with plasma, gases superheated so much that they separate into an electric flow of ions and free electrons. Eventually, it continues outward as the solar wind, a supersonic stream of plasma permeating the entire solar system. And so, it is that humans live well within the extended atmosphere of our Sun. To fully understand the corona and all its secrets is to understand not only the star that powers life on Earth, but also, the very space around us.

A 150-year-old mystery

Most of what we know about the corona is deeply rooted in the history of total solar eclipses. Before sophisticated instruments and spacecraft, the only way to study the corona from Earth was during a total eclipse, when the Moon blocks the Sun's bright face, revealing the surrounding, dimmer corona.

The story of the coronal heating problem begins with a green spectral line observed during an 1869 total eclipse. Because different elements emit light at characteristic wavelengths, scientists can use spectrometers to analyze light from the Sun and identify its composition. But the green line observed in 1869 didn't correspond to any known elements on Earth. Scientists thought perhaps they'd discovered a new element, and they called it coronium.

Not until 70 years later did a Swedish physicist discover the element responsible for the emission is iron, superheated to the point that it's ionized 13 times, leaving it with just half the electrons of a normal atom of iron. And therein lies the problem: Scientists calculated that such high levels of ionization would require coronal temperatures around 2 million degrees Fahrenheit -- nearly 200 times hotter than the surface.

For decades, this deceptively simple green line has been the Mona Lisa of solar science, baffling scientists who can't explain its existence. Since identifying its source, we've come to understand the puzzle is even more complex than it first appeared.

"I think of the coronal heating problem as an umbrella that covers a couple of related confusing problems," said Justin Kasper, a space scientist at the University of Michigan in Ann Arbor. Kasper is also principal investigator for SWEAP, short for the Solar Wind Electrons Alphas and Protons Investigation, an instrument suite aboard Parker Solar Probe. "First, how does the corona get that hot that quickly? But the second part of the problem is that it doesn't just start, it keeps going. And not only does heating continue, but different elements are heated at different rates." It's an intriguing hint at what's going on with heating in the Sun.

Since discovering the hot corona, scientists and engineers have done a great deal of work to understand its behavior. They've developed powerful models and instruments and launched spacecraft that watch the Sun around the clock. But even the most complex models and high-resolution observations can only partially explain coronal heating, and some theories contradict each other. There's also the problem of studying the corona from afar.

We may live within the Sun's expansive atmosphere, but the corona and solar plasma in near-Earth space differ dramatically. It takes the slow solar wind around four days to travel 93 million miles and reach Earth or the spacecraft that study it -- plenty of time for it to intermix with other particles zipping through space and lose its defining features.

Studying this homogenous soup of plasma for clues to coronal heating is like trying to study the geology of a mountain, by sifting through sediment in a river delta thousands of miles downstream. By traveling to the corona, Parker Solar Probe will sample just-heated particles, removing the uncertainties of a 93-million-mile journey and sending back to Earth the most pristine measurements of the corona ever recorded.

"All of our work over the years has culminated to this point: We realized we can never fully solve the coronal heating problem until we send a probe to make measurements in the corona itself," said Nour Raouafi, Parker Solar Probe deputy project scientist and solar physicist at the Johns Hopkins University Applied Physics Laboratory in Laurel, Maryland.

Traveling to the Sun is an idea older than NASA itself, but it's taken decades to engineer the technology that makes its journey possible. In that time, scientists have determined exactly what kinds of data -- and corresponding instruments -- they need in order to complete a picture of the corona and answer this ultimate of burning questions.

Explaining the corona's secrets

Parker Solar Probe will test two chief theories to explain coronal heating. The outer layers of the Sun are constantly boiling and roil with mechanical energy. As massive cells of charged plasma churn through the Sun -- much the way distinct bubbles roll up through a pot of boiling water -- their fluid motion generates complex magnetic fields that extend far up into the corona. Somehow, the tangled fields channel this ferocious energy into the corona as heat -- how they do so is what each theory attempts to explain.

One theory proposes electromagnetic waves are the root of the corona's extreme heat. Perhaps that boiling motion launches magnetic waves of a certain frequency -- called Alfvén waves -- from deep within the Sun out into the corona, which send charged particles spinning and heat the atmosphere, a bit like how ocean waves push and accelerate surfers toward the shore.

Another suggests bomb-like explosions, called nanoflares, across the Sun's surface dump heat into the solar atmosphere. Like their larger counterparts, solar flares, nanoflares are thought to result from an explosive process called magnetic reconnection. Turbulent boiling on the Sun twists and contorts magnetic field lines, building up stress and tension until they explosively snap -- like breaking an over-wound rubber band -- accelerating and heating particles in their wake.

The two theories aren't necessarily mutually exclusive. In fact, to complicate matters, many scientists think both may be involved in heating the corona. Sometimes, for example, the magnetic reconnection that sets off a nanoflare could also launch Alfvén waves, which then further heat surrounding plasma.

The other big question is, how often do these processes happen -- constantly or in distinct bursts? Answering that requires a level of detail we don't have from 93 million miles away.

"We're going close to the heating, and there are times Parker Solar Probe will co-rotate, or orbit the Sun at the same speed the Sun itself rotates," said Eric Christian, a space scientist at NASA's Goddard Space Flight Center in Greenbelt, Maryland, and member of the mission's science team. "That's an important part of the science. By hovering over the same spot, we'll see the evolution of heating."

Uncovering the evidence

Once Parker Solar Probe arrives at the corona, how will it help scientists distinguish whether waves or nanoflares drive heating? While the spacecraft carries four instrument suites for a variety of types of research, two in particular will obtain data useful for solving the coronal heating mystery: the FIELDS experiment and SWEAP.

Surveyor of invisible forces, FIELDS, led by the University of California, Berkeley, directly measures electric and magnetic fields, in order to understand the shocks, waves and magnetic reconnection events that heat the solar wind.

SWEAP -- led by the Harvard-Smithsonian Astrophysical Observatory in Cambridge, Massachusetts -- is the complementary half of the investigation, gathering data on the hot plasma itself. It counts the most abundant particles in the solar wind -- electrons, protons and helium ions -- and measures their temperature, how fast they're moving after they've been heated, and in what direction.

Together, the two instrument suites paint a picture of the electromagnetic fields thought to be responsible for heating, as well as the just-heated solar particles swirling through the corona. Key to their success are high-resolution measurements, capable of resolving interactions between waves and particles at mere fractions of a second.

Parker Solar Probe will swoop within 3.9 million miles of the Sun's surface -- and while this distance may seem great, the spacecraft is well-positioned to detect signatures of coronal heating. "Even though magnetic reconnection events take place lower down near the Sun's surface, the spacecraft will see the plasma right after they occur," said Goddard solar scientist Nicholeen Viall. "We have a chance to stick our thermometer right in the corona and watch the temperature rise. Compare that to studying plasma that was heated four days ago from Earth, where a lot of the 3D structures and time-sensitive information are washed out."

This part of the corona is entirely unexplored territory, and scientists expect sights unlike anything they've seen before. Some think the plasma there will be wispy and tenuous, like cirrus clouds. Or perhaps it will appear like massive pipe cleaner-like structures radiating from the Sun.

"I'm pretty sure when we get that first round of data back, we'll see the solar wind at lower altitudes near the Sun is spiky and impulsive," said Stuart Bale, University of California, Berkeley, astrophysicist and FIELDS principal investigator. "I'd lay my money on the data being much more exciting than what we see near Earth."

The data is complicated enough -- and comes from multiple instruments -- that it will take scientists some time to piece together an explanation for coronal heating. And because the Sun's surface isn't smooth and varies throughout, Parker Solar Probe needs to make multiple passes over the Sun to tell the whole story. But scientists are confident it has the tools to answer their questions.

The basic idea is that each proposed mechanism for heating has its own distinct signature. If Alfvén waves are the source of the corona's extreme heat, FIELDS will detect their activity. Since heavier ions are heated at different rates, it appears that different classes of particles interact with those waves in specific ways; SWEAP will characterize their unique interactions.

If nanoflares are responsible, scientists expect to see jets of accelerated particles shooting out in opposite directions -- a telltale sign of explosive magnetic reconnection. Where magnetic reconnection occurs, they should also detect hot spots where magnetic fields are rapidly changing and heating the surrounding plasma.

Discoveries lie ahead

There is an eagerness and excitement buzzing among solar scientists: Parker Solar Probe's mission marks a watershed moment in the history of astrophysics, and they have a real chance of unraveling the mysteries that have confounded their field for nearly 150 years.

By piecing together the inner workings of the corona, scientists will reach a deeper understanding of the dynamics that spark space weather events, shaping conditions in near-Earth space. But the applications of this science extend beyond the solar system too. The Sun opens a window into understanding other stars -- especially those that also exhibit Sun-like heating -- stars that could potentially foster habitable environments but are too far to ever study. And illuminating the fundamental physics of plasmas could likely teach scientists a great deal about how plasmas behave elsewhere in the universe, like in clusters of galaxies or around black holes.

It's also entirely possible that we haven't even conceived of the greatest discoveries to come. It's hard to predict how solving coronal heating will shift our understanding of the space around us, but fundamental discoveries such as this have the capacity to change science and technology forever. Parker Solar Probe's journey takes human curiosity to a never-before-seen region of the solar system, where every observation is a potential discovery.

"I'm almost certain we'll discover new phenomena we don't know anything about now, and that's very exciting for us," Raouafi said. "Parker Solar Probe will make history by helping us understand coronal heating -- as well as solar wind acceleration and solar energetic particles -- but I think it also has the potential to steer the direction of solar physics' future."

New knowledge about biological processes related to the heart's electrical activity has been gained through a major genome science study. The research had the largest sample size ever of a project of this type.

The molecular mechanisms explored in this study offer insights into cardiac electrical diseases and could suggest avenues of drug research for preventing and treating heart rhythm or conduction problems.

The recent cardiac genomics project involved more than 125 researchers at several institutions across the globe. Results appear this week in Nature Communications.

University of Washington Cardiovascular Health Research Unit members Dr. Nona Sotoodehnia, the Laughlin Endowed Professor of Medicine, Division of Cardiology, and Dr. Sina A. Gharib, associate professor of medicine, Division of Pulmonary, Critical Care and Sleep Medicine, both at the University of Washington School of Medicine in Seattle, were among the five supervising scientists for the international study. Dr. Jessica van Setten of the University of Utrecht, The Netherlands, was the lead author of the study's published paper.

The researchers were particularly interested in the part of the electrocardiogram, or heart recording, called the PR interval.

Generally speaking, the PR interval, measured in milliseconds, traces electrical conduction from the heart's sinus node throughout the atria to its ventricles.

The sinus node is the pacemaker of the heart. The atria are the two smaller, upper heart chambers that collect blood from the body and prime the pump. The ventricles are the two larger, left-and-right, lower chambers that collect and pump the blood back to the rest of the body.

The PR interval initiates the onset of atria contraction. The PR interval ends when the ventricles are readied to push the blood out.

Earlier studies in twins and in families suggest that the inheritability of the PR interval is between 40 percent and 60 percent. This large study with multiple ethnicities enabled the researchers to identify genes and processes involved in atrial conduction. These findings extended what was known biologically and clinically from previous research.

The researchers performed a genome-wide association study of more than 92,000 individuals of European descent. Genome-wide association studies are projects that examine the DNA of different individuals to find genetic variations that might be associated with a particular trait or disease.

In this study, millions of genetic markers were examined throughout the genome to identify genetic variants associated with atrial conduction.

The study investigators identified 44 chromosomal regions related to the PR interval. Of these loci, 34 had not been identified before.

"Genes in these 44 loci are overrepresented in cardiac disease processes, including heart block, sick sinus syndrome, and atrial fibrillation," the researchers wrote.

Atrial fibrillation is an abnormal heart rhythm that can increase risk of heart failure and sudden death. It also increases the risk of clots forming in the heart and of moving into the brain to cause a stroke. Heart block is an interference with the electrical waves that power the motion of the heart. It, and other conduction defects, sometimes necessitate a pacemaker implantation.

Additional analyses, using various or combined methods, were done examining more than 105,000 people of African and European ancestry. These yielded six more loci relevant to the heart's atrial or atrioventricular electrical activities.

The findings pointed to a number of different processes involved in atrial and atrioventricular conduction. Developmental pathways in the heart, particularly the formation of the chambers and the development of the system that allows conduction of the electrical signal throughout the heart, were implicated in the origin of these sorts of heart diseases.

Certain gene transcription factors, ion channel genes, and cell junction or cell signaling proteins involved in the conduction of the heart's electrical waves also showed possible contributions to abnormalities.

The researchers also uncovered gene regulators that were found only in the heart's atrial tissues. This observation, they noted, underscores the reason for examining certain genomic data in the tissue types relevant to the disease or trait in question, not just in blood samples. Conversely, the researchers also spotted overlapping factors that influenced both cardiac and blood vessel formation.

Moreover, the researchers performed trans-ethnic analyses that showed that a majority of the genetic associations found in the study's European population were also present in the study's African-American population. They pointed out, nonetheless, that a few noteworthy interethnic differences were present.