Culture

ARLINGTON HEIGHTS, IL - (DECEMBER 18, 2019) - A new article in Annals of Allergy, Asthma and Immunology, the scientific journal of the American College of Allergy, Asthma and Immunology (ACAAI) shows most people allergic to peanuts can safely eat tree nuts. Nevertheless, nearly 40 percent choose voluntary avoidance of all tree nuts for a variety of reasons, the most common being the potential risk of cross contact

"The results showed that nearly 90 percent of people with a peanut allergy in the study could potentially tolerate almonds, but 33 percent of that group preferred strict avoidance due to fear of an allergic reaction," says allergist Shahzad Mustafa, MD, ACAAI member and lead author. "The most common reason for choosing to avoid all tree nuts was to minimize the risk of cross contact. This can happen when a food is cooked with or near something that contains an allergen. Kitchen tools such as knives or spoons can also contribute to cross contact when they are used to mix multiple foods."

Of the 258 people with peanut allergy enrolled in the study, 37 percent consumed all tree nuts, 24 percent consumed some but not all, and 39 percent consumed no tree nuts. Of the 100 people avoiding all tree nuts, 50 percent reported it was due to fear of cross contact, 16 percent said they had no desire to consume any tree nuts, 13 percent were avoiding tree nuts due to young age and 12 percent were avoiding tree nuts due to a high likelihood of being allergic.

"We found people allergic to peanut who consume foods with precautionary labeling (PAL) are more likely to choose to eat tree nuts as compared to those who don't eat foods with PAL," says allergist Allison Ramsey, MD, ACAAI member of the ACAAI Anaphylaxis Committee and co-author of the study. "In the study, 37 percent of those with peanut allergy consumed foods with PAL and 63 percent reported avoiding all foods with PAL." Foods with PAL include statements such as "may contain," "processed in a facility that also processes" or "made on equipment with." These warnings often follow the ingredients list and are voluntarily included by manufacturers but don't indicate if a product is safe to consume or not.

"People with peanut allergy should be aware that it may be safe to consume some, if not all tree nuts, and tree nut consumption can contribute to a nutritious diet," says Dr. Mustafa. "In addition, our data indicated that avoiding foods with PAL may have an overly restrictive impact on the diet of people with peanut allergy. Eating foods with PAL is something people with food allergies should discuss with their allergist and take into consideration when creating their diet."

URBANA, Ill. - Experiences of racial discrimination are a common source of stress for African Americans, and research shows discrimination can have a damaging impact on the physical and emotional health of African American individuals.

Family studies researchers at the University of Illinois, knowing the interdependence of individuals in close, romantic relationships, wanted to know if this link between racial discrimination and health might be different for those in committed relationships. They specifically questioned whether racism-specific support, shared between African American partners, could lessen--or worsen--the health effects associated with discrimination.

Their findings, recently published in the Journal of Social and Personal Relationships, show that racism-specific support was associated with better mental and physical health for husbands, and better physical and general health for wives. However, wives had compromised mental health when they perceived low levels of racism-specific support from their husbands, particularly when they and their husbands experienced elevated levels of racial discrimination.

Sharde Smith, an assistant professor in the Department of Human Development and Family Studies at U of I, explains how race-related stress from experiences of discrimination can transmit among those in close, interpersonal relationships such as romantic couples.

"For example, if I were to experience racial discrimination, I would likely communicate my experience with my husband or a close friend, confiding in them for support," Smith says. "So it's not only affecting me; it ends up affecting them as well. I'm interested in that transmission of race-related stress and the management of it among those in close relationships.

"We're interested in how that close friend or family member actually helps manage it, and how they are supportive. Our paper explores this idea by examining racism-specific support by asking, 'if you were to experience racial discrimination, how likely is it that talking with your partner will help you feel better?' General support could be helpful in these circumstances, but what does it look like if we're talking specifically about racism?"

Racial discrimination that leads to stress could be subtle or overt, ranging from physical encounters or not being treated with courtesy by others to policies and practices embedded in institutions, Smith explains. "It may not even be things that are blatantly racist or discriminatory, but the fact that it could even be conceivable that it is racist or discriminatory, is also part of the problem. The reality is that racial discrimination is ingrained in our society, and so the constant questioning of whether any experience is or is not discriminatory, is also part of the impact on one's health. This questioning or perception of racial discrimination contributes to how these experiences can take a toll on you physically, mentally, and psychologically."

For the study, Smith and colleagues looked at data from 487 African American, heterosexual couples who were either married or engaged. The participants answered questions assessing the frequency at which they experienced racism or discrimination. For example, one question asked how often someone said something derogatory or insulting to them or their partner because they are African American or part of an African American family.

Participants then answered questions about racism-related support, with "helpful support" defined as feeling better when they discussed racial discrimination with their partners. Finally, participants reported on their general, mental, and physical health.

Smith says the findings show some differences within couples of how that stress is transmitted or managed within the couple context, particularly for Black women.

"Supporting one's partner in the context of racial discrimination can be helpful because you're able to have those conversations and lend some support, but we're also finding it can be burdensome to have to deal with your partner's discrimination experiences, especially if you're also dealing with it yourself," Smith explains.

"While it's important to be able to have those conversations with others who have an understanding and can validate those discrimination experiences, even the validation of those experiences can be taxing on the person providing support," she adds.

Smith says in the current study and another study she conducted, findings show support can be particularly burdensome for Black women. "They're not only affected by their own experiences of racial discrimination, but they're also affected by their partner's. Black women are there for Black men, but then who is there for Black women? Our findings do not suggest that Black men are not present for Black women, but we are finding these particularly harmful or burdensome effects on Black women in these relationships."

Smith says future research should focus on looking at where Black women go for racism-specific support. "What are some supportive resources that Black women can draw on? Or, how can we make sure that Black men are providing the type of support that Black women need? The Black men are not necessarily being unsupportive, but there's some type of disconnect where the burden is on women."

Whether wives were experiencing high or low levels of racial discrimination, it was helpful for them to receive some racism-specific support from their husbands. But it did not provide stress-buffering effects, which Smith says, means this support is not actually reducing or mitigating the risk for mental health issues. "But we are seeing that for Black men it is stress-buffering, even at high levels of discrimination."

Smith adds, based on the findings, practitioners or relational therapists who see African American couples should pay attention to the levels and types of support that couples are providing each other and how comfortable they even feel talking with their partners about these experiences.

Deep in our Milky Way galaxy's center, a candy cane emerges as the centerpiece of a new, colorful composite image from a NASA camera, just in time for the holidays.

The image--captured by a NASA-designed and built instrument called the Goddard-IRAM Superconducting 2-Millimeter Observer, or GISMO--shows the inner part of our galaxy, which hosts the largest, densest collection of giant molecular clouds in the Milky Way. These vast, cool clouds contain enough dense gas and dust to form tens of millions of stars like the Sun. The view spans a part of the sky about 1.5 degrees across, equivalent to roughly three times the apparent size of the Moon.

Two papers describing the image, one led by Johannes Staguhn at The Johns Hopkins University and the other led by Richard Arendt at The University of Maryland, were recently published in The Astrophysical Journal.

"The galactic center is an enigmatic region with extreme conditions where velocities are higher and objects frequently collide with each other," says Staguhn, who leads the GISMO team at NASA'S Goddard Space Flight Center.

"GISMO gives us the opportunity to observe microwaves with a wavelength of 2 millimeters at a large scale, combined with an angular resolution that perfectly matches the size of galactic center features we are interested in. Such detailed, large-scale observations have never been done before."

The studies detail how, after spending 8 hours looking at the sky and collecting data, GISMO detected the most prominent radio filament in the galactic center, making this the shortest wavelength where these curious structures have been observed. Scientists say the filaments delineate the edges of a large bubble produced by some energetic event at the galactic center.

"We're very intrigued by the beauty of this image; it's exotic. When you look at it, you feel like you're looking at some really special forces of nature in the universe," muses Staguhn.

The image is a composite of different color codes for emission mechanisms. Blue and cyan features reveal cold dust in molecular clouds where star formation is still in its infancy. Yellow features reveal the presence of ionized gas and show well-developed star factories; this light comes from electrons that are slowed but not captured by gas ions, a process also known as free-free emission. Red and orange regions show areas where synchrotron emission occurs, such as in the prominent Radio Arc and Sagittarius A, the bright source at the galaxy's center that hosts its supermassive black hole.

To make the image, the team acquired GISMO data, shown in green, in April and November 2012. They then used archival observations from the European Space Agency's Herschel satellite to model the far-infrared glow of cold dust, which they then subtracted from the GISMO data. Next, they added, in blue, existing 850-micrometer infrared data from the SCUBA-2 instrument on the James Clerk Maxwell Telescope. Finally, they added, in red, archival longer-wavelength 19.5-centimeter radio observations from the National Science Foundation's Karl G. Jansky Very Large Array. The higher-resolution infrared and radio data were then processed to match the lower-resolution GISMO observations. The team used GISMO in concert with a 30-meter radio telescope located on Pico Veleta, Spain.

Moving forward, Staguhn hopes to upgrade and take GISMO to the Greenland Telescope to make large surveys on the sky looking for the first galaxies in the universe where stars formed.

"There's a good chance that a significant part of star formation that occurred during the universe's infancy is obscured and can't be detected by tools we've been using, and GISMO will be able to help detect what was previously unobservable," says Staguhn.

A feature resembling a candy cane appears at the center of this colorful composite image of our Milky Way galaxy's central zone. But this is no cosmic confection. It spans 190 light-years and is one of a set of long, thin strands of ionized gas called filaments that emit radio waves.

This image includes newly published observations using an instrument designed and built at NASA's Goddard Space Flight Center in Greenbelt, Maryland. Called the Goddard-IRAM Superconducting 2-Millimeter Observer (GISMO), the instrument was used in concert with a 30-meter radio telescope located on Pico Veleta, Spain, operated by the Institute for Radio Astronomy in the Millimeter Range headquartered in Grenoble, France.

"GISMO observes microwaves with a wavelength of 2 millimeters, allowing us to explore the galaxy in the transition zone between infrared light and longer radio wavelengths," said Johannes Staguhn, an astronomer at Johns Hopkins University in Baltimore who leads the GISMO team at Goddard. "Each of these portions of the spectrum is dominated by different types of emission, and GISMO shows us how they link together."

GISMO detected the most prominent radio filament in the galactic center, known as the Radio Arc, which forms the straight part of the cosmic candy cane. This is the shortest wavelength at which these curious structures have been observed. Scientists say the filaments delineate the edges of a large bubble produced by some energetic event at the galactic center, located within the bright region known as Sagittarius A about 27,000 light-years away from us. Additional red arcs in the image reveal other filaments.

"It was a real surprise to see the Radio Arc in the GISMO data," said Richard Arendt, a team member at the University of Maryland, Baltimore County and Goddard. "Its emission comes from high-speed electrons spiraling in a magnetic field, a process called synchrotron emission. Another feature GISMO sees, called the Sickle, is associated with star formation and may be the source of these high-speed electrons."

Two papers describing the composite image, one led by Arendt and one led by Staguhn, were published on Nov. 1 in the Astrophysical Journal.

The image shows the inner part of our galaxy, which hosts the largest and densest collection of giant molecular clouds in the Milky Way. These vast, cool clouds contain enough dense gas and dust to form tens of millions of stars like the Sun. The view spans a part of the sky about 1.6 degrees across -- equivalent to roughly three times the apparent size of the Moon -- or about 750 light-years wide.

To make the image, the team acquired GISMO data, shown in green, in April and November 2012. They then used archival observations from the European Space Agency's Herschel satellite to model the far-infrared glow of cold dust, which they then subtracted from the GISMO data. Next, they added, in blue, existing 850-micrometer infrared data from the SCUBA-2 instrument on the James Clerk Maxwell Telescope near the summit of Maunakea, Hawaii. Finally, they added, in red, archival longer-wavelength 19.5-centimeter radio observations from the National Science Foundation's Karl G. Jansky Very Large Array, located near Socorro, New Mexico. The higher-resolution infrared and radio data were then processed to match the lower-resolution GISMO observations.

The resulting image essentially color codes different emission mechanisms.

Blue and cyan features reveal cold dust in molecular clouds where star formation is still in its infancy. Yellow features, such as the Arches filaments making up the candy cane's handle and the Sagittarius B1 molecular cloud, reveal the presence of ionized gas and show well-developed star factories; this light comes from electrons that are slowed but not captured by gas ions, a process also known as free-free emission. Red and orange regions show areas where synchrotron emission occurs, such as in the prominent Radio Arc and Sagittarius A, the bright source at the galaxy's center that hosts its supermassive black hole.

Budgeting resources isn't just a problem for humans preparing a holiday dinner, or squirrels storing up nuts for the winter.

A new model of how animals budget their energy sheds light on how they live and explains why they tend to evolve toward larger body sizes. The research, published in PNAS, proposes that animal energy budgets are governed by a key mechanism: resource variation -- a measure of how spread out or clumped up food and water are.

"Every single thing has to do this, from single-celled life forms all the way up to mammals or dinosaurs," says co-author Justin Yeakel (University of California Merced). "Animals have to decide how they route their energy, whether it's to build more mass onto themselves, or invest in reproduction, or what have you."

To map an animal's theoretical life-history, the authors rely on several key variables: how much energy an animal has stored, its metabolism, the cost of reproduction, and how much stored energy is delivered to its offspring. "An animal is described just by its energy state -- like a video game with health points," says lead author Uttam Bhat (University of California Merced). In this way, the rise and fall of each individual's energy budget over a lifetime gives its history.

But acquiring resources isn't necessarily easy; food doesn't always grow on trees -- literally. According to Bhat, previous models of energy allocation have often assumed that resources automatically came to animals, as if through a pipeline. In their new model, the authors give resources a spatial dimension. Resources can be spread out over an area uniformly, like grassy plains, or clustered, like fruit bushes. Fluctuations in the availability of these resources, such as the distance between fruit bushes becoming larger, can have an enormous impact on animals.

"If you have a lot of uncertainty, you want to have a lot of buffers in your body," says Bhat. Typically, this means an increase in body size -- bigger bodies have more room for energy storage.

Cope's rule proposes that the size of animals generally increases across their evolutionary lineage. The fossil record bears this out for most mammals: tens of millions of years ago, the ancestors of elephants and blue whales were tiny, mouse-sized creatures. (Mice-sized mammals, of course, are also still around.)

The new model shows that the more spread out and patchy an animal's food is, the more unstable its population, with smaller animals more affected and likely to go extinct.

Between twenty million years ago and five million years ago, grasslands sprouted up around the world. For mammals that adapted by growing large enough to graze on grasslands, food was ubiquitous; mammals that remained small were unable to partake, and less certain to secure dinner. If you plug in the variables to the authors' model, what you get is what the fossil record shows: an evolutionary pressure for herbivores to grow larger, from rodent-sized to bison.

"It's sort of fun, I think, that we build up from single-organism risk all the way to long-term evolutionary trends," says co-author Chris Kempes (Santa Fe Institute). "I think the push to address lots of the major questions in this way is where much of the future of ecology lies."

This interdisciplinary work was initiated at the Santa Fe Institute and blends the physics, biology, and statistics expertise of authors Bhat, Yeakel, and Kempes.

As an embryo develops, its cells must learn what to do with the thousands of genes they've been equipped with. That's why each cell comes with a detailed gene-expression manual outlining exactly which genes should be switched on, to what extent, and when.

To execute their respective manuals, the cells employ so-called chromatin reader proteins that identify which gene is up for expression. Now a new study has found that a problem in this gene-regulatory process may cause normal cells to turn malignant and produce Wilms' tumor, the most common kidney cancer in children.

The findings, published in Nature, open up new treatment possibilities for the disease, which is currently treated by surgery and chemotherapy.

The findings also raise intriguing questions about other cancer types. The researchers found that the implicated reader protein causes problems by acquiring a new property and being too active.

"We have never seen this type of mechanism before," says Liling Wan, a former postdoctoral associate in the Rockefeller lab of C. David Allis, and now an assistant professor at the University of Pennsylvania. "It raises the question whether this type of molecular mechanism is also hijacked in other cancer types."

Reading too well

A few years ago, Wan discovered that a reader protein called ENL is involved in blood cancer leukemia by activating the cancer-causing genes. Her attention was turned to Wilms' tumor recently, when it was discovered that some people with Wilms' tumor carry mutations in the gene that codes for ENL.

To see whether these mutations are indeed involved in the formation of Wilms' tumor, Wan and her colleagues introduced the mutations to mouse embryonic stem cells, and then instructed the cells to develop all the way into kidneys in a petri dish. "Quite strikingly, when you insert the mutation, you start to see a tumor-like structure appearing in the developing kidney, which resembles what we typically see in human Wilms tumor," Wan says.

The team then took a closer look to understand how mutations in ENL turn these cells into tumor cells. In both the cells that carry the mutation and in unaltered cells, they saw ENL proteins land on the same locations in the genome, suggesting there was nothing wrong with the mutant ENL protein's ability to recognize which genes should be expressed. The mutant proteins, however, clumped at these sites, causing the genes to be constantly transcribed into RNA, the first steps before turning into proteins.

"This abnormal gene expression confuses the cells as to what they want to become," Wan says. "Instead of differentiating into mature kidney cells, they start to proliferate more and get stuck in the immature stage, which leads to the formation of a tumor."

Having discovered this previously unknown mechanism in cancer, Wan and her colleagues are now asking if it might be possible to revert cancer cells back to normal, for instance with drugs that disrupt ENL's ability to bind to the genome or to form clumps.

"So far we have proof of concept that intervening in any stage of this process can stabilize the gene expression levels and allow the cells to develop normally," Wan says.

Researchers at Baylor College of Medicine report today in the journal Neuron evidence that refutes the link between increased levels of herpes virus and Alzheimer's disease. In addition, the researchers provide a new statistical and computational framework for the analysis of large-scale sequencing data.

About 50 million people worldwide are affected by Alzheimer's disease, a type of progressive dementia that results in the loss of memory, cognitive abilities and verbal skills, and the numbers are growing rapidly. Currently available medications temporarily ease the symptoms or slow the rate of decline, which maximizes the time patients can live and function independently. However, there are no treatments to halt progression of Alzheimer's disease.

"Like all types of dementia, Alzheimer's disease is characterized by massive death of brain cells, the neurons. Identifying the reason why neurons begin and continue to die in the brains of Alzheimer's disease patients is an active area of research," said corresponding author Dr. Zhandong Liu, associate professor of pediatrics at Baylor and the Jan and Dan Duncan Neurological Research Institute at Texas Children's Hospital.

One theory that has gained traction in the past year is that certain microbial infections, such as those caused by viruses, can trigger Alzheimer's disease. A 2018 study reported increased levels of human herpesvirus 6A (HHV-6A) and human herpesvirus 7 (HHV-7) in the postmortem brain tissues of more than 1,000 patients with Alzheimer's disease when compared to the brain tissues of healthy-aging subjects or those suffering from a different neurodegenerative condition.

Presence of elevated levels of genetic material of herpes viruses indicated active infections, which were linked to Alzheimer's disease. In less than a year, this study generated a flurry of excitement and led to the initiation of several studies to better understand the link between viral infections and Alzheimer's disease.

Surprisingly, when co-author Dr. Hyun-Hwan Jeong, a postdoctoral fellow in Dr. Liu's group and others, reanalyzed the data sets from the 2018 study using the identical statistical methods with rigorous filtering, as well as four commonly used statistical tools, they were unable to produce the same results.

The team was motivated to reanalyze the data from the previous study because they observed that while the p-values (a statistical parameter that predicts the probability of obtaining the observed results of a test, assuming that other conditions are correct) were highly significant, they were being ascribed to data in which the differences were not visually appreciable.

Moreover, the p-values did not fit with simple logistic regression - a statistical analysis that predicts the outcome of the data as one of two defined states. In fact, after several types of rigorous statistical tests, they found no link between the abundance of herpes viral DNA or RNA and likelihood of Alzheimer's disease in this cohort.

"As high-throughput 'omics' technologies, which include those for genomics, proteomics, metabolomics and others, become affordable and easily available, there is a rising trend toward 'big data' in basic biomedical research. In these situations, given the massive amounts of data that have to be mined and extracted in a short time, researchers may be tempted to rely solely on p-values to interpret results and arrive at conclusions," Liu said.

"Our study highlights one of the potential pitfalls of over-reliance on p-values. While p-values are a very valuable statistical parameter, they cannot be used as a stand-alone measure of statistical correlation - data sets from high-throughput procedures still need to be carefully plotted to visualize the spread of the data," Jeong said. "Data sets also have to be used in conjunction with accurately calculated p-values to make gene-disease associations that are statistically correct and biologically meaningful."

"Our goal in pursuing and publishing this study was to generate tools and guidelines for big data analysis, so the scientific community can identify treatment strategies that will likely benefit patients," Liu said.

One in five children in Cuyahoga County, Ohio, are either exposed to, or are victims of, violence and trauma, according to a new study from the Jack, Joseph and Morton Mandel School of Applied Social Sciences at Case Western Reserve University.

In a diverse sample of 6,676 high-risk children up to age 7, researchers from the Mandel School's Begun Center for Violence Prevention Research and Education found that those children had trouble going to sleep at least sometimes (16%), had cried or had a tantrum to exhaustion (16%) and had difficulty concentrating or focusing (16%), significantly higher than normal. Levels of exposure to violence and victimization were also high.

With such high rates of emotional and behavioral issues, researchers at the Begun Center have developed a new tool to quickly and reliably identify children who need attention from social services.

"We were getting feedback that there wasn't an easy-to-use screener available to evaluate these kids," said Daniel Flannery, the Dr. Semi J. and Ruth Begun Professor and director of the Begun Center at the Mandel School. "So, we developed one and put it in place."

The 22-question screener was designed to assess children--not diagnose them--within a few minutes. Flannery said that current measures take much longer, can be expensive and require specialized training to administer.

"We found that our screener held up," Flannery said. "The idea is that it can be completed quickly and administered by minimally trained staff in public systems and community-based agencies, who can then refer children and families to necessary assessment and treatment services."

KNOXVILLE, Tenn. -- A new study published in Nature reports the 409-megabase genome sequence of the blue-petal water lily (Nymphaea colorata). The conclusion of the 47 coauthors is that although a rose is a rose, most flowering plants may owe their success, including employing floral scent for attracting pollinators, in part to the genetic innovations observed in the delicate water lily.

Known the world over, water lilies are beloved features in ponds and a frequent subject in art from paintings to sculptures. Some religions consider them symbolic of life.

Those beliefs may not be too far from the mark. The study's authors analyzed the genes of Nymphaeales, the order of flowering water plants that includes water lilies, and their results point to Nymphaeales as one of two sister lineages to all other flowering plants, possibly due to a whole genome duplication event some 147 - 185 million years ago. The other lineage is Amborellales, an order of flowering shrubs that includes only one species, Amborella trichopoda.

Flowering plants, also known as angiosperms, are the most diverse group of land plants, with 64 orders, 416 families, approximately 13,000 known genera and 300,000 known species.

The international coalition of researchers that collaborated on the study includes Feng Chen, a professor of plant sciences in the University of Tennessee Institute of Agriculture, his colleague Xinlu Chen and doctoral student Chi Zhang from the same department, and doctoral student Qidong Jia of the Genome Science and Technology Graduate program at UT. Feng Chen is an adjunct member of the faculty for that program. Coauthors also include another scientist named Chen--Fei Chen--who is from Nanjing Agricultural University (NAU), China, to which UTIA's Chen is also an adjunct faculty through the Center of Agricultural Plant Biology established by UT and NAU in 2017. "This paper demonstrates the importance of multidisciplinary collaborations", says UTIA's Chen. He is among the six supervising collaborators for the entire project.

The UT group contributed to the analysis of the genetic basis of floral scent biosynthesis in water lilies. "Floral scent for attracting pollinators is critical for both the diversity of plants and plant-based agricultural production," says Chen. According to the USDA Natural Resource Conservation Service, three-fourths of the world's flowering plants and about 35 percent of the world's food crops depend on animal pollinators, including insects, to reproduce. Many of those pollinators rely on floral scent to help them locate a plant's flowers. "The flowers of A. trichopoda are scentless", according to Chen, who was a coauthor of a Science article reporting the genome of A. trichopoda in 2013. "It is therefore intriguing to understand when and how flowering plants evolved scent," he says.

The study explains that among the genes retained from the Nymphaeales' whole-genome duplication event are homologues of genes that regulate flowering transition and flower development in all flowering plants. Specifically, the UTIA group studied N. colorata.

"Water lilies have evolved attractive floral scents and colors, which are features shared with core angiosperms," said Chen. "The chemical compounds and biosynthetic genes we analyzed--those that produce the floral scents--suggest that the scents of water lilies have evolved in parallel to those in core angiosperms. Because of its unique phylogenetic position, the innovations in scent biosynthesis and other traits revealed from the N. colorata genome shed light on the early evolution of all angiosperms."

NORMAN, OKLA. - A new University of Oklahoma study could have implications on our understanding of how certain sensory signals are transmitted through the body. An OU experiment led by neuroscientist Christian Lemon, Ph.D., Department of Biology, set out to discover how menthol's irritant sensation is transmitted by the nervous system.

Menthol, perhaps best-known as the cooling agent in peppermint, has a cooling sensation when diluted, but can be an irritant at elevated concentrations. The study focused on menthol's interaction with an ion channel known as TRPM8. This channel is associated with menthol, as it is often described as a menthol detector, and is the primary channel that functions as a sensor of cold.

However, genetically engineered mice deficient in TRPM8 did not show significant differences in how they reacted to licking mentholated water from a control group. Instead, mice deficient in a different channel - TRPA1 - did. The TRPA1 channel is more of an "alert" channel - it is known as a sensor for environmental irritants that gives rise to responses such as pain or itching.

For this study, mouse-licking responses were measured in special devices that capture behaviors controlled by sensations arising from the tongue and mouth. The devices record the number of licks and the rate of licking, which both decrease when aversion is present. Control-like decreases in responding to menthol were evident in mice genetically deficient for TRPM8 but not TRPA1.

This data could have implications for how input from TRPA1 and TRPM8 shapes behaviors guided by senses throughout the body. Eventually, understanding these inputs could have implications on everything from the flavor response to pain management.

CHAMPAIGN, Ill. -- While DNA sequencing is a useful tool for determining what's going on in a cell or a person's body, it only tells part of the story. Protein sequencing could soon give researchers a wider window into a cell's workings. A new study demonstrates that nanopores can be used to identify all 20 amino acids in proteins, a major step toward protein sequencing.

Researchers at the University of Illinois at Urbana-Champaign, Cergy-Pontoise University in France and the University of Freiburg in Germany published the findings in the journal Nature Biotechnology.

"DNA codes for many things that can happen; it tells us what is potentially possible. The actual product that comes out - the proteins that do the work in the cell - you can't tell from the DNA alone," said Illinois physics professor Aleksei Aksimentiev, a co-leader of the study. "Many modifications happen along the way during the process of making protein from DNA. The proteins are spliced, chemically modified, folded, and more."

A DNA molecule is itself a template designed for replication, so making copies for sequencing is relatively easy. For proteins, there is no such natural machinery by which to make copies or to read them. Adding to the difficulty, 20 amino acids make up proteins, as compared with the four bases in DNA, and numerous small modifications can be made to each amino acid during protein production and folding.

"Many amino acids are very similar," Aksimentiev said. "For example, if you look at leucine and isoleucine, they have the same atoms, the same molecular weight, and the only difference is that the atoms are connected in a slightly different order."

Nanopores, small protein channels embedded in a membrane, are a popular tool for DNA sequencing. Previously, scientists thought that the differences in amino acids were too small to register with nanopore technology. The new study shows otherwise.

The researchers used a membrane channel naturally made by bacteria, called aerolysin, as their nanopore. In both computer modeling and experimental work, they chopped up proteins and used a chemical carrier to drive the amino acids into the nanopore. The carrier molecule also kept the amino acids inside the pore long enough for it to register a measurable difference in the electrical signature of each amino acid - even leucine and isoleucine, the near-identical twins.

"This work builds confidence and reassures the nanopore community that protein sequencing is indeed possible," said Abdelghani Oukhaled, a professor of biophysics at Cergy-Pontoise whose team carried out much of the experimental work.

The researchers found they could further differentiate modified forms of amino acids by using a more sensitive measurement apparatus or by treating the protein with a chemical to improve differentiation. The measurements are precise enough to potentially identify hundreds of modifications, Aksimentiev said, and even more may be recognized by tweaking the pore.

"This is a proof-of-concept study showing that we can identify the different amino acids," he said. "The current method for protein characterization is mass spectrometry, but that does not determine the sequence; it compares a sample to what's already in the database. Its ability to characterize new variations or mutations is limited. With nanopores, we finally could look at those modifications which have not yet been studied."

The aerolysin nanopore could be integrated into standard nanopore setups, Aksimentiev said, making it accessible to other scientists. The researchers are now exploring approaches to read the amino acids in sequential order as they are cut from the protein. They also are considering other applications for the system.

"One potential application would be to combine this with immunoassays to fish out proteins of interest and then sequence them. Sequencing them will tell us whether they're modified or not, and that could lead to a clinical diagnostic tool," Aksimentiev said.

"This work shows that there's really no limit to how precisely we can characterize biological molecules," he said. "Very likely, one day we will be able to tell the molecular makeup of the cell - what we are made of, down to the level of individual atoms."

With growing populations and climate uncertainty, water security is a global concern. Many nations operate desalination plants, which remove salt from seawater to make it drinkable. These facilities typically discharge excess salt as hypersaline brine back into the ocean, with uncertain ecological effects. Now, researchers in Environmental Science & Technology report that a large desalination plant in Australia has the unexpected benefit of attracting some species of fish, increasing their abundance at the discharge site.

The city of Sydney, Australia, began operating the Sydney Desalination Plant in 2010 to improve water security for Australia's largest city. Because of an ongoing drought, the plant is now supplementing Sydney's water supply with up to 66 million gallons per day. During operation, the Sydney Desalination Plant releases hypersaline solution from two outlets above a rocky reef about 328 yards offshore and 26 yards below the ocean surface. Brendan Kelaher and colleagues investigated how this hypersaline discharge impacted reef fish community structure and abundance.

The researchers used scuba divers to take videos of fish at the outlet sites and at multiple reference sites a couple of miles away over a 7-year period before and after the desalination plant's operation, as well during a timeframe when the plant temporarily ceased operations. Fish, including some commercially important species, were three times more plentiful around the outlet during hypersaline discharge than before or after. The largest increase was observed for fish, such as the one-spot puller, that feed on zooplankton. These differences were not observed at the reference sites. Because local changes in seawater salinity and temperature were relatively small following hypersaline discharge, the team says that the turbulence caused by the high-pressure release of the salty solution could have attracted the fish. Careful regulation of fishing around desalination discharge outlets might be needed to prevent local depletion of fish populations on the broader reef complex, the researchers say.

Can't remember something? Try waiting until later in the day. Researchers identified a gene in mice that seems to influence memory recall at different times of day and tracked how it causes mice to be more forgetful just before they normally wake up.

"We may have identified the first gene in mice specific to memory retrieval," said Professor Satoshi Kida from the University of Tokyo Department of Applied Biological Chemistry.

Every time you forget something, it could be because you didn't truly learn it -- like the name of the person you were just introduced to a minute ago; or it could be because you are not able to recall the information from where it is stored in your brain -- like the lyrics of your favorite song slipping your mind.

Many memory researchers study how new memories are made. The biology of forgetting is more complicated to study because of the difficulties of distinguishing between not knowing and not recalling.

"We designed a memory test that can differentiate between not learning versus knowing but not being able to remember," said Kida.

Researchers tested the memories of young adult male and female mice. In the "learning," or training, phase of the memory tests, researchers allowed mice to explore a new object for a few minutes.

Later, in the "recall" phase of the test, researchers observed how long the mice touched the object when it was reintroduced. Mice spend less time touching objects that they remember seeing previously. Researchers tested the mice's recall by reintroducing the same object at different times of day.

They did the same experiments with healthy mice and mice without BMAL1, a protein that regulates the expression of many other genes. BMAL1 normally fluctuates between low levels just before waking up and high levels before going to sleep.

Mice trained just before they normally woke up and tested just after they normally went to sleep did recognize the object.

Mice trained at the same time -- just before they normally woke up -- but tested 24 hours later did not recognize the object.

Healthy mice and mice without BMAL1 had the same pattern of results, but the mice without BMAL1 were even more forgetful just before they normally woke up. Researchers saw the same results when they tested mice on recognizing an object or recognizing another mouse.

Something about the time of day just before they normally wake up, when BMAL1 levels are normally low, causes mice to not recall something they definitely learned and know.

According to Kida, the memory research community has previously suspected that the body's internal, or circadian, clock that is responsible for regulating sleep-wake cycles also affects learning and memory formation.

"Now we have evidence that the circadian clocks are regulating memory recall," said Kida.

Researchers have traced the role of BMAL1 in memory retrieval to a specific area of the brain called the hippocampus. Additionally, researchers connected normal BMAL1 to activation of dopamine receptors and modification of other small signaling molecules in the brain.

"If we can identify ways to boost memory retrieval through this BMAL1 pathway, then we can think about applications to human diseases of memory deficit, like dementia and Alzheimer's disease," said Kida.

However, the purpose of having memory recall abilities that naturally fluctuate depending on the time of day remains a mystery.

"We really want to know what is the evolutionary benefit of having naturally impaired memory recall at certain times of day," said Kida.

About the research

Mice are naturally nocturnal. When measured in units of time using zeitgeber, the environmental cue of light turning on, mice are usually asleep from Zeitgeber Time 1 to 12 and awake from Zeitgeber Time 12 to 24. The term "just before normally waking up" refers to Zeitgeber Time 10, while the term "just after normally going to sleep" refers to Zeitgeber Time 4.

Artificial intelligence (AI) technology developed by the RIKEN Center for Advanced Intelligence Project (AIP) in Japan has successfully found features in pathology images from human cancer patients, without annotation, that could be understood by human doctors. Further, the AI identified features relevant to cancer prognosis that were not previously noted by pathologists, leading to a higher accuracy of prostate cancer recurrence compared to pathologist-based diagnosis. Combining the predictions made by the AI with predictions by human pathologists led to an even greater accuracy.

According to Yoichiro Yamamoto, the first author of the study published in Nature Communications, "This technology could contribute to personalized medicine by making highly accurate prediction of cancer recurrence possible by acquiring new knowledge from images. It could also contribute to understanding how AI can be used safely in medicine by helping to resolve the issue of AI being seen as a 'black box.'"

The research group led by Yamamoto and Go Kimura, in collaboration with a number of university hospitals in Japan, adopted an approach called "unsupervised learning." As long as humans teach the AI, it is not possible to acquire knowledge beyond what is currently known. Rather than being "taught" medical knowledge, the AI was asked to learn using unsupervised deep neural networks, known as autoencoders, without being given any medical knowledge. The researchers developed a method for translating the features found by the AI--only numbers initially--into high-resolution images that can be understood by humans.

To perform this feat the group acquired 13,188 whole-mount pathology slide images of the prostate from Nippon Medical School Hospital (NMSH), The amount of data was enormous, equivalent to approximately 86 billion image patches (sub-images divided for deep neural networks), and the computation was performed on AIP's powerful RAIDEN supercomputer.

The AI learned using pathology images without diagnostic annotation from 11 million image patches. Features found by AI included cancer diagnostic criteria that have been used worldwide, on the Gleason score, but also features involving the stroma--connective tissues supporting an organ--in non-cancer areas that experts were not aware of. In order to evaluate these AI-found features, the research group verified the performance of recurrence prediction using the remaining cases from NMSH (internal validation). The group found that the features discovered by the AI were more accurate (AUC=0.820) than predictions made based on the human-established cancer criteria developed by pathologists, the Gleason score (AUC=0.744). Furthermore, combining both AI-found features and the human-established criteria predicted the recurrence more accurately than using either method alone (AUC=0.842). The group confirmed the results using another dataset including 2,276 whole-mount pathology images (10 billion image patches) from St. Marianna University Hospital and Aichi Medical University Hospital (external validation).

"I was very happy," says Yamamoto, "to discover that the AI was able to identify cancer on its own from unannotated pathology images. I was extremely surprised to see that AI found features that can be used to predict recurrence that pathologists had not identified."

He continues, "We have shown that AI can automatically acquire human-understandable knowledge from diagnostic annotation-free histopathology images. This 'newborn' knowledge could be useful for patients by allowing highly-accurate predictions of cancer recurrence. What is very nice is that we found that combining the AI's predictions with those of a pathologist increased the accuracy even further, showing that AI can be used hand-in-hand with doctors to improve medical care. In addition, the AI can be used as a tool to discover characteristics of diseases that have not been noted so far, and since it does not require human knowledge, it could be used in other fields outside medicine."

After a day hiking in the forest, the last thing a person wants to discover is a tick burrowing into their skin. Days after plucking off the bloodsucking insect, the hiker might develop a rash resembling a bull's-eye, a tell-tale sign of Lyme disease. Yet not everybody who contracts Lyme disease gets the rash. Now, researchers reporting in ACS Nano have devised a blood test that quickly and sensitively diagnoses the disease at early stages.

About 300,000 cases of Lyme disease, which is caused by the tick-borne bacteria Borrelia burgdorferi, are diagnosed in the U.S. each year, according to the U.S. Centers for Disease Control and Prevention. Early symptoms of the disease include the characteristic skin rash, along with fever, headache, chills and muscle aches. If not treated promptly with antibiotics, more severe symptoms, such as facial palsy, nerve pain, heart palpitations and arthritis, can occur. However, 10-20% of infected people do not develop the rash, and existing diagnostic blood tests are slow, costly or insensitive at early stages, when treatment is most effective. Aydogan Ozcan and colleagues wanted to develop a fast, easy-to-use and inexpensive blood test to diagnose Lyme disease soon after infection.

The researchers built a handheld, paper-based device to detect antibodies against the B. burgdorferi bacteria in serum samples. The device included a sensing membrane that contained several spots covering seven bacterial antigens and a synthetic peptide. Antibodies from serum samples that attached to the spots were detected with a solution that changed color, depending on the amount of antibody captured. The researchers took pictures of the color changes on a smart phone, then analyzed all of the spots with a neural network they developed that could determine whether the sample was positive or negative for Lyme disease. When tested on 50 blood samples from people with or without early-stage Lyme disease, the assay had a specificity of 96.3% and a sensitivity of 85.7%. In addition to being much more sensitive than existing tests, the assay requires 15 minutes to complete and costs only 42 cents per test.