Culture

With little cases of ethanol to preserve tissue samples for total genomic DNA analysis, a trio covered much ground in the mountains of Japan and Korea to elucidate the evolution of the scorpionfly. The rugged scientists set out to use molecular phylogenetic analysis to show that the "alpine" type of scorpionfly and "general" type must be different species. After all, the alpine type exhibit shorter wings than the general type, and alpine type females also have very dark and distinct markings on their wings.

However, what they found in the DNA surprised them.

Casually called the scorpionfly because the males have abdomens that curve upward and are shaped like the stinger of scorpions, the Panorpodes paradoxus do not sting. Tomoya Suzuki, postdoc research fellow of the Faculty of Science at Shinshu University, Suzuki's father, expert of scorpionflies, Nobuo Suzuki, professor at the Japan Women's College of Physical Education and Koji Tojo, professor at the only Institute for Mountain Science in Japan, Shinshu University, were able to indicate parallel evolutions of Japanese scorpionflies through Bayesian simulations and phylogenetic analyses.

Insects are among the most diverse organism on earth and many fall captive to their elegant beauty as did the scientists dedicated to their study. Insects are very adaptive to their habitat environments, making them excellent subjects to study ecology, evolution and morphology. Phylogenetics is the study of evolutionary history, often visualized in the form of ancestral trees. The team studied the Japanese scorpionfly by collecting samples of the Panorpodes paradoxus throughout Japan and parts of the Korean peninsula searching for samples in altitude of up to 3033 meters.

In a previous study, Professor Tojo was able to correlate plate tectonic geological events in Japan by studying the DNA of insects from a relatively small area of Nagano prefecture. By testing DNA, they discovered the different lineages align with how the land formations occurred in Japan, with some insect types having a more similar background to those on the Asian continent.

The Japanese archipelago used to be a part of mainland East Asia. About 20 million years ago, the movement of the tectonic plates caused the Japanese land mass to tear away from the continent. By around 15 million years ago, the Japanese islands were completely detached and isolated from the mainland. Ancestral lineages of the Japanese Panorpodes therefore, diverged from the continental types around this time. The two major phenotypes of scorpionflies in Japan; the "alpine" type that live in higher altitudes and have shorter wings, and their "general" type counterparts. It is hypothesized that the shorter wings are better suited for the colder climate of higher elevations. The alpine and general types also have slightly different seasonal periods when they can be observed in the wild.

Through Bayesian simulations which are estimates through probability, the divergence time of the genealogical lineages were estimated. Simulations were run for over 100 million generations. The divergence time of the continental and Japanese Panorpodes was estimated to be 8.44 million years ago. The formation of the mountains in the Japanese Archipelago which began around 5 million years ago could be seen in the estimated evolution of the alpine type of P. paradoxus. Another estimated evolution time coincided with climate change cooling times. Cool weather is a tough environment for insects and serves as a genetic selection process. The cool glacial periods encouraged local adaptation of the scorpionflies in the northeast part of the island of Honshu.

With DNA tests of the various scorpionfly specimens, the group was able to show how the P. paradoxus "ecomorphed" or evolved to have forms and structural features adapted to their ecology. This parallel evolution started about 5 million years ago, when the mountain ranges in central Japan formed. Gene flow between the samples collected at different mountains were not detected, evidence of the parallel evolution. Interestingly however, gene flow between the general and alpine types might be happening, one indicator that they are not different species.

In conclusion, the alpine type and general type were not separate species as they suspected, but the alpine scorpionfly ecomorphed, explaining why they looked different. Through a next generation sequencer the team hope to elucidate the exact moment of difference. What sort of genetic basis underlies the alpine ecomorph? What type of genes emerged to facilitate the shortening of the wings? The team hope to study the genetic basis for the ecomorph. To do so, Dr. Suzuki wishes to breed scorpionflies to further elucidate the differences in the gene expression from the alpine and general types. Breeding is necessary to perform the next generation sequencer but what the larva feeds on and other growing conditions remain a mystery. The trio hope to unlock each of these steps to further identify the unknown aspects of the Japanese scorpionfly, as well as continue cutting edge research at the Institute for Mountain Science in Japan, Shinshu University, which is blessed to be surrounded by the Alps in the heart of Japan.

Supercomputer simulations of galaxies have shown that Einstein's theory of General Relativity might not be the only way to explain how gravity works or how galaxies form.

Physicists at Durham University, UK, simulated the cosmos using an alternative model for gravity - f(R)-gravity, a so called Chameleon Theory.

The resulting images produced by the simulation show that galaxies like our Milky Way could still form in the universe even with different laws of gravity.

The findings show the viability of Chameleon Theory - so called because it changes behaviour according to the environment - as an alternative to General Relativity in explaining the formation of structures in the universe.

The research could also help further understanding of dark energy - the mysterious substance that is accelerating the expansion rate of the universe.

The findings are published in Nature Astronomy.

General Relativity was developed by Albert Einstein in the early 1900s to explain the gravitational effect of large objects in space, for example to explain the orbit of Mercury in the solar system.

It is the foundation of modern cosmology but also plays a role in everyday life, for example in calculating GPS positions in smartphones.

Scientists already know from theoretical calculations that Chameleon Theory can reproduce the success of General Relativity in the solar system.

The Durham team has now shown that this theory allows realistic galaxies like our Milky Way to form and can be distinguished from General Relativity on very large cosmological scales.

Research co-lead author Dr Christian Arnold, in Durham University's Institute for Computational Cosmology, said: "Chameleon Theory allows for the laws of gravity to be modified so we can test the effect of changes in gravity on galaxy formation.

"Through our simulations we have shown for the first time that even if you change gravity, it would not prevent disc galaxies with spiral arms from forming.

"Our research definitely does not mean that General Relativity is wrong, but it does show that it does not have to be the only way to explain gravity's role in the evolution of the universe."

The researchers looked at the interaction between gravity in Chameleon Theory and supermassive black holes that sit at the centre of galaxies.

Black holes play a key role in galaxy formation because the heat and material they eject when swallowing surrounding matter can burn away the gas needed to form stars, effectively stopping star formation.

The amount of heat spewed out by black holes is altered by changing gravity, affecting how galaxies form.

However, the new simulations showed that even accounting for the change in gravity caused by applying Chameleon Theory, galaxies were still be able to form.

General Relativity also has consequences for understanding the accelerating expansion of the universe.

Scientists believe this expansion is being driven by dark energy and the Durham researchers say their findings could be a small step towards explaining the properties of this substance.

Research co-lead author Professor Baojiu Li, of Durham University's Institute for Computational Cosmology, said: "In General Relativity, scientists account for the accelerated expansion of the universe by introducing a mysterious form of matter called dark energy -- the simplest form of which may be a cosmological constant, whose density is a constant in space and time.

"However, alternatives to a cosmological constant which explain the accelerated expansion by modifying the law of gravity, like f(R) gravity, are also widely considered given how little is known about dark energy."

The Durham researchers expect their findings can be tested through observations using the Square Kilometre Array (SKA) telescope, based in Australia and South Africa, which is due to begin observations in 2020.

SKA will be the world's largest radio telescope and aims to challenge Einstein's theory of General Relativity, look at how the first stars and galaxies formed after the Big Bang, and help scientists to understand the nature or dark energy.

Theranostics is an emerging field of medicine whose name is a combination of "therapeutics" and "diagnostics". The idea behind theranostics is to combine drugs and/or techniques to simultaneously - or sequentially - diagnose and treat medical conditions, and also monitor the response of the patient. This saves time and money, but can also bypass some of the undesirable biological effects that may arise when these strategies are employed separately.

Today, theranostics applications increasingly use nanoparticles that unite diagnostic molecules and drugs into a single agent. The nanoparticles act as carriers for molecular "cargo", e.g. a drug or a radioisotope to cancer patients undergoing radiotherapy, targeting specific biological pathways in the patient's body, while avoiding damage to healthy tissues.

Once at their target tissue, the nanoparticles produce diagnostic images and/or deliver their cargo. This is the cutting-edge technology of "nanotheranostics", which has become a major focus of research - albeit with many limitations to overcome.

Now, the lab of Sandrine Gerber at EPFL, working with physicists at the University of Geneva, have developed a new nanotheranostic system that overcomes several problems with previous approaches. The system uses "harmonic nanoparticles" (HNPs), a family of metal-oxide nanocrystals with exceptional optical properties, in particular their emission in response to excitation from ultraviolet to infrared light, and their high photostability. It was this feature that brought HNPs into nanotheranostics, when scientists were trying to solve some problems with fluorescent probes.

"Most light-activated nanotheranostic systems need high-energy UV light to excite their photoresponsive scaffolds," says Gerber. "The problem is that this results in poor penetration depth and can damage living cells and tissues, which limits biomedical applications."

The new system that Gerber's group developed avoids these problems by using silica-coated bismuth-ferrite HNPs functionalized with light-responsive caged molecular cargos. These systems can be easily activated with near-infrared light (wavelength 790 nanometers) and imaged at longer wavelength for both detection and drug release processes. Both these features render the system medically safe for patients.

Once light-triggered, the HNPs release their cargo - in this case, L-tryptophan, used as a model. The scientists monitored and quantified the release with a technique that combines liquid chromatography and mass spectrometry, covering the imaging-diagnostic part of the nanotheranostic system.

The authors state that "this work is an important step in the development of nanocarrier platforms allowing decoupled imaging in tissue depth and on-demand release of therapeutics."

By combining two well-established antibiotics for the first time, a scientific team led by Case Western Reserve University School of Medicine and Louis Stokes Cleveland VA Medical Center has delivered a "double whammy" against the pervasive Pseudomonas aeruginosa, a potentially deadly form of bacteria that is a major source of hospital-based infections.

In a recent Journal of Infectious Diseases study, investigators showed using two antibiotic drugs to fight P. aeruginosa in mouse models was significantly more effective than either antibiotic alone. The antibiotics were ceftazidime-avibactam, a combination drug used to treat a wide variety of serious bacterial infections, and fosfomycin, used to primarily treat infections of the urinary tract.

"By successfully combining these two drugs against this widespread form of bacteria, we hope to lay a foundation for eventually eradicating the infection," said the study's lead author Krisztina M. Papp-Wallace, PhD, an assistant professor of medicine at the School of Medicine and a research scientist at the Cleveland VA Medical Center. "These findings have significant implications for further studies directed at clinical applications and could bring benefits to numerous patients worldwide."

Immunocompromised patients, such as those with cancer or cystic fibrosis, burn victims and patients on ventilators, are at particular risk from the bacterium, which can be spread by the hands of health-care workers or contaminated equipment.

Bacteria and other microorganisms have increasingly developed resistance to antibiotics, making infections harder to treat and expanding the risk of contamination to others. As a result, health-care costs are also growing. Microorganisms that develop antimicrobial resistance are sometimes referred to as "superbugs." While such resistance typically occurs naturally over time, usually through spontaneous genetic changes, the misuse and overuse of antibiotics in humans and animals is accelerating this process.

The new approach described in the paper is directed at destroying enzymes in the cell wall of the bacterium. Homing in on a particular strain of P. aeruginosa known as CL232, the researchers found that, after 24 hours, the ceftazidime-avibactam-fosfomycin combination was much more effective in reducing the presence of the bacterium than the medications individually.

"Dr. Papp-Wallace's insight about combining the two antibiotics proved to be right on target," said the study's senior author, Robert A. Bonomo, MD, professor of medicine, pharmacology, molecular biology and microbiology at the School of Medicine and chief of the medical service at the Cleveland VA Medical Center. "This is superb bench-to-bedside science and has positive implications for future patients worldwide."

Irvine, Calif., July 8, 2019 -- University of California, Irvine researchers have developed and tested on mice a therapeutic treatment that uses engineered stem cells to target and kill cancer bone metastases while preserving the bone.

This new approach, reported in the journal EBioMedicine, equips engineered mesenchymal stem cells with targeting agents that drive them to bone metastatic sites, where they offload therapeutics. Link to study: https://www.sciencedirect.com/science/article/pii/S2352396419304281?via%3Dihub

"What's powerful about this strategy is that we deliver a combination of both anti-tumor and anti-bone resorption agents so we can effectively block the vicious circle between cancers and their bone niche," said the study's lead author, Weian Zhao, associate professor of pharmaceutical sciences and biomedical engineering. "This is a safe and almost nontoxic treatment compared to chemotherapy, which often leaves patients with lifelong issues."

Sandra Spivey, an Orange County patient advocate who has been living with metastatic breast cancer since 1997, has experienced firsthand the ravages of traditional treatment. "Chemotherapy can kill both cancer cells and normal cells and create drastic side effects," she said. "I have lost my hair; I have lost sensation in my hands and feet. Most of all, chemotherapy really robs you of your time. This new targeted approach could improve quality of life both during and after treatment."

The strategy could also be implemented with other bone diseases that are usually difficult to manage, such as multiple myeloma and osteoporosis.

"This study will pave the way to a clinical trial in the short term, as this type of stem cell has already been tested and deemed safe in the clinic," Zhao said. "UCI's Department of Pharmaceutical Sciences, Sue & Bill Gross Stem Cell Research Center and Chao Family Comprehensive Cancer Center are fully equipped to conduct this type of clinical trial. We will look to target patients with bone metastases."

Bottom Line: An observational study of 663 caregivers and the patients with dementia they care for suggests caregiver depression is associated with increased emergency department visits for their patients. A total of 84 caregivers had depression at the study start and it was associated with an increase in rates of emergency department use by patients after accounting for a number of other potential mitigating factors including patient age and the severity of dementia. There were 196 patients with dementia who had at least one emergency department visit in the first six months of the study. Caregiver depression was associated with an additional 0.7 emergency department visits per person-year for patients compared to caregivers without depression (1.5 vs. 0.8 visits) on an absolute scale. Limitations of the study to consider include selection bias because those caregivers with higher depression may have declined to participate. Other factors may also influence the results, including socioeconomic status. Still, the results reveal an important potential caregiver vulnerability that if overlooked in clinical encounters could neglect an important component of care and limit the ability to maximize patient outcomes.

Authors: Elan L. Guterman, M.D., of the University of California, San Francisco, and coauthors

(doi:10.1001/jamaneurol.2019.1820)

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

Bottom Line: This research letter reports on the association between the legalization of medical and recreational marijuana and teen marijuana use. Researchers used data from the Youth Risk Behavior Surveys from 1993 to 2017, when 27 states and Washington, D.C., contributed data to the survey before and after medical marijuana laws were adopted and seven states contributed data before and after recreational marijuana laws were adopted. More than 1.4 million high school students were included in the final study. The study reports medical marijuana laws weren't associated with either the likelihood of marijuana use in the past 30 days or frequent marijuana use. Recreational marijuana laws appear to be associated with a decrease in the odds of both measures of marijuana use, which may be because it is more difficult for teenagers to get marijuana if drug dealers are replaced by licensed dispensaries that require proof of age.

Author: D. Mark Anderson, Ph.D., of Montana State University, Bozeman, and coauthors

(doi:10.1001/jamapediatrics.2019.1720)

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

A global survey shows that a family of gut bacteria viruses called crAssphage is found in people - and their sewage - all over the world. Closely related viruses are found in monkeys and apes, so crAssphage has probably been with us for millions of years. These viruses are called phages, and they reproduce in bacterial cells, not in human cells. They make up the majority of gut viruses in healthy people. The work was published July 8 in the journal Nature Microbiology.

The team led byProfessor Robert Edwards from San Diego State University and Bas Dutilh from the Utrecht University in the Netherlands included 115 scientists from 65 countries and sampled every continent except Antarctica. Samuel Díaz Muñoz, assistant professor in the Department of Microbiology and Molecular Genetics participated by collecting samples in from wastewater treatment plants in New York (with collaborators at New York University), in Davis, California, and from a body of water San Juan, Puerto Rico.

Back in the lab, Díaz Muñoz amplified and sequenced genes from the crAssphage virus in his samples and sent the data to the lead authors. The virus was present in the New York and Davis samples but did not show up in Puerto Rico.

Edwards and Dutilh put their collaboration together with social media: In 2015, Edwards tweeted an invitation to anyone to donate samples. Michael Cranfield, director emeritus and chief veterinary officer for the Mountain Gorilla Veterinary Project at the UC Davis School of Veterinary Medicine, is also an author on the paper.

"True crowdsourcing and showing the importance of social media in science!" Díaz Muñoz said.

CrAssphage is not associated with positive or negative health outcomes, and may be a natural part of the human gut biota. This virus has been tested as a marker for fecal pollution in bodies of water and might one day help scientists target harmful gut bacteria.

A new breakthrough has the potential to improve sensors used to test for diseases and detect doping in sports.

An international research team led by scientists from Lancaster University have created a coating only one molecule thick that modifies the surface of sensor electrodes.

The molecule used, called beta-cyclodextrin, has a funnel shape with a hydrophobic inside and a hydrophilic outside. The combination of these two properties works together to ensure that only molecules of the correct size and type will fit inside - thus ensuring the sensor only detects substances it is tuned for.

The process, which involves electrochemically grafting the beta-cyclodextrin onto the surface of graphite electrodes, is also easy to apply - it can be added in one simple step within minutes, without any special equipment or harmful chemicals - something the researchers believe makes the process cheap and scalable.

Although the use of cyclodextrin on sensors is not new, other methods to create similar sensor coatings have been, up until now, more complex and expensive. Tests showed this new method also produces sensors around ten times more sensitive than the best existing sensors based on cyclodextrin. This means that it has the potential to detect specific molecules at much lower concentrations.

Dr Stijn Mertens, Senior Lecturer in Electrochemical Surface Science at Lancaster University's Department of Chemistry, and lead researcher, said: "This one-step modification holds substantial promise for the routine production of inexpensive, yet robust and high-performing electrochemical sensors.

"It is very selective, only picking up molecules that fit within the cyclodextrin. This is important because it means we can analyse samples without time-consuming and therefore expensive pre-treatment, such as separation from other substances. We believe that the excellent performance of the sensor may be related to its simple and well-defined structure, as the cyclodextrin is attached directly and strongly to the electrode surface."

The researchers tested the sensor on dopamine - a neurotransmitter chemical that helps to send signals between nerve cells and is therefore very important in biochemistry.

"Even though we only tested it on dopamine as a biologically relevant molecule, we expect that the sensor will work for many other small biomolecules, or drugs. This could prove useful in helping to diagnose diseases, such as Parkinson's, or detecting drugs in athletes."

The research is currently at an early proof-of-concept stage, though sensors with these coatings have the potential to be used by scientists within labs to test blood or tissue samples.

The research is outlined in the paper 'One-Step Covalent Immobilization of beta-Cyclodextrin on sp2 Carbon Surfaces for Selective Trace Amount Probing of Guests', which is published in the journal Advanced Functional Materials.

The research, which also involved researchers from KU Leuven and Ghent University in Belgium, was funded by the Fund Scientific Research-Flanders, KU Leuven and the European Research Council.

Quantum computing and quantum information processing technology have attracted attention in recently emerging fields. Among many important and fundamental issues in nowadays science, solving Schroedinger Equation (SE) of atoms and molecules is one of the ultimate goals in chemistry, physics and their related fields. SE is "First Principle" of non-relativistic quantum mechanics, whose solutions termed wave functions can afford any information of electrons within atoms and molecules, predicting their physicochemical properties and chemical reactions. Researchers from Osaka City University (OCU) in Japan, Dr. K. Sugisaki, Profs. K. Sato and T. Takui and coworkers have found a novel quantum algorithm enabling us to determine whether quantum chemical calculations performed on quantum computers give correct wave functions as exact solutions of SE in a desired manner. These issues are intractable with any currently available supercomputers. Such a quantum algorithm contributes to the acceleration of implementing practical quantum computers. Nowadays chemistry and physics have sought to predict complex chemical reactions by invoking Full-CI approaches since 1929, but never been successful until now. Now Full-CI calculations are potentially capable of predicting chemical reactions, and a new Full-CI approach suitable for predicting the physicochemical properties has already been implemented on quantum computers. Now, the possible methodological implementation of "observables on quantum computers" such as calculating the spin quantum numbers of arbitrary wave functions, which is a crucial issue in quantum chemistry, has been established by the OCU research group.

The paper has been published at 4:00 PM on July 4, 2019 (JST, Japan Time Zone) in Physical Chemistry Chemical Physics (Royal Chemical Society).

They said, "As Dirac claimed in 1929 when quantum mechanics was established, the exact application of mathematical theories to solve SE leads to equations too complicated to be soluble1. In fact, the number of variables to be determined in the Full-CI method grows exponentially against the system size, and it easily runs into astronomical figures such as exponential explosion. For example, the dimension of the Full-CI calculation for benzene molecule C6H6, in which only 42 electrons are involved, amounts to 1044, which are impossible to be dealt with by any supercomputers. What is worse, molecular systems during the dissociation process are characterized by extremely complex electronic structures (multiconfigurational nature), and relevant numerical calculations are impossible on any supercomputers. Besides these intrinsic difficulties, there has been a difficult issue in the emerging fields such as determining physical quantities relevant to quantum chemistry on quantum computers."

ANN ARBOR--If you're getting your news from a smartphone, size matters.

Heart rate variability decreases and changes in sweat are muted when viewing video news content on smaller screens. Both are indications of reduced attentiveness and engagement with content, according to a new study involving researchers at the University of Michigan and Texas A&M University.

The findings are in line with previous work focused on movie and television screens. This study, however, finds significant differences for news content, even across rather small changes in screen size.

"We are, to our knowledge, the first to find this effect for news content, and the first to focus on the move from a laptop to smartphone-size screen. This finding is of some significance given the trend towards news consumption on mobile technology," said Stuart Soroka, the Michael W. Traugott Collegiate Professor of Communication Studies and Political Science and faculty associate at the Institute for Social Research at U-M.

Soroka and colleague Johanna Dunaway, associate professor of communication at Texas A&M and the study's lead author, said that results in the current study suggest that cell phone technology may have both mobilizing and demobilizing effects.

Even as mobile technology facilitates news consumption for a large number of citizens, at almost any time and place, the reduced screen size means that news consumers may be less attentive and activated by what they are viewing, the researchers say. News consumption on small screens may be less informative and mobilizing than news consumption on larger screens, they say.

Participants watched a news program on a computer monitor, using a randomized sample of seven news stories, both international and domestic. Stories varied widely in subject matter, from a fire in Peru to a Labor Day parade to an American man making bagpipes.

The size of the video varied from roughly 13 inches wide (large) to just 5 inches wide (small). Heart rate and skin conductance was measured during viewing. Analyses find that participants had reduced reactions and attentiveness to the smaller screen.

The findings appear in Information, Communication & Society.

DUARTE, Calif. — A special blood test may one day predict if a newly diagnosed breast cancer patient will likely relapse years later, a City of Hope study suggests.
 
“This is the first success linking a solid tumor with blood biomarkers – an indicator of whether a patient will remain in remission,” said Peter P. Lee, M.D., chair of the Department of Immuno-Oncology at City of Hope and corresponding author of the study. “When patients are first diagnosed with cancer, it is important to identify those at higher risk for relapse for more aggressive treatments and monitoring. Staging and new tests based on genomics analysis of the tumor are currently available for risk stratification. However, a predictive blood test would be even more attractive but is not yet available. We are trying to change the status quo.”
 
The effectiveness of a person’s anti-tumor immune response is determined by the balance between pro-inflammatory and anti-inflammatory signaling pathways in response to cytokines, according to the July 8 Nature Immunology study. Lee and his colleagues used data on 40 breast cancer patients who were followed for a median of four years. Results were validated in a separate cohort of 38 additional breast cancer patients to create a benchmark that predicts if a breast cancer patient will likely relapse within a handful of years.
 
The balance of cytokine signaling responses in “peripheral blood immune cells” – the engine behind a healthy immune system – are indicators of the overall state of a person’s immune system, said Lee, the Billy and Audrey L. Wilder Professor in Cancer Immunotherapeutics at City of Hope.
 
“So, these findings may go beyond cancer to address other diseases the immune system must battle,” he added. “This general approach may also be useful for predicting outcomes in patients with autoimmune and infectious diseases.”
 
A cancer patient’s peripheral blood immune cells, a critical part of the immune system, tends to have decreased pro-inflammatory cytokine signaling responses and increased immune suppressive cytokine signaling responses, meaning a systemic immune environment is created that is conducive to the spread of cancer.
 
Lee and his colleagues analyzed signaling responses to many pro- and anti-inflammatory cytokines in different immune cell types that are found in peripheral blood from breast cancer patients who were newly diagnosed with the disease. They found altered signaling to four different cytokines (two pro- and two anti-inflammatory) in regulatory T cells in some patients. These cytokine signaling patterns in peripheral blood at diagnosis reflects the state of the immune system and predicts future relapse three to five years later.
 
The scientists used their data to create a cytokine signaling index (CSI), a sort of benchmark. The idea is that a patient could go in for a blood test and have their data run through an algorithm that will output a number which informs doctors what the patient’s risk of cancer recurrence is within three to five years.
 
“Knowing the chance of cancer relapse will inform doctors how aggressive a particular patient’s cancer treatment should be,” Lee said. “The CSI is an overall reflection of a patient’s immune system at diagnosis, which we now know is a major determinant of future relapse.”
 
Scientists from UCLA also contributed to the study, which was supported by the U.S. Department of Defense Breast Cancer Research Program, Stand Up to Cancer, Breast Cancer Research Foundation and the V Foundation.
# # #
 
About City of Hope
City of Hope is an independent biomedical research and treatment center for cancer, diabetes and other life-threatening diseases. Founded in 1913, City of Hope is a leader in bone marrow transplantation and immunotherapy such as CAR T cell therapy. City of Hope’s translational research and personalized treatment protocols advance care throughout the world. Human synthetic insulin and numerous breakthrough cancer drugs are based on technology developed at the institution. A National Cancer Institute-designated comprehensive cancer center and a founding member of the National Comprehensive Cancer Network, City of Hope is ranked one of America's "Best Hospitals" in cancer by U.S. News & World Report. Its main campus is located near Los Angeles, with additional locations throughout Southern California. For more information about City of Hope, follow us on Facebook, Twitter, YouTube or Instagram.

Journal

Nature Immunology

The risk of developing Alzheimer's disease increases with age. Susanne Wegmann of the German Center for Neurodegenerative Diseases (DZNE) in Berlin and colleagues have uncovered a possible cause for this connection: Certain molecules involved in the disease, termed tau-proteins, spread more easily in the aging brain. This has been determined in laboratory experiments. The current study was carried out in close collaboration with researchers in the US at Harvard Medical School and Massachusetts General Hospital. The results were recently published in the journal "Science Advances".

Alzheimer's disease usually begins with memory decline and later affects other cognitive abilities. Two different kinds of protein deposits in the patient's brain are involved in the disease: "Amyloid beta plaques" and "tau neurofibrillary tangles". The emergence of tau neurofibrillary tangles reflects disease progression: they first manifest in the brain's memory centers and then appear in other areas in the course of the disease. Tau proteins or tau aggregates probably migrate along nerve fibers and thereby contribute to the spreading of the disease throughout the brain.

Tau spreads more rapidly in aging brains

What is the role of aging in tau propagation? If the protein spread more easily in older brains, this could explain the increased susceptibility of older people to Alzheimer's disease. Wegmann and her colleagues tested this hypothesis.

Using a "gene vector" - a tailored virus particle - the scientists channeled the blueprint of the human tau protein into the brains of mice. Individual cells then began to produce the protein. Twelve weeks later, the researchers examined how far the tau protein had travelled from the production site. "Human tau proteins spread about twice as fast in older mice as compared to younger animals," Wegmann summarized the results.

The experimental part of the study was carried out in the laboratory of Bradley Hyman at Harvard Medical School in Boston, USA, where Susanne Wegmann worked for several years. In 2018, she moved to the DZNE's Berlin site, where her research group addresses various questions on tau-related disease mechanisms. Here, the major part of data analysis and summarizing the results took place.

Healthy and pathological tau

The experimental setting also allowed the scientists to analyze tau propagation in more detail. The protein exists in a healthy, soluble form in every neuron of the brain. However, in Alzheimer's disease, it can change its shape and convert into a pathological form prone to aggregate into fibrils. "It has long been thought that it is primarily the pathological form of tau that passes from one cell to the next. However, our results show that the healthy version of the protein also propagates in the brain and that this process increases in old age. Cells could also be harmed by receiving and accumulating large amounts of healthy tau," said Wegmann.

The findings from the study raise a number of questions that Wegmann will now tackle with her research group at the DZNE: Which processes underlie the increased spreading of tau in the aging brain? Is too much tau protein produced or too little defective protein removed? Answering these questions may open up new therapeutic options in the long term.

Boredom is a common human experience. But how people cope with or handle being bored is important for mental health.

"Everybody experiences boredom," said Sammy Perone, Washington State University assistant professor in the Department of Human Development. "But some people experience it a lot, which is unhealthy. So, we wanted to look at how to deal with it effectively."

The brains of people who are prone to boredom react differently, compared to those who don't, Perone and his colleagues found in a new paper recently published in the journal Psychophysiology.

Among their findings, those who experience boredom more often tend to have more anxiety and are more prone to depression.

Perone conducted his research and wrote the paper with WSU assistant professor Elizabeth Weybright and WSU graduate student Alana Anderson.

"Previously, we thought people who react more negatively to boredom would have specific brain waves prior to being bored," Perone said. "But in our baseline tests, we couldn't differentiate the brain waves. It was only when they were in a state of boredom that the difference surfaced."

That means the big difference between people who experience boredom often is how they react to a boring situation. The implication is they can be taught coping mechanisms to avoid those negative responses.

How to bore people

To study how the brain reacts to boredom, you must first get a baseline screening, then bore people almost to tears. So Perone studied 54 people in his lab, where they came in, filled out a survey, and were fitted with a special cap that measures brain waves at 128 spots on the scalp.

The survey consisted of a series of questions about boredom and how participants react to it. Next, researchers measured the brain waves of each participant with their eyes open and then eyes closed to get the baseline reading. Then the boredom started.

The subjects sat in front of a computer displaying eight pegs on the screen. Their job was to click on the peg that got highlighted. Each click turned the peg a quarter turn. Then another would be highlighted. The experiment consisted of 320 quarter turns, taking around 10 minutes.

"I've never done it, it's really tedious," Perone said. "But in researching previous experiments, this was rated as the most boring task tested. That's what we needed."

Reactions to boredom are key

When analyzing the brain wave results, researchers looked at two specific areas. The right frontal and left frontal areas of the brain are active for different reasons. Left frontal activity is higher when people are looking to engage or stimulate themselves by thinking about other things. The right frontal activity is increased when people are feeling more negative emotions or becoming more anxious.

In baseline testing, there was no difference between the people who reacted with more left brain activity vs. right brain activity. But people who answered the survey questions saying that they're more prone to experience boredom in their daily life had more right frontal brain activity as they got more bored doing the peg activity.

"We found that the people who are good at coping with boredom in everyday life, based on the surveys, shifted more toward the left," Perone said. "Those that don't cope as well in everyday life shifted more right."

Coping with boredom

There are several ways that people cope positively with boredom, Perone said. They seek out a book or something to read. They create a grocery list or think about what they're going to make for dinner, for example.

"We had one person in the experiment who reported mentally rehearsing Christmas songs for an upcoming concert. They did the peg turning exercise to the beat of the music in their head," Perone said. "Doing things that keep you engaged rather than focusing on how bored you are is really helpful."

Real-world application

The next steps for the research will involve how to get people to be more proactive in their thinking when bored.

"The results of this paper show that reacting more positively to boredom is possible," Perone said. "Now we want to find out the best tools we can give people to cope positively with being bored. So, we'll still do the peg activity, but we'll give them something to think about while they're doing it.

"It's really important to have a connection between the lab and the real world. If we can help people cope with boredom better, that can have a real, positive mental health impact."

Scientists have pinpointed the "pace" and "shape" of life as the two key elements in animal life cycles that affect how different species get by in the world. Their findings, which come from a detailed assessment of 121 species ranging from humans to sponges, may have important implications for conservation strategies and for predicting which species will be the winners and losers from the global environment crisis.

"Pace of life" relates to how fast animals reach maturity, how long they can expect to live, and the rate at which they can replenish a population with offspring. "Shape of life", meanwhile, relates to how an animal's chance of breeding or dying is spread out across its lifespan.

The scientists, from the National University of Ireland Galway, Trinity College Dublin, Oxford University, the University of Southampton, and the University of Southern Denmark, have today [Monday July 8] published their work in leading journal, Nature Ecology & Evolution.

The wide range of animal life cycles

Animal life cycles vary to a staggering degree. Some animals, such as the turquoise killifish (a small fish that can complete its life cycle in 14 days) grow fast and die young, while others, like the Greenland shark, (a fish that glides around for up to 500 years), grow slowly and have extraordinarily long lifespans.

Similarly, the spread of death and reproduction across animal life cycles also varies greatly. Salmon, for example, spawn over a short period of time with the probability of dying being particularly high both at the start of their life cycle and when they reproduce. Fulmars and some other sea birds, on the other hand, have wider time periods of reproduction and face relatively similar chances of dying throughout their lives.

Humans and Asian elephants have long lifespans and face a relatively low risk of mortality until later ages but have a fairly narrow age range for reproduction because they have long juvenile periods and live a long time after the reproductive part of their life-cycles. Both species share a similar lifespan with the Australian freshwater crocodile, but the crocodile has a completely different reproductive strategy - its reproduction is spread relatively evenly throughout its lifespan but its young have a low chance of reaching adulthood and reproducing.

The puzzle of different life cycles - why so many?

Why animal life cycles vary so much has long been an important puzzle that scientists have sought to solve. Among the reasons are that understanding why animals age, reproduce and grow at different rates may 1) help shed light on the evolution of aging itself, and 2) help identify how species will respond to global environmental change.

In their study, the scientists used population data to compare detailed life cycles for species ranging from sponges to corals, salmon to turtles, and vultures to humans. By mapping 121 life cycles, the scientists noticed that certain animal ecologies and physiologies were associated with certain life cycles.

Dr Kevin Healy who conducted the research at Trinity and is now Lecturer of Zoology at the National University of Ireland Galway, is the lead author of the study. He said: "When we mapped out the range of life cycles in the animal kingdom we saw that they follow general patterns. Whether you are a sponge, a fish or a human, your life cycle can, in general, be described by two things - how fast you live and how your reproduction and chance of dying is spread out across your lifespan."

"As we expected, species with low metabolic rates and slow modes-of-life were associated with slower life cycles. This makes sense; if you don't burn much energy per second, you are restricted in how fast you can grow. Similarly, if you are an animal that doesn't move around a lot, such as a sponge or a fish that lives on the sea bed, playing a longer game in terms of your pace of life makes sense as you may need to wait for food to come to you."

Conservation implications

The scientists also investigated whether certain life cycles made animals more susceptible to ecological threats, by looking for associations between an animal's life cycle and its position on the IUCN red list of endangered species.

Professor of Zoology and Head of the Zoology Department at Trinity, Yvonne Buckley, is co-senior author of the research. She said: "We found that extinction risks were not confined to particular types of life history for the 121 species. Despite these animals having very different ways of maintaining their populations, they faced similar levels of threat."

"Populations of a particular species, like the Chinook salmon or Freshwater crocodile, vary more in how mortality and reproduction are spread across their life-spans than they vary in their pace of life. This is important for the animal populations that we need to conserve as it suggests it may be wiser to consider actions that boost reproduction and/or impart bigger effects on the periods of the life cycles when mortality and reproduction are more likely - rather than simply aiming to extend the lifespans of these animals."

Associate Professor in Ecology at the University of Oxford, Dr Rob Salguero-Gómez, is also co-senior author of the research. He said: "This comparative work, which builds on previous research we have developed testing basic assumptions of how life structures the Plant Kingdom, highlights important commonalities in the ways that both animals and plants go about making a living and adapting to different environments. Indeed, classical works in life history theory predicted a single way to structure life strategies. Our work with plants and now here with animals shows the range of possibilities is much wider than previously believed."

"The unparalleled wealth of animal demographic schedules used in this research produced by an initiative led by Assoc. Prof Salguero-Gómez & co-author Assoc. Prof. Owen Jones, opens up new exciting ways to explore what are the most common strategies used by different species to thrive in their environments, but also to use demographic models to make predictions about what species will be the winners and losers of climate change."