Culture

ITHACA, N.Y. - Approximately one-third of all U.S. counties do not exempt grocery foods from the general sales tax, which means the lowest-income families living in those areas are most susceptible to food insecurity. New research from Cornell University finds that even a slight grocery tax-rate increase could be problematic for many.

"An increase of 1% to 4% may sound small, but after several trips to the grocery store, the extra costs can create serious burdens for the lowest-income families," said co-author Harry Kaiser, professor of applied economics and management in the Charles H. Dyson School of Applied Economics and Management. "We found that even the slightest increase in tax rate correlated to an increased likelihood of food insecurity. Grocery taxes that rose by just one percentage point led to a higher risk of hunger in households."

The study focused on sales taxes on foods at retail outlets such as grocery and convenience stores. Kaiser and his co-authors found that, across 14 states, the average grocery tax is just over 4%.

In 2020, grocery food tax policy varied at both state and county levels. A total of 17 states impose grocery taxes, and several states are debating whether to remove or impose taxes. Kaiser's group looked at data from low-income households in the 48 contiguous states plus Washington, D.C., and excluded households with annual income above $30,000.

This threshold was based on the federal poverty level, a measure that accounts for household income relative to household size. For example, in 2017 the poverty level for a single-person household was $12,060; for a two-person household, it was $16,240.

In Alabama, for example, where the grocery tax rate is as high as 9%, the average annual expense in grocery taxes is $630. For households living at or near the poverty level, this tax expense represents a sizeable portion of their household income.

Kaiser's team predicts that the average food insecurity for households with income less than $30,000 will decrease by 3.2% due to the tax removal.

"We hope that by sharing our current data and findings on grocery taxes as it relates to food insecurity," Kaiser said, "policymakers will take a much closer look at the tax burden in certain areas which are hit hardest."

It's well known that reptiles depend on temperature cues while in the egg to determine a hatchling's sex. Now, researchers writing in the journal Trends in Ecology & Evolution on May 26 say that embryos of many different animal species also rely on acoustic signals in important ways. They call this phenomenon "acoustic developmental programming."

"Acoustic developmental programming occurs when a sound informs embryos about the environment they'll encounter postnatally and changes their development to better suit this environment," said Mylene Mariette (@MyleneMariette) of Deakin University in Australia.

Because this is a newly discovered phenomenon, the evidence is just beginning to accumulate. And, yet, it seems to be rather widespread among animals.

"We have found evidence of this happening in birds, where parental calls can warn embryos about heatwaves or predators," Mariette says. "Before that, there was also evidence that cricket nymphs use male songs to predict the level of competition for mates. However, what is most striking from the evidence we've gathered is how common it is for embryos across species to rely on sound information.

"For example," she adds, "across all animal groups that lay eggs, such as insects, frogs, reptiles and birds, embryos use sound or vibration to know when the best time is to hatch. This suggests that acoustic developmental programming is likely to happen in many animal species and for a whole range of conditions. But, until recently, we did not know it was happening."

Mariette got interested in acoustic developmental programming while studying how zebra finch parents communicate with each other through calls to coordinate parental care duties. "I noticed that when a parent was alone incubating, it would sometimes produce a strange high-pitched call," she says.

She wondered if those calls had further implications for the developing embryos. To find out, she captured many audio recordings in nests and played them to eggs incubated artificially in the lab. It turned out that the finch parents only produced that particular call when it was very hot out. Upon hearing it from inside the egg, nestlings adjusted their development to prepare for the heat.

"I became very curious about how just hearing a sound before hatching could alter development," Mariette says.

She started searching for evidence in the literature of embryos using sound in other animals. She also dug into the neurobiology to try and understand how it could happen. So far, it's not clear exactly how it works, but the new report identifies some likely mechanisms.

"In crickets, when developing nymphs hear many sexy songs, female develop quickly to make the most of the opportunity, whereas males delay metamorphosis to grow bigger and invest more in reproduction," Mariette says. "In zebra finches, embryos exposed to parental heat calls grow less to reduce the physiological damage of heat exposure, which then allows them to produce more babies at adulthood. But embryos cannot decide to change their development, it just happens.

"This is because sound directly impacts behavior and physiology, without any conscious processing," she continues. "This is why, for example, music triggers spontaneous emotions of sadness or happiness, without us having to remember which movie that soundtrack came from, or in fact without us even noticing our reaction to the music. It seems to occur on its own, because there are direct connections in the brain between the auditory pathway and the areas that control emotion, reflex learning, and hormone production, so the higher cortical areas do not need to decode the information. Sound experienced early in life could trigger the same spontaneous reactions and, in fact, have long-lasting effects, because this is when the brain is developing, and consolidating connections. For the same reason, the downstream effects on physiology and then morphology can persist for life."

The bottom line for now is that sound has a much more profound impact on development than had been realized. Mariette suggest that it may be important to preserve natural soundscapes that may be crucial for animal adaptation, particularly in fast-changing environments.

Mariette's lab continues to study the physiological traits in zebra finches that may be affected by heat-calls. "It is quite amazing that sound alone can prepare babies for heat, particularly given the alarming rate of climate change," she says.

Skokie, IL - The International Society for Stem Cell Research (ISSCR), today released updated guidelines for stem cell research and its translation to medicine. The update reflects emerging advances including, stem cell-based embryo models, human embryo research, chimeras, organoids, and genome editing.

"The 2021 update presents practical advice for oversight of research posing unique scientific and ethical issues for researchers and the public," said Robin Lovell-Badge, PhD, FRS, Chair, ISSCR Guidelines task force and Senior Group Leader and Head of the Division of Stem Cell Biology and Developmental Genetics at The Francis Crick Institute, UK. "They provide confidence to researchers, clinicians, and the public alike that stem cell science can proceed responsibly, ethically, and remain responsive to public and patient interests," he said.

Scientists, research organizations, and scientific journals have long relied upon the ISSCR Guidelines as the international standard for scientific and ethical rigor, oversight, and transparency in stem cell research. The guidelines also provide a basis for implementation of new regulatory frameworks in countries without existing oversight systems. Adherence to the guidelines provides assurance that research is conducted with integrity and new therapies are safe, effective, and evidence-based.

"This is a significant update, building upon the society's longstanding commitment to excellence in all areas of stem cell research." said Christine Mummery, PhD, ISSCR president and professor of Developmental Biology at Leiden University Medical Center, the Netherlands. "The updates address new methods of understanding fundamental biological processes that may ultimately lead to the alleviation of debilitating diseases and disorders."

The 2021 ISSCR Guidelines update is the result of a two-year collaboration with international experts and respected leaders in areas of stem cell science, ethics, and law, and was peer-reviewed by scientists and ethicists from 14 countries. They are publicly available at isscr.org/guidelines.

Additional information is available here:

"Why stem cell guidelines needed an update: New criteria aim to reassure the public to permit progress in contentious research," by Lovell-Badge (Nature), publishing on 26 May 2021, 11:00 a.m. EDT

"ISSCR Guidelines for Stem Cell Research and Clinical Translation: The 2021 Update," by Lovell-Badge et al., ISSCR Guidelines Taskforce (Stem Cell Reports), under embargo until 26 May 2021, 11:00 a.m. EDT. Publishing on 27 May 2021, 11:00 a.m. EDT. 10.1016/j.stemcr.2021.05.012

"Human Embryo Research, Stem Cell-derived Embryo Models and In Vitro Gametogenesis: Considerations Leading to the Revised ISSCR Guidelines," Clark et al., (Stem Cell Reports), under embargo until 26 May 2021, 11:00 a.m. EDT. Publishing on 27 May 2021, 11:00 a.m. EDT. 10.1016/j.stemcr.2021.05.008

"ISSCR Guidelines for the Transfer of Human Pluripotent Stem Cells and Their Direct Derivatives into Animal Hosts," by Hyun et al. (Stem Cell Reports), under embargo until 26 May 2021, 11:00 a.m. EDT. Publishing on 27 May 2021, 11:00 a.m. EDT. 10.1016/j.stemcr.2021.05.005

"ISSCR's Guidelines for Stem Cell Research and Clinical Translation: Supporting the Development of Safe and Efficacious Stem Cell-Based Interventions," by Turner (Stem Cell Reports), under embargo until 26 May 2021, 11:00 a.m. EDT. Publishing on 27 May 2021, 11:00 a.m. EDT. 10.1016/j.stemcr.2021.05.011

Communities benefit from sharing knowledge and experience among their members. Following a similar principle - called "swarm learning" - an international research team has trained artificial intelligence algorithms to detect blood cancer, lung diseases and COVID-19 in data stored in a decentralized fashion. This approach has advantage over conventional methods since it inherently provides privacy preservation technologies, which facilitates cross-site analysis of scientific data. Swarm learning could thus significantly promote and accelerate collaboration and information exchange in research, especially in the field of medicine. Experts from the DZNE, the University of Bonn, the information technology company Hewlett Packard Enterprise (HPE) and other research institutions report on this in the scientific journal Nature.

Science and medicine are becoming increasingly digital. Analyzing the resulting volumes of information - known as "big data" - is considered a key to better treatment options. "Medical research data are a treasure. They can play a decisive role in developing personalized therapies that are tailored to each individual more precisely than conventional treatments," said Joachim Schultze, Director of Systems Medicine at the DZNE and professor at the Life & Medical Sciences Institute (LIMES) at the University of Bonn. "It's critical for science to be able to use such data as comprehensively and from as many sources as possible."

However, the exchange of medical research data across different locations or even between countries is subject to data protection and data sovereignty regulations. In practice, these requirements can usually only be implemented with significant effort. In addition, there are technical barriers: For example, when huge amounts of data have to be transferred digitally, data lines can quickly reach their performance limits. In view of these conditions, many medical studies are locally confined and cannot utilize data that is available elsewhere.

Data Remains on Site

In light of this, a research collaboration led by Joachim Schultze tested a novel approach for evaluating research data stored in a decentralized fashion. The basis for this was the still young "Swarm Learning" technology developed by HPE. In addition to the IT company, numerous research institutions from Greece, the Netherlands and Germany - including members of the "German COVID-19 OMICS Initiative" (DeCOI) - participated in this study.

Swarm Learning combines a special kind of information exchange across different nodes of a network with methods from the toolbox of "machine learning", a branch of artificial intelligence (AI). The linchpin of machine learning are algorithms that are trained on data to detect patterns in it - and that consequently acquire the ability to recognize the learned patterns in other data as well. "Swarm Learning opens up new opportunities for collaboration in medical research, as well as in business. The key is that all participants can learn from each other without having to share confidential data," said Dr. Eng Lim Goh, Senior Vice President and Chief Technology Officer for artificial intelligence at HPE.

In fact, with Swarm Learning, all research data remains on site. Only algorithms and parameters are shared - in a sense, lessons learned. "Swarm Learning fulfills the requirements of data protection in a natural way," Joachim Schultze emphasized.

Collaborative Learning

Unlike "federated learning", in which the data also remains locally, there is no centralized command center, the Bonn scientist explained. "Swarm Learning happens in a cooperative way based on rules that all partners have agreed on in advance. This set of rules is captured in a blockchain." This is a kind of digital protocol that regulates information exchange between the partners in a binding manner, it documents all events and all parties have access to it. "The blockchain is the backbone of Swarm Learning," Schultze said. "All members of the swarm have equal rights. There is no central power over what happens and over the results. So there is, in a sense, no spider controlling the data web."

Thus, the AI algorithms learn locally, namely on the basis of the data available at each network node. The learning outcomes of each node are collected as parameters through the blockchain and smartly processed by the system. The outcome, i. e. optimized parameters, are passed on to all parties. This process is repeated multiple times, gradually improving the algorithms' ability to recognize patterns at each node of the network.

Lung Images and Molecular Features

The researchers are now providing practical proof of this approach through the analysis of X-ray images of the lungs and of transcriptomes: The latter are data on the gene activity of cells. In the current study, the focus was specifically on immune cells circulating in the blood - in other words, white blood cells. "Data on the gene activity of blood cells are like a molecular fingerprint. They hold important information about how the organism reacts to a disease," Schultze said. "Transcriptomes are available in large numbers just like X-ray images, and they are highly complex. This is exactly the kind of information you need for artificial intelligence analysis. Such data is perfect for testing Swarm Learning."

The research team addressed a total of four infectious and non-infectious diseases: two variants of blood cancer (acute myeloid leukemia and acute lymphoblastic leukemia), as well as tuberculosis and COVID-19. The data included a total of more than 16,000 transcriptomes. The swarm learning network over which the data were distributed typically consisted of at least three and up to 32 nodes. Independently of the transcriptomes, the researchers analyzed about 100,000 chest X-ray images. These were from patients with fluid accumulation in the lung or other pathological findings as well as from individuals without anomalies. These data were distributed across three different nodes.

A High Rate of Success

The analysis of both the transcriptomes and the X-ray images followed the same principle: First, the researchers fed their algorithms with subsets of the respective data set. This included information about which of the samples came from patients and which from individuals without findings. The learned pattern recognition for "sick" or "healthy" was then used to classify further data, in other words it was used to sort the data into samples with or without disease. The accuracy, i.e. the ability of the algorithms to distinguish between healthy and diseased individuals, was around 90 percent on average for the transcriptomes (each of the four diseases was evaluated separately); in the case of the X-ray data, it ranged from 76 to 86 percent.

"The methodology worked best in leukemia. In this disease, the signature of gene activity is particularly striking and thus easiest for artificial intelligence to detect. Infectious diseases are more variable. Nevertheless, the accuracy was also very high for tuberculosis and COVID-19. For X-ray data, the rate was somewhat lower, which is due to the lower data or image quality," Schultze commented on the results. "Our study thus proves that Swarm Learning can be successfully applied to very different data. In principle, this applies to any type of information for which pattern recognition by means of artificial intelligence is useful. Be it genome data, X-ray images, data from brain imaging or other complex data."

The study also found that Swarm Learning yielded significantly better results than when the nodes in the network learned separately. "Each node benefits from the experience of the other nodes, although only local data is ever available. The concept of Swarm Learning has thus passed the practical test," Schultze said.

A Vision for the Future

"I am convinced that swarm learning can give a huge boost to medical research and other data-driven disciplines. The current study was just a test run. In the future, we intend to apply this technology to Alzheimer's and other neurodegenerative diseases," Schultze said. "Swarm Learning has the potential to be a real game changer and could help make the wealth of experience in medicine more accessible worldwide. Not only research institutions but also hospitals, for example, could join together to form such swarms and thus share information for mutual benefit."

New research published in Nature provides a powerful yet surprisingly simple way to determine the number of visitors to any location in a city.

Scientists* from the Santa Fe Institute, MIT, and ETH Zürich have discovered and developed a scaling law that governs the number of visitors to any location based on how far they are traveling and how often they are visiting. The visitation law opens up unprecedented possibilities for accurately predicting flows between locations, which could ultimately have applications in everything from city planning to preventing the spread of the next major pandemic.

"Imagine you are standing on a busy plaza, say in Boston, and you see people coming and going. This may look pretty random and chaotic, but the law shows that these movements are surprisingly structured and predictable. It basically tells you how many of these people are coming from 1, 2 or 10 kilometers away and how many are visiting once, twice or 10 times a month", says lead author Markus Schläpfer of ETH Zurich's Future Cities Laboratory. "And the best part is that this same regularity holds not only in Boston, but across cities worldwide."

The researchers' findings are a result of an analysis of mobile phone data from millions of anonymized cell phone users in highly diverse urban regions across the world, including Greater Boston in the United States, Lisbon in Europe, Singapore in Asia, and Dakar in Africa. Schläpfer began the analysis and development of the theory while he was a post-doctoral fellow at the Santa Fe Institute working together with senior author Geoffrey West, a physicist who leads the Cities, Scaling, and Sustainability project. It was later extended to include researchers at the MIT Sensible Cities Laboratory under the leadership of the architect Carlo Ratti.

Universally, they found that the number of visitors to any urban location scales as the inverse square of both travel distance from home and the visitation frequency. Like the gravitational pull of a large planet, an attractive city plaza with fine museums and famous shops draws relatively more visitors from more distant locations, though less frequently than those coming from nearby locations, their relative numbers being predictably determined by the inverse square law. A further surprising consequence of this new visitation law is that the same number of people visit the location whether they are coming from, say, 10km away 3 times a week, or from 3km away 10 times a week.

While previous research has used mobile phone data to study human movement from the perspectives of individual people -- where they go, when, and how often -- this is the first systematic study to focus on the frequency of visits from the perspective of places, using mobile phone data to understand the relative attractiveness or utility of an urban area.

"There's an optimization problem going on here in terms of the amount of energy people are using, the distance they're travelling, and the number of trips they're making," says Geoffrey West. "When we travel for leisure we choose our destinations. During everyday life, those choices are more forced because we have to go to work, say, five times a week, pick up the kids two times, etc. But there's this remarkable conservation inherent in the visitation law -- namely, the average amount of energy that people allocate to travel is the same whether they try to do it across different distances or at different frequencies."

Schläpfer says the new paper can give urban planners "a baseline for understanding which locations in their cities are over- or under-performing," in terms of the number of people they attract. It can inform planners about where to add amenities like parks and restaurants, or how much public transportation is needed for new urban developments.

The law of visitation joins a growing body of research in the science of cities, which SFI researchers and their collaborators have pioneered since 2007, when they first uncovered universal laws governing growth, innovation, and the pace of life in cities.

"All of the problems that we face, especially climate change are generated in cities because that's where the people are," West says. "So understanding cities, and how people move within them, plays into fundamental questions about the future of life on this planet."

What The Study Did: Researchers conducted a review of studies examining the frequency and variety of persistent symptoms after COVID-19 infection.

Authors: Steven N. Goodman, M.D., M.H.S., Ph.D., of Stanford University in Stanford, California, is the corresponding author.

To access the embargoed study: Visit our For The Media website at this link https://media.jamanetwork.com/

(doi:10.1001/jamanetworkopen.2021.11417)

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

In the human gut, good bacteria make great neighbors.

A new Northwestern University study found that specific types of gut bacteria can protect other good bacteria from cancer treatments -- mitigating harmful, drug-induced changes to the gut microbiome. By metabolizing chemotherapy drugs, the protective bacteria could temper short- and long-term side effects of treatment.

Eventually, the research could potentially lead to new dietary supplements, probiotics or engineered therapeutics to help boost cancer patients' gut health. Because chemotherapy-related microbiome changes in children are linked to health complications later in life -- including obesity, asthma and diabetes -- discovering new strategies for protecting the gut is particularly important for pediatric cancer patients.

"We were really inspired by bioremediation, which uses microbes to clean up polluted environments," said Northwestern's Erica Hartmann, the study's senior author. "Usually bioremediation applies to groundwater or soil, but, here, we have applied it to the gut. We know that certain bacteria can breakdown toxic cancer treatments. We wondered if, by breaking down drugs, these bacteria could protect the microbes around them. Our study shows the answer is 'yes.' If some bacteria can break down toxins fast enough, that provides a protective effect for the microbial community."

The research will be published on May 26 in the journal mSphere.

Hartmann is an assistant professor of environmental biology at Northwestern's McCormick School of Engineering. Ryan Blaustein, a former postdoctoral fellow in Hartmann's laboratory, is the paper's first author. He is now a postdoctoral fellow at the National Institutes of Health.

Although cancer treatments are life-saving, they also cause profoundly harsh and painful side effects, including gastrointestinal issues. Chemotherapies, in particular, can obliterate the healthy, "good" bacteria in the human gut.

"Chemotherapy drugs do not differentiate between killing cancer cells and killing microbes," Hartmann said. "Microbes in your gut help digest your food and keep you healthy. Killing these microbes is especially harmful for children because there's some evidence that disruption in the gut microbiome early in life can lead to potential health conditions later in life."

Working with Dr. Patrick Seed, a professor of pediatrics and microbiology-immunology at the Northwestern University Feinberg School of Medicine, Hartmann's lab learned from Raoultella planticola. Naturally occurring in the human gut in low abundances, Raoultella planticola can break down chemotherapy drug doxorubicin, which has been demonstrated in other research.

To test whether or not this breakdown effect could protect the entire microbiome, the team developed simplified microbial communities, which included various types of bacteria typically found in the human gut. The "mock gut communities" included bacteria strains (Escherichia coli and Klebsiella pneumoniae) that are good at breaking down doxorubicin, strains (Clostridium innocuum and Lactobacillus rhamnosus) that are especially sensitive to doxorubicin and one strain (Enterococcus faecium) that is resistant to doxorubicin but does not break it down.

The team then exposed these mock gut communities" to doxorubicin and found increased survival among sensitive strains. The researchers concluded that, by degrading doxorubicin, certain bacteria made the drugs less toxic to the rest of the gut.

Although the research highlights a promising new pathway for potentially protecting cancer patients, Hartmann cautions that translating the new findings into treatments is still far off.

"There are several eventual applications that would be great to help cancer patients -- particularly pediatric patients -- not experience such harsh side effects," she said. "But we're still far from actually making that a reality."

Flowering plants (angiosperms) dominate most terrestrial ecosystems, providing the bulk of human food. However, their origin has been a mystery since the earliest days of evolutionary thought.

Angiosperm flowers are hugely diverse. The key to clarifying the origin of flowers and how angiosperms might be related to other kinds of plants is understanding the evolution of the parts of the flower, especially angiosperm seeds and the fruits in which the seeds develop.

Fossil seed-bearing structures preserved in a newly discovered Early Cretaceous silicified peat in Inner Mongolia, China, provide a partial answer to the origin of flowering plants, according to a study led by Prof. SHI Gongle from the Nanjing Institute of Geology and Paleontology of the Chinese Academy of Sciences (NIGPAS).

The study was published in Nature on May 26.

The fossils, which date from about 126 million years ago, support an earlier idea that the distinctive outer covering of developing seeds of flowering plants--the so-called second integument--is fundamentally comparable to structures that occur in certain extinct non-angiosperm seed plants from the "Age of Dinosaurs."

The seeds of cycads, ginkgo and conifers are enclosed and protected by a single integument, which is believed to correspond to the inner integument in flowering plants. However, the outer (second) integument is a unique structure. Its development is linked to its curious recurved form and is controlled by different genes than those responsible for the development of the inner integument.

These fossils, exceptionally well preserved and abundant in the silicified peat from China, have two seeds enclosed inside a specialized recurved structure--the cupule.

Similar cupules occur in several groups of extinct plants from the Mesozoic that are known only from fossils, and while it has been suggested some of these cupules may be precursors of the second integument of flowering plants, discussions have been hampered by inadequate information.

The new fossils from China, along with the reexamination of previously described fossils, suggest that the recurved cupules found in several groups of extinct seed plants from the Mesozoic are all fundamentally similar and are likely the precursors of the second integument of flowering plants.

The recurved structure seen in the young seeds of flowering plants is therefore a holdover from an earlier pre-angiosperm phase of evolution. Variation among extinct Mesozoic seed plants in the number of seeds per cupule and other features likely reflect differences relating to pollination, as well as seed output, protection and dispersal.

Recognition of extinct seed plants with a structure comparable to a key feature of living angiosperms provides a partial answer to the question of flowering plant origins. It also helps focus future work on understanding how living and fossil groups of seed plants are interrelated, and has important implications for ideas on the origin of another diagnostic feature of flowering plants that evidently came later--the carpel--the structure that forms the fruit wall in which the seeds develop.

LEXINGTON, Ky. (May 26, 2021) - Using novel imaging methods for studying brain metabolism, University of Kentucky researchers have identified the reservoir for a necessary sugar in the brain. Glycogen serves as a storage depot for the sugar glucose. The laboratories of Ramon Sun, Ph.D., assistant professor of neuroscience, Markey Cancer Center at the University of Kentucky College of Medicine, and Matthew Gentry, Ph.D., professor of molecular and cellular biochemistry and director of the Lafora Epilepsy Cure Initiative at the University of Kentucky College of Medicine discovered that glucose - the sugar used for cellular energy production - was not the only sugar contained in glycogen in the brain. Brain glycogen also contained another sugar called glucosamine. The full study was recently published in Cell Metabolism.

Some forms of glucosamine, such as glucosamine sulfate and glucosamine hydrochloride, are common supplements used to improve joint movement. However, within cells, glucosamine is an essential sugar needed for the complex carbohydrate chains that are attached to proteins in a process called glycosylation. These sugar chains decorate proteins and the sugar decorations are critical for the appropriate function of myriad proteins.

Discovering that glucosamine is a major component of brain glycogen provides key insight into neurological diseases caused by aberrant glycogen-like cellular aggregates called polyglucosan bodies (PGBs). Lafora disease is a rare, inherited childhood dementia caused by PGBs and this study demonstrates that the Lafora disease PGBs sequester glucosamine, leading to numerous cellular perturbations. PGBs also accumulate in the brain as people age and in people with other forms of dementia. Thus, the discovery that glycogen is also a storage cache for glucosamine has broad implications for understanding neurological changes associated with aging.

Using biochemical approaches, the researchers determined the sugar composition of glycogen in the muscle, liver, and brain of mice. Unlike muscle glycogen, which had only 1% glucosamine, and liver glycogen, which had less than 1% glucosamine, brain glycogen contained 25% glucosamine. "The discovery that brain glycogen is comprised of 25% glucosamine was stunning," stated Sun.

Upon making this surprising discovery, they then identified the enzymes responsible for incorporating glucosamine into glycogen and for releasing glucosamine from glycogen. Again, the discovery was unexpected as these enzymes are the same ones used to incorporate glucose into and release glucose from glycogen.

To understand the implications of their findings for Lafora disease and neurological problems arising from PGBs, the researchers used their newly developed technique called matrix-assisted laser desorption/ionization traveling-wave ion-mobility high-resolution mass spectrometry (MALDI TW IMS) to measure and visualize the amount of glycogen in different regions of the brain. They also used this technique to quantify changes in the specific patterns of the sugar decorations on proteins in multiple regions of the brain.

The team applied MALDI TW IMS to analyze the brains of healthy mice and of two different mouse models of glycogen storage diseases: a model of Lafora disease and a model of glucose storage disease (GSD) type III. Sun commented, "This new technique allows us to quantify the amount of these sugars with high accuracy while also maintaining the spatial distribution within the brain regarding where the sugars are located. It is crucial that the brain has the correct sugars in the right location within the brain."

These studies revealed that without the ability to properly regulate brain glycogen metabolism, not only do PGBs form, which perturbs cell metabolism, but the sugar decoration of proteins is also altered. Excitingly, they could restore protein sugar decoration by injecting an antibody-enzyme fusion (VAL-0417) into the brains of Lafora disease mice to degrade the PGBs. Their findings show a direct connection between abnormal glycogen storage and defective protein function in the brain. Their findings have implications for many other GSDs and congenital disorders of glycosylation, which cause severe neurological symptoms, including epilepsy and dementia.

"Multiple neurological diseases have blockades in these metabolic pathways. I'm sure these pathways are going to be important in other neuro-centric diseases as well. Brain glycogen is comprised of glucose and glucosamine and brain metabolism has to balance both in order to stay healthy," explained Gentry.

The Gentry and Sun laboratories collaborated with several others from UK College of Medicine including Drs. Craig Vander Kooi, professor of molecular and cellular biochemistry, Charles Waechter, professor of molecular and cellular biochemistry, Lance Johnson, assistant professor of physiology, Christine Brainson, assistant professor of toxicology and cancer biology. They also worked with researchers from Indiana University School of Medicine including Drs. Anna A. DePaoli-Roach, professor of biochemistry and molecular biology, Peter J. Roach, professor of biochemistry and molecular biology, Thomas D. Hurley, professor of biochemistry and molecular biology. Richard Taylor, professor of chemistry and biochemistry, from the University of Notre Dame, and Richard Drake, professor of cell and molecular pharmacology and experimental therapeutics from the Medical University of South Carolina, also contributed to this work.

"This type of transdisciplinary collaborative research takes place at UK because of strong leadership from College of Medicine Dean Robert DiPaola, Dr. Mark Evers, Vice President for Research Lisa Cassis, Ph.D. and others," stated Sun.

Berkeley -- The lifestyle of the horned passalus beetle, commonly known as the bessbug or betsy beetle, might seem downright disgusting to the average human: Not only does this shiny black beetle eat its own poop, known as frass, but it uses its feces to line the walls of its living space and to help build protective chambers around its developing young.

Gross as it may seem, a new study suggests that this beetle's frass habits are actually part of a clever strategy for protecting the insect's health -- and could help inform human medicine, too.

Researchers at the University of California, Berkeley, have discovered that the frass of the horned passalus beetle is teeming with antibiotic and antifungal chemicals similar to the ones that humans use to ward off bacterial and fungal infections. These compounds are produced by a host of beneficial bacteria called actinomycetes that live in the beetle's frass and that appear to be passed from beetle to beetle, and from colony to colony, via the process of coprophagy -- the technical term for eating poop.

Understanding the symbiotic relationship between bessbug beetles, actinomycetes and their antimicrobial compounds could help speed the search for new antibiotic drugs, and help doctors create better strategies for preventing the rise of antibiotic-resistant infections, the researchers said.

"Most of the antibiotics and antifungals that humans take are actually made by microbes, and we're really interested in how microbes are using these molecules in the environment," said study senior author Matthew Traxler, an assistant professor of plant and microbial biology at UC Berkeley. "When scientists discover a new antibiotic and bring it into the clinic, it often only takes a few years before the pathogen population starts to develop antibiotic resistance. But these microbes have been using the same molecules for millions of years, and that tells us that the way the microbes are using them is different from how we use them."

With the discovery, bessbug beetles join a handful of other insects, including leaf-cutter ants, southern pine beetles and beewolves, or bee-killer wasps, that benefit from symbiotic relationships with actinomycete bacteria. Leaf-cutter ants and beewolves have even evolved special structures in their bodies -- in their thoraxes and antennae, respectively -- to carry these microbes.

No special structures for harboring bacteria have been identified on the bessbug beetle, but that may be the beetle's advantage. While the ants and wasps are each known to associate with only one specific species of actinomycete bacteria, the researchers identified more than 30 actinomycete species associated with bessbug beetle "galleries," the hollowed-out tunnels inside dead logs where they live. The greater diversity of actinomycetes in bessbug beetle frass appears to contribute to a greater diversity of protective antibiotics and antifungals in their galleries.

"We collected samples from galleries all over the southern and eastern U.S., and for almost all of them, we were able to detect some form of antibiotic. This was really surprising, because these compounds are usually very difficult to detect in the environment," said study lead author Rita de Cassia Pessotti, who completed the research as a postdoctoral researcher at UC Berkeley. "We think that we are seeing larger diversity of molecules because there's a more diverse set of bacteria, as well."

Having a diversity of antibiotic and antifungal compounds all working in tandem may be one of the reasons why these chemicals are able to stay ahead in the evolutionary battle against pathogens, the researchers said.

"When humans take antibiotics to treat diseases, we usually just take a single molecule, and that means that whatever pathogen we are fighting only has to become resistant to one compound," Traxler said. "But in these galleries, there are a variety of these molecules for a pathogen to overcome. On top of that, sometimes the molecules can work synergistically, meaning they become more potent when added together against a specific pathogen. This can make it very difficult for a pathogen to outsmart them, even over ecological and evolutionary time spans."

A cross-country trek in search of beetles

Before Traxler and Pessotti began their study, the complex digestive system of the bessbug beetle had already caught the attention of Javier Ceja-Navarro and Eoin Brodie, research scientists at Lawrence Berkeley National Laboratory. Ceja-Navarro and Brodie were intrigued by the beetle's ability to convert tough, difficult-to-digest plant polymers, like lignin and cellulose, into nutrient-rich frass, a digestive process that could inspire new ways to convert woody by-products into useful biofuels. To study this process, Ceja-Navarro and Brodie maintained an active bessbug beetle gallery in their lab.

Traxler and Pessotti were searching for a way to study actinomycete bacteria in the wild, and learned that actinomycetes had been found living in the guts of tropical beetles closely related to the bessbug beetle. They decided to ask Ceja-Navarro and Brodie, friends and colleagues of theirs, if they could test their beetles for the bacteria.

"I collected samples from all over the beetles and their gallery -- I even washed a beetle's mouth with some buffers to see what was in there -- and no matter where the sample came from, I always found the same species of Streptomyces," a type of actinomycete bacteria, Pessotti said. "We were pretty surprised that it was so common."

This strain of Streptomyces bacteria wasn't unique to Ceja-Navarro's beetles. Pessotti discovered that she could mail order bessbug beetles online -- "If you want to have a pet beetle, you can," she said -- and found that these beetles, originally from Georgia and North Carolina, also carried the same species of Streptomyces.

However, it took a trip to Oklahoma to finally convince Traxler and Pessotti that bessbug beetles could provide the ideal system for studying actinomycetes. After Traxler spotted Facebook photos of a beetle gallery located in his cousin's backyard in Oklahoma, Pessotti flew to the state to collect her first set of samples from beetles in the wild.

Sure enough, the Oklahoma beetles harbored now-familiar species of Streptomyces.

"That finding is what gave us the courage to go out and do this giant sampling trip, which in itself was a tremendous feat," Traxler said. "Rita is from Brazil, but at this point, I think she's probably visited more states in the U.S. than I have."

Pessotti spent a month crisscrossing the Southeastern U.S., trekking through forests to locate beetle galleries and gather samples to take back to the lab in Berkeley. In the end, she collected samples from a total of 22 galleries spread across 11 states.

In addition to managing logistical challenges -- like rerouting part of her trip at the last minute to avoid Hurricane Florence -- Pessotti also had to teach herself how to spot beetle galleries amidst the detritus of the forest floor. In the beginning, she made ample use of the cell phone app iNaturalist, in which naturalists and lay people alike can upload photos and descriptions of plants and animals, geotagged to their location.

The key to finding bessbug beetle galleries, she soon learned, is to keep an eye out for their sawdust-like frass.

"You don't need to go super far into the forest to find a beetle gallery -- I've actually found some next to trails," Pessotti said. "Usually, you can see tiny holes on the surface of a log with frass coming out of them, and frass all over the log and on the ground. And if you see evidence of frass by a log, that is a good hint there probably is a beetle in there."

The protective power of poop

Back in the lab, Pessotti isolated more than 300 strains of actinomycete bacteria from her gallery samples and detected antifungal and antibiotic compounds in all but one.

With the help of former UC Berkeley undergraduate student Jewel Reaso, Pessotti also devised a special experiment to confirm that actinomycete bacteria actually do help protect the beetles from infection. In the assay, Pessotti mixed sterilized beetle frass with a strain of Streptomyces isolated from the beetle galleries inside a test tube. She then exposed the frass to a fungal beetle pathogen she had collected during her field trip and observed what happened over the course of a week.

"I was super-lucky that doing the trip: I spotted a dead beetle laying on the top of a log -- it was like the beetle was waiting for me. And this dead beetle had a white/green material coming out of its body that I thought could be some sort of fungus," Pessotti said. "So, I brought this dead beetle to the lab, isolated the microbe that was responsible for the green/white material, and it turned out to be a strain of Metarhizium anisopliae, a fungal pathogen that can kill insects."

Pessotti's experiments showed that sterilized frass that had been mixed with Streptomyces bacteria was better able to resist the growth of the Metarhizium anisopliae pathogen than sterilized frass on its own, even in warm, damp conditions similar to that of a decaying log. Her findings confirmed that the antibiotic and antifungal molecules produced by actinomycete bacteria can, in fact, help ward off beetle pathogens found in the wild.

The results shine a new light on bessbug beetles' close relationship with their own poop: When the beetles use frass to line their galleries and to construct protective chambers around their developing larvae, they are actually defending themselves against fungal and bacterial pathogens that might otherwise thrive in the decaying logs where they build their homes. And when the beetles eat their own frass, and feed it to their young, they are ensuring that the bacteria stick around to benefit a new generation.

Traxler plans to continue studying the microbial communities associated with beetle galleries, both to better understand how the relationship between beetles and actinomycetes has evolved, and to potentially discover new antibiotics that can be used in human medicine.

"If you're out there in the world, and you see one of these bessbug beetles or their galleries, I hope you recognize that it's full of antibiotics and antifungals," Traxler said. "And, the beetles are using theses in a way that's pretty similar to how we would use them ourselves -- which is pretty cool."

In a new study, scientists at The Hong Kong University of Science and Technology (HKUST) have revealed that most T cell epitopes known to be targeted upon natural infection are seemingly unaffected by current SARS-CoV-2 variants.

In their latest research, the team compiled and analysed data from 18 immunological studies of T cell responses involving over 850 recovered COVID-19 patients from across four continents who are well-distributed in age, gender, disease severity and blood collection time. They demonstrated that T cells in these patients targeted fragments (epitopes) of almost all of the virus' proteins, including the spike protein that is a main target of many existing vaccines. As an important finding, based on analysis of over 850,000 SARS-CoV-2 genetic sequences from around the world, most of these epitopes appeared to be unaffected by the current variants of concern.

"We focused specifically on recovered COVID-19 patients as their immune responses are representative of effective responses against the virus," said Prof. Ahmed Abdul QUADEER, Research Assistant Professor from the Department of Electronic and Computer Engineering, who is the first author of the research.

"We believe this is good news, particularly for vaccines. In contrast to antibody responses which have been shown to be affected by variants, our analysis would suggest T cell responses may be relatively robust, assuming that vaccine responses mimic those of natural infection," said Prof. Matthew MCKAY from the Departments of Electronic and Computer Engineering and Chemical and Biological Engineering, who co-led the research.

While revealing more than 700 T cell epitopes, the team's analysis identified 20 specific epitopes--which they refer to as immunoprevalent--that induced T cell responses in multiple independent cohorts and in a large fraction of tested patients. Of these, five appeared highly immunoprevalent, registering T cell responses in at least four separate immunological studies.

"The identified immunoprevalent epitopes appear to represent parts of the virus that are commonly targeted by T cells in recovered COVID-19 patients," added Prof. McKay. "It is possible, but subject to further experimental investigation, that targeting these epitopes may play a role in contributing to favourable disease outcomes."

The compiled data has been integrated into a web platform, which the team plans to keep updated as more immunological studies of SARS-CoV-2 T cell epitopes are reported.

"The platform is an online resource for the global research community and complements ongoing research on understanding T cell responses against SARS-CoV-2. It serves to guide studies related to COVID-19 vaccines and diagnostics," added Prof. Quadeer.

Rough night of sleep? Relying on caffeine to get you through the day isn't always the answer, says a new study from Michigan State University.

Researchers from MSU's Sleep and Learning Lab, led by psychology associate professor Kimberly Fenn, assessed how effective caffeine was in counteracting the negative effects of sleep deprivation on cognition. As it turns out, caffeine can only get you so far.

The study -- published in the most recent edition of Journal of Experimental Psychology: Learning, Memory, & Cognition -- assessed the impact of caffeine after a night of sleep deprivation. More than 275 participants were asked to complete a simple attention task as well as a more challenging "placekeeping" task that required completion of tasks in a specific order without skipping or repeating steps.

Fenn's study is the first to investigate the effect of caffeine on placekeeping after a period of sleep deprivation.

"We found that sleep deprivation impaired performance on both types of tasks and that having caffeine helped people successfully achieve the easier task. However, it had little effect on performance on the placekeeping task for most participants," Fenn said.

She added: "Caffeine may improve the ability to stay awake and attend to a task, but it doesn't do much to prevent the sort of procedural errors that can cause things like medical mistakes and car accidents."

Insufficient sleep is pervasive in the United States, a problem that has intensified during the pandemic, Fenn said. Consistently lacking adequate sleep not only affects cognition and alters mood, but can eventually take a toll on immunity.

"Caffeine increases energy, reduces sleepiness and can even improve mood, but it absolutely does not replace a full night of sleep, Fenn said. "Although people may feel as if they can combat sleep deprivation with caffeine, their performance on higher-level tasks will likely still be impaired. This is one of the reasons why sleep deprivation can be so dangerous."

Fenn said that the study has the potential to inform both theory and practice.

"If we had found that caffeine significantly reduced procedural errors under conditions of sleep deprivation, this would have broad implications for individuals who must perform high stakes procedures with insufficient sleep, like surgeons, pilots and police officers," Fenn said. "Instead, our findings underscore the importance of prioritizing sleep."

Reverse transcription-polymerase chain reaction (RT-PCR) has been the gold standard for diagnosis during the COVID-19 pandemic. However, the PCR portion of the test requires bulky, expensive machines and takes about an hour to complete, making it difficult to quickly diagnose someone at a testing site. Now, researchers reporting in ACS Nano have developed a plasmofluidic chip that can perform PCR in only about 8 minutes, which could speed diagnosis during current and future pandemics.

Rapid diagnosis of COVID-19 and other highly contagious viral diseases is important for timely medical care, quarantining and contact tracing. Currently, RT-PCR -- which uses enzymes to reverse transcribe tiny amounts of viral RNA to DNA, and then amplify the DNA so that it can be detected by a fluorescent probe -- is the most sensitive and reliable diagnostic method. But because the PCR portion of the test requires 30-40 cycles of heating and cooling in special machines, it takes about an hour to perform, and samples must typically be sent away to a lab, meaning that a patient usually has to wait a day or two to receive their diagnosis. Ki-Hun Jeong and colleagues wanted to develop a plasmofluidic PCR chip that could quickly heat and cool miniscule volumes of liquids, allowing accurate point-of-care diagnosis in a fraction of the time.

The researchers devised a postage stamp-sized polydimethylsiloxane chip with a microchamber array for the PCR reactions. When a drop of sample is added to the chip, a vacuum pulls the liquid into the microchambers, which are positioned above glass nanopillars with gold nanoislands. Any microbubbles, which could interfere with the PCR reaction, diffuse out through an air-permeable wall. When a white LED is turned on beneath the chip, the gold nanoislands on the nanopillars quickly convert light to heat, and then rapidly cool when the light is switched off. The researchers tested the device on a piece of DNA containing a SARS-CoV-2 gene, accomplishing 40 heating and cooling cycles and fluorescence detection in only 5 minutes, with an additional 3 minutes for sample loading. The amplification efficiency was 91%, whereas a comparable conventional PCR process has an efficiency of 98%. With the reverse transcriptase step added prior to sample loading, the entire testing time with the new method could take 10-13 minutes, as opposed to about an hour for typical RT-PCR testing. The new device could provide many opportunities for rapid point-of-care diagnostics during a pandemic, the researchers say.

Adults with schizophrenia have an elevated risk of dying from suicide. Yet there's only limited understanding of when and why people with schizophrenia die of suicide --in part because research studies have looked at relatively small groups of patients.

Now a new study from Columbia that looked at a large population of adults diagnosed with schizophrenia has found the youngest group (18-34) had the highest suicide risk and those aged 65 and older had the lowest. By comparison, in the general U.S. population, younger adults have less risk and older age groups have greater risk.

The Columbia study, published online May 26 in the journal JAMA Psychiatry, (LINK TK) also showed that people with schizophrenia, overall, have a 4.5-fold increased risk of dying from suicide, the 10th leading cause of death in the United States.

"When a person with schizophrenia is becoming suicidal, an attempt can happen with little warning," said Mark Olfson, Elizabeth K. Dollard professor of psychiatry at Columbia and co-author of the study. "Often, suicidal behavior in schizophrenia is driven by psychotic processes. This aspect can make it difficult to anticipate and prevent."

The study, which provides a significant amount of data on age and suicide risk, could help suicide prevention efforts for people with schizophrenia. "Knowing more about which age groups and what personal characteristics are linked to higher risk could increase attention and support for the most vulnerable patients," Olfson said.

To conduct their research, the study's authors examined the records of 668,836 people diagnosed with schizophrenia aged 18 years and over.. All were covered by Medicare.

Much is still unknown about why suicide risk in people with schizophrenia declines across the life span, although some risk factors appear to be linked to age.

Young people with schizophrenia are more likely to experience suicidal ideation, suicide attempts, substance use disorders, inpatient mental health admissions, and emergency department visits. These characteristics might help to explain why younger adults with schizophrenia are at greater risk of dying of suicide, Olfson said.

Such factors occur less frequently as individuals age, leading to older males with schizophrenia having a suicide rate similar to older people in the general U.S. population. There also may be a "healthy survivor" bias for the decline in suicide risk with advancing age. This may occur because older people with schizophrenia have survived earlier health risks and those individuals who are most susceptible to suicide may have died at an earlier age.

Other serious psychiatric disorders have high risks of suicide as well. According to Olfson, schizophrenia falls in the middle of diagnoses linked to increased suicide, ranking below mood disorders including major depression and bipolar disorder.

The study's findings underscore the high risk of suicide among young adults with schizophrenia and the need for vigilance by therapists and physicians, especially for that group.

Suicide prevention for all with schizophrenia may be improved, the authors note, by expanding access to the antipsychotic clozapine, treating co-occurring substance use disorders, making early psychosis detection programs more widely available, providing suicide risk screening, and using cognitive behavioral therapy to counter hallucinations and reduce suicidal symptoms.

When enjoying a chocolate bar, most people don't think about how the molecules within it are organized. But different arrangements of the fats in chocolate can influence its taste and texture. Now, researchers reporting in ACS' Crystal Growth & Design have found that the side of a chocolate bar facing the mold has a more orderly crystalline structure than the side facing air, knowledge that might help chocolatiers produce tastier confections, the researchers say.

Chocolate is a mixture of cocoa solids, cocoa butter, sugar and other ingredients that interact with each other in complex ways. In particular, the fat molecules, or triacylglycerols, can remain liquid or crystallize into several phases with different melting points. The temperature at which a particular chocolate melts affects its taste and texture, with a melting point near body temperature being ideal. When chocolatiers make bars, they pour tempered chocolate into a mold and let it cool at temperatures that favor the most desirable crystal form. Fumitoshi Kaneko and colleagues wondered how the mold, which conveys heat more efficiently than air and also provides a physical barrier, affects fat crystallization.

To find out, the researchers analyzed the structure of fat components at three different positions in a chocolate bar using polarized Fourier transform infrared spectroscopy and attenuated total reflection sampling. They found that the mold-side face of the bar contained highly ordered, regularly packed fatty acid chains, whereas the air-side face had disordered, irregularly packed chains, and the midpoint showed intermediate characteristics. The mold side also contained more of the most desirable fat crystal form than the other locations. These results could be explained by the large difference in thermal conductivity between the mold's material and air, which causes the chocolate to preferentially cool and crystallize on the mold-side face. The mold also provides a barrier that controls the direction of crystallization, yielding a more orderly arrangement. These results suggest that a chocolate bar's structure is much less uniform than previously thought, and that improving the crystallization process might lead to better-tasting, melt-in-your-mouth and better-looking chocolate bars, the researchers say.