Culture

A medical robotic hand could allow doctors to more accurately diagnose and treat people from halfway around the world, but currently available technologies aren't good enough to match the in-person experience.

Researchers report in Science Advances that they have designed and produced a smart electronic skin and a medical robotic hand capable of assessing vital diagnostic data by using a newly invented rubbery semiconductor with high carrier mobility.

Cunjiang Yu, Bill D. Cook Associate Professor of Mechanical Engineering at the University of Houston and corresponding author for the work, said the rubbery semiconductor material also can be easily scaled for manufacturing, based upon assembly at the interface of air and water.

That interfacial assembly and the rubbery electronic devices described in the paper suggest a pathway toward soft, stretchy rubbery electronics and integrated systems that mimic the mechanical softness of biological tissues, suitable for a variety of emerging applications, said Yu, who also is a principal investigator at the Texas Center for Superconductivity at UH.

The smart skin and medical robotic hand are just two potential applications, created by the researchers to illustrate the discovery's utility.

In addition to Yu, authors on the paper include Ying-Shi Guan, Anish Thukral, Kyoseung Sim, Xu Wang, Yongcao Zhang, Faheem Ershad, Zhoulyu Rao, Fengjiao Pan and Peng Wang, all of whom are affiliated with UH. Co-authors Jianliang Xiao and Shun Zhang are affiliated with the University of Colorado.

Traditional semiconductors are brittle, and using them in otherwise stretchable electronics has required special mechanical accommodations. Previous stretchable semiconductors have had drawbacks of their own, including low carrier mobility - the speed at which charge carriers can move through a material - and complicated fabrication requirements.

Yu and collaborators last year reported that adding minute amounts of metallic carbon nanotubes to the rubbery semiconductor of P3HT - polydimethylsiloxane composite - improves carrier mobility, which governs the performances of semiconductor transistors.

Yu said the new scalable manufacturing method for these high performance stretchable semiconducting nanofilms and the development of fully rubbery transistors represent a significant step forward.

The production is simple, he said. A commercially available semiconductor material is dissolved in a solution and dropped on water, where it spreads; the chemical solvent evaporates from the solution, resulting in improved semiconductor properties.

It is a new way to create the high quality composite films, he said, allowing for consistent production of fully rubbery semiconductors.

Electrical performance is retained even when the semiconductor is stretched by 50%, the researchers reported. Yu said the ability to stretch the rubbery electronics by 50% without degrading the performance is a notable advance. Human skin, he said, can be stretched only about 30% without tearing.

JUPITER, FL -- Failures in a quality control system that protects protein-building fidelity in cells can lead to motor neuron degeneration and related diseases, according to a new study from an international team co-directed by Scripps Research molecular biologist Claudio Joazeiro, PhD.

Motor neurons control movement, breathing, swallowing and speaking. Their death is a hallmark of progressive diseases such as spinal muscular atrophy and ALS, also known as Lou Gehrig's disease. Understanding what can cause motor neurons to die is a key to developing precision treatments. Scientists are finding that the causes of motor neuron diseases are many.

The study, appearing Sept. 15, 2020 in the journal Nature Communications, singles out several variants of a gene called NEMF as a new driver of motor neuron diseases. NEMF, short for "nuclear export mediator factor," is known for its role in helping clear glitches that inevitably occur during protein production by cellular organelles called ribosomes.

Healthy NEMF helps the cell recycle garbled protein fragments produced in error. But several mutant forms of NEMF in mice interfered with the system and resulted in neuromuscular, neurodegenerative or other disease, the scientists found.

The research was led by both Joazeiro, who has joint appointments at Scripps Research in Jupiter, Florida and the Center for Molecular Biology of Heidelberg University in Germany, and Gregory Cox, PhD, of the Jackson Laboratory of Mammalian Genetics in Bar Harbor, Maine.

A decade ago, Joazeiro discovered an enzyme, the E3 ubiquitin ligase listerin/Ltn1, that works in a specialized quality control process now known as RQC, or ribosome-associated quality control. He and his team also found that inactivation of the enzyme causes motor neuron degeneration in mice. However, whether neurodegeneration resulted from defective ribosome-associated quality control or some other function of listerin remained unclear. At the Jackson Laboratory, Cox had been studying mice with mutations in another quality control factor, NEMF. They exhibited movement difficulties including walking and gripping. The labs teamed up to investigate whether those defects resulted from a neurodegenerative process. They wanted to find the molecular mechanisms at work.

"The results provide strong evidence that dysfunction of ribosomal quality control causes neurodegeneration," Joazeiro says.

Within cells, millions of ribosomes transform genetic code into proteins by stringing together one amino acid at a time. Mistakes occasionally happen, some of which lead to the production of potentially toxic protein fragments. When that happens, manufacturing may be suspended, and the cell's ribosome protein quality control system chops up the garbled pieces for recycling.

But whether defective ribosome quality control contributed to human disease had remained unknown. Human data backed up the team's mouse and yeast-based investigations.

Working through GeneMatcher, a tool for patients developed at the Baylor-Hopkins Center for Mendelian Genomics in Texas, the team identified nine patients from seven unrelated families who had likely pathogenic NEMF variants and displayed neuromuscular disease, along with a variety of developmental issues including speech delay and intellectual disability.

"It was amazing to see how our early and new mouse data, together with the knowledge acquired on molecular mechanisms, were so predictive of these findings in human patients," Joazeiro says. "We're hopeful these advances will one day prove helpful to families affected by these difficult diseases."

The team is now investigating the role of ribosome-associated quality control in other related diseases, he adds.

Another fascinating takeaway from this research is that this pathway of protein quality control appears to be necessary across species, he adds.

"Last year we reported that it is also present in bacteria, and is likely to have already been active in the last universal common ancestor, the organism that gave rise to all domains of life," Joazeiro says.

Together with the findings that disabling the system results in neurodegeneration, this evolutionary conservation highlights the importance of aberrant protein disposal, and also suggests the system's development may have played a critical role enabling the evolution of complex organisms, Joazeiro says.

"This research shows that failure of ribosome-associated quality control is a cause of motor neuron disease that should be explored in greater detail," he says.

Research led by Dr. Wonmuk Hwang has led to better understanding on how components of the body's immune system find intruding or damaged cells, which could lead to novel approaches to viral and cancer treatments.

Hwang, associate professor in the Department of Biomedical Engineering at Texas A&M University, has written about this in an article recently published in the journal Proceedings of the National Academy of Sciences.

When viruses enter the body, the immune system kicks into gear to seek out and destroy the intruder. T-cells are one component of the immune system, and they seek out viruses hiding in host cells, acting as an ultimate line of defense against antigens, or foreign bodies. T-cells probe the surface of other cells, examining materials scooped from inside the cell and presented by the major histocompatibility complex (MHC) molecules on the surface of the cells.

"The problem is there are hundreds of thousands of MHC molecules displaying peptides, and only a few are from invading cells, if at all," Hwang said. "The rest of them are normal products of cellular metabolism, which means the T-cell needs to be able to see that needle in the haystack."

Researchers have discovered recently that T-cells increase their detection power mechanically: when T-cells probe the surface of other cells, there is a natural contact force created. If the cell is infected by an antigen, the applied force results in a "catch bond" between the T-cell receptors (TCRs) and MHC molecules, which strengthens the contact. This bond does not occur between TCRs and MCH molecules that do not carry specific antigens.

However, it is almost impossible to see this interaction in atomic details experimentally, so Hwang developed a computer simulation that could realistically demonstrate and analyze the interaction between TCRs and MHC molecules when force is applied.

"Only the simulation can see and analyze molecular motion under load. A lab experiment doesn't have the resolution," Hwang said. "Experimentally determined atomic structures of proteins are static snapshots, but when the molecule moves, you have basically no way to see the motion."

What Hwang discovered was how the motion between the parts of the TCR controls their interaction with the MHC molecules. When force is applied, the motion is suppressed only when the MHC molecule has the matching antigen, thereby stabilizing the entire complex. Other cases will refuse to interlock with the TCR, and the constant motion between the two eventually leads to them disconnecting. It is like a lock-and-key system where the lock and key constantly change shape, and only with a perfect match and under an adequate level of force, can the molecules interlock.

Hwang said the knowledge of which parts of the molecule respond to force can help tailor T-cells for certain applications. Other than fighting infections, TCRs are also the rising stars of cancer therapy.

"If you can train the T-cell to see those cancerous antigens, it'll be really specific therapy," Hwang said. "Chemotherapy kills all the cells. But T-cells you can train to recognize cancer cells with extreme accuracy."

Hwang said the next step for him is to investigate what is general and what pertains to specific T-cell receptor systems.

"To see how this principle applies to different T-cell receptors, I'm going to expand this initial finding," Hwang said. "This is the very first work that has found the operation mechanism of T-cell receptors under force."

LA JOLLA, CA--Ever since SARS-CoV-2 first appeared, researchers have been trying to understand whether sometimes the immune system does more harm than good during the acute phase of COVID-19. The latest study by researchers at La Jolla Institute for Immunology clearly argues in favor of the immune system.

Their work, published in the Sept. 16, 2020, online issue of Cell, confirms that a multi-layered, virus-specific immune response is important for controlling the virus during the acute phase of the infection and reducing COVID-19 disease severity, with the bulk of the evidence pointing to a much bigger role for T cells than antibodies. A weak or uncoordinated immune response, on the other hand, predicts a poor disease outcome. The findings suggest that vaccine candidates should aim to elicit a broad immune response that include antibodies, helper and killer T cells to ensure protective immunity.

"Our observations could also explain why older COVID-19 patients are much more vulnerable to the disease," says senior author Shane Crotty, Ph.D., who co-led the study with Alessandro Sette, Dr. Biol.Sci., both professors in LJI's Center for Infectious Disease and Vaccine Research. "With increasing age, the reservoir of T cells that can be activated against a specific virus declines and the body's immune response becomes less coordinated, which looks to be one factor making older people drastically more susceptible to severe or fatal COVID-19."

Adds Sette, "What we didn't see was any evidence that T cells contribute to a cytokine storm, which is more likely mediated by the innate immune system."

When SARS-CoV-2 (or any other virus) infiltrates the body, the innate immune system is first on the scene and launches a broad and unspecific attack against the intruder. It releases waves of signaling molecules that incite inflammation and alert the immune system's precision forces to the presence of a pathogen.

Within days, the so-called adaptive immune system tools up and moves with pinpoint precision against the virus, intercepting viral particles and killing infected cells.

The adaptive immune system consists of three branches: antibodies; helper T cells (Th), which assist B cell to make protective antibodies; and killer T cells (CTL), which seek out virus-infected cells and eliminate them.

For their latest study, the researchers collected blood samples from 50 COVID-19 patients and analyzed all three branches of the adaptive immune system--SARS-CoV-2 specific antibodies, helper and killer T cells--in great detail.

"It was particularly important to us to capture the whole range of disease manifestation from mild to critically ill so we could identify differentiating immunological factors," says co-first author and infectious disease specialist Sydney Ramirez, M.D., Ph.D., who spearheaded the sample collection.

What the team found was that similar to their previous study all fully recovered individuals had measurable antibody, helper and killer T cell responses, while the adaptive immune response in acute COVID-19 patients varied more widely with some lacking neutralizing antibodies, others helper or killer T cells or any combination thereof.

"When we looked at a combination of all of our data across all 111 measured parameters we found that in general, people who mounted a broader and well-coordinated adaptive response tended to do better. A strong SARS-CoV-2 specific T cell response, in particular, was predictive of milder disease," says co-first author and postdoctoral research Carolyn Moderbacher, Ph.D. "Individuals whose immune response was less coordinated tended to have poorer outcomes."

The effect was magnified when the researchers broke down the dataset by age. "People over the age of 65 were much more likely to have poor T cell responses, and a poorly coordinated immune response, and thus have much more severe or fatal COVID-19," says Crotty. "Thus, part of the massive susceptibility of the elderly to COVID-19 appears to be a weak adaptive immune response, which may be because of fewer naïve T cells in the elderly."

Naïve T cells are inexperienced T cells that have not met their viral match yet and are waiting to be called up. As we age, the immune system's supply of deployable naïve T cells dwindles and fewer cells are available to be activated to respond to a new virus. "This could either lead to a delayed adaptive immune response that is unable to control a virus until it is too late to limit disease severity or the magnitude of the response is insufficient," says Moderbacher.

In line with what other research teams had found before, antibodies don't seem to play an important role in controlling acute COVID-19. Instead, T cells and helper T cells in particular are associated with protective immune responses. "This was perplexing to many people," says Crotty, "but controlling a primary infection is not the same as vaccine-induced immunity, where the adaptive immune system is ready to pounce at time zero."

If a vaccination is successful, vaccine-induced antibodies are ready to intercept the virus when it shows up at the doorstep. In contrast, in a normal infection the virus gets a head start because the immune system has never seen anything like it. By the time the adaptive immune system is ready to go during a primary infection, the virus has already replicated inside cells and antibodies can't get to it.

"Thus, these findings indicate it is plausible T cells are more important in natural SARS-CoV-2 infection, and antibodies more important in a COVID-19 vaccine," says Crotty, "although it is also plausible that T cell responses against this virus are important in both cases."

WASHINGTON -- Researchers have developed an automated 3D printing method that can produce multicolor 3D microstructures using different materials. The new method could be used to make a variety of optical components including optical sensors and light-driven actuators as well as multimaterial structures for applications such as soft robotics and medical applications.

"Combining multiple kinds of materials can be used to create a function that cannot be realized with a single material," said research team leader Shoji Maruo from Yokohama National University in Japan. "Methods like ours that allow single-step fabrication of multimaterial structures eliminates assembling processes, allowing the production of devices with high precision and low cost."

In The Optical Society (OSA) journal Optical Materials Express, Maruo and colleagues describe their new 3D printing method and demonstrate it by creating various multicolor 3D structures. Their technique is based on stereolithography, a 3D printing method that is ideal for making microdevices because it uses a tightly focused laser beam to make intricately detailed features.

"The ability to make multimaterial microscale optical elements using 3D printing could aid in the miniaturization of optical devices used for medical treatments and diagnoses," said Maruo. "This could improve the ability to use these devices in or on the body while also enabling them to be disposable, which would help provide an advanced and safe medical diagnosis."

Optimizing color stereolithography

Stereolithography builds up a high-precision 3D structure by using a laser to harden light-activated materials known as photocurable resins in a layer by layer fashion. Microfluidics are often used to hold the liquid resins, but it is challenging to keep the different resins from contaminating each other when switching materials without creating large amounts of waste or forming air bubbles in the printed object.

In the new work, the researchers developed a way to hold the various materials in a droplet state, which allows them to be more easily exchanged in a closed space such as a microchannel without creating waste. To suppress air bubbles, the 3D-printed structure is moved around inside the resin each time a resin is replaced. They also integrated a two-step process for cleaning the 3D printed structure when the resins are changed to completely prevent cross-contamination.

To implement this optimized approach, the researchers created a palette to hold multiple resins and placed it, two cleaning tanks and an air blow nozzle on a motorized stage. "All the processes, including 3D printing, resin replacement, bubble removal and cleaning are sequentially carried out using software we developed," said Maruo. "This allows multicolor 3D microstructures to be created automatically."

Creating multicolor 3D structures

The researchers tested the approach by placing various types of photocurable resins in a palette and using them to create 3D microstructures. For one of these demonstration structures, a tiny multicolor cube just 1.5 millimeters across, the 3D printing system exchanged five colors of resin 250 times during a 6-hour fabrication process. The researchers also showed that adjusting the number of layers of multicolor resins made it possible to adjust absorbance of each part of the structure, allowing them to create microstructures with colors such as black by combining layers of red, blue, green and yellow.

"This method can be applied not only to multicolor resins but also to a wider variety of materials," said Maruo. "For example, mixing various ceramic micro- or nanoparticles with a photocurable resin can be used to 3D print various types of glass. It could also be used with biocompatible ceramic materials to create scaffolds for regenerating bones and teeth."

The researchers are now working to shorten the time required for processes such as resin replacement and bubble removal to allow for even faster fabrication. They also plan to use technology they previously demonstrated to build a multiscale fabrication system in which the fabrication resolution can be changed from less than a micrometer to several tens of micrometers by modifying the focusing lens and laser exposure conditions.

New Rochelle, NY, September 16, 2020—A novel taxonomic approach to obesity prevention using existing U.S. obesity prevention studies is highlighted in a special supplement of the peer-reviewed journal Childhood Obesity. The studies demonstrate an approach to breaking down and reaggregating study specifics to enable a determination of which obesity intervention strategies work and under what circumstances. Click here to read the supplement now. 

The work is a collaborative effort between the National Collaborative on Childhood Obesity Research (NCCOR) and Mission Measurement. NCCOR is a partnership between The Centers for Disease Control and Prevention (CDC); National Institutes of Health (NIH); Robert Wood Johnson Foundation (RWJF); and the United States Department of Agriculture (USDA).

“The Childhood Obesity Evidence Base Project” is guest edited by Deborah Young-Hyman, PhD, National Institutes of Health, and Laura Kettel Khan, PhD, Centers for Disease Control and Prevention.

The issue includes these studies:

A Rationale for Taxonomic Versus Conventional Meta-Analysis 
Methods for Taxonomy Development for Application in Taxonomic Meta-Analysis
A Systematic Review and Meta-Analysis of a New Taxonomy of Intervention Components to Improve Weight Status in Children 2-5 Years of Age, 2005-2019
Building Translational Capacity Through Meta-Analytic Methods

Shiriki Kumanyika, PhD, MPH, Drexel University, presents a Commentary entitled "Learning More from What We Already Know About Childhood Obesity Prevention."  Christina Economos, PhD, Tufts University, and Debra Haire-Joshu, PhD, Brown School at Washington University, St. Louis, present their perspective in a Commentary entitled "Preventing Obesity in 2-5-Year Olds: A Pathway to Advancing Intervention Research.”

The research reported in this supplement was supported by the Office of Behavioral and Social Sciences Research of the NIH under contract number GS-00F-0007M. The findings and conclusions in these articles are those of the authors and do not necessarily represent the official position of the NIH or the CDC

About the Journal
Childhood Obesity is a bimonthly peer-reviewed journal, published in print and online, and the journal of record for all aspects of communication on the broad spectrum of issues and strategies related to weight management and obesity prevention in children and adolescents. Led by Editor-in-Chief Tom Baranowski, PhD, Baylor College of Medicine, and Editor Elsie M. Taveras, MD, MPH, Massachusetts General Hospital for Children & Harvard Medical School, the Journal provides authoritative coverage of new weight management initiatives, early intervention strategies, nutrition, clinical studies, comorbid conditions, health disparities and cultural sensitivity issues, community, and public health measures, and more. Complete tables of content and a sample issue may be viewed on the Childhood Obesity website.

About the Publisher
Mary Ann Liebert, Inc., publishers is known for establishing authoritative medical and biomedical peer-reviewed journals. A complete list of the firm’s 90 journals, newsmagazines, and books is available on the Mary Ann Liebert, Inc., publishers website.

Journal

Childhood Obesity

DOI

10.1089/chi.2020.0137

The cover for issue 37 of Oncotarget features Figure 7, "The combination of romidepsin and KU60019 is synergistic in a xenograft model of MCL," by Scotto, et al. which reported that the antiproliferative effect induced by histone deactylase inhibitors is associated with the up-regulated expression of the cyclin-dependent kinase inhibitor p21. Paradoxically, the increased expression of p21 correlates with a reduced cell killing to the drug.

HDAC inhibitors appear to activate p21 expression via ataxia telangiectasia mutated activity.

The Oncotarget authors explored the potential synergistic interaction of the ATM inhibitor with romidepsin, given the potential complementary impact around p21. A synergistic cytotoxic effect was observed in all lymphoma cell lines examined when the HDACi was combined with KU60019. The increase in apoptosis correlates with decreased expression of p21 due to the ATM inhibitor.

KU60019 decreased expression of the cyclin-dependent kinase inhibitor at the transcriptional level, compromising the ability of HDACi to induce p21 and cell cycle arrest and ultimately facilitating a shift toward the apoptotic phase.

Central to the increased apoptosis observed when romidepsin is combined with KU60019 is the reduced expression of p21 and the absence of a G2/M cell cycle arrest that would be exploited by the tumor cells to evade the cytotoxic effect of the HDAC inhibitor.

Dr. Owen A. O'Connor from The Columbia University Medical Center said, "HDAC inhibitors (HDACi) have emerged as valuable drugs in the treatment of select lymphomas and synergize with a diverse range of pharmacological and biological agents."

The observation leads to the following hypothesis: if induction of p21 compromises the efficacy of HDAC inhibitors, then strategies to mitigate HDAC inhibitor induced p21 expression could lead to promising synergistic combinations.

Induction of p21 by HDAC inhibitors is compromised in A-T cells given that ATM activity is essential for HDAC inhibitor-induced p21 expression.

Collectively, these observations have led to the following hypothesis: If ATM activity is necessary for HDAC inhibitor mediated p21 induction, then selective ATM inhibitors could mitigate the HDAC induced p21 expression and potentiate its cytotoxic effect.

The ATM inhibitor nullifies HDAC induction of p21 expression resulting in a synergistic interaction.

KU60019 reduces p21 expression at the transcriptional level and antagonizes romidepsin transcriptional induction of p21. In both instances, the result is a markedly down-regulation of p21 expression at the protein level.

The O'Connor Research Team concluded in their Oncotarget Research Paper that it is intuitive that pleotropic drugs like HDACi are likely to have both favorable and unfavorable effects on cell growth and survival.

Strategies directed toward understanding how to mitigate the unfavorable influences of the class can lead to improved efficacy in rational combinations.

Many examples of drug synergy with HDAC inhibitors have been driven by random efforts in mixing and matching in order to identify possible complementary partners.

Obviously, a clear understanding of the molecular pharmacologic features of pleotropic drug classes like HDAC inhibitors can afford unique opportunities to think about logical combinations.

Ultimately, these approaches need to be translated to the clinic in order to establish therapeutic merit in the clinic.

Sign up for free Altmetric alerts about this article

DOI - https://doi.org/10.18632/oncotarget.27723

Full text - https://www.oncotarget.com/article/27723/text/

Correspondence to - Owen A. O'Connor - owenaoconnor@gmail.com

Keywords -
lymphoma,
HDAC inhibitor,
ATM inhibitor,
p21,
cell cycle

About Oncotarget

Oncotarget is a weekly, peer-reviewed, open access biomedical journal covering research on all aspects of oncology.

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Journal

Oncotarget

DOI

10.18632/oncotarget.27723

In another fascinating snapshot from deep time, an international team of paleontologists has reported the discovery of specimens of a minuscule crustacean that dates back to the Cretaceous (about 100 million years ago), conserved in samples of amber from Myanmar. The most spectacular find is a single female, which turns out on closer examination to contain giant sperm cells in its reproductive tract. In fact, this is the oldest fossil in which sperm cells have been conclusively identified. Moreover, the specimen represents a previously unknown species of crustacean, which has been named Myanmarcypris hui. M. hui was an ostracod, as clearly indicated by the paired calcareous valves that form the carapace, whose form recalls that of a mussel shell. Ostracods have been around for 500 million years, and thousands of modern species have been described. They are found in the oceans and in freshwater lakes and rivers. Fossilized shells of these crustaceans are by no means rare, but the specimens preserved in Burmese amber reveal details of their internal organs, including those involved in reproduction. "The finds gave us an extremely rare opportunity to learn more about the evolution of these organs," says Ludwig-Maximilians-Universitaet (LMU) in Munich geobiologist Renate Matzke-Karasz, who played a major role in the morphological analysis of the fossils. 

During the Cretaceous period, ostracods must have lived in the coastal and inland waters of what is now Myanmar, which were fringed by forests dominated by trees that produced huge quantities of resin. The newly described specimens are among the many organisms that were trapped in the oozing blobs of the gooey substance. In recent years, the amber found in the province of Kachin has yielded a spectacular trove of fossils, including frogs and snakes, as well as part of a putative dinosaur (according to new evidence, that specimen may actually represent an unusual lizard). Over the past 5 years, hundreds of previously unknown species have been described based on these inclusions. Indeed, many of them have forced evolutionary biologists to reconsider conventional hypotheses concerning phylogenetic and ecological relationships. 

The new ostracod specimens were analyzed with the aid of computer-assisted 3D X-ray reconstructions. The images revealed astonishing details of the anatomy of these animals, ranging from their tiny limbs to their reproductive organs. - And in one female specimen, Matzke-Karasz and her colleagues discovered ripe sperm. The cells were discovered in the paired sperm receptacles in which they were stored after copulation, ready for release when the female's eggs matured. "This female must have mated shortly before being encased in the resin," says He Wang of the Chinese Academy of Sciences in Nanjing. The X-ray images also revealed the sperm pumps and the pair of penises that male ostracods insert into the twin gonopores of the females.

The finds in Burmese amber provide unprecedented insights into an unexpectedly ancient and advanced instance of evolutionary specialization. "The complexity of the reproductive system in these specimens raises the question of whether the investment in giant sperm cells might represent an evolutionarily stable strategy, says Matzke-Karasz. The males of most animal species (including humans) produce very large numbers of very small sperm. Comparatively few animals, including some fruit flies - and of course, ostracods - have opted for a different approach. They make a relatively small numbers of oversized sperm, whose motile tails are several times longer than the animal itself. 

"In order to prove that the use of giant sperm is not an extravagant whim on the part of evolution, but a viable strategy that can confer an enduring advantage that enables species to survive for long periods of time, we must establish when this mode of reproduction first appeared," says Matzke-Karasz. Examples of fossilized sperm cells are extremely rare. The oldest known ostracod sperm (prior to the new discovery) are 17 million years old, and the previous record age, 50 Myr, was held by a species of worm. The new evidence extends that age by a factor of at least two. The fact that animals had already developed giant sperm 100 million years ago implies that this reproductive strategy can indeed be successful in the (very) long term, Matzke-Karasz points out. "That's a pretty impressive record for a trait that requires a considerable investment from both the males and females of the species. From an evolutionary point of view, sexual reproduction with the aid of giant sperm must therefore be a thoroughly profitable strategy."

Slower growing broiler chickens are healthier and have more fun than conventional breeds of birds, new evidence from an independent commercial scale farm trial has shown. The study carried out by researchers from FAI Farms, the University of Bristol and The Norwegian University of Life Sciences, is published today [16 September], in Scientific Reports.

The majority of broilers produced for consumption are so called conventional, fast-growing breeds. This study is the first to highlight the welfare differences between fast and slower growing broilers in a commercial setting utilising a comprehensive suite of positive and negative welfare indictors. The authors conclude that, while there are benefits of providing chickens with more space - by slightly lowering the animal density, changing to a slower growing breed results in much better health and more positive experiences for these birds.

Annie Rayner, FAI's lead researcher, said: "Broilers are motivated to perform a range of positive behaviours. These positive behaviours create positive experiences, resulting in enjoyment or pleasure. Displaying positive behaviours improves an animal's quality of life. Our seminal study found slow growing birds to have better health and perform more positive behaviours than conventional fast growing broilers. A shift away from fast-growing breeds would provide the most significant improvement for the lives of the 142 million chickens produced in Europe every week".

Dr Siobhan Mullan, Senior Research Fellow in Animal Welfare at the Bristol Vet School, added: "This first independent commercial scale trial provides robust evidence of the health and welfare benefits of slower growing breeds of chicken. We hope that it will help to drive changes in supply chains and large companies to bring about real improvements to chicken welfare."

The NGO-backed European Chicken Commitment (ECC) has attracted widespread attention from commercial broiler production with several major brands already having signed up - including KFC, Nestle, M&S and Nando's. This study set out to interrogate the commercial welfare implications of two critical aspects of the commitment - a move to slower growing breeds and lowering the stocking density.

The commercial-scale farm trial explored a comprehensive suite of positive and negative welfare indicators in four production systems varying in stocking density and breed. One slower growing breed (the slowest) was stocked at a planned maximum density of 30 kg/m2, a second slower growing breed at planned densities of 30 kg/m2 and 34 kg/m2, and the welfare outcomes were compared to those of a standard fast-growing breed stocked at 34kg/m2.

At the lower density, the slowest growing breed was found to have slightly better welfare than the other slower growing breed - as indicated by lower mortality, fewer rejections at processing and better walking ability. Differences in welfare of the slower growing breed stocked at two densities were small. However, prominent differences were found between the standard fast-growing birds stocked at 34kg/m2 and birds in the three other systems. The standard birds experienced poorer health as indicated by higher levels of mortality, hock burn and pododermatitis as well as greater rejections at processing. Furthermore, the conventional birds showed less perching on enrichment bales as well as fewer positive 'play' and 'exploration' behaviours.

Professor Ruth Newberry and Dr Judit Vas at The Norwegian University of Life Sciences Faculty of Biosciences point to the importance of including indicators of positive experiences in animal welfare studies. "Until recently, play was hardly ever mentioned in studies of chickens. We found that, when you walk through a commercial flock, you just have to turn around and look behind you to see chickens frolicking in your footsteps. This was especially the case in the slower growing flocks."

The California Channel Islands are renowned for their archaeological, biological and paleontological significance and richness, containing some of the most important early human sites in North America. This importance is only growing with new excavation, chemical, and biomolecular techniques, expanding our vision of this dynamic ecosystem and its enduring importance to humans and wildlife alike. 

Today, a team of researchers from the University of Oklahoma, the Smithsonian National Museum of Natural History, the University of Oregon and others report the first occurrence of the extinct giant short-faced bear, Arctodus simus, from the California Channel Islands. This fearsome beast - weighing by some estimates 2,000 lbs. - once roamed diverse environments from Alaska to Mexico, but has never been found in such an isolated island context. While this is not the first strange mammal to be found on the California Channel Islands, which was once home to a pygmy mammoth and a giant mouse, it is the first case of a potentially native megafaunal carnivore, which would challenge previous models of colonization and evolution of the islands's biodiversity.

This little bone, excavated in 1996, was long assumed to be from a seal, but experts suggested that it was from a bear - the first and only bear ever recorded for California's Channel Islands.

"Found in a stratum dated to over 13,000 years ago, the bone posed a significant mystery," said Jon Erlandson, a University of Oregon professor who has directed investigations at Daisy Cave since the 1990s. Was it from a large grizzly or black bear? The specimen rested safely in Erlandson's lab for more than 20 years. 

In 2016, the toe bone arrived at the Laboratories of Molecular Anthropology & Microbiome Research at the University of Oklahoma.

"From the moment I heard this could be a unique specimen, I handled it with extra care. I remember having a hard time cutting the bone piece out; it was such a rigid, morphologically well-preserved sample, thanks to the cave's environment. Luckily, its DNA was well-preserved, too," said Nihan Dagtas, who successfully extracted amplifiable DNA at the world-class clean room facility of LMAMR.

In parallel, the specimen was analyzed for ancient bone proteins (collagen) at the University of Manchester in the UK, producing chemical fingerprints that most closely matched a reference of the spectacled bear from South America- - the only living relative of the short-faced bear. These two independent molecular analyses, combined with traditional morphological evidence of the shape and size of the toe, confirmed its identity as belonging, unexpectedly, to a giant short-faced bear. 

Torben Rick, who participated in the Daisy Cave excavations and is now at the Smithsonian's National Museum of Natural History, was excited to apply a suite of new, minimally destructive technologies (aDNA, proteomics, etc.) to help resolve the questions surrounding this mysterious bone. "When the results came back that this was a short-faced bear dated to roughly 17,000 years ago, we were all really intrigued about the implications for island biogeography and ecology," said Rick.

Researchers were puzzled at first - what was a giant short-faced bear doing so far away from its known range on the California mainland? They developed a set of hypotheses to test whether it arrived at the island before or after death, and weighed the evidence.

If the bear died on the island, it might imply that a native population of short-faced bears swam to the islands and evolved over thousands of years alongside the pygmy mammoths. Or did a single individual swim to the island in search of a snack? The researchers suggest that a "pre mortem" arrival of the toe was unlikely, as it is the only specimen from the species ever found on the islands, and bears that die in caves are usually found intact. 

Then, researchers turned to a "post mortem" hypothesis: the toe was brought to the island by something or someone. "A human transport of the toe bone seems unlikely given its age and excellent preservation, but numerous animals - condors, eagles, seagulls, and others - are known to scavenge and transport bones and shells in coastal areas," Erlandson said.

The research team suggests that the most likely mode of transport was by wing. Chemical analyses known as stable isotopes indicate that this bear was feeding opportunistically on marine mammal carcasses, perhaps putting it at the right time and right place for its own carcass to eventually be scavenged by a bird, such as a California Condor or bald eagle. 

"We were able to integrate interdisciplinary toolkits, including morphology, ancient DNA, collagen fingerprinting, radiocarbon dating and stable isotopes, to develop a robust hypothesis testing framework allowing us to explore the origins of this mysterious bone," said Courtney Hofman, assistant professor of anthropology at the University of Oklahoma, co-director of LMAMR, and senior author of the study. 

Despite once being so widespread, there is significant debate over the ecology and behavior of short-faced bears, and available data are sparse. Previous studies relying on tooth shape and cavities suggested that short-faced bears from Los Angeles' famed La Brea Tar Pits ate large amounts of carbohydrates, whereas other studies using stable isotopes suggested the species relied on animal protein in Alaska and Canada. Surprisingly, this toe was the first specimen to test dietary hypotheses in the same way in California.

"This little toe helped us lay the groundwork for addressing some big questions in paleontology," notes Alexis Mychajliw, a postdoctoral research associate at the University of Oklahoma, research associate at the La Brea Tar Pits, and lead author of the study. "Southern California was packed with large carnivores 17,000 years ago, and it's possible that the opportunistic use of marine resources helped short-faced bears survive some tough competition. That is, until climates changed, and humans arrived."

Primary forests are forests without any signs of past human use and where ecological processes are not disrupted by human influence. These forests are of outstanding ecological value. They are an irreplaceable part of our natural heritage and critical for conserving forest biodiversity. In Europe, where millennia of land use have transformed forested landscapes, very few such primary forests remain, and these are mostly found in remote and relatively unproductive areas.

Even if scarce and irreplaceable, many of these forests are not legally protected and continue to be logged in Europe. The newly released 'EU Biodiversity Strategy for 2030' explicitly recognizes the intrinsic value of primary and old-growth forests and the need to protect them. The question is: Which areas should be prioritised?

An international assessment of primary forest status

A research team of scientists from 28 institutions led by Dr Francesco Sabatini (iDiv; MLU) and Prof Tobias Kuemmerle (HU) has now presented the very first assessment of the conservation status of primary forests in Europe. With the help of a large spatial database on where the last primary forests in Europe are found - a database that took over five years to create - the team was able to tackle three crucial questions: 1) Are the remaining primary forests representative of Europe's forest types? 2) Where are these forests sufficiently protected? And: Where are so few primary forests left that forest restoration is needed?

Conservation challenges and opportunities in Europe

"While many primary forests are in fact well protected, we also found many regions where they are not - particularly where primary forests are still common," said lead author Sabatini. "And in some cases, the level of protection is inadequate to ensure these forests will be conserved in the long term."

The study also highlights that remaining primary forests are unevenly distributed across Europe. "Some regions, particularly in Scandinavia and Finland as well as Eastern Europe, still have many primary forests. But often those countries do not realize how unique their forests are at the European scale and how important it is to protect them," explained Prof Tobias Kuemmerle (HU), senior author of the study. "At the same time, we were shocked to see that there are many natural forests in Europe without any remains of primary forest at all, particularly in Western Europe."

Primary forests in Europe are in a perilous state

Overall, the study shows Europe's primary forests are in a perilous state and their long-term protection should be a top priority. Where no primary forests are left, forest restoration is the only option. "Restoring forests to resemble and function like primary forests will take a long time, but it is attractive because such forests will not only benefit biodiversity but also store a lot of carbon and, therefore, help mitigate climate change," said Kuemmerle. "The good news is that there is a wide range of opportunities to restore primary forests even within existing protected areas, which means that restoration efforts would not necessarily require reducing the area of forests used for timber production."

Expanding Europe's protected forest areas by 1% is enough

The researchers have calculated that even an expansion of the protected areas by only about 1% would suffice to protect most remaining primary forests in Europe. This corresponds to only two or three thousandths of the total European land area.

"Now is the time to be ambitious. There is a lot of momentum for forest conservation and restoration in Europe," said Sabatini, referring to the EU's recently released 'Biodiversity Strategy for 2030'. "The new strategy explicitly recognizes the irreplaceable value of primary forests. Our study provides a foundation for putting this strategy into practice."

The lead author received funding from the European Union's Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant agreement No 658876.

People who have experienced post-traumatic stress disorder (PTSD) are up to twice as likely to develop dementia later in life, according to a new study by UCL researchers.

The research, published in the British Journal of Psychiatry, is the first meta-analysis of global evidence on PTSD and dementia risk.

For the study, the researchers analysed findings from 13 studies conducted on four continents, including data from a total of 1,693,678 people, investigating whether a PTSD diagnosis was associated with increased risk of dementia up to 17 years later.

By pooling data from eight of the studies, the researchers found that people with PTSD faced a 61% higher risk of dementia. Analysing data from two studies that used different methods, they found that PTSD was associated with double the odds of developing dementia.*

Dementia risk among people who have had PTSD was higher in the general population compared to veterans, as in the general population people with a PTSD diagnosis were more than twice as likely to develop dementia. The researchers say this may point to an effect of treating PTSD: veterans are typically more likely to receive treatment for PTSD (at least in the countries the studies were conducted), so the findings suggest that treating PTSD may reduce subsequent dementia risk.

Senior author Dr Vasiliki Orgeta (UCL Psychiatry) said: "Our study provides important new evidence of how traumatic experiences can impact brain health, and how the long-term effects of trauma may impact the brain in many ways increasing vulnerability to cognitive decline and dementia.

"A lot of people with PTSD don't access treatment, sometimes due to a lack of mental health care capacity but also because of stigma which often keeps people away from seeking help. We now have more evidence of how traumatic experiences and accessing treatment could have a long-lasting impact for individuals and influence future risk of developing dementia."

The researchers say the risk could be higher than the studies suggest, as PTSD also increases the likelihood of developing other known dementia risk factors, such as depression, social isolation, or elevated alcohol intake. Most of the studies adjusted for some of these factors, so the overall findings might underestimate the true cost of PTSD.

It remains unclear how PTSD raises dementia risk, but the researchers say it may be related to hypervigilance and recurrent re-experiencing of trauma, contributing to threat and stress-related activity in the brain, while withdrawal from social life may reduce cognitive reserve and resilience.

The study's first author, Mia Maria Günak, led the research as part of her MSc dissertation in Dr Orgeta's lab at UCL. She commented: "Our findings add to a growing body of evidence that dementia can sometimes be prevented by addressing risk factors throughout an individual's life course.

"Here we have identified an additional group of people who face an elevated risk of dementia, who may benefit from further mental health support."

Dr Orgeta added: "PTSD, which appears to be common among people who have been hospitalised with Covid-19, remains an underdiagnosed, undertreated, and under researched mental health condition, yet it can have serious long-term consequences. As our study has shown, PTSD impacts our brain health by increasing vulnerability to dementia. An important question is how, and whether we could learn from these findings to develop preventative treatments for those with elevated risk."

The researchers were supported by the NIHR University College London Hospitals Biomedical Research Centre and the Alzheimer's Society.

This research is the latest in a series of UCL-led studies investigating how modifiable factors across the lifespan can affect dementia risk, including a major review and meta-analysis of 12 risk factors such as lack of education, hearing loss, and smoking, as well as other recent studies on how repetitive negative thinking and living alone can increase dementia risk.

* Eight studies used hazard ratios to estimate the impact of PTSD on dementia risk, while two others used odds ratios, so they were pooled separately. Three other studies were included in the meta-analyses but were not part of the pooled data.

Durham, NC - Human pluripotent stem cells (hPSCs) hold promise in the field of regenerative medicine for how they give rise to every other cell type in the body and for their ability to propagate indefinitely. Their potential, however, is hampered by the body's tendency to reject any "allogeneic" cells or tissue, which means that the cells come from a donor other than the patient. This rejection is due to the body's immune system labeling the cells as "foreign invaders" and setting in motion a series of strategies intended to ward off what it deems an attack -- leaving researchers scrambling for a way around this protective measure.

A paper released today in STEM CELLS details a method that might provide the answer. The authors report on how they genetically edited out a key set of proteins found on the surface of the hPSCs that are the targets of immune rejection, basically rendering them invisible to the body's immune system.

The multi-institutional research team was led by Xiaoqing Zhang, M.D., Ph.D., and Lin Ma, Ph.D., from the Tongji University School of Medicine. "What we have done is taken advantage of the non-classical human leukocyte antigen (HLA) molecules, which encode the main targets of allograft rejection, to construct hypoimmunogenic hPSCs," Dr. Zhang said. "Our strategy not only ameliorates the body's main immune-rejection weapons -- T cells (especially CD8+ Ts), natural killer (NK) cells and antigen-presenting cells -- but also attenuates cell contact-triggered cell killing and immunogenicity of the allograft environment."

The work grew out of their knowledge that the HLA-G family is one of the most prominently expressed HLA class I molecules in the placenta, with the job of protecting fetal tissue from the mother's immune system. "It's a remarkable example of immune accommodation in mammals," Dr. Zhang explained. "So we engineered hPSCs using CRISPR/Cas9 gene-editing technology for beta-2 microglobulin (?2m) knock out, or for biallelic knock-in of HLA-G1 within the endogenous ?2m loci. Elimination of the surface expression of the HLA proteins protected the hPSCs from cytotoxicity mediated by the CD8+ T and NK cells. The lack of surface expression also resulted in missing-self recognition and aberrant NK cell activation."

Dr. Jan Nolta, Editor-in-Chief of STEM CELLS, said, "the development of this method to shelter pluripotent stem cell derivatives from the immune system is a "game-changer" in the field. If this innovative technique can next be carried forward to clinical trials it could mean that recipients of the cells would need no immune suppression. We are very happy to publish this novel and potentially paradigm-shifting research."

Dr. Ma added, "To the best of our knowledge, this is the first study to report that engineered β2m- HLA-G5 proteins are soluble, secretable and can efficiently protect donor cells from immune responses. This not only provides a novel strategy to generate hypoimmunogenic human cells for allografting, but also sheds light on the role of HLA-G in immune tolerance during pregnancy and organ transplantation."

The next step, the two say, will be to address any safety concerns with the engineered cells, including whether they have a higher risk of growing tumors given their capability to escape immune surveillance. "Introducing a controllable suicide gene might provide an efficient way to remove the risk," Dr. Ma said. "If all goes well, the engineered hPSCs could serve as an unlimited cell source for generating universally compatible 'off-the-shelf' cell grafts in the future."

PULLMAN, Wash. - Researchers in recent years have demonstrated the health benefits of soy, linking its consumption to reduced risk of cardiovascular disease, obesity, cancer and improved bone health.

Now, WSU researchers are hoping to use the health benefits of the popular legume to improve post-operative treatment of bone cancer.

Reporting in the journal, Acta Biomaterialia, graduate student Naboneeta Sarkar and Professor Susmita Bose in WSU's School of Mechanical and Materials Engineering showed that the slow release of soy-based chemical compounds from a 3D-printed bone-like scaffold resulted in a reduction in bone cancer cells while building up healthy cells and reducing harmful inflammation.

"There is not much research in this area of natural medicinal compounds in biomedical devices," Bose said. "Using these natural medicines, one can make a difference to human health with very minimal or no side effects, although a critical issue remains composition control."

Although rare, osteosarcoma occurs most often in children and young adults. Despite medical advances, patients with osteosarcoma and metastatic bone cancer experience a high rate of recurrence, and osteosarcoma is second leading cause of cancer death in children.

Treatment involves surgery to remove the tumor as well as pre- and post-operative chemotherapy. Large areas of bone need to be removed and repaired, and patients often experience a significant amount of inflammation during bone reconstruction, which slows healing. High doses of chemotherapy before and after surgery can also have harmful side effects.

Researchers would like to develop gentler treatment options, especially after surgery when patients are trying to recover from bone damage at the same time that they are taking harsh drugs to suppress tumor growth. Bose's team has been studying bone tissue engineering as an alternative strategy to repair the bone, using materials science principles and advanced manufacturing techniques to develop effective biomedical devices.

As part of this study, the researchers used 3D printing to make patient-specific, bone-like scaffolds that included three soy compounds and then slowly released the compounds into samples containing bone cancer as well as healthy bone cells. Soybeans contain isoflavones, plant-derived estrogens that have been shown to impede cancer cell growth for many types of cancer without being toxic to normal cells. Isoflavones have also been shown to improve bone health and possibly prevent osteoporosis.

One of the soybean compounds caused a 90% reduction in bone cancer cell viability in their samples after 11 days. Two other soy compounds, meanwhile, significantly improved the growth of healthy bone cells. Furthermore, using the soy compounds in animal models also reduced inflammation, which could benefit bone health as well as overall recovery.

"These results advance our understanding in providing therapeutic approaches in using synthetic bone grafts as a drug delivery vehicle," Bose said.

The researchers are continuing the unique area of research, studying the specific pathways of the genetic expression of natural compounds and the benefits of integrating them in biomedical technology. More detailed long-term studies are needed, using animal research as well as other malignant cells, she said.

The work was funded by the National Institutes of Health.

Initial findings reported by the Arizona COVID-19 Genomics Union (ACGU) suggest that following Arizona's first reported case of COVID-19 in late January, the state experienced no subsequent cases that went undetected and was COVID-free until at least 11 distinct incursions occurred between mid-February and early April.

The published results appear in the scientific journal mBio.

Faculty at Northern Arizona University (NAU), the Translational Genomics Research Institute (TGen), an affiliate of City of Hope, University of Arizona (UArizona) and Arizona State University (ASU) launched the ACGU in early April with the express purpose of tracking the causative agent of COVID-19, SARS-CoV-2: how it evolves and how it spreads into, within and out of Arizona.

The ACGU sequenced the SARS-CoV-2 genomes in as many virus-positive patient samples in Arizona as possible, and working with Arizona's public health officials, applied the results toward statewide efforts to test and track patients, as well as provide guidance for Arizona public policy makers.

Quick action by ASU and Maricopa County public health officials, ACGU scientists agree, likely kept the first identified COVID-19 patient in Arizona -- a student who had just returned from Hubei, the Chinese province where the disease originated -- from igniting an outbreak, and prevented Arizona from becoming an early epicenter for the contagion.

"This is a great example of how a rapid and thorough public health response can be successful in preventing the spread of this disease," said Paul Keim, ACGU co-founder and director, NAU Regents' Professor of Biological Sciences and Cowden Endowed Chair in Microbiology and Executive Director of NAU's Pathogen and Microbiome Institute (PMI). Seven additional PMI scientists also contributed to this study as co-first authors or co-authors.

"Similar steps could be taken when shaping future efforts to reopen businesses and schools, even though the virus continues to circulate and people remain susceptible," added Keim, who is also a Distinguished Professor and Co-Director of TGen's Pathogen and Microbiome Division.

Michael Worobey, an ACGU co-founder and the head of University of Arizona's Department of Ecology and Evolutionary Biology, agrees.

"It's a combination of the patient doing the right things to isolate himself and be aware that he possibly had this disease, and public health officials doing all the right things. Stopping an incursion of COVID-19 was a victory for the state of Arizona," Worobey said.

This bought Arizona valuable time for preparedness efforts. The first reported case of "community" transmission occurred in Arizona in early March descended from the Washington state outbreak that was discovered in February. More than 80 percent of the SARS-CoV-2 genome sequences from Arizona COVID-19 cases descended from at least 11 separate lineages that were initially circulating widely in Europe, and by travel have since dominated the outbreak throughout the U.S. None of the observed transmission clusters are epidemiologically linked to the original travel-related case in the Arizona, suggesting successful early isolation and quarantine.

The ACGU uses state-of-the-art sequencers, custom computational analysis workflows and supercomputers to determine the sequence of the virus's RNA genome, which is just under 30,000 bases long. In contrast, there are nearly 3 billion bases in the human genome, which determine traits as simple as eye and hair color, and as complex as an individual's propensity for cancer and other disease.

TGen has so far sequenced SARS-CoV-2 genomes from almost 3,000 COVID-19 positive samples for the ACGU, and additional sequencing was performed at ASU and UA, from among the more than 200,000 positive cases in Arizona, making it one of the most robust such efforts in the nation. ACGU receives Arizona samples collected by state, county, tribal and private healthcare systems.

With the massive amount of data generated through the genomic sequencing, even the most advanced computing resources would not be able to keep pace; custom software was developed to support the ACGU work. Greg Caporaso, NAU Associate Professor of Biology and Director of PMI's Center for Applied Microbiome Science, observed, "Integrating the SARS-CoV-2 genomes sequenced from patients in Arizona with those sequenced around the world required us to work quickly to develop new software to support our work. Our new software allows us to identify a highly informative subset of the globally available genomes to analyze, which make the analysis more computationally tractable while retaining information that is essential for contextualizing the Arizona sequences." Caporaso's team has released the new software under an open source license, which is free for all use as a contribution to global coronavirus research; see this paper describing the software.

ACGU scientists take advantage of small changes or mutations in the virus' genome, which naturally occur over time as the virus reproduces, to track the spread of the virus. By comparing mutations observed in Arizona to those present in strains circulating across the globe, they can determine when and from where the virus has been introduced to Arizona.

Crystal Hepp, NAU Assistant Professor in the School of Informatics, Computing, and Cyber Systems and Assistant Director of PMI, noted, "The rate that mutations accumulate in the virus or viral population can be used as a 'molecular clock' to understand when it arrived in Arizona and to further estimate the magnitude of the outbreak." The ACGU researchers found that the majority of Arizona sequences are represented by two lineages -- and several sub-lineages -- most of which were likely introduced through domestic travel, but with some evidence for international importation.

Jason Ladner, NAU Assistant Professor of Biology and Assistant Director of PMI, used similar analysis on the Ebola outbreak in West Africa. He said, "evolutionary analysis of disease outbreaks is one of the most important tools for understanding the origins of new viruses, like this novel coronavirus. Applying this technology to Arizona gives us local insights into how the disease has been spreading and what interventions will likely be most beneficial to control the spread of the virus."

"Through the ACGU, we are harnessing expertise in virology, genomics, evolution and bioinformatics from throughout Arizona in order to rapidly distill these genomic data into actionable insights that can complement the state's public health response," Keim said. "These results demonstrate the power of public health contact tracing and self-isolation following a positive test for stemming the tide of infections moving forward."

David Engelthaler, Director of TGen North in Flagstaff, which includes the institute's infectious disease branch, said the initial ACGU findings show how each community, each state is writing its own story for what is happening in the COVID-19 pandemic.

"We need to understand all of those plot lines that have led to where we are now," said Engelthaler, an ACGU co-founder. "Once this disease was detected in Arizona on Jan. 26, public health immediately jumped in to make sure that all contacts were identified, samples were collected and the patient was watched very closely for the next couple of weeks to make sure there were not any more cases."

In the coming months, he said, it will be necessary to track COVID-19 outbreaks and build epidemiological walls around each case, especially for those most at risk: persons older than 65, those in long-term care facilities, prisons and those with pre-existing health problems.

"When you don't have eyes on this, when you don't have contact tracing, then it can really easily move from person-to-person," Engelthaler said. "It's really useful for public policy makers to be making locally-informed decisions."

Efrem Lim, a virologist who leads the ASU team, said the SARS-CoV-2 genome sequence data can give health care providers and public policy makers an edge in fighting the pandemic.

"Tracking the transmission of the virus and its mutations ensures that therapeutics and vaccines being developed are on the right course," said Lim, an assistant professor at ASU's Biodesign Institute. "We now have a handle on what the SARS-CoV-2 virus in our communities looks like at the sequence level."