“As a surgeon, I am most excited about using measurements collected with osseosurface electronics to someday provide my patients with individualized orthopedic care — with the goal of accelerating rehabilitation and maximizing function after traumatic injuries,” said study co-senior author Dr. David Margolis, an assistant professor of orthopedic surgery in the UArizona College of Medicine — Tucson and orthopedic surgeon at Banner — University Medical Center Tucson.

Fragility fractures associated with conditions like osteoporosis account for more days spent in the hospital than heart attacks, breast cancer or prostate cancer. Although not yet tested or approved for use in humans, the wireless bone devices could one day be used not only to monitor health, but to improve it, said study co-senior author Philipp Gutruf, an assistant professor of biomedical engineering and Craig M. Berge faculty fellow in the College of Engineering.

“Being able to monitor the health of the musculoskeletal system is super important,” said Gutruf, who is also a member of the university’s BIO5 Institute. “With this interface, you basically have a computer on the bone. This technology platform allows us to create investigative tools for scientists to discover how the musculoskeletal system works and to use the information gathered to benefit recovery and therapy.”

Because muscles are so close to bones and move so frequently, it is important that the device be thin enough to avoid irritating surrounding tissue or becoming dislodged, Gutruf explained.

“The device’s thin structure, roughly as thick as a sheet of paper, means it can conform to the curvature of the bone, forming a tight interface,” said Alex Burton, a doctoral student in biomedical engineering and co-first author of the study. “They also do not need a battery. This is possible using a power casting and communication method called near-field communication, or NFC, which is also used in smartphones for contactless pay.”

Ceramic Adhesive Grows to Bone

The outer layers of bones shed and renew just like the outer layers of skin. So, if a traditional adhesive was used to attach something to the bone, it would fall off after just a few months. To address this challenge, study co-author and BIO5 Institute member John Szivek — a professor of orthopedic surgery and biomedical engineering — developed an adhesive that contains calcium particles with an atomic structure similar to bone cells, which is used as to secure osseosurface electronics to the bone.

“The bone basically thinks the device is part of it, and grows to the sensor itself,” Gutruf said. “This allows it to form a permanent bond to the bone and take measurements over long periods of time.”

For instance, a doctor could attach the device to a broken or fractured bone to monitor the healing process. This could be particularly helpful in patients with conditions such as osteoporosis, since they frequently suffer refractures. Knowing how quickly and how well the bone is healing could also inform clinical treatment decisions, such as when to remove temporary hardware like plates, rods or screws.

Some patients are prescribed drugs designed to speed up bone healing or improve bone density, but these prescriptions can have side effects. Close bone monitoring would allow physicians to make more informed decisions about drug dosage levels.

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Materials provided by University of Arizona College of Engineering. Original written by Emily Dieckman. Note: Content may be edited for style and length.

LSU Maya archaeologist Heather McKillop and her team have excavated salt kitchens where brine was boiled in clay pots over fires in pole and thatch buildings preserved in oxygen-free sediment below the sea floor in Belize. But where these salt workers lived has been elusive, leaving possible interpretations of daily or seasonal workers from the coast or even inland. This gap left nagging questions about the organization of production and distribution.

New findings on the organization of the salt industry to supply this basic dietary commodity to inland cities during the Classic Maya civilization are reported in a recent article by McKillop and LSU alumna Cory Sills, who is an associate professor at University Texas-Tyler. The article “Briquetage and brine: Living and Working at the Ek Way Nal Salt Works, Belize” was published in the journal Ancient Mesoamerica.

McKillop and Sills began this new project in search of residences where the salt workers lived and to understand the energetics of production of salt with funding from the National Science Foundation. Although field work at Ek Way Nal, where the Paynes Creek Saltworks is located, has been postponed since March 2020 due to the pandemic, the researchers turned to material previously exported for study in the LSU Archaeology lab, including hundreds of wood samples from pole and thatch buildings, as well as pottery sherds.

“The Archaeology lab looks like a Tupperware party, with hundreds of plastic containers of water, but they are keeping the wood samples wet so they don’t dry out and deteriorate,” said McKillop, who is the Thomas & Lillian Landrum Alumni Professor in the LSU Department of Geography and Anthropology.

She explained the strategy to continue research in the lab: “I decided to submit a wood post sample for radiocarbon dating from each building at Ek Way Nal to see if they all dated to the same time, which was suggested by the visibility of artifacts and buildings on the sea floor.”

When the dates started coming in, two at a time, McKillop identified a building construction sequence that began in the Late Classic at the height of Maya civilization and continued through the Terminal Classic when the dynastic leaders of inland city states were losing control and eventually the cities were abandoned by A.D. 900.

According to McKillop, “Using the well-studied site, Sacapulas, Guatemala, as a model, worked well to develop archaeological expectations for different activities for brine boiling in a salt kitchen, a residence and other activities, including salting fish.”

In the Ancient Mesoamerica article, they report a 3-part building construction sequence with salt kitchens, at least one residence and an outdoor area where fish were salted and dried. The archeologists’ strategy of radiocarbon dating each building had produced a finer grain chronology for Ek Way Nal that they are using for more sites.

The new analysis verifies McKillop’s estimate that 10 salt kitchens were in production at a time at the Paynes Creek Salt Works, which she reported in her book “Maya Salt Works” (2019, University Press of Florida).

“The research underscores the importance of radiocarbon dating each pole and thatch building at the salt works in order to evaluate production capacity of this dietary necessity. The research also shows the value of individually mapping artifacts and posts on the sea floor at the underwater sites in order to interpret building use. Using Sacapulas salt works as a model from which to develop archaeological correlates fits with Ek Way Nal and suggests the Maya living permanently at the community were engaged in surplus household production of salt that was well integrated in the regional economy, allowing them to acquire a variety of nonlocal goods,” she said.

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The findings, published in the Journal of Consulting and Clinical Psychology, ultimately may lead to more personalized clinical practices and trainings for therapists to help maximize their therapeutic impact and improve patient outcomes.

“Research has tended to focus on the contributions of the patient or treatment type to therapy outcomes, which makes sense in a lot of ways, but unfortunately the therapist contribution has been somewhat neglected,” says lead author Alice Coyne, now a post-doctoral researcher at Case Western Reserve University and a Ph.D. graduate of UMass Amherst. “Our current trainings, which are often standardized across therapists, tend not to promote consistent improvements in patient outcomes. Instead, we believe that personalizing training to therapists’ unique strengths and weaknesses could enhance training outcomes down the line.”

Working with co-author Michael Constantino, professor of clinical psychology and director of the Psychotherapy Research Lab at UMass Amherst, Coyne initially conducted the research as part of her Ph.D. dissertation, which received the 2020 dissertation award from the Society for the Exploration of Psychotherapy Integration.

“Her work is the first of its kind, and it will blaze a trail in our field,” Constantino predicts.

As her dissertation’s first aim, Coyne was interested in testing the prediction that patients experience more symptomatic and functional improvement in psychotherapy when a higher-quality patient-therapist alliance exists, as well as when the patient has a more positive expectation for change.

For the second aim, Coyne was interested in seeing if these associations differed based on who the therapist is. “A given technique in the hands of one therapist may look very different than that same technique in the hands of another therapist,” Coyne says. “To put it simply, one therapist may use their relationship with their patients as a key means to facilitate improvement; whereas for another therapist, their relationships with patients may be less important for patient improvement than their use of other strategies, such as cultivating positive expectations for change.”

Finally, for the third aim, Coyne looked at whether certain therapist characteristics predict which therapists tend to use relationship and belief processes to more therapeutic benefit across their caseloads.

To test these questions, the researchers analyzed data from 212 adults who were treated by 42 psychotherapists as part of a randomized trial that compared case-assignment methods in community-based mental health care. Throughout treatment, which varied in length and type, patients repeatedly completed surveys that measured their alliance quality with the therapist and their expectations for improvement.

Coyne and Constantino correctly hypothesized that, in general, better alliance quality and more positive outcome expectation associated with better treatment outcomes. Also, as predicted, therapists exhibited different strengths and weaknesses in their use of relationship and belief processes.

Finally, there was preliminary support that the therapists who used the alliance most effectively to promote patient improvement are the ones “… who are humbler in assessing their own alliance-fostering abilities,” the paper states.

Humbly know thyself may be one helpful takeaway from the research. “If you learn the things that you do particularly well as a therapist, then you can tailor your practice and play to your strengths,” Coyne says.

The ability to proliferate and evolve is one of the defining characteristics of living organisms. However, no artificial materials with these characteristics have been created. In order to develop an artificial molecular system that can multiply and evolve, the information (genes) coded in DNA must be translated into RNA, proteins must be expressed, and the cycle of DNA replication with those proteins must continue over a long period in the system. To date, it has been impossible to create a reaction system in which the genes necessary for DNA replication are expressed while those genes simultaneously carry out their function.

The group succeeded in translating the genes into proteins and replicating the original circular DNA with the translated proteins by using a circular DNA carrying two genes necessary for DNA replication (artificial genomic DNA) and a cell-free transcription-translation system⁽¹⁾. Furthermore, they also successfully improved the DNA to evolve to a DNA with a 10-fold increase in replication efficiency by continuing this DNA replication cycle for about 60 days.

By adding the genes necessary for transcription and translation to the artificial genomic DNA developed by the group, it could be possible to develop artificial cells that can grow autonomously simply by feeding them low-molecular-weight compounds such as amino acids and nucleotides, in the future. If such artificial cells can be created, we can expect that useful substances currently produced using living organisms (such as substances for drug development and food production) will become more stable and easier to control.

This research has been led by Professor Norikazu Ichihashi, a research director of the project “Development of a self-regenerative artificial genome replication-transcription-translation system” in the research area “Large-scale genome synthesis and cell programming” under the JST’s Strategic Basic Research Programs CREST (Team type). In this research area, JST aims to elucidate basic principles in relation to the structure and function of genomes for the creation of a platform technology for the use of cells.

*(1) A cell-free transcription and translation system

A reaction solution containing all the factors necessary for the RNA transcription from genes encoded in DNA and translation into proteins outside the cell. The present study used the reconstituted PURE system (Shimizu et al. Nat Biotechnol. 2001), composed entirely of purified, known proteins and RNA. Hence, the system is free of unknown elements. This system was developed by Yoshihiro Shimizu (RIKEN Center for Frontier Biosciences) and his colleagues in the Takuya Ueda’s laboratory at the University of Tokyo.

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A research group under Professor Seung-Jae V. Lee from the Department of Biological Sciences identified a single amino acid change in the tumor suppressor protein phosphatase and tensin homolog (PTEN) that dramatically extends healthy periods while maintaining longevity. This study highlights the importance of the well-conserved tumor suppressor protein PTEN in health span regulation, which can be targeted to develop therapies for promoting healthy longevity in humans. The research was published in Nature Communications on September 24, 2021.

Insulin and insulin-like growth factor-1 (IGF-1) signaling (IIS) is one of the evolutionarily conserved aging-modulatory pathways present in life forms ranging from tiny roundworms to humans. The proper reduction of IIS leads to longevity in animals but often causes defects in multiple health parameters including impaired motility, reproduction, and growth.

The research team found that a specific amino acid change in the PTEN protein improves health status while retaining the longevity conferred by reduced IIS. They used the roundworm C. elegans, an excellent model animal that has been widely used for aging research, mainly because of its very short normal lifespan of about two to three weeks. The PTEN protein is a phosphatase that removes phosphate from lipids as well as proteins. Interestingly, the newly identified amino acid change delicately recalibrated the IIS by partially maintaining protein phosphatase activity while reducing lipid phosphatase activity.

As a result, the amino acid change in the PTEN protein maintained the activity of the longevity-promoting transcription factor Forkhead Box O (FOXO) protein while restricting the detrimental upregulation of another transcription factor, NRF2, leading to long and healthy life in animals with reduced IIS.

Professor Lee said, “Our study raises the exciting possibility of simultaneously promoting longevity and health in humans by slightly tweaking the activity of one protein, PTEN.” This work was supported by the MInistry of Science and ICT through the National Research Foundation of Korea.

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Life-threatening fungal infections impact the health of millions of humans across the globe each year. With the limited efficacy of commercially available drugs, the need for novel antifungal compounds is on the rise.

The Wang research team examined the structural dynamics of fungal polysaccharides and their responses to cell wall stress. Specifically, the team examined the cell wall of Aspergillus fumigatus, a fungal pathogen that causes life-threatening disease in immunocompromised individuals.

The research team coupled its expertise in solid-state nuclear magnetic resonance spectroscopy with a functional genomics approach using multiple mutants of Aspergillus fumigatus, each of which selectively eliminates a single type of structural carbohydrate at one time.

“This research strategy allowed us to evaluate the structural role of each major carbohydrate by tracking the changes in cell wall structure after the removal of a component,” Wang said. “The spectroscopy method provided atomic resolution on the structure of polysaccharides and associated proteins using intact fungal cell walls free from any treatment that might perturb the native status of these biomolecules.”

The data led to the development of a revised model of fungal cell wall organization and the assembly of five categories of polysaccharides, including chitin, β-glucan, mannan, α-glucan, and galactosaminogalactan. The findings confirmed an overlooked but prominent role of α-glucans in the cell wall structuration. The mutants produce stiffer and more water-proof cell walls for better protection, which might be a general mechanism used by these microbes to handle stresses.

The research involved an interdisciplinary collaboration with scientists from Institut Pasteur in France, University of Crete in Greece, as well as the Guangxi Academy of Sciences and Chinese Academy of Sciences in China. Scientists involved in this study also utilized instrumentation at the National Science Foundation’s National High Magnetic Field Laboratory in Tallahassee, Fla.

“Now that we revealed the structural principles used by fungi to respond to cell wall defects, it is time to explore how fungi reconstruct this carbohydrate armor to survive through antifungal treatments and severe environments,” said Wang.

Their findings and methodology may open a new research avenue of looking at these complex biomaterials in many different pathogenic fungal species and assessing the mode of actions of novel antifungal molecules, which will assist in the combat against invasive fungal infections.

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“We found some unexpected things when we started looking at the effect of these sensory stimuli on individual cells and connections within the worms’ brains,” says Chalasani, member of the Molecular Neurobiology Laboratory and senior author of the new work, published in the journal PLOS Computational Biology on November 9, 2021.

Chalasani is interested in how, at a cellular level, the brain processes information from the outside world. Researchers can’t simultaneously track the activity of each of the 86 billion brain cells in a living human — but they can do this in the microscopic worm Caenorhabditis elegans, which has only 302 neurons. Chalasani explains that in a simple animal like C. elegans, researchers can monitor individual neurons as the animal is carrying out actions. That level of resolution is not currently possible in humans or even mice.

Chalasani’s team set out to study how C. elegans neurons react to smelling each of five different chemicals: benzaldehyde, diacetyl, isoamyl alcohol, 2-nonanone, and sodium chloride. Previous studies have shown that C. elegans can differentiate these chemicals, which, to humans, smell roughly like almond, buttered popcorn, banana, cheese, and salt. And while researchers know the identities of the small handful of sensory neurons that directly sense these stimuli, Chalasani’s group was more interested in how the rest of the brain reacts.

The researchers engineered C. elegans so that each of their 302 neurons contained a fluorescent sensor that would light up when the neuron was active. Then, they watched under a microscope as they exposed 48 different worms to repeated bursts of the five chemicals. On average, 50 or 60 neurons activated in response to each chemical.

By looking at basic properties of the datasets — such as how many cells were active at each time point — Chalasani and his colleagues couldn’t immediately differentiate between the different chemicals. So, they turned to a mathematical approach called graph theory, which analyzes the collective interactions between pairs of cells: When one cell is activated, how does the activity of other cells change in response?

This approach revealed that whenever C. elegans was exposed to sodium chloride (salt), there was first a burst of activity in one set of neurons — likely the sensory neurons — but then about 30 second later, triplets of other neurons began to strongly coordinate their activities. These same distinct triplets weren’t seen after the other stimuli, letting the researchers accurately identify — based only on the brain patterns — when a worm had been exposed to salt.

“C. elegans seems to have attached a high value to sensing salt, using a completely different circuit configuration in the brain to respond,” says Chalasani. “This might be because salt often represents bacteria, which is food for the worm.”

The researchers next used a machine-learning algorithm to pinpoint other, more subtle, differences in how the brain responded to each of the five chemicals. The algorithm was able to learn to differentiate the neural response to salt and benzaldehyde but often confused the other three chemicals.

“Whatever analysis we’ve done, it’s a start but we’re still only getting a partial answer as to how the brain discriminates these things,” says Chalasani.

Still, he points out that the way the team approached the study — looking at the brain’s network-wide response to a stimulus, and applying graph theory, rather than just focusing on a small set of sensory neurons and whether they’re activated — paves the way toward more complex and holistic studies of how brains react to stimuli.

The researchers’ ultimate goal, of course, isn’t to read the minds of microscopic worms, but to gain a deeper understanding of how humans encode information in the brain and what happens when this goes awry in sensory processing disorders and related conditions like anxiety, attention deficit hyperactivity disorders (ADHD), autism spectrum disorders and others.

The other authors of the new study were Saket Navlakha of Cold Spring Harbor Laboratory and Javier How of UC San Diego. The work was supported by grants from the Pew Charitable Trusts, the National Institutes of Health and the National Science Foundation.

The work stems from a discovery made over a decade ago by the late Simon Chan, associate professor of plant biology in the UC Davis College of Biological Sciences, and colleagues.

Plants, like other sexual organisms, inherit a matching set of chromosomes from each parent. In order to transmit a favorable trait, such as pest or drought resistance, to all their offspring, the plant would have to carry the same genetic variant on each chromosome. But creating plants that “breed true” in this way can take generations of cross-breeding.

In 2010, Chan and postdoctoral fellow Ravi Maruthachalam serendipitously discovered a way to eliminate the genetic contribution from one parent while breeding the lab plant Arabidopsis. They had modified a protein called CENH3, found in the centromere, a structure in the center of a chromosome. When they tried to cross wildtype Arabidopsiswith plants with modified CENH3, they got plants with half the normal number of chromosomes. The part of the genome from one parent plant had been eliminated to create a haploid plant.

That work was published in Nature in March 2010, setting off efforts to achieve the same result in crop plants such as maize, wheat and tomato.

Clearing up a mystery

But replicating Chan’s exact strategy outside Arabidopsis has so far proved fruitless, said Professor Luca Comai, UC Davis Department of Plant Biology and Genome Center, who is senior author on the new paper. Recently, other labs have created plants with one set of chromosomes by manipulating CENH3, but it’s not clear how the results are related.

“The mechanistic basis of CENH3 effects on haploid induction was mysterious,” Comai said. There appear to be different rules for each species, he said.

Much of that mystery has now been cleared up. Mohan Marimuthu, researcher at the UC Davis Genome Center and Department of Plant Biology, with Comai, Maruthachalam (now at the Indian Institute of Science Education and Research, Kerala) and colleagues found that when CENH3 protein is altered, it is removed from the DNA in the egg before fertilization, weakening the centromere.

“In the subsequent embryonic divisions, the CENH3-depleted centromeres contributed by the egg fail to compete with the CENH3-rich ones contributed by the sperm and the female genome is eliminated,” Comai said.

The finding that any selective depletion of CENH3 engenders centromere weakness explains the original results by Chan and Maruthachalam as well as new results from other labs in wheat and maize, Comai said. This new knowledge should make it easier to induce haploids in crop plants, he said.

Additional authors on the paper are: at UC Davis, Anne Britt and Sundaram Kuppu; Ramesh Bondada, Indian Institute of Science Education and Research; and Ek Han Tan, University of Maine. The work was supported by grants from CSIRO (Australia), Bill and Melinda Gates Foundation, Gordon and Betty Moore Foundation, Howard Hughes Medical Institute, and the Indian Ministry of Education.

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Materials provided by University of California – Davis. Original written by Andy Fell. Note: Content may be edited for style and length.