Dr. Adam Knowlden, associate professor of health science with the UA College of Human Environmental Sciences, investigated time management and how it influences sleep health in full-time college students in the areas of setting goals and priorities, mechanics of time management, and preference for organization.

“College students tend to deal with lifestyle-related sleep problems,” said Knowlden. “For example, balancing academic and social obligations can be challenging for college students. Stress and anxiety also impact college students and we know that stress can impact the sleep quality college students receive by causing insomnia.”

According to Knowlden, more than 65% of college students describe their sleep quality as poor.

The study, which was recently published in the American Journal of Health Education, found the three factors associated with time management significantly influenced the overall sleep quality of college students. Knowlden reported that time management explained around 20% of the sleep quality outcomes measured.

“Among the three factors, having a preference for organization was the most crucial factor influencing sleep quality,” said Knowlden. “This suggests that individuals who prioritize and maintain an organized environment tend to experience better sleep quality.”

Knowlden, who has also conducted sleep health studies related to body composition and stress, says time management strategies should be learned and implemented prior to the start of the school year.

“We know that there is a tradition of college students staying up late, sometimes an entire 24 hours, to study or cram for exams,” said Knowlden. “This is a tell-tale sign of the need for more focus on time management.

“However, until now, no study has looked specifically at time management to determine how much influence it has on the sleep of college students. We felt this was important to investigate because time management is something college students can work on improving.”

Knowlden recommends blocking out eight to nine hours of sleep and making it the most important appointment of the day.

“We know that during sleep is when learning takes place,” said Knowlden. “You can think of your mind like a computer. When we sleep, our brain is getting rid of information it doesn’t need, and keeping information it does need. This is why students that prioritize sleep do better academically.”

The new study, published August 7, 2023, in the journal Nature Structural & Molecular Biology, shows how a mitochondrial protein structure is necessary to activate the cell’s integrated stress response (ISR) — a critical pathway that helps our cells maintain health. The researchers believe this mitochondrial structure, made up of a protein called DELE1, could serve as a target for future therapeutics for age-related diseases.

“Understanding the molecular details of this signaling pathway could help us potentially develop treatments for a range of diseases, such as neurodegenerative diseases, cancer and heart disease,” says first author Jie Yang, PhD, a postdoctoral fellow in the lab of Gabriel Lander at Scripps Research.

In order to maintain cellular function and health, mitochondria must continually sense and respond to stressors, such as viral infections and iron deficiency. However, their ability to do so decreases as people age.

“Just like every other part of our body, mitochondria age and become slightly less productive,” says co-author Kelsey Baron, a graduate student in the lab of Luke Wiseman at Scripps Research. “When you have this loss of mitochondrial productivity, your cells don’t have as much energy to fight different stressors, and many people believe that is a major trigger of neurodegeneration.”

One method by which mitochondria deal with stress is by activating the ISR. Prior studies have shown that the DELE1 protein is involved in activating this integrated stress response, but before now, little was known about the protein’s molecular structure. Characterizing DELE1’s structure is a key step towards understanding and treating diseases associated with mitochondrial stress.

The researchers focused on a fragment of DELE1 — the C terminus — that is known to be actively involved in initiating the ISR. When they isolated this fragment, they were surprised to find that it was much heavier than expected, which suggested that multiple copies of the protein fragment were binding together. Using electron microscopy, the team showed that this protein complex (or oligomer) was a highly symmetrical cylinder composed of eight identical fragments — in other words, an octamer.

“It was completely unexpected that it was forming this much larger, oligomeric structure,” says study co-senior author Gabriel Lander, PhD, professor in the Department of Integrative Structural and Computational Biology at Scripps Research. “It’s kind of like two four-legged spiders whose legs are intertwined to form this flexible cylindrical structure.”

The researchers captured more than 12,000 electron microscope images of the octamer and then used algorithms to produce a three-dimensional structural model. Then, by looking at the positions of different amino acids (the building blocks of proteins) within the structure, they were able to identify which amino acids are involved in binding and assembling the octamer.

To test whether this oligomerization of DELE1 is required to activate the ISR, the researchers then introduced mutations into some of the key amino acids, which would disrupt the ability of DELE1 to bind together. When they cultured cells that contained this mutated, un-oligomerizable version of DELE1, the cells were unable to activate the ISR — suggesting that oligomerization is critical to activating this stress signaling pathway.

The next step is to find ways to use this structural information to manipulate these pathways — notably in different diseases and disorders, the researchers say.

“Knowing that this oligomerization step is a potential site of regulation gives us a platform for potential drug development,” says co-senior author Luke Wiseman, PhD, professor in the Department of Molecular medicine at Scripps Research. “We think that targeting this pathway has potential for improving outcomes in a variety of different disorders.”

As well as Jie Yang, Kelsey Baron, Luke Wiseman, and Gabriel Lander, authors of the study “DELE1 oligomerization promotes integrated stress response activation,” include Daniel E. Pride, Anette Schneemann, Wenqian Chen, and Albert S. Song of Scripps Research; and Xiaoyan Guo, Giovanni Aviles and Martin Kampmann of the University of California, San Francisco.

This study was funded by the National Institutes of Health (grants NS095892 and NS125674 and fellowship F31AG071162) and the Olson-King Endowed Skaggs Fellowship from Scripps Research.

Now, an interdisciplinary Cornell team has identified a new mechanism regulating tumor growth in the skeleton, the primary site of breast cancer metastasis: mineralization of the bone matrix, a fibrous mesh of organic and inorganic components that determines the unique biochemical and biomechanical properties of our skeleton.

The team’s paper, “Bone-Matrix Mineralization Dampens Integrin-Mediated Mechanosignalling and Metastatic Progression in Breast Cancer,” published Aug. 7 in Nature Biomedical Engineering. The co-lead authors are research associate Siyoung Choi and doctoral student Matthew Whitman.

The project is the latest collaboration between co-senior authors Claudia Fischbach, the Stanley Bryer 1946 Professor of Biomedical Engineering, and Lara Estroff, the Herbert Fisk Johnson Professor of Industrial Chemistry, both in Cornell Engineering, who together have been exploring the metastatic spread of breast cancer to bone for more than a decade.

Fischbach’s lab uses biomaterials in combination with cellular and tissue engineering approaches to understand how the tissue microenvironment regulates cancer in different contexts, while Estroff’s group specializes in biomineralization – the way biological organisms control the growth of crystals in their tissues.

“We know that cancer cells behave like seeds that need the right soil to grow, and we’re very interested in how the extracellular matrix, which is basically the material in between cells that holds everything together, affects tumor growth,” Fischbach said.

During physiological mineralization, bone mineral particles are deposited in and around collagen type I fibers. This process occurs naturally and is necessary for bone health but decreases with age – for example, due to hormonal changes as seen in women undergoing menopause. It can also result from dietary changes or chemotherapy.

A connection between reduced bone health and the behavior of tumor cells is well-established. For example, decreased bone-mineral density has been correlated with increased risk for metastasis, and incomplete fracture healing has been shown to enhance bone metastasis. However, no one had been able to isolate which specific role bone-matrix mineralization plays in this process.

“You can’t study some these connections unless you have model systems in which you can control bone matrix properties in a defined way,” Fischbach said.

The researchers were able to create such systems by combining organic and inorganic matrix components, including collagen and the bone mineral hydroxyapatite, in a manner that mimicked physiological and pathologic mineralization. Estroff led the necessary materials synthesis and characterization techniques of the different bone matrix models, which the team then used to investigate tumor cell behavior, first in vitro and then in vivo through mouse models.

The presence of bone mineral reduced the growth of tumor cells in both settings. The presence of mineral also caused tumor cells to promote genes that were associated with better patient prognosis. These findings suggest that healthy bone matrix can reduce the risk for breast cancer skeletal metastasis.

Co-authors Matthew Paszek, associate professor in the Smith School of Chemical and Biomolecular Engineering, and Olivier Elemento, director of the Englander Institute for Precision Medicine and a professor of physiology and biophysics and of computational genomics in computational biomedicine at Weill Cornell Medicine, helped elucidate how bone matrix regulates cellular mechanosignaling, and connect the potential molecular mechanisms to patient data.

“This study basically shows for the first time that physiological interactions between mineral particles and collagen may be able to inhibit the activation of tumor cells that have spread to bone,” Fischbach said. “Now we’re broadly interested in how other cell types are influenced by varied bone-matrix mineralization. And how do mineral-dependent changes of their behavior regulate tumor cells?”

Co-authors include doctoral students Adrian Shimpi and Nicole Sempertegui; Aaron Chiou, Ph.D. ’20; Joseph Druso, Ph.D. ’16; Akanksha Verma, Ph.D. ’20; Stephanie Lux ’21; and Zhu Cheng, Ph.D. ’20.

The research was supported by the Human Frontier Science Program; the National Cancer Institute through the Center on the Physics of Cancer Metabolism; the National Institutes of Health; the Stem Cell Program of Cornell University; and the National Science Foundation.

The researchers made use of the Cornell Center for Materials Research, which is supported by the National Science Foundation’s MRSEC program; the Cornell NanoScale Facility, a member of the NSF-supported National Nanotechnology Coordinated Infrastructure; and the Cornell Biotechnology Resource Center.

Fungal infections are killing thousands of Americans each year, some with a morbidity rate of nearly 80%. To make matters worse, only a handful of antifungal treatments are available, and even those are becoming less effective as fungi become more resistant. However, University of Oklahoma researchers recently published findings in the Journal of Natural Products indicating that a novel breakthrough treatment may have been discovered.

“The molecule we’re excited about is called persephacin,” said Robert Cichewicz, Ph.D., principal investigator and Regents Professor in the Department of Chemistry and Biochemistry, Dodge Family College of Arts and Sciences at OU. “This antifungal discovery appears to work on a broad spectrum of infectious fungi, and it is reasonably non-toxic to human cells, which is a huge deal because many current treatments are toxic to the human body.”

The rise in fungal infections is due, in part, to the successful treatment of other diseases. As people live longer and successfully undergo treatments like chemotherapy and organ transplants, they often live with weakened immune systems. When drugs that treat arthritis and other ailments that also weaken immune systems are added to the mix, a perfect storm is created for potentially deadly fungal infections.

Cichewicz, who has been researching fungi for nearly 20 years, leads the Natural Products Discovery Group at OU. This team of researchers discovered this novel molecule and developed a unique method for testing plants for their antifungal properties.

“Fungi are found throughout the botanical world, and plants and fungi often work together. Some of these fungi kill competitors or deter insects from eating the plant,” Cichewicz said. “We hypothesized that if these plant-dwelling fungi, known as endophytes, could help the plants fight off infections by killing the invading fungi, then these molecules might also be able to protect humans and animals from fungal pathogens. As it turns out, we were right.”

The team developed a novel way to procure leaf samples using a laser device called the Fast Laser-Enabled Endophyte Trapper, or FLEET. This method helps generate samples in a sterile environment and drastically increases the number of samples that can be acquired.

“Using traditional methods, we could process roughly four to six samples per minute,” Cichewicz said. “But our FLEET system is capable of aseptically generating between 500-600 tissue specimens in 10 minutes. This allows us to rapidly screen more samples and enhances the opportunity for potential drug discoveries.”

With assistance from the Office of Technology Commercialization at the University of Oklahoma, Cichewicz was awarded a U.S. patent for using persephacin to control infectious pathogens.

“It’s taken us a long time to get to this point, but now we’re hoping to work with an industry partner to help us develop this treatment,” Cichewicz said. “Antifungal resistance keeps evolving, and this could provide a new alternative. That’s why this molecule is so exciting.”