In recent years, this on-the-ground work has received a big boost from what might seem to be an unlikely source: NASA.

In a new scholarly paper that details research in northwest Wyoming, University of Wyoming researchers explain how NASA’s Global Ecosystem Dynamics Investigation (GEDI) mission can provide valuable information about the world’s forests for wildlife scientists. The article appears in the journal Forest Ecology and Management.

Using a light detection and ranging (LiDAR) laser instrument installed on the International Space Station, GEDI collects high-resolution observations of the three-dimensional structure of Earth’s forest — including precise measurements of forest canopy height, canopy cover and vertical structure. GEDI was attached to the International Space Station in 2018 for a two-year mission that has been extended until January 2023; it is expected to collect over 10 billion samples of Earth’s tropical and temperate forests.

“Our work indicated that spaceborne LiDAR collected from the GEDI mission provided a ready sampling of forest structure that could be combined with other remotely sensed data to improve our understanding of animal-habitat relationships,” wrote the researchers, led by Austin Smith, now an assistant research scientist for the team of Assistant Professor Joe Holbrook in UW’s Haub School of Environment and Natural Resources.

Working in the greater Yellowstone ecosystem — including two national parks, parts of three national forests, one national wildlife refuge and Bureau of Land Management land — the researchers deployed 107 camera traps for three consecutive winters. Based on photographs of target species, they calculated habitat use for Pacific martens, Rocky Mountain red foxes and coyotes, along with prey species red squirrels and snowshoe hares.

The scientists then paired data from GEDI with other remote-sensing platforms to create forest height and structure maps, which they used to run computer models to evaluate animal-environment relationships. They found that the pairing of GEDI data with other sensors resulted in a substantial improvement in characterizing vertical and horizontal forest structure, which aided efforts to understand important habitat features for the animals studied.

“Our successes are likely transferrable to other landscapes and animal species, which is important given the large-scale disturbances that are occurring in Western forests, such as wildfire and bark beetle outbreaks,” the researchers say.

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Now, a team led by scientists at Harvard Medical School and Harvard T. H. Chan School of Public Health has made progress in unraveling the mechanism underlying a type of dementia that strikes early in life.

In a study published Oct. 7 in Nature Communications, researchers discovered that a genetic form of frontotemporal dementia (FTD) is associated with accumulation of specific lipids in the brain — and this accumulation results from a protein deficiency that interferes with cell metabolism.

The results, based on experiments in human brain cells and in animal models, provide new insights into FTD that could inform the design of new therapies. Additionally, the findings highlight a mechanism of metabolic disruption that may be relevant in other forms of neurodegeneration, the researchers said.

A Black Box

There are several different types of dementia, each with complicated genetics that involve various mutations. FTD, characterized by a loss of cells in the frontal and temporal lobes of the brain, accounts for 5 to 10 percent of dementia cases. Often diagnosed in patients between 45 and 65 years old, the genetic forms tend to cluster in families. Around 15 percent of the time, FTD is linked to a specific mutation in the GRN gene, which causes brain cells to stop making a protein called progranulin.

Previous studies have linked progranulin to parts of the cell called lysosomes, which are responsible for cleanup and other metabolic activities in cells. However, “the function of the protein, including its role in the lysosome, has remained sort of a black box,” said co-senior author Wade Harper, the Bert and Natalie Vallee Professor of Molecular Pathology in the Department of Cell Biology in the Blavatnik Institute at HMS.

Harper collaborated on the study with co-senior authors Tobias Walther and Robert Farese Jr., who were professors of cell biology at HMS and professors of molecular metabolism at Harvard Chan School when they conducted the research, as well as lead authors Sebastian Boland, a former research fellow in the Farese & Walther Lab, and Sharan Swarup, a former research fellow in the Harper lab.

The researchers initially found that progranulin-deficient human cell lines and mouse brains, as well as brain cells from patients with FTD, had an accumulation of gangliosides — lipids commonly found throughout the nervous system.

Next, the team used recently developed technology for purifying lysosomes to analyze the types and amounts of proteins and lipids present inside them. Using this technique, the scientists found that lysosomes in these cells and tissues from brains with FTD had reduced levels of progranulin, as well as lower-than-normal levels of a lipid called BMP, which is required to break down gangliosides, the lipids commonly found in the central nervous system. However, when researchers added BMP to cells, they observed that these cells accumulated far lower levels of gangliosides.

Together, the findings suggest that progranulin in lysosomes helps maintain the BMP levels needed to prevent gangliosides from accumulating in brain cells — buildup that may contribute to FTD.

“We’ve uncovered a role for progranulin in supporting proper degradation of gangliosides,” while also showing that it may be possible to correct the problem, Farese said.

“People are already working on treatments that involve giving patients a source of progranulin, and our results are consistent with that approach potentially being therapeutically beneficial,” Walther added. Moreover, it may be possible to develop therapies that focus on replacing BMP rather than progranulin, he said, and thus target a different part of the mechanism.

The researchers also think that a similar lysosome-based mechanism could be relevant for neurodegenerative diseases beyond FTD — an idea that they note is rapidly gaining ground in the field.

“The lysosome may be a key feature of many kinds of neurodegenerative diseases — but these diseases likely all connect with the lysosome in different ways,” Harper said. For example, scientists already know that a protein implicated in a genetic form of Parkinson’s disease controls aspects of lysosomal function. More research is needed, Farese added, to understand precisely how various lipids and proteins interact with lysosomes within the context of different neurodegenerative diseases.

Now, the researchers are studying several genes linked with lysosomal function, including genes associated with lysosomal storage diseases, to find connections between them. A central remaining question is how progranulin elevates BMP levels in the brain. Additional studies are needed to further elucidate the steps of the mechanism the team uncovered and to explain how lipid accumulation translates into cognitive decline.

“This study demonstrates the power of collaboration and following the science,” Walther said. “By using the right tools and asking the right detailed questions, you can sometimes uncover things that are unexpected.”

Funding and authorship

Additional authors included Yohannes Ambaw, Pedro Malia, Ruth Richards, Alexander Fischer, Shubham Singh, and Joao Paulo of HMS and Harvard Chan School; Geetika Aggarwal and Andrew Nguyen of Saint Louis University School of Medicine; Salvatore Spina, Alissa Nana, Lea Grinberg, and William Seeley of the University of California, San Francisco; Michal Surma and Christian Klose of Lipotype GmbH.

The study was supported by the Bluefield Project to Cure FTD, the National Institutes of Health (R01NS083524; R01GM132129), Google Ventures, Third Rock Ventures, the Aligning Science Across Parkinson’s (ASAP-000282) initiative, the Canadian Institutes of Health Research, and the Howard Hughes Medical Institute.

Now, a new study, in which University of Wyoming researchers played key lead roles, shows that people on Earth with extended visuomotor experience with inverted movements — such as vertical dancers — can overcome the inversion effect in perceiving biological motion.

Qin Zhu, a UW professor of kinesiology and health, was lead and senior author of a paper titled “Extended Visuomotor Experience With Inverted Movements Can Overcome the Inversions of Effect in Biological Motion Perception” that was published Oct. 20 in Scientific Reports, an online peer-reviewed, open-access journal that covers all areas of the natural sciences.

“As indicated by the title of the article, we proved that the inversion effect in biological motion perception (BMP) can be overcome,” Zhu says. “BMP is intriguing because it is a survival skill humans and animals both share. We can read the motions produced by others in same or different species and figure out who the actor is and what is intended by the actor. So, we can better prepare our response, either to escape or engage. However, if the motion is performed upside-down, or inverted, such a capability will be greatly impaired.”

Margaret Wilson, professor and head of the UW Department of Theatre and Dance, was second author of the paper. For the study, Wilson provided the list of vertical dance movements; facilitated motion-capture of the movements; recruited vertical dancers for the experiment; and revised the paper.

Xiaoye Wang, a postdoctoral fellow in the Department of Kinesiology and Physical Education at the University of Toronto, was another lead author of the paper. Zhu worked with Wang to conceptualize and implement the study; analyze results; and draft and revise the paper.

Other contributors were from Shanghai University of Sport and Shanghai University of Finance and Economics, who helped recruit participants in China to help increase the diversity of sample sizes of the study.

The study was composed of 52 adult volunteers — 15 participants without any dance experience; 21 participants with an average of 7.71 years of typical dance experience; and 16 participants with 4.75 years of vertical dance experience. The vertical dancers were from UW and Europe.

Subjects were presented 40 dance movements as point-light displays on a computer. There were 10 pairs of dance movements, with each pair including a dance movement performed on the ground and another performed in the air. In half of the test trials, the display was artificially inverted. Vertical dancers, traditional dancers and non-dancers were asked whether the display was artificially inverted or as it was.

Only vertical dancers could identify the inversion movements performed in the air. Vertical dancers were equally capable of identifying an artificial inversion regardless of whether the dance movement was performed on the ground or in the air.

Traditional dancers and non-dancers — who had no experience with performing inverted movement — could not distinguish the inversion on the point-light display for the inverted movements performed in the air, according to the paper. The paper’s findings suggest that visuomotor experience with inverted movements plays a more critical role in allowing observers to identify in the inverted biological motion.

Zhu says those with experience viewing and/or performing inverted movements while suspended in the air can use that experience to perceive and understand the inverted movements.

“Therefore, spectators who have seen vertical dance performances before will have a better understanding of inverted movements than those who have never seen such a performance,” Zhu says. “And, for those who want to learn and perform vertical dance in the future, both visual and motor training — with respect to the inverted movements — are required to improve awareness and perception of self-movements in relation to partners or spectators while performing vertical dance.”

Zhu adds that people without any dance experience can judge the upright dance movements “pretty well” compared to trained dancers, which suggests that there are similarities between upright dance movements and movements in daily life.

“Relating to science fiction, Spiderman should have a superior ability over others to read any inverted movements,” Zhu says.

A follow-up study, using an eye tracker, has been performed to examine the visual search patterns of vertical dancers versus traditional dancers while each group observes the point-light displays to judge the actions.

“Based on the research findings, a visual training program will be designed to train students who are enrolled in UW vertical dance classes,” Zhu says.

George Alexandrakis, UT Arlington bioengineering professor, and Dr. Vinoop Daggubati of Shani Biotechnologies LLC conducted a clinical study at UT Arlington with 16 healthy volunteers and measured their hemoglobin and oxygen content using the newly developed technology. The team compared the results to those obtained using a commercially available pulse-oximeter for accuracy and variability.

Racial disparities in hemoglobin and blood oxygen measurements are an urgent public health issue. Currently available devices are inaccurate in people with dark skin. The U.S. Food and Drug Administration has issued a safety communication and organized an advisory committee meeting on Nov. 1, 2022, to discuss this issue at length.

The findings from the UTA team’s research are encouraging, and the new technology has massive potential to address this clinical unmet need. Alexandrakis said their intent is to develop a wearable device, such as a watch or a monitor, that would read the blood through the skin.

Most currently available methods for monitoring hemoglobin require blood samples and expensive equipment. The available noninvasive spectroscopic methods have a high degree of variability and often are inaccurate in people of color due to differences in skin melanin. There is a significant unmet need for a reliable, noninvasive device to estimate hemoglobin, irrespective of skin color.

Currently available pulse-oximeters use red-infrared light and are based on technology first designed more than 50 years ago. In contrast, the team’s device relies on the spectroscopic properties of hemoglobin in the blue-green light spectra.

“We have used the green-blue light and have successfully tested the device in preclinical and clinical studies,” Daggubati said. “Our group has addressed the issues around shorter wavelength, scattering of light and the impact of skin melanin. The scientific community should open its mind to the concept of green light for these measurements. The Shani device has huge potential to eliminate this racial disparity.”

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To that end, a new study from Washington University indicates that as patients age, the disease gradually impairs an important cellular housekeeping process called autophagy, which is responsible for eliminating waste from cells. This housekeeping is significant in Huntington’s because a buildup of waste in a specific kind of neuron leads to such cells’ untimely deaths.

The researchers also showed that enhancing the autophagy pathway in such neurons that were created from skin cells of Huntington’s patients protects those cells from dying.

“Our study reveals how aging triggers a loss of the crucial process of autophagy — and hints at how we might try to restore this important function, with the aim of delaying or even preventing Huntington’s disease,” said senior author Andrew S. Yoo, PhD, a Washington University professor of developmental biology.

The study, published Oct. 27 in the journal Nature Neuroscience, also may offer clues to understanding cognitive decline in aging generally.

Huntington’s disease destroys a specific type of brain cell called medium spiny neurons, the loss of which causes involuntary muscle movements, impaired mental health and cognitive decline. Patients typically live about 20 years after signs of the disease first appear.

For this study, the researchers reprogrammed patients’ skin cells into medium spiny neurons using a technique they developed that allows adult skin cells to be transformed directly into various types of brain cells, depending on the specific recipe of signaling molecules to which the skin cells are exposed. More common techniques involve use of stem cells — but stem cells reset the cells’ biological clocks to an early developmental state, which is not useful when studying diseases that only become symptomatic in adulthood.

“We collected skin cell samples from different patients at a range of ages and modeled the disease before and after symptoms developed, which allowed us to identify the differences between younger and older patients with Huntington’s disease,” Yoo said. “We knew there must be some change that takes place as patients age. They all have a genetic mutation in the Huntingtin gene. We wanted to find the difference between young patients who have no symptoms and older patients who actively show signs of the disease.”

Yoo and his colleagues, including co-first authors Youngmi Oh, PhD, and Seongwon Lee, PhD, both staff scientists in Yoo’s lab, found that medium spiny neurons reprogrammed from skin cells of older patients with symptomatic Huntington’s produced very high levels of a microRNA molecule called miR-29b-3p. These high levels were not seen in reprogrammed neurons of younger Huntington’s patients or in reprogrammed neurons from healthy individuals of any age. The investigators showed that the microRNA set off a chain of events that included impairing autophagy in these cells. When the skin cells completed the conversion into neurons, they began producing the problematic microRNA, autophagy slowed down, and the cells began dying.

The researchers went on to show that reducing levels of this microRNA allowed autophagy to continue and protected the neurons from dying. In addition, they found that enhancing autophagy with a chemical compound called G2 protected the diseased neurons from death. As the researchers increased the dose of G2, the protection from cell death improved as well.

G2 is derived from a series of analogs that were discovered in the labs of co-authors David Perlmutter, MD, executive vice chancellor for medical affairs, the George and Carol Bauer Dean of the School of Medicine, and the Spencer T. and Ann W. Olin Distinguished Professor; Gary Silverman, MD, PhD, the Harriet B. Spoehrer Professor and head of the Department of Pediatrics; and Stephen C. Pak, PhD, a professor of pediatrics in the Division of Newborn Medicine. G2 was identified via high throughput screening for autophagy enhancer drugs that could correct the cellular accumulation of variant alpha-1-antitrypsin Z that causes liver disease in alph-1-antitrypsin deficiency (ATD). The G2 compounds could therefore represent attractive candidates for preventing neurodegeneration in Huntington’s disease, liver disease in alpha-1-antitrypsin deficiency and perhaps other diseases in which aberrant accumulation of misfolded proteins is toxic to cells.

The study also uncovered what may be a tantalizing clue for understanding cognitive decline in normal aging. When comparing the symptomatic neurons to pre-symptomatic neurons and to healthy neurons from both young and older adults, the researchers found that the neurons of healthy older adults produced slightly elevated levels of the harmful microRNA, but in far smaller amounts than the neurons of symptomatic Huntington’s disease patients. The study suggests that even in normal, healthy aging, medium spiny neurons gradually produce low levels of this microRNA, which may interfere with autophagy’s healthy cellular housekeeping.

“By modeling different stages of the disease across the life span, we can identify how aging plays a role in disease onset,” Yoo said. “With that information, we can begin to look for ways to delay that onset. Our study also suggests that the triggering molecule for the onset of Huntington’s disease may play some role in age-associated decline in neuronal function generally. Understanding the component of aging that sets off neurodegeneration may help in developing new strategies for treatment and prevention of Huntington’s disease and other neurodegenerative conditions that develop at older ages.”

Yoo and his team also are working with other collaborators using their cellular reprogramming technique to investigate forms of Alzheimer’s disease, tauopathy, and other neurodegenerative conditions.

This work was supported by the National Institutes of Health (NIH), grant numbers RF1AG056296 and R01NS107488; the Cellular and Molecular Biology Training Program, grant number T32 GM007067; the Cure Alzheimer’s Fund; the CHDI Fund; a Hereditary Disease Foundation Grant; the Farrell Foundation Fund; and a Mallinckrodt Scholar Award.

In a new paper, published August 22, 2022 in the journal JCI Insight, researchers at University of California San Diego School of Medicine address the question of whether rehabilitation can augment functional outcomes when combined with pro-regenerative therapies, such as stem cell grafting.

Using a rat model, researchers induced a cervical lesion that impaired the animals’ ability to grasp with its forelimbs. There were four groups: animals who underwent the lesion alone; animals who received a subsequent grafting of neural stem cells designed to grow and connect with existing nerves; animals who received rehabilitation only; and animals who received both stem cell therapy and rehabilitation.

Rehabilitation therapy for some animals began one month after initial injury, a time point that approximates when most human patients are admitted to SCI rehabilitation centers. Rehabilitation consisted of daily activities that rewarded them with food pellets if they performed grasping skills.

The researchers found that rehabilitation enhanced regeneration of injured corticospinal axons at the lesion site in rats, and that a combination of rehabilitation and grafting produced significant recovery in forelimb grasping when both treatments occurred one month after injury.

“These new findings indicate that rehabilitation plays a critically important role in amplifying functional recovery when combined with a pro-regenerative therapy, such as a neural stem cell transplant,” said first author Paul Lu, PhD, associate adjunct professor of neuroscience at UC San Diego School of Medicine and research health science specialist at the Veterans Administration San Diego Healthcare System.

“Indeed, we found a surprisingly potent benefit of intensive physical rehabilitation when administered as a daily regimen that substantially exceeds what humans are now provided after SCI.”

Senior author Mark H. Tuszynski, MD, PhD, professor of neurosciences and director of the Translational Neuroscience Institute at UC San Diego School of Medicine, and colleagues have long worked to address the complex challenges of repairing SCIs and restoring function.

In 2020, for example, they reported on the observed benefits of neural stem cell grafts in mice and in 2019, described 3D-printed implantable scaffolding that would promote nerve cell growth.

Spinal cord injuries remain a largely unresolved medical challenge. Nearly 18,000 people in the United States suffer SCIs each year, with another 294,000 persons living with an SCI, usually involving some degree of permanent paralysis or diminished physical function, such as bladder control or difficulty breathing.

“There is a great unmet need to improve regenerative therapies after SCI,” said Tuszynski. “We hope that our findings point the way to a new potential combination treatment consisting of neural stem cell grafts plus rehabilitation, a strategy that we hope to move to human clinical trials over the next two years.”

Co-authors include: Camila Marques De Freria, Lori Graham, Amanda N. Tran and Dena Yassin, all at UC San Diego; Ashley Villarta, Veterans Administration Medical Center, San Diego; J. Russell Huie and Adam R. Ferguson, UC San Francisco.

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