Groundcherry research bears new fruits

Over 34 million people in the U.S. don’t have enough food. More diverse and adaptable crops are needed to address challenges in food production made worse by climate change. Small, sweet berries called groundcherries may not feed the country, but along with other related “orphan crops,” they could strengthen food supplies. Unfortunately, these distant relatives of tomatoes aren’t ready for large-scale production — at least not yet.

Cold Spring Harbor Laboratory (CSHL) Professor and HHMI Investigator Zachary Lippman is working to change that. Alongside CSHL and HHMI postdoc Jia He, Lippman built genetic blueprints, or models, for two types of groundcherry. These new models can guide plant geneticists toward unlocking groundcherries’ untapped potential. They may also be key in scaling up other nightshade plants for widespread use. Lippman says:

“The nightshade family encompasses more than 20 crops. There’s the major crops — potato, tomato, eggplant — and then there are minor crops, or orphan crops, which are either semi-domesticated or simply wild. A lot of those have not received a lot of research attention, but might have more potential for greater production if they could be developed further.”

Groundcherries are ideal models of the nightshade family because of their similar genetics and long evolutionary history. They’re also common in North America, easy to grow, and easy to genetically modify. But their most interesting attribute, Lippman says, might be the papery, balloon-like husk, or inflated calyx, that surrounds their berries.

“It seems to have evolved independently multiple times in flowering plants,” Lippman explains. “It’s not clear whether it’s a quirk of evolution, an adaptive trait, or both. But one thing, in my mind, is very clear — it’s one of the coolest evolutionary novelties to emerge in plants.”

Previous research on nightshades suggested genes called MADS-box were responsible for the inflated calyx’s emergence. Using the genome editing tool CRISPR on their new groundcherry models, Lippman and He switched off the MADS-box genes one by one. They found that the plants still grew an inflated calyx whether they had the genes or not. The models also allowed them to uncover a gene essential for inflated calyx development. He says:

“Without these genomic resources, it’s very hard to pinpoint the molecular mechanisms underlying some of the traits that arose through evolution. We think with our new resource, our new genomes, we can dissect this whole process.”

Lippman calls the new groundcherry models “the poster children” for what’s coming next from his lab. Their goal is to pepper the nightshade family with many new plant models, which will make it easier to improve crops through genome editing. These models will also help provide a better understanding of plants’ evolutionary development.

“Beyond improving crops, these new models can give us the means to answer the fundamental question of how new traits emerge in plants,” Lippman says. “I think Jia’s going to be the one to tackle that going forward.”

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Materials provided by Cold Spring Harbor Laboratory. Original written by Nick Wurm. Note: Content may be edited for style and length.

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Antarctic summer thaw starts earlier, ends later than previously believed

New research from Colgate University changes our understanding of seasonal thawing in parts of Antarctica, as scientists have learned that summer thawing occurs nearly a month earlier, and stays thawed for a full two months longer than previously believed.

The research, “Timing and duration of ephemeral Antarctic water tracks and wetlands using high temporal-resolution satellite imagery, high spatial-resolution satellite imagery, and ground-based sensors in the McMurdo Dry Valleys,” is published today in Arctic, Antarctic, and Alpine Research.

Researchers used newly available satellite imaging from Planet, which can scan the surface of the Earth daily or even multiple times per day. The new stream of data is having a major impact, as researchers in the past had to rely on far fewer satellite images, or had to make the voyage to Antarctica to conduct soil measurements in person.

“What we found was that when you can scan coastal Antarctica almost every day, not just a couple of times a summer, we see that the ground is actually thawing and turning into icy swamps a full month earlier than we used to think, and it’s staying wet and thawed a full two months later, even into March,” Said Levy.

“What’s even more fascinating is that this ground is thawing and staying thawed at temperatures below freezing, so we know salts must be helping it to melt and keeping it muddy, like salting a road during a snowstorm,” he said.

Levy explains that this extended melt is great for organisms that need meltwater to survive in the harsh climate, but it is bad news for the long-term stability of the permafrost. Co-authors of the paper include Levy’s former student, Lily Kuentz ’21, who is now studying at the University of Oregon, and Mark Salvatore of Northern Arizona University.Funded in part by a grant from the National Science Foundation, former Colgate students Kyle Baun ’21, Max Wang ’22, MC Rapoza ’22, Izzy King ’22, and Gary Kuang ’22 all contributed to the paper while they were completing their undergraduate degrees.

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Materials provided by Colgate University. Original written by Daniel DeVries. Note: Content may be edited for style and length.

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Artificial intelligence approach may help identify melanoma survivors who face a high risk of cancer recurrence

Most deaths from melanoma — the most lethal form of skin cancer — occur in patients who were initially diagnosed with early-stage melanoma and then later experienced a recurrence that is typically not detected until it has spread or metastasized.

A team led by investigators at Massachusetts General Hospital (MGH) recently developed an artificial intelligence-based method to predict which patients are most likely to experience a recurrence and are therefore expected to benefit from aggressive treatment. The method was validated in a study published in npj Precision Oncology.

Most patients with early-stage melanoma are treated with surgery to remove cancerous cells, but patients with more advanced cancer often receive immune checkpoint inhibitors, which effectively strengthen the immune response against tumor cells but also carry significant side effects.

“There is an urgent need to develop predictive tools to assist in the selection of high-risk patients for whom the benefits of immune checkpoint inhibitors would justify the high rate of morbid and potentially fatal immunologic adverse events observed with this therapeutic class,” says senior author Yevgeniy R. Semenov, MD, an investigator in the Department of Dermatology at MGH.

“Reliable prediction of melanoma recurrence can enable more precise treatment selection for immunotherapy, reduce progression to metastatic disease and improve melanoma survival while minimizing exposure to treatment toxicities.”

To help achieve this, Semenov and his colleagues assessed the effectiveness of algorithms based on machine learning, a branch of artificial intelligence, that used data from patient electronic health records to predict melanoma recurrence.

Specifically, the team collected 1,720 early-stage melanomas — 1,172 from the Mass General Brigham healthcare system (MGB) and 548 from the Dana-Farber Cancer Institute (DFCI) — and extracted 36 clinical and pathologic features of these cancers from electronic health records to predict patients’ recurrence risk with machine learning algorithms. Algorithms were developed and validated with various MGB and DFCI patient sets, and tumor thickness and rate of cancer cell division were identified as the most predictive features.

“Our comprehensive risk prediction platform using novel machine learning approaches to determine the risk of early-stage melanoma recurrence reached high levels of classification and time to event prediction accuracy,” says Semenov. “Our results suggest that machine learning algorithms can extract predictive signals from clinicopathologic features for early-stage melanoma recurrence prediction, which will enable the identification of patients who may benefit from adjuvant immunotherapy.”

Additional Mass General co-authors include Ahmad Rajeh, Michael R. Collier, Min Seok Choi, Munachimso Amadife, Kimberly Tang, Shijia Zhang, Jordan Phillips, Nora A. Alexander, Yining Hua, Wenxin Chen, Diane, Ho, Stacey Duey, and Genevieve M. Boland.

This work was supported by the Melanoma Research Alliance, the National Institutes of Health, the Department of Defense, and the Dermatology Foundation.

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Materials provided by Massachusetts General Hospital. Note: Content may be edited for style and length.

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Covid: Boris Johnson WhatsApp messages requested by inquiry

The messages, alongside other documents, are part of the probe into political decision-making.

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Call to ban nicotine pouch sale to under-18s

They should fall under the same UK legal age restrictions as cigarettes and vapes, say campaigners.

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Lebanon cholera: ‘We’re afraid of everything now’

The infectious disease is spreading fast in a country ill-equipped to stop it.

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NASA laser project benefits animal researchers

Scientists researching forest carnivores such as martens, foxes and coyotes spend hours clambering through rugged terrain, sometimes in deep snow, placing and baiting camera traps to learn about animals’ behavior in relation to their habitat.

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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Materials provided by University of Wyoming. Note: Content may be edited for style and length.

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New clues into a serious neurodegenerative disease

Dementia encompasses a range of neurodegenerative conditions that lead to memory loss and cognitive deficiencies and affect some 55 million people worldwide. Yet despite its prevalence, there are few effective treatments, in part because scientists still don’t understand how exactly dementia arises on a cellular and molecular level.

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.

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Inverted dancers have more acute visuomotor perception

Previous studies have determined that astronauts can judge inverted movements better than people on Earth due to the astronauts’ unique visuomotor experience with inverted movements in space.

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.

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New tech aims to reduce racial disparities in blood measurements

A team led by a University of Texas at Arlington bioengineering professor and an Austin businessman has published key findings in the British Medical Journal Innovations that illustrate how a new device measures hemoglobin more accurately in individuals with darker skin pigmentations.

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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Materials provided by University of Texas at Arlington. Note: Content may be edited for style and length.

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