The study, appearing in the Journal of Clinical Investigation, provides powerful evidence that a modified version of the naturally occurring hormone kisspeptin can be used to treat non-alcoholic fatty liver disease (NAFLD). Globally, NAFLD is the most common form of chronic liver disease that affects children and adults and is linked to the rise in obesity and Type 2 diabetes.

NAFLD is known as a “silent” disease because it starts off with few or no symptoms. It begins with the accumulation of fat in the liver, resulting in a condition known as ‘fatty liver’. As the disease worsens, the liver becomes inflamed resulting in non-alcoholic steatohepatitis (NASH). This is followed by fibrosis and cirrhosis, where the liver becomes scarred and irreversibly damaged. A subset of NASH patients with cirrhosis will also develop liver cancer. Currently, there are no approved therapeutics to treat NASH.

Study lead investigator, Moshmi Bhattacharya, an associate professor in the Department of Medicine at the Rutgers Robert Wood Johnson Medical School, has spent over 15 years studying kisspeptin in health and disease. Kisspeptin, encoded by the KISS1 gene, was discovered in Hershey, Pa. and named for the iconic Hershey chocolate “kisses.” In addition to playing key roles in pubertal development and maintaining reproductive function, kisspeptin has also been linked to appetite and sexual attraction.

Bhattacharya along with co-author Andy Babwah, an associate professor in pediatrics at Rutgers Robert Wood Johnson Medical School, initiated this study to decipher the roles of kisspeptin in the liver, under healthy and obese conditions. The study’s first author, Stephania Guzman, is a Ph.D. candidate in Rutgers Molecular Biosciences Graduate Program. This collaborative study also included researchers led by Waljit Dhillo at the Imperial College London, U.K.

The researchers fed mice a high-fat, high-sugar ‘Western’ diet to induce obesity and NAFLD. The study showed that kisspeptin given to these mice protected them from the development of fatty liver, NASH and fibrosis. Kisspeptin works by binding its receptor, a protein called KISS1R. The study also showed that when KISS1R is deleted from liver cells, kisspeptin cannot function and mice on western diet develop fatty liver. These experiments uncover a powerful relationship between kisspeptin and the reduction of liver fat and fibrosis.

The study found:

• Kisspeptin helps reduce fat deposited in the liver and reverse more advanced disease.
• The mechanism by which kisspeptin functions in the liver is now understood.
• Blood kisspeptin levels change in human NAFLD patients and in a mouse model of NAFLD.

“This work shows the kisspeptin receptor signaling pathway has a potential therapeutic role in NAFLD,” said co-author, Vinod K Rustgi, director of hepatology and a Distinguished Professor of Medicine at the Rutgers Robert Wood Johnson Medical School. “It does this by protecting against the development of fat in the liver and reducing inflammation and fibrosis. As such, it has the potential to favorably impact the health and lives of millions of patients around the globe.”

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Deaf studies scholar Naomi Caselli and a team of researchers found that American Sign Language (ASL) signs that are challenging to perceive — those that are rare or have uncommon handshapes — are made closer to the signer’s face, where people often look during sign perception. By contrast, common ones, and those with more routine handshapes, are made further away from the face, in the perceiver’s peripheral vision. Caselli, a Boston University Wheelock College of Education & Human Development assistant professor, says the findings suggest that ASL has evolved to be easier for people to recognize signs. The results were published in Cognition.

“Every time we use a word, it changes just a little bit,” says Caselli, who’s also codirector of the BU Rafik B. Hariri Institute for Computing and Computational Science & Engineering’s AI and Education Initiative. “Over long periods of time, words with uncommon handshapes have evolved to be produced closer to the face and, therefore, are easier for the perceiver to see and recognize.”

Although studying the evolution of language is complex, says Caselli, “you can make predictions about how languages might change over time, and test those predictions with a current snapshot of the language.”

With researchers from Syracuse University and Rochester Institute of Technology, she looked at the evolution of ASL with help from an artificial intelligence (AI) tool that analyzed videos of more than 2,500 signs from ASL-LEX, the world’s largest interactive ASL database. Caselli says they began by using the AI algorithm to estimate the position of the signer’s body and limbs.

“We feed the video into a machine learning algorithm that uses computer vision to figure out where key points on the body are,” says Caselli. “We can then figure out where the hands are relative to the face in each sign.” The researchers then match that with data from ASL-LEX — which was created with help from the Hariri Institute’s Software & Application Innovation Lab — about how often the signs and handshapes are used. They found, for example, that many signs that use common handshapes, such as the sign for children — which uses a flat, open hand — are produced further from the face than signs that use rare handshapes, like the one for light (see videos).

This project is part of a new and growing body of work connecting computing and sign language at BU.

“The team behind these projects is dynamic, with signing researchers working in collaboration with computer vision scientists,” says Lauren Berger, a Deaf scientist and postdoctoral fellow at BU who works on computational approaches to sign language research. “Our varying perspectives, anchored by the oversight of researchers who are sensitive to Deaf culture, helps prevent cultural and language exploitation just for the sake of pushing forward the cutting edge of technology and science.”

Understanding how sign languages work can help improve Deaf education, says Caselli, who hopes the latest findings also bring attention to the diversity in human languages and the extraordinary capabilities of the human mind.

“If all we study is spoken languages, it is hard to tease apart the things that are about language in general from the things that are particular to the auditory-oral modality. Sign languages offer a neat opportunity to learn about how all languages work,” she says. “Now with AI, we can manipulate large quantities of sign language videos and actually test these questions empirically.”

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The study, led by researchers from the University of Michigan in collaboration with Florida Atlantic University, Temple University, and the National Institute on Deafness and Other Communication Disorders, National Institutes of Health, used genetically engineered mice to examine the neural and behavioral effects of a choline transporter (CHT) variant. Prior work by the team has shown that the variant associated with heightened distractibility in humans, though whether the variant was itself causal for inattention was unclear.

In the new study, researchers made a single change in the gene encoding the neuronal CHT and then searched for physiological changes in the brain, focusing on their ability to sustain production and release of the powerful brain chemical acetylcholine, which is synthetized from choline.

In humans, disruption of acetylcholine signaling impairs one’s capacity to filter distractors and to perform focus-demanding tasks. A total loss of CHT function in mice and people leads to early death due to the role played by acetylcholine in muscle contraction, particularly the muscles that control breathing. Lesser reductions in CHT activity allow for normal growth and movement, but mice with these changes exhibit premature fatigue when made to run on a treadmill. Work from the new study reveals that the mice show signs of mental fatigue as well.

Results of the study, published in The Journal of Neuroscience, indicate that the CHT gene variant known as Val89, reduces the rate of choline uptake and the capacity to sustain acetylcholine production during attention-demanding conditions, effects that lead to diminished cognitive performance when the mice are faced with attentional challenges. Evidence from the mouse studies provides direct evidence that Val89 drives increased vulnerability to distraction and provides a mechanistic basis for the diminished frontal cortex activation observed in Val89-expressing humans.

“Our mouse studies, along with prior behavioral and brain imaging studies, indicate that a single copy of the variant is sufficient to change acetylcholine availability and its resulting cognitive effects,” said Randy D. Blakely, Ph.D., co-author, executive director of the FAU Stiles-Nicholson Brain Institute and professor, FAU Schmidt College of Medicine. “Seeing effects from a single copy of Val89 suggests that choline transport may be mediated by a pair of CHT proteins such that one poorly functioning copy can impact the normal function of the other, leading to stronger effects than expected from simply having one copy compromised.”

This finding has been reported before in people with neuromuscular disorder causing CHT mutations, but this also appears to be the case for brain function.

“Val89 mice lack cognitive flexibility in response to an attentional challenge,” said Eryn Donovan, lead author and a graduate student in the Department of Psychology, University of Michigan. “Our findings from this mouse model suggest the potential for a more complete investigation of the effects of the CHT Val89 mutation in the brain as well as the development of therapeutic strategies for those with disrupted acetylcholine signaling.”

According to the United States Centers for Disease Control and Prevention, the estimated number of children ever diagnosed with ADHD, according to a 2016 parent survey, is 6.1 million. This same survey shows that 6 in 10 children with ADHD had at least one other mental, emotional or behavioral disorder and 62 percent were taking ADHD medication. Although ADHD most often occurs in children, it also can be diagnosed in adulthood.

“We think that the CHT Val89 mouse can be a valuable model to study heritable risk for cognitive disorders that arise from cholinergic dysfunction,” said Blakely. “We now can gain much more insight into the brain effects of the Val89 variant in ways that cannot be done in humans and possibly lead to new ways to treat disorders associated with brain acetylcholine signaling that appear in childhood, such as ADHD, or during aging, as with Parkinson’s disease and Alzheimer’s disease.”

In addition to new insights into a potential risk factor for psychiatric and neurological disorders, Martin Sarter, Ph.D., a professor of psychology and neuroscience at the University of Michigan and the communicating author of the study says that their findings explain why healthy humans expressing this genetic variant exhibit robust attentional vulnerabilities.

“As this genetic variant is quite common, occurring in about 9 to 10 percent of humans, we now understand exactly how this variant influences the brain mechanisms that are essential for paying attention,” said Sarter.

Other study co-authors are Cassandra Avila, a graduate student and Sarah Klausner, an undergraduate student, Department of Psychology, University of Michigan; Vinay Parikh, Ph.D., an associate professor of psychology and neuroscience, Temple University; Maria Cristina Fenollar Ferrer, Ph.D., Laboratory of Molecular Genetics, Section of Human Genetics, National Institute on Deafness and Other Communication Disorders.

According to a study led by the University of South Florida, the average lifespan of a Florida horse conch is between eight and 10 years, and it doesn’t start reproducing until about age six, giving birth to up to 28,000 offspring each year. This is a dramatic shift from previous belief that a horse conch could live for half a century — meaning far fewer offspring are born to replace those removed as a result of harvest or natural causes.

The interdisciplinary research team, which includes the Florida Fish and Wildlife Conservation Commission (FWC) and current and former USF graduate students, also found that the largest Florida horse conch is no more than 16 years old. The two-foot shell is on display at the Bailey-Matthews National Shell Museum in Sanibel. The team’s results, published in PLOS ONE, were based on analyses of museum specimens, reducing harm to an already fragile population if they removed shells from the wild.

To estimate horse conch ages, researchers analyzed chemical bands in the shell, which track water temperature as the snail grows and can be counted like tree rings to measure the passage of time. Unlike tree rings, which are visible, the chemical bands can only be determined by geochemical analysis.

The team was also able to determine the horse conch’s amount of growth each year by wrapping string around each coil and then straightening and measuring the string. They found females grow rapidly each year of their lives, whereas males slow down early and mature at a much smaller size. Researchers determined that female horse conchs start laying eggs at about age six, based on spikes in shell carbon levels.

“Our research shows that horse conch reproduction is less likely to keep pace with intense harvest than previously thought,” said lead author Greg Herbert, associate professor from the USF School of Geosciences. “Horse conch populations are important. They create habitat for other species by leaving empty shells of dead prey around for fish, crabs and other animals to use as homes. They also contribute to the unique experience that we have in Florida of being able to go to the beach and seeing one of the largest seashells in the world at the water’s edge.”

Data from FWC shows that there has been a steady population decline since the mid-1990s. Commercial fishermen reported a peak count of 14,511 Florida horse conchs in 1996, followed by 6,124 in 2000, 1,461 in 2015 and just 67 in 2020.

“We still know very little about how many horse conchs exist and where their preferred habitats or what their optimal environmental conditions are,” said co-author Stephen Geiger, research scientist at the FWC. “Because we have no dedicated funding for more than 1,500 species of mollusks found in the waters that surround Florida, we continue to seek grants that enable us to study their biological traits, including those that will help managers decide if some species are in need of better protection.”

The shells that were studied were collected from the Dry Tortugas, Vaca Key, Sanibel Island and Cape Romano. Researchers say the further north you go, the smaller the Florida horse conch, possibly due to overexploited fisheries and recreational collecting.

An international team of researchers including John Dattilo — professor of recreation, park, and tourism management at Penn State — has been studying how to increase leisure and reduce loneliness during the pandemic among both international college students and older adults.

Across two different studies, the researchers found that people who had meaningful, challenging experiences were less lonely — even when higher levels of social contact and support were not available.

“There is a well-known saying: ‘Time flies when you are having fun,'” said Dattilo. “The unspoken corollary is that time drags when you are bored. Our research shows that both of these ideas are true. By engaging in meaningful activities during free time that demand focus, people can reduce loneliness and increase momentary happiness.”

Loneliness and the pandemic

Despite — or perhaps in part because of — technology that can connect people anywhere at any time, previous research has shown that loneliness has increased over recent decades.

Loneliness touches people of all ages, from children to young adults to older adults. The COVID-19 pandemic, which caused many people to alter their social behavior to prevent the spread of disease, exacerbated the problem of loneliness around the world.

“Loneliness is very connected to our health,” Dattilo explained. “Psychological, emotional, and cognitive health are all challenged when people are lonely. Loneliness is associated with depression and other mental health challenges.”

“Troublingly,” continued Dattilo, “there is a loneliness epidemic. And while the COVID-19 pandemic has increased loneliness for many people, the silver lining is that the pandemic has also exposed the scope of the loneliness problem. Anything we can do as a society to reduce loneliness should improve health and happiness for people everywhere.”

In a new article that appears in Leisure Sciences, the researchers explored loneliness among international university students in Taiwan. The same research team also published an article about reducing loneliness among nursing home residents late in 2021.

Prior research has shown that loneliness among international university students is common around the world. International students are removed from their social networks and live in a different culture, often one that speaks a different language. Typically, international students can prevent loneliness by participating in social activities to receive ‘social support,’ the sense that they are cared for by the people with whom they socialize. During the pandemic, however, many group-based activities and social gatherings have been cancelled or prohibited.

Additionally, the researchers identified that the online social opportunities that became available in the pandemic may be less accessible to international students because of language and cultural differences.

Flow reduces loneliness

According to the researchers, reduced loneliness is associated with engaging in enjoyable activities that require both concentration and skill.

“When people become engrossed in what they are doing, they enter a state that is called ‘flow,'” Dattilo explained. “Flow can be achieved by engaging in mental or physical activities that we value and that require us to concentrate fully to use our skills.”

For people to achieve a state of flow, an activity must require a good deal of their skill but not be so difficult that it seems impossible. Additionally, it must demand concentration to execute and be meaningful to the participant. Artistic endeavors like playing the piano or painting can induce flow. So can physical activities like skiing or chopping wood, along with mental tasks like writing or storytelling. What induces flow differs from person to person based on individual skills and values.

“When we enter a state of flow, we become absorbed and focused, and we experience momentary enjoyment,” Dattilo continued. “When we leave a state of flow, we are often surprised by how much time has passed.”

People with extensive free time — like college students who are locked down during a pandemic, or people who live in a nursing home — can achieve flow when they engage in activities they find to be meaningful. In this way, time passes quickly for them, their life has meaning, and their experience of loneliness is reduced, according to the researchers.

Social support from friends and acquaintances is a primary way that people reduce loneliness. For many people, however, obtaining adequate social support can be challenging. Though the researchers found that students with high levels of social support were less lonely, they found that flow was even more important to reducing loneliness. Helping people achieve flow can reduce loneliness in situations where social support is insufficient. More importantly, it can reduce loneliness for people in any situation.

Encouraging flow for everyone

Some activities never induce flow, while other activities may or may not, depending on the individual. According to Dattilo, there is nothing wrong with watching television, but, typically, it does not help people enter a state of flow because they are unlikely to experience any challenges. Additionally, different people find different activities meaningful and enjoyable. Nursing home residents are unlikely to enjoy playing bingo if they did not enjoy similar games when they were younger, said Dattilo.

“Learning which activities might enable someone to enter a state of flow requires asking questions and listening,” said Dattilo. “People tend to thrive on healthy engagement and challenge. My collaborators and I hope that this research will help people live fuller, happier, healthier lives.”

This research was funded by the Ministry of Science and Technology in Taiwan. Liang-Chih Chang of National Open University in New Taipei City, Taiwan was the lead author of this research. Pei-Chun Hseih of Brock University in Ontario, Canada and Fei-Hsin Huang of Lungwha University of Science and Technology in Taoyuan City, Taiwan also contributed to this research.