Saturday, September 28, 2024

 

Fruit juice offers a fresh take on kombucha




American Chemical Society
Fruit juice offers a fresh take on kombucha 

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Researchers brewed kombucha (left) and kombucha-like beverages from passion fruit (center) and apple (right) juices and found that the apple-based drink had the most flavonoids and ranked most favorable among a panel of taste testers.

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Credit: Adapted from ACS Agricultural Science & Technology 2024, DOI:10.1021/acsagscitech.4c00372





Kombucha is a fizzy, tangy drink made by fermenting tea. But brewers are now fermenting other plant-based drinks to explore nutritional properties and flavors. Researchers in ACS Agricultural Science & Technology compared the biochemistry and flavor of kombucha with brews made from apple and passion fruit juices. They found that the apple beverage contained high levels of bioactive compounds called flavonoids and ranked highly among taste testers, signaling its promise as a kombucha alternative.

To make kombucha, brewers ferment sweetened tea with a spongy disk of microbes known as a SCOBY, or symbiotic culture obacteria and yeast. The resulting beverage contains beneficial bacteria from the fermentation process and bioactive compounds from the tea, including flavonoids, phenolics and anthocyanins that may have antioxidant and anti-inflammatory properties. Few studies have investigated whether liquids other than tea could be brewed as kombucha-like beverages with boosted antioxidant levels or unique flavors. So, Socorro Vanesca, Frota Gaban and coworkers fermented antioxidant-rich apple and passion fruit juices with a SCOBY to find out.

After fermenting apple juice, passion fruit juice, and tea in separate jars for 10 days at room temperature, the researchers measured the levels of several bioactive compounds in each brew and found that:

  • The apple beverage had the highest level of flavonoids, followed by kombucha and the passion fruit drink.
  • The kombucha and apple beverages had comparable levels of phenolic compounds that were higher than those of the passion fruit beverage.
  • All three brews had similar amounts of anthocyanin, a red-colored antioxidant.

The researchers asked 12 volunteer taste testers to evaluate each beverage’s color, aroma and flavor. The taste testers noted an amber color for the apple beverage, yellow for passion fruit and gold for the kombucha. The volunteers reported stronger, fruitier aromas for the fermented fruit juices compared with the tea. However, the passion fruit drink tasted more bitter than the sweeter apple and tea drinks, both of which received equal votes as the favorite beverage. Because fermented apple juice has more flavonoids and a pleasant taste compared with the other beverages, the researchers say it could be a successful alternative to kombucha made from tea. They plan to explore health benefits and flavors of other fermented fruits in the future.

The authors acknowledge funding from the Coordination for the Improvement of Higher Education Personnel.

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The American Chemical Society (ACS) is a nonprofit organization chartered by the U.S. Congress. ACS’ mission is to advance the broader chemistry enterprise and its practitioners for the benefit of Earth and all its people. The Society is a global leader in promoting excellence in science education and providing access to chemistry-related information and research through its multiple research solutions, peer-reviewed journals, scientific conferences, e-books and weekly news periodical Chemical & Engineering News. ACS journals are among the most cited, most trusted and most read within the scientific literature; however, ACS itself does not conduct chemical research. As a leader in scientific information solutions, its CAS division partners with global innovators to accelerate breakthroughs by curating, connecting and analyzing the world’s scientific knowledge. ACS’ main offices are in Washington, D.C., and Columbus, Ohio.

Registered journalists can subscribe to the ACS journalist news portal on EurekAlert! to access embargoed and public science press releases. For media inquiries, contact newsroom@acs.org.

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Increased antioxidants and phenolic compounds produced in salted red perilla leaves during Japanese apricot pickling



Antioxidant content and activity are increased during the processing and digestion of Japanese apricots pickled with salted red perilla leaves



Chiba University

Comparison of Processing Components and Red-Colored Shiso-Zuke Umeboshi with Control Group. 

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Sampling was conducted at three stages: during simple salt pickling, after 30 days of pickling with salted perilla leaves, and after 60 days of pickling with salted perilla leaves. The resulting Shiso-zuke Umeboshi had a distinctive red appearance.

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Credit: Prof. Yukiharu Ogawa from Chiba University




The diverse biochemical composition of Japanese apricot fruits explains their broad spectrum of action on the human body. The high levels of key phenolic compounds and hydroxycinnamic acids contribute to various health benefits including anti-inflammatory, antioxidant, and antimicrobial properties.

A recent study published in Food Research International on July 19, 2024, led by Prof. Yukiharu Ogawa and Jutalak Suwannachot from Chiba University, quantitatively evaluated the changes in phenolic compounds and antioxidant activity during the production of Shiso-zuke Umeboshi (PP). The study also simulated the digestive process to characterize the release of these compounds and their antioxidant activity.

“Some of the benefits have been observed in pickling with red perilla (PP), but the current data are still limited. Many recent efforts have been focused on creating functional foods, which are designed to provide health benefits and essential nutrients in addition to the traditional micronutrients. However, there remains uncertainty regarding the specific effects of apricot pickled with red perilla (Shiso-zuke Umeboshi, PP). This motivated our study,” explains Prof. Ogawa.

In this study, the production of perilla-pickled apricots involved three methods: simple salt pickling (SP), pickling with salted perilla leaves for 30 days (30-PP), and pickling with salted perilla leaves for 60 days (PP). The pickle samples underwent ultrasonic-assisted treatment, after which the supernatants were extracted from the mixture by centrifugation to quantify free and esterified phenolics in the aqueous phase. The remaining residue was used to analyze the insoluble-bound phenolics in the organic phase.

All three phenolic fractions were assessed using liquid chromatography-mass spectrometry (HPLC-PDA-QDa), with a focus on their peak areas at 280 and 320 nm wavelengths.

The researchers evaluated total phenolic content (TPC) using the Folin-Ciocalteu reagent test. The Total flavonoid content (TFC) was determined via a 96-well microplate method combined with an aluminum chloride (AlCl3) colorimetric assay. Antioxidant activity was then assessed at 740 nm, with results expressed in millimoles (mmol).

The scientists modeled the gastrointestinal digestion of apricot pickles. They adjusted the sample’s pH to simulate the conditions of the different parts of the digestive tract. Next, digestive enzymes were introduced, and the digested fractions were filtered. The components were then identified, and their antioxidant activity was measured.

The HPLC chromatogram revealed rosmarinic, caffeic, p-coumaric, and ferulic acids as the main phenolic compounds detected. A comparative analysis of the three samples showed an increase in the concentration of bioactive compounds from the 30-day pickling stage (30-PP) to the finished product (PP). Among all phenolics, rosmarinic acid (RA) was the most predominant in all the samples. Ferulic acid was detected in smaller concentrations, particularly in esterified fractions that also showed higher levels of caffeic and p-coumaric acids. The lower concentration of ferulic acid is likely due to its low water solubility.

In the simulated in vitro digestion, differences between salt pickling (SP) and salt pickling with perilla (PP) were analyzed at various stages: before digestion (G0), 60 minutes after gastric digestion (G60), at the transition to intestinal digestion after 60 minutes (G60), and 120 min into small intestinal digestion (I120).

The highest release of bioactive compounds occurred at G0, while the lowest levels were observed at G60. However, a significant increase in bioactive compound release was noted between G60 and I120. At I120, both SP and PP showed the highest release of TPC and TFC. These results can be attributed to the influence of pH conditions and intestinal enzymes, which likely enhanced TPC and TFC levels.

For antioxidant activity, PP demonstrated a higher potential throughout the in vitro gastrointestinal digestion from 1 hour of gastric digestion through the final stage of small intestinal digestion, in contrast, SP exhibited a more steady trend. Overall, the acidic conditions during pickling appear to enhance the availability of RA and other perilla compounds.

“The health benefits of Japanese apricot pickles are mainly derived from the antioxidant compounds of the red perilla, which acts as both a natural food color and a health-promoting ingredient,” concludes the lead researcher Jutalak Suwannachot.

About Professor Yukiharu Ogawa
Yukiharu Ogawa is a Professor at the Graduate School and Faculty of Horticulture, Chiba University, Japan. He has previously held positions at National Food Research Institute in Tsukuba, the USDA Western Regional Research Center in California as a post-doctoral fellow, and at Kurashiki-Sakuyo University as a lecturer. The main area of his scientific work is agricultural and food process engineering, with a specific focus on food quality evaluation. His work aims to understand the impact of postharvest, food processing, and cooking procedures on the digestibility of processed food materials using simulated in vitro digestion techniques. He is also involved in developing long-term storage methods for fresh-cut vegetables and fruits monitored using atmospheric and lighting parameters.

 

Artificial intelligence may enhance patient safety, say BU researchers


Study marks an important first step towards leveraging AI technology to reduce preventable harms, achieve better healthcare outcomes




Boston University School of Medicine




(Boston) — Generative artificial intelligence (genAI) uses hundreds of millions, sometimes billions, of data points to train itself to produce realistic and innovative outputs that can mimic human-created content. Its applications include personalized recommendations for online shoppers, creating audio and visual content and accelerating engineering design. In healthcare, possible genAI uses include enhancing imaging technologies, predicting the course of a disease in an individual patient and discovering new vaccines.

BU researchers tested an advanced publicly available genAI model, GPT-4, to determine its ability to answer questions across five key areas of patient safety in the 50-question self-assessment for the Certified Professional in Patient Safety (CPPS) exam, a standardized multiple-choice certification exam for patient safety professionals. GPT-4 answered 88% of the questions correctly, demonstrating a high level of performance.

“While other studies have looked at genAI's performance on exams from different healthcare specialties over the past year, ours is the first robust test of its proficiency specifically in patient safety,” said corresponding author Nicholas Cordella, MD, MSc, assistant professor of medicine at BU Chobanian & Avedisian School of Medicine. 

James Moses, MD, MPH, formerly an associate professor of pediatrics at the school and now chief  of quality, safety and patient experience at Corewell Health in Michigan, is a co-author of the study.

The researchers presented questions from the CPPS self-assessment exam to the GPT-4 model without any additional training or medical fine-tuning. They then evaluated the model's performance across various exam categories. They found GPT-4 performed particularly well in the domains of Patient Safety and Solutions, Measuring and Improving Performance, and Systems Thinking and Design/Human Factors. Based on the strength of those results, the researchers outlined areas where patient safety professionals could begin to conduct more testing of the real-world strengths and weaknesses of AI.

“Our findings suggest that AI could help doctors better recognize, address and prevent mistakes in hospitals and clinics. While more research is needed to fully understand what current AI can do in patient safety, this study shows that AI has some potential to improve healthcare by assisting clinicians in addressing preventable harms,” said Cordella who also is medical director for quality and patient safety at Boston Medical Center.

He believed the use of AI holds promise for improving patient safety systems and better tackling the intractable problem of medical errors, which are estimated to cause approximately 400,000 deaths every year.

Cordella said the study aligns with the broader idea that AI can help professionals, including doctors, enhance their work. By using AI to support their tasks, clinicians may be able to improve the safety and efficiency of healthcare, similar to how other knowledge workers are adapting AI to boost their performance.

The study also revealed limitations in current AI technology and cautioned that users must remain vigilant for bias, false confidence, fabricated data or hallucinations in large language model (like GPT-4) responses.

"Our findings suggest that AI has the potential to significantly enhance patient safety, marking an enabling step towards leveraging this technology to reduce preventable harms and achieve better healthcare outcomes. However, it's important to recognize this as an initial step, and we must rigorously test and refine AI applications to truly benefit patient care," said Cordella.

These findings appear online in the Joint Commission Journal on Quality and Patient Safety.

 

Alarming surge: Global crisis of childhood overweight and obesity



Researchers ‘sound the alarm’ in commentary



Florida Atlantic University

Global Crisis of Childhood Overweight and Obesity 

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The deleterious consequences of this epidemic are already evident: childhood hypertension, type 2 diabetes, among others. Researchers sound the alarm and discuss both challenges and potential solutions. 

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Credit: Alex Dolce, Florida Atlantic University




Since 1990, the rise in childhood overweight and obesity has surged across every continent, almost doubling in prevalence. While the United States has the highest prevalence, other nations are not far behind.

In Southern Europe, including Greece, Italy and Spain, 10 to 15% of children are obese, while Eastern European countries have somewhat lower rates, but are experiencing a rapid increase that may soon match Southern Europe. Globally, Asia has nearly half of all overweight children under the age of 5, and Africa has one-quarter of such children. In Latin America, about 20% of children under 20 are overweight. Many developing countries face the dual challenge of both overweight/obesity and malnutrition in their children.

The deleterious consequences of this epidemic are already evident: childhood hypertension, type 2 diabetes, among others. Researchers from Florida Atlantic University’s Schmidt College of Medicine and colleagues sound the alarm and discuss both challenges and potential solutions in a commentary published in The Maternal and Child Health Journal.

“Pediatric overweight and obesity have reached epidemic levels in the U.S. and are becoming a pandemic globally. These conditions lead to high blood pressure, type 2 diabetes and lipid disorders, which contribute to metabolic syndrome. In adults, these issues significantly increase the risks of heart attacks, stroke, liver disease, obstructive sleep apnea, arthritis and certain cancers – many of which are now occurring at younger ages,” said Charles H. Hennekens, M.D., first author and the first Sir Richard Doll Professor of Medicine and Preventive Medicine, FAU Schmidt College of Medicine. “Through coordinated clinical and public health efforts, we can address these troubling trends and work toward a healthier future for children and families globally.”

In the commentary, the authors report on the leading causes of this epidemic including high body mass index (BMI), which increases the risks of many serious health issues. In the U.S., a preschooler is considered overweight if their BMI exceeds the 85th percentile. Research shows that these children are at a significantly higher risk of being overweight during adolescence compared to those with a BMI at the 50th percentile. This underscores the misconception that children simply “outgrow” overweight issues.

In addition, the authors note that health care providers and public health practitioners face major challenges in boosting daily physical activity among children, which is crucial for increasing metabolic rates, lowering BMI, and reducing future risks of coronary heart disease.

“With declining physical education in schools and excessive time spent on electronic devices, many children fail to meet recommended activity guidelines. This sedentary behavior contributes to overweight and obesity through poor diet, reduced sleep, and decreased physical activity,” said Panagiota “Yiota” Kitsantas, Ph.D., co-author and professor and chair, FAU Department of Population Health and Social Medicine, Schmidt College of Medicine. “Encouraging organized, enjoyable activities rather than competitive ones can help children achieve necessary physical activity levels.”

The authors also caution that while increasing levels of daily physical activity is necessary, it isn’t sufficient to make a major impact on the rates of childhood overweight and obesity. The rise of high sugar containing foods, along with consumption of ultra-processed foods also are major contributors.

“Nearly 70% of the average U.S.-based child’s diet is made up of ultra-processed foods,” said Hennekens. “Moreover, consumption of ultra-processed foods among children under 24 months is rising worldwide, triggering not only the potential of developing obesity but also decreased immunological protection.”

The authors say that more research is needed to pinpoint which components of ultra-processed foods contribute to weight gain in children. However, they warn that a diet high in ultra-processed foods is linked to rising rates of overweight and obesity, with schools being a major source of these foods.

“Evidence suggests that enhancing school lunch nutritional standards could help reduce obesity, particularly among low-income children,” said Kitsantas. “We recommend adopting school food policies that remove ultra-processed foods from menus and promote healthier alternatives, alongside educational programs on healthy eating, despite the challenges posed by external influences on children.”

Among the challenges highlighted in the commentary is the use of social media and advertising, which significantly affect children’s food choices and behaviors that include sharing unhealthy food posts and recognizing many unhealthy food brands upon exposure. 

“Despite recommendations from the World Health Organization and public health authorities to restrict food marketing aimed at children, few countries have implemented such measures,” said Hennekens. “The effectiveness of existing regulations in today’s media landscape is uncertain, creating an opportunity for health providers and public health practitioners to educate families about the impact of this advertising.”

The authors explain that addressing the rising pediatric obesity epidemic requires a multifaceted approach. In 2023, the American Academy of Pediatrics endorsed WHO guidelines and released their own recommendations for managing pediatric overweight and obesity. These guidelines advise health care providers and public health practitioners to tackle social determinants of health, use motivational interviewing to modify nutrition and activity behaviors, and consider pharmacotherapy or surgery to meet personalized patient goals.

However, the authors say that while there are approved drug therapies available, before prescribing pharmacologic options, maternal and child health care providers should employ therapeutic lifestyle changes.

“While the ultimate goal is prevention of pediatric overweight and obesity as well as metabolic syndrome, to paraphrase Voltaire, we should not ‘let the perfect be the enemy of the good,’” said Hennekens.

In conclusion, the authors urge leveraging all available resources to at least stabilize the rising rates of childhood obesity and its associated health issues. Ignoring these challenges could lead to an unprecedented global epidemic of childhood and adolescent obesity, with severe future health consequences, as seen in the U.S.

“Health care and public health professionals must collaborate across disciplines to address these issues with patients, families, communities and policymakers. United efforts can help reverse these troubling trends and ensure a healthier future for children worldwide,” said Kitsantas.

Other co-authors are Dawn Harris Sherling, M.D.; Allison H. Ferris, M.D., associate professor and chair, Department of Medicine, FAU Schmidt College of Medicine; Alicia Caceres, a fourth-year premedical student at Tufts University; Katerina Benson, a third-year pre-medical student at FAU; Alexandra Rubenstein, a second-year medical student at Tufts University School of Medicine; and Sarah K. Wood, M.D., director, Harvard Macy Institute, Harvard Medical School, and former interim dean and professor and chair of maternal and child health, FAU Schmidt College of Medicine.

- FAU -

About the Charles E. Schmidt College of Medicine:

FAU’s Charles E. Schmidt College of Medicine is one of approximately 157 accredited medical schools in the U.S. The college was launched in 2010, when the Florida Board of Governors made a landmark decision authorizing FAU to award the M.D. degree. After receiving approval from the Florida legislature and the governor, it became the 134th allopathic medical school in North America. With more than 70 full and part-time faculty and more than 1,300 affiliate faculty, the college matriculates 64 medical students each year and has been nationally recognized for its innovative curriculum. To further FAU’s commitment to increase much needed medical residency positions in Palm Beach County and to ensure that the region will continue to have an adequate and well-trained physician workforce, the FAU Charles E. Schmidt College of Medicine Consortium for Graduate Medical Education (GME) was formed in fall 2011 with five leading hospitals in Palm Beach County. The Consortium currently has five Accreditation Council for Graduate Medical Education (ACGME) accredited residencies including internal medicine, surgery, emergency medicine, psychiatry, and neurology.

 

About Florida Atlantic University:
Florida Atlantic University, established in 1961, officially opened its doors in 1964 as the fifth public university in Florida. Today, the University serves more than 30,000 undergraduate and graduate students across six campuses located along the southeast Florida coast. In recent years, the University has doubled its research expenditures and outpaced its peers in student achievement rates. Through the coexistence of access and excellence, FAU embodies an innovative model where traditional achievement gaps vanish. FAU is designated a Hispanic-serving institution, ranked as a top public university by U.S. News & World Report and a High Research Activity institution by the Carnegie Foundation for the Advancement of Teaching. For more information, visit www.fau.edu.

 

 

Statement by NIH on research misconduct findings




NIH/Office of the Director



 

Following an investigation, the National Institutes of Health (NIH) has made findings of research misconduct against Eliezer Masliah, M.D., due to falsification and/or fabrication involving re-use and relabel of figure panels representing different experimental results in two publications. NIH will notify the two journals of its findings so that appropriate action can be taken. NIH initiated its research misconduct review process in May 2023 after it received allegations from the HHS Office of Research Integrity (ORI) that same month. NIH began its investigation phase in December 2023, concluded its investigation of these allegations on September 15, 2024, and notified HHS ORI of its findings.

 

Dr. Masliah joined the agency in the summer of 2016 as director of the Division of Neuroscience (DN) at the National Institute on Aging and an NIH intramural researcher investigating synaptic damage in neurodegenerative disorders. He has published numerous papers as an NIH intramural researcher. Currently, Dr. Masliah is not serving in the capacity of director of the NIA DN. Amy Kelley, M.D., NIA Deputy Director, is also serving as the Acting NIA DN Director. Beyond this information, NIH does not discuss personnel matters.

 

Any allegations involving Dr. Masliah’s NIH-supported extramural research prior to joining NIH would be referred to HHS ORI, consistent with NIH policies and procedures.  

 

Satellite data fusion enhances the early detection of convective clouds




Institute of Atmospheric Physics, Chinese Academy of Sciences
Developing cumulus clouds 

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Developing cumulus clouds

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Credit: Yang Gao




As global warming continues, convective weather events are becoming more frequent. The early stage of these storms, known as convective initiation (CI), can be monitored using geostationary satellites. However, detecting CI accurately remains a challenge. The current detection methods still have a high rate of false alarms and missed events. One key reason for this is that the resolution of existing geostationary meteorological satellites is not yet precise enough to meet the requirements for better detection.

To address this issue, researchers from the National Satellite Meteorological Center in China have proposed a new fusion method in which the high-resolution texture information provided by Gaofen-4 (GF-4), an Earth observation satellite, is combined with the multispectral data of Fengyun-4A (FY-4A), a geostationary meteorological satellite. This approach retains the detection advantages of each satellite, ensuring the accuracy of spectral information, while fully considering the early growth patterns of convective clouds, thereby significantly enhancing the capability to detect CI. The results have recently been published in Atmospheric and Oceanic Science Letters.

The fused data revealed a notable improvement in the detection of smaller-scale convective clouds, which often develop rapidly and can be difficult to capture using traditional observation methods. By leveraging high-resolution Earth observation satellites, forecasters gain the ability to identify these clouds much earlier in their formation.

"This early detection is particularly important as small convective clouds can quickly evolve into severe weather systems, such as thunderstorms or localized heavy rainfall", says the corresponding author, Prof. Xin Wang. "The integration of these detailed satellite data helps improve the timing of forecasts, allowing meteorologists to track cloud development with greater accuracy and issue earlier, more reliable warnings".

Beyond simply detecting clouds earlier, the integration of high-resolution satellite data enhances the precision of identifying where these clouds will form and intensify. This added spatial accuracy is crucial in understanding localized weather patterns, which may have been previously overlooked.

"For decision-makers, this means not only having a more detailed picture of the early stages of convective cloud development, but also having access to data that informs strategic responses," says Yang Gao, one of the other authors of the paper.

By pinpointing the exact locations of potential severe weather systems, this advanced detection method enables more targeted and efficient disaster preparedness and mitigation efforts.

"Ultimately, it improves our ability to safeguard communities from the impacts of extreme weather," Professor Wang concludes.

 ANOTHER AQUARIST FAVORITE

Stowers scientists uncover a critical component that helps killifish regenerate their fins



The findings are a step toward closing the gap on how we could one day deploy regenerative medicine in humans



Stowers Institute for Medical Research

Stowers scientists discuss new insights into how killifish regenerate their fins 

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Stowers scientists discuss findings of killifish limb regeneration research, shedding light on the evolutionary aspects of regeneration and the potential for developing novel therapeutic strategies in regenerative medicine for humans. 

 

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Credit: Stowers Institute for Medical Research





KANSAS CITY, MO—September 26, 2024—Spontaneous injuries like the loss of a limb or damage to the spinal cord are impossible for humans to repair. Yet, some animals have an extraordinary capacity to regenerate after injury, a response that requires a precise sequence of cellular events. Now, new research from the Stowers Institute for Medical Research has unveiled a critical timing factor—specifically how long cells actively respond to injury—involved in regulating regeneration.

recent study published in iScience on September 20, 2024, sought to understand exactly how an organism knows how much tissue has been lost post-injury. Led by former Predoctoral Researcher Augusto Ortega Granillo, Ph.D., in the lab of Stowers President and Chief Scientific Officer Alejandro Sánchez Alvarado, Ph.D., the team investigated how African killifish properly regrow their tail fin following damage. By analyzing tissue dynamics during regrowth, they found that in addition to known factors, including how many cells are participating and where they are located, the length of time cells spend engaged in the repair process is also key.

“One of the greatest unsolved mysteries of regeneration is how an organism knows what has been lost after injury,” said Sánchez Alvarado. “Essentially, the study points to a new variable in the equation of regeneration. If we can modulate the rate and the length of time that a tissue can launch a regenerative response, this could help us devise therapies that may activate and perhaps prolong the regenerative response of tissues that normally would not do so.”

Shortly after a killifish tail injury, the remaining tissue needs to know how much damage has occurred. Then, this tissue must enlist the right number of repair cells to the site of injury for the right amount of time. Damage sensing, repair cell recruitment, and timing somehow must work together to regrow the tail.

“If an animal that can regenerate extremities, like a tail, loses just a tiny portion, how does it know not to regenerate a whole new tail but just the missing piece?” said Sánchez Alvarado. To address this question, the team probed different locations of injury in the killifish tail fin.

They found that skin cells both near an injury and in distant, uninjured regions launch a genetic program that primes the whole animal to prepare for a repair response. Then, skin cells at the site of injury sustain this response and temporarily change their state to modify the surrounding material called the extracellular matrix. Ortega Granillo likens this matrix to a sponge that absorbs secreted signals from the injured tissue that then guides repair cells to get to work. If the signals are not received or not interpreted correctly, the regeneration process may not restore the tail’s original shape and size.

“We very clearly defined when and where—at 24 hours post-injury and in the extracellular matrix—the transient cell state is acting in the fin tissue,” said Ortega Granillo. “Knowing when and where to look allowed us to make genetic disruptions and gain a better understanding of the function of these cell states during regeneration.”

To investigate whether these distinct cellular states communicate information to the extracellular matrix—the supportive structure surrounding cells—during the repair process, the researchers employed the CRISPR-Cas9 gene editing technique. They specifically targeted a gene known to modify the extracellular matrix, as they had observed its activation at the onset of the regeneration response. By disrupting the function of this gene, the team aimed to determine its role in relaying information from cells to the matrix during regeneration.  

“These modified animals no longer know how much tissue was lost,” said Ortega Granillo. “They still regenerated, but the speed of tissue growth was deficient. This is telling us that by changing the extracellular space, skin cells inform the tissue how much was lost and how fast it should grow.”

Indeed, the speed and amount of tissue regenerated in these genetically modified killifish increased regardless of whether the tail injury was mild or severe. This finding opens the possibility that cell states that modify the matrix increase regenerative regrowth. If the cell states could be adjusted, it may be a way to stimulate a more robust regeneration response.  

From an evolutionary perspective, understanding why certain organisms excel at regeneration while others, such as humans, have limited regenerative abilities is a driving force in the field of regenerative biology. By identifying general principles in organisms with high regenerative capacity, researchers aim to potentially apply these insights to enhance regeneration in humans. This comparative approach not only sheds light on the evolutionary aspects of regeneration but also holds promise for developing novel therapeutic strategies in regenerative medicine.

“Our goal is to understand how to shape and grow tissues,” said Ortega Granillo. “For people who sustain injuries or organ failure, regenerative therapies could restore function that was compromised during illness or following injury.”

Additional authors include Daniel Zamora, Robert Schnittker, Allison Scott, Alessia Spluga, Jonathon Russell, Carolyn Brewster, Eric Ross, Daniel Acheampong, Ning Zhang, Ph.D., Kevin Ferro, Ph.D., Jason Morrison, Boris Rubinstein, Ph.D., Anoja Perera, and Wei Wang, Ph.D.

This work was funded by institutional support from the Stowers Institute for Medical Research and the Howard Hughes Medical Institute.

About the Stowers Institute for Medical Research

Founded in 1994 through the generosity of Jim Stowers, founder of American Century Investments, and his wife, Virginia, the Stowers Institute for Medical Research is a non-profit, biomedical research organization with a focus on foundational research. Its mission is to expand our understanding of the secrets of life and improve life’s quality through innovative approaches to the causes, treatment, and prevention of diseases.

The Institute consists of 21 independent research programs. Of the approximately 500 members, over 370 are scientific staff that include principal investigators, technology center directors, postdoctoral scientists, graduate students, and technical support staff. Learn more about the Institute at www.stowers.org and about its graduate program at www.stowers.org/gradschool.

The African Killifish