. Scientific Frontline

Thursday, December 21, 2023

The future of canine stem cell therapy: unprecedented, painless, and feeder-free

Generating canine induced pluripotent stem cells (iPSCs) without using feeder cells   Scientists created canine iPSCs from urine-derived cells with great efficiency     
Illustration Credit: Shingo Hatoya, Osaka Metropolitan University

Dog owners may need to learn to appreciate their best friend’s urine. Scientists at Osaka Metropolitan University have devised an efficient, non-invasive, and pain-free method to reprogram canine stem cells from urine samples, bringing furry companions one step closer to veterinary regenerative treatment.

Induced pluripotent stem cells (iPSCs) have been widely employed in studies on human generative medicine. With the growing importance of advanced medical care for dogs and cats, there is an expectation that new therapies utilizing iPSCs will be developed for these companion animals, just as they have been for humans. Unfortunately, canine somatic cells exhibit lower reprogramming efficiency compared to those of humans, limiting the types of canine cells available for generating iPSCs. IPSC induction often involves using feeder cells from a different species. However, considering the associated risks, minimizing xenogeneic components is often advisable, signifying the need to improve the efficiency of reprogramming various types of canine cells in dogs without using feeder cells.

Moderation surpasses excess

DYRK1A bound to FAM53C in the cytoplasm is less active. DYRK1A not bound to FAM53C in the nucleus is highly active. Functional abnormalities cause various neuropsychiatric developmental and functional disorders. 
Illustration Credit: KyotoU/Gakuji Tobiyama/Yoshihiko Miyata

Down syndrome, a congenital disorder stemming from abnormal cell division and differentiation, is most common in newborns fated to neurodevelopmental delays and other health complications.

The genetic defect causes the dysfunction of the protein kinase DYRK1A, which is encoded on chromosome 21 and is deeply associated with both Down syndrome and autism spectrum disorder. DYRK1A has attracted attention as a target molecule for treating various diseases, but specific cellular mechanisms regulating the enzyme DYRK1A have yet to be made clear.

Now, researchers at Kyoto University have identified the FAM53C protein and its DYRK1A-inhibiting effect that keeps the protein kinase inactive inside the cytoplasm.

Artery calcification more common in night owls


Artery calcification is almost twice as common in night owls compared to early birds, according to a study from the University of Gothenburg, Sweden. Circadian rhythm appears to be particularly important for the heart and blood vessels during the early stages of the disease.

Artery calcification, or atherosclerosis as it is also known, involves fatty deposits accumulating on the inside of the arteries, making it harder for blood to pass through. The disease develops over a very long period of time, and is not noticed until it leads to angina, blood clots, heart attack, or stroke. Previous research has shown that people with late-night habits have an increased risk of cardiovascular disease, but this is the first study to show how circadian rhythm specifically affects artery calcification.

Coronary artery calcification

The study, which has been published in the journal Sleep Medicine, involved 771 men and women aged between 50 and 64, all of whom are part of the larger population study SCAPIS. The degree of artery calcification in the heart’s coronary arteries was examined using computer tomography. Participants themselves indicated their so called chronotype on a five-point scale: extreme morning type, morning type to some extent, neither morning nor evening type, evening type to some extent, or extreme evening type.

Common insect species are suffering the biggest losses

The invasive Asian Ladybeetle (Harmonia axyridis)
Photo Credit: Melani Marfeld

Insect decline is being driven by losses among the locally more common species, according to a new study published in Nature. Led by researchers at the German Centre for Integrative Biodiversity Research (iDiv) and the Martin Luther University Halle-Wittenberg (MLU), the meta-analysis of 923 locations around the world notes two significant trends: Species with the most individuals are disproportionately decreasing in number, and no other species have increased to the high numbers previously seen. This likely explains the frequent observation that there are fewer insects around now than ten, twenty, or thirty years ago.

Researchers at iDiv looked at long-term trends of land-based insects, such as beetles, moths, and grasshoppers, and found that decreases in the number of the formerly most common species have contributed most to local insect declines. Common or abundant insect species are those species that are locally found in the highest numbers, but which species these are differ among locations. The study’s findings challenge the idea that changes in insect biodiversity result from rarer species disappearing.

The study follows the recent sounding of alarm bells about insect loss, as researchers note dramatic declines in the total number of insects in many parts of the world. However, little is known about the general trends among locally rare and abundant species over long periods. "It was obvious this needed exploring," says Roel van Klink, lead author of the study and senior scientist at iDiv and MLU. "We had to know whether observations about declines in total abundances of insects differed among common and rare species, and how this translated into changes in the overall insect diversity."

Multitasking microbes: UW–Madison scientists engineer bacteria to make two valuable products from plant fiber

Ben Hall, Genetics Ph.D. Student, holds a mixed sample of microbes and carotenoids, in Tim Donohue’s lab.
Photo Credit: Chelsea Mamott

We often look to the smallest lifeforms for help solving the biggest problems: Microbes help make foods and beverages, cure diseases, treat waste and even clean up pollution. Yeast and bacteria can also convert plant sugars into biofuels and chemicals traditionally derived from fossil fuels — a key component of most plans to slow climate change.

Now University of Wisconsin–Madison researchers have engineered bacteria that can produce two chemical products at the same time from underutilized plant fiber. And unlike humans, these multitasking microbes can do both things equally well.

“To my knowledge, it’s one of the first times you can make two valuable products simultaneously in one microbe,” says Tim Donohue, UW–Madison professor of bacteriology and director of the Great Lakes Bioenergy Research Center.

The discovery, detailed in a paper in the December issue of the journal Applied and Environmental Microbiology, could help make biofuels more sustainable and commercially viable.

“In principle, the strategy lowers the net greenhouse gas emissions and improves the economics,” Donohue says. “The amount of energy and greenhouse gas that you need to make two products in one pot is going to be less than running two pots to make one product in each pot.”

Novel Catalyst System for CO2 Conversion

Kevinjeorjios Pellumbi with the experimental setup for CO2 conversion
Photo Credit: © RUB, Marquard

Researchers are constantly pushing the limits of technology by breaking new ground in CO2 conversion. Their goal is to turn the harmful greenhouse gas into a valuable resource.

Research groups around the world are developing technologies to convert carbon dioxide (CO2) into raw materials for industrial applications. Most experiments under industrially relevant conditions have been carried out with heterogeneous electrocatalysts, i.e. catalysts that are in a different chemical phase to the reacting substances. However, homogeneous catalysts, which are in the same phase as the reactants, are generally considered to be more efficient and selective. To date, there haven’t been any set-ups where homogeneous catalysts could be tested under industrial conditions. A team headed by Kevinjeorjios Pellumbi and Professor Ulf-Peter Apfel from Ruhr University Bochum and the Fraunhofer Institute for Environmental, Safety and Energy Technology UMSICHT in Oberhausen has now closed this gap. The researchers outlined their findings in the journal Cell Reports Physical Science.

“Our work aims to push the boundaries of technology in order to establish an efficient solution for CO2 conversion that will transform the climate-damaging gas into a useful resource,” says Ulf-Peter Apfel. His group collaborated with the team led by Professor Wolfgang Schöfberger from the Johannes Kepler University Linz and researchers from the Fritz Haber Institute in Berlin.

New brain-like transistor mimics human intelligence

An artistic interpretation of brain-like computing.
Illustration Credit: Xiaodong Yan/Northwestern University

Taking inspiration from the human brain, researchers have developed a new synaptic transistor capable of higher-level thinking.

Designed by researchers at Northwestern University, Boston College and the Massachusetts Institute of Technology (MIT), the device simultaneously processes and stores information just like the human brain. In new experiments, the researchers demonstrated that the transistor goes beyond simple machine-learning tasks to categorize data and is capable of performing associative learning.

Although previous studies have leveraged similar strategies to develop brain-like computing devices, those transistors cannot function outside cryogenic temperatures. The new device, by contrast, is stable at room temperatures. It also operates at fast speeds, consumes very little energy and retains stored information even when power is removed, making it ideal for real-world applications.

“The brain has a fundamentally different architecture than a digital computer,” said Northwestern’s Mark C. Hersam, who co-led the research. “In a digital computer, data moves back and forth between a microprocessor and memory, which consumes a lot of energy and creates a bottleneck when attempting to perform multiple tasks at the same time. On the other hand, in the brain, memory and information processing are co-located and fully integrated, resulting in orders of magnitude higher energy efficiency. Our synaptic transistor similarly achieves concurrent memory and information processing functionality to more faithfully mimic the brain.”

Gravity data could reveal underwater volcanoes with high potential for devastating eruptions

This looping video shows an umbrella cloud generated by the underwater eruption of the Hunga Tonga-Hunga Ha’apai volcano on Jan. 15, 2022. The GOES-17 satellite captured the series of images that also show crescent-shaped shock waves and lightning strikes.
Video Credit: NASA Earth Observatory image by Joshua Stevens using GOES imagery courtesy of NOAA and NESDIS

New research led by Carnegie’s Hélène Le Mével reveals new details about the system of magma chambers under the Hunga volcano, both before and after its disastrous 2022 eruption. The team’s findings, published last week in Science Advances, demonstrate a new method for probing submarine volcanoes for their potential to cause similar damage.

The eruption came at the end of a month-long period of volcanic unrest, following a seven-year hiatus for the volcano—devastating the Kingdom of Tonga islands and causing a global tsunami, an unprecedented amount of volcanic lightning, and perturbations in the upper atmosphere. . It was the largest explosive eruption recorded since Pinatubo in 1991.

“Although we have a wealth of data about the Hunga eruption’s effects both locally and globally, we know very little about its subsurface structure,” Le Mével explained.

Wednesday, December 20, 2023

Researchers uncover on/off switch for breast cancer metastasis

Songnan Wang (left) and Lingyin Li (right) found that a protein called ENPP1 acts as an on/off switch for breast cancer metastases. High protein levels lead to a high chance of metastasis (as seen by cells growing in the dish on the left), while low levels lead to no metastasis (as seen by no cells growing in the dish on the right).
Photo Credit: Lingyin Li and Songnan Wang

New research from Stanford and the Arc Institute could lead to a new and more effective immunotherapy and help clinicians better predict patient response to existing medicines.

Despite their promise, immunotherapies fail to treat many cancers, including over 80% of some of the most advanced breast cancers. And many of those patients who do respond still experience metastases eventually. New research from Stanford University and the Arc Institute has revealed a better way to predict and improve patient responses.

A team led by Lingyin Li, associate professor of biochemistry at Stanford and Arc Core Investigator, found that a protein called ENPP1 acts as an on/off switch that controls breast cancer’s ability to both resist immunotherapy and metastasize. The study, published on Dec. 20 in the Proceedings of the National Academy of Sciences, showed that ENPP1 is produced by cancer cells and by healthy cells in and around the tumor, and that high patient ENPP1 levels are linked to immunotherapy resistance and subsequent metastases. The research could lead to new, more effective immunotherapies and help clinicians better predict patient response to existing medicines.

“Our study should offer hope for everyone,” said Li, who is also an institute scholar at Sarafan ChEM-H.

RIT researchers develop new technique to study how cancer cells move

Vinay Abhyankar, right, assistant professor of biomedical engineering, works closely with two doctoral students, Mehran Mansouri, left, and Indranil Joshi, on research to assess cancer cell migration processes.
Photo Credit: A. Sue Weisler/RIT

In tumors, cells follow microscopic fibers, comparable to following roads through a city. Researchers at the Rochester Institute of Technology developed a new technique to study different features of these “fiber highways” to provide new insights into how cells move efficiently through the tumor environment.

The study, published in the journal Advanced Functional Materials, focused on contact guidance, a process where migrating cells follow aligned collagen fibers. Understanding this process is crucial, as it plays a key role in cancer metastasis, the spread of cancer to other parts of the body.

“Previous research on contact guidance, a process where cancer cells migrate along aligned collagen fibers, has been largely studied in collagen gels with uniform fiber alignment,” said Vinay Abhyankar, associate professor of biomedical engineering in RIT’s Kate Gleason College of Engineering, and study co-author. “However, the tumor microenvironment also features subtle variations or gradients in fiber alignment, and their role in cell migration has been largely unexplored. We suspected that alignment gradients could efficiently direct cell movement but lacked the technology to test the hypothesis.”

Featured Article

Discovery of unexpected collagen structure could ‘reshape biomedical research’

Jeffrey Hartgerink is a professor of chemistry and bioengineering at Rice. Photo Credit: Courtesy of Jeffrey Hartgerink / Rice University Co...

Top Viewed Articles