. Scientific Frontline

Monday, November 6, 2023

Potential inheritable effects and ethical considerations of epigenome editing

Illustration Credit: Courtesy of Institute for the Advanced Study of Human Biology

Epigenome editing is an emerging technology used to regulate gene function by controlling epigenetic states at specific locations on the genome. This method is distinct from traditional genetic editing, which involves permanently altering the DNA sequence. Notably, the intervention effects of epigenome editing are thought to be reversible, making this technology particularly attractive for its potential therapeutic applications in the treatment of genetic disorders and chronic diseases. Although some researchers argue that it presents fewer ethical issues compared with permanent genome editing, especially in terms of its impact on offspring, the potential for transgenerational epigenetic inheritance has also been reported, suggesting that epigenetic changes could be inherited across generations in mammals. This study sought to examine the ethical and practical questions of epigenome editing and its use for therapeutic purposes, especially in the context of transgenerational epigenetic inheritance and the potential consequences for future generations.

Sunday, November 5, 2023

Urbanization threatens ecological health of South China’s Greater Bay Area

Photo Credit: Professor Joe Lee Shing-yip

Rapid urbanization in South China’s Greater Bay Area poses a significant threat to the ecological well-being of Deep Bay and its surrounding wetlands, new research shows.

The study, by the Chinese University of Hong Kong (CUHK) and the University of Exeter, highlights the urgent need to address the impact of urbanization on the region’s fragile coastal wetland ecosystems, especially their vital role in supporting migratory waterbirds.

It focused on Deep Bay, in the Pearl River estuary, which plays a crucial role as a refueling ground for migratory waterbirds along the East Asian-Australasian Flyway.

The team analyzed long-term environmental data spanning over 40 years to reveal the alarming consequences of dramatic changes.

They revealed a 30% decline in various water bodies such as mudflats, fishponds and geiwais (shallow ponds found in mangrove areas) between 1988 and 2020. Simultaneously, there was a 15.6 km2 increase in impervious surface coverage, primarily due to the conversion of fishponds and wetlands into concrete structures.

New study findings call into question the superiority of stem cell therapy for treating knee pain

Image Credit: rawpixel

Characterized by extensive damage to joints and debilitating pain, osteoarthritis (OA) impacts millions of people worldwide and has long posed a substantial clinical and economic burden.

In spite of advances in diagnosis, medications, and short-term pain management solutions, the elusive goal of a disease-modifying OA drug has remained out of reach. In recent years though, the use of stem cell therapy has gained traction as a promising alternative to surgery and for improving patients’ quality of life.  

Through a grant from the Marcus Foundation, an Emory team of investigators in collaboration with other recruitment sites throughout the nation explored the potential of mesenchymal stem cells as a game-changing treatment option for knee OA, one of the most common causes of chronic knee pain. This type of treatment seeks to harness the ability of a patient’s own cells to repair damaged tissue. However, the availability of robust data from well-designed randomized controlled trials has been limited, particularly in comparison to the gold-standard of treatment for knee OA, corticosteroid injections (CSI).

Thursday, November 2, 2023

Molecular blueprint of circuits governing locomotor speed

Zebra fish
Photo Credit: Lars Bräutigam

Researchers at Karolinska Institutet, Sweden have uncovered the molecular logic underpinning the assembly of spinal circuits that control the speed of locomotion in adult zebrafish. The study has recently been published in Nature Neuroscience.

What does the study show?

A fundamental hallmark of motor actions is the flexibility of their timing, speed and strength that is central to rapid adaptation to the ever-changing world around us. This is particularly apparent during locomotion, a behavior that involves full-body coordination characterized by sudden changes in speed and strength.

“In this study, we used single-cell RNA sequencing in adult zebrafish to link the molecular diversity of motoneurons and interneurons with their modular circuit organization that is responsible for changes in locomotor speed” says Abdel El Manira, Professor at the Department of Neuroscience at Karolinska Institutet, and corresponding author of the article.

One Punch Isn’t Enough to Overcome a Common Cancer Mutation

Acute myeloid leukemia as seen under a microscope.
Image Credit: Animalculist
(CC BY-SA 4.0)

Cancer cells are often a mess of mutations. About 20 to 25 percent of cancers involve mutations in a complex of molecules called SWI/SNF. Yet drugs designed to block SWI/SNF activity haven’t always worked as expected.

Researchers at Harvard Medical School have now figured out why.

As reported Nov. 2 in Cell, the team found that when drugs block SWI/SNF, a second molecule steps up to compensate.

Blocking this second molecule alongside SWI/SNF suppressed cancer cell growth in lab dishes, suggesting that a two-drug approach could make treatments more effective in people.

“I am excited about this work because it shows an alternative path forward for treating cancers in which the SWI/SNF complex is mutated,” said senior author Karen Adelman, the Edward S. Harkness Professor of Biological Chemistry and Molecular Pharmacology in the Blavatnik Institute at HMS, whose lab conducted the work.

“What’s interesting and meaningful about this study is it shows that a one-two punch, a double-agent therapy, could be really useful for keeping these cancer cells at bay,” she said.

Study links changes in global water cycle to higher temperatures

Over last 2,000 years, rising and falling temperatures have altered the way water moves around the planet
Photo Credit: Giulia Veneziano

It’s a multibillion-dollar question: What will happen to water as temperatures continue to rise? There will be winners and losers with any change that redistributes where, when and how much water is available for humans to drink and use.

To find answers and make informed predictions, scientists look to the past. Reconstructions of past climate change using geologic data have helped to show the far-reaching influence of human activity on temperatures since the industrial age. But assembling hydroclimate records for the same timeframe has proved to be much harder.

A study from the Past Global Changes (PAGES) Iso2k project team, led by Bronwen Konecky at Washington University in St. Louis, takes an important step toward reconstructing a global history of water over the past 2,000 years. Using geologic and biologic evidence preserved in natural archives — including 759 different paleoclimate records from globally distributed corals, trees, ice, cave formations and sediments — the researchers showed that the global water cycle has changed during periods of higher and lower temperatures in the recent past.

Jurassic worlds might be easier to spot than modern Earth

Modeling by Cornell astronomers finds that telescopes could more easily detect an exoplanet with higher levels of atmospheric oxygen than modern Earth, as existed during the dinosaur age.
Illustration Credit: Rebecca Payne/Carl Sagan Institute

Might a tyrannosaur roam on Trappist-1e, a protoceratops on Proxima Centauri b, or a quetzalcoatlus on Kepler 1047c?

Things may not have ended well for dinosaurs on Earth, but Cornell astronomers say the “light fingerprint” of the conditions that enabled them to emerge here – including abundant atmospheric oxygen – provides a crucial missing piece in our search for signs of life on planets orbiting other stars.

Modeling by Cornell astronomers finds that telescopes could more easily detect an exoplanet with higher levels of atmospheric oxygen than modern Earth, as existed during the dinosaur age.

Their analysis of the most recent 540 million years of Earth’s evolution, known as the Phanerozoic Eon, finds that telescopes could better detect potential chemical signatures of life in the atmosphere of an Earth-like exoplanet more closely resembling the age the dinosaurs inhabited than the one we know today.

Two key biosignature pairs – oxygen and methane, and ozone and methane – appeared stronger in models of Earth roughly 100 million to 300 million years ago, when oxygen levels were significantly higher. The models simulated the transmission spectra, or light fingerprint, generated by an atmosphere that absorbs some colors of starlight and lets others filter through, information scientists use to determine the atmosphere’s composition.

FSU researchers capture high-resolution images of magnesium ions interacting with CRISPR gene-editing enzyme

Hong Li, professor in the Department of Chemistry and Biochemistry and director of the Institute of Molecular Biophysics.
Photo Credit: Devin Bittner/FSU College of Arts and Sciences

The gene-editing technology known as CRISPR has led to revolutionary changes in agriculture, health research and more.

In research published in Nature Catalysis, scientists at Florida State University produced the first high-resolution, time-lapsed images showing magnesium ions interacting with the CRISPR-Cas9 enzyme while it cut strands of DNA, providing clear evidence that magnesium plays a role in both chemical bond breakage and near-simultaneous DNA cutting.

“If you are cutting genes, you don’t want to have only one strand of DNA broken, because the cell can repair it easily without editing. You want both strands to be broken,” said Hong Li, professor in the Department of Chemistry and Biochemistry and director of the Institute of Molecular Biophysics. “You need two cuts firing close together. Magnesium plays a role in that, and we saw exactly how that works.”

Brain health in over 50s deteriorated more rapidly during the pandemic

Photo Credit: Gabriel Porras

Brain health in over 50s deteriorated more rapidly during the pandemic, even if they didn’t have COVID-19, according to major new research linking the pandemic to sustained cognitive decline.

Researchers looked at results from computerized brain function tests from more than 3,000 participants of the online PROTECT study, who were aged between 50 and 90 and based in the UK. The remote study, led by teams at the University of Exeter and the Institute of Psychiatry, Psychology & Neuroscience (IoPPN) at King’s College London, and part-funded by NIHR Maudsley BRC, tested participants’ short-term memory and ability to complete complex tasks.

Through analyzing the results from this big dataset, researchers found that cognitive decline quickened significantly in the first year of the pandemic, when they found a 50 per cent change to the rate of decline across the study group. This figure was higher in those who already had mild cognitive decline before the pandemic, according to the research published in The Lancet Healthy Longevity.

Atherosclerosis: RNA fragment creates prospect for new therapies

Image Credit: © Weber Lab, IPEK

Atherosclerosis is considered a frequent cause of cardiovascular diseases and strokes. Despite medical progress, case numbers are constantly rising. Targeted new therapeutic approaches are therefore more important than ever. An international team led by Professor Christian Weber, Director of the Institute for Cardiovascular Prevention (IPEK) at the University Hospital of Munich, and Professor Donato Santovito, leader of the Translational Vascular Therapy research group at IPEK, has now identified a specific microRNA molecule as a promising starting point for the investigation of new therapies.

Some time ago, the researchers had already demonstrated that the transmembrane protein CXCR4 plays a significant role in the development of atherosclerosis. The protein transmits signals to the cell interior. If CXCR4 is specifically silenced in arterial endothelial cells or in smooth muscle cells, it results in more severe atherosclerotic lesions. At the same time, there is increased leukocyte ingress into the cell, which leads to inflammatory processes. With regard to leukocytes, however, the presence of CXCR4 can also promote the development of inflammatory processes. “It made sense, therefore, to only boost the expression of CXCR4 on the cells of the vascular wall in order to counteract the atherosclerosis,” says Santovito. “The challenge, however, is not to influence any biological processes, as the protein occurs in all cells and exercises various important functions.”

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