Category Archives: Biochemistry

Biochemistry

Biochemistry and transcriptomic analyses of Phthorimaea absoluta (Lepidoptera: Gelechiidae) response to insecticides … – Nature.com

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Zheng, C. et al. Reference gene selection for expression analyses by qRT-PCR in Dendroctonus valens. https://doi.org/10.3390/insects11060328.

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Biochemistry and transcriptomic analyses of Phthorimaea absoluta (Lepidoptera: Gelechiidae) response to insecticides ... - Nature.com

Biochemistry

Differential responses of Hollyhock (Alcea rosea L.) varieties to salt stress in relation to physiological and biochemical … – Nature.com

Wang, D. et al. Effects of salt stress on the antioxidant activity and malondialdehyde, solution protein, proline, and chlorophyll contents of three malus species (2022).

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Differential responses of Hollyhock (Alcea rosea L.) varieties to salt stress in relation to physiological and biochemical ... - Nature.com

Biochemistry

Life’s Origins: How Fissures in Hot Rocks May Have Kickstarted Biochemistry – Singularity Hub

How did the building blocks of life originate?

The question has long vexed scientists. Early Earth was dotted with pools of water rich in chemicalsa primordial soup. Yet biomolecules supporting life emerged from the mixtures, setting the stage for the appearance of the first cells.

Life was kickstarted when two components formed. One was a molecular carrierlike, for example, DNAto pass along and remix genetic blueprints. The other component was made up of proteins, the workhorses and structural elements of the body.

Both biomolecules are highly complex. In humans, DNA has four different chemical letters, called nucleotides, whereas proteins are made of 20 types of amino acids. The components have distinct structures, and their creation requires slightly different chemistries. The final products need to be in large enough amounts to string them together into DNA or proteins.

Scientists can purify the components in the lab using additives. But it begs the question: How did it happen on early Earth?

The answer, suggests Dr. Christof Mast, a researcher at Ludwig Maximilians University of Munich, may be cracks in rocks like those occurring in the volcanoes or geothermal systems that were abundant on early Earth. Its possible that temperature differences along the cracks naturally separate and concentrate biomolecule components, providing a passive system to purify biomolecules.

Inspired by geology, the team developed heat flow chambers roughly the size of a bank card, each containing minuscule fractures with a temperature gradient. When given a mixture of amino acids or nucleotidesa prebiotic mixthe components readily separated.

Adding more chambers further concentrated the chemicals, even those that were similar in structure. The network of fractures also enabled amino acids to bond, the first step towards creating a functional protein.

Systems of interconnected thin fractures and cracksare thought to be ubiquitous in volcanic and geothermal environments, wrote the team. By enriching the prebiotic chemicals, such systems could have provided a steady driving force for a natural origins-of-life laboratory.

Around four billion years ago, Earth was a hostile environment, pummeled by meteorites and rife with volcanic eruptions. Yet somehow among the chaos, chemistry generated the first amino acids, nucleotides, fatty lipids, and other building blocks that support life.

Which chemical processes contributed to these molecules is up for debate. When each came along is also a conundrum. Like a chicken or egg problem, DNA and RNA direct the creation of proteins in cellsbut both genetic carriers also require proteins to replicate.

One theory suggest sulfidic anions, which are molecules that were abundant in early Earths lakes and rivers, could be the link. Generated in volcanic eruptions, once dissolved into pools of water they can speed up chemical reactions that convert prebiotic molecules into RNA. Dubbed the RNA world hypothesis, the idea suggests that RNA was the first biomolecule to grace Earth because it can carry genetic information and speed up some chemical reactions.

Another idea is meteor impacts on early Earth generated nucleotides, lipids, and amino acids simultaneously, through a process that includes two abundant chemicalsone from meteors and another from Earthand a dash of UV light.

But theres one problem: Each set of building blocks requires a different chemical reaction. Depending on slight differences in structure or chemistry, its possible one geographic location might have skewed towards one type of prebiotic molecule over another.

How? The new study, published in Nature, offers an answer.

Lab experiments mimicking early Earth usually start with well-defined ingredients that have already been purified. Scientists also clean up intermediate side-products, especially for multiple chemical reaction steps.

The process often results in vanishingly small concentrations of the desired product, or its creation can even be completely inhibited, wrote the team. The reactions also require multiple spatially separated chambers, which hardly resembles Earths natural environment.

The new study took inspiration from geology. Early Earth had complex networks of water-filled cracks found in a variety of rocks in volcanos and geothermal systems. The cracks, generated by overheating rocks, formed natural straws that could potentially filter a complex mix of molecules using a heat gradient.

Each molecule favors a preferred temperature based on its size and electrical charge. When exposed to different temperatures, it naturally moves towards its ideal pick. Called thermophoresis, the process separates a soup of ingredients into multiple distinct layers in one step.

The team mimicked a single thin rock fracture using a heat flow chamber. Roughly the size of a bank card, the chamber had tiny cracks 170 micrometers across, about the width of a human hair. To create a temperature gradient, one side of the chamber was heated to 104 degrees Fahrenheit and the other end chilled to 77 degrees Fahrenheit.

In a first test, the team added a mix of prebiotic compounds that included amino acids and DNA nucleotides into the chamber. After 18 hours, the components separated into layers like tiramisu. For example, glycinethe smallest of amino acidsbecame concentrated towards the top, whereas other amino acids with higher thermophoretic strength stuck to the bottom. Similarly, DNA letters and other life-sustaining chemicals also separated in the cracks, with some enriched by up to 45 percent.

Although promising, the system didnt resemble early Earth, which had highly interconnected cracks varying in size. To better mimic natural conditions, the team next strung up three chambers, with the first branching into two others. This was roughly 23 times more efficient at enriching prebiotic chemicals than a single chamber.

Using a computer simulation, the team then modeled the behavior of a 20-by-20 interlinked chamber system, using a realistic flow rate of prebiotic chemicals. The chambers further enriched the brew, with glycine enriching over 2,000 times more than another amino acids.

Cleaner ingredients are a great start for the formation of complex molecules. But lots of chemical reaction require additional chemicals, which also need to be enriched. Here, the team zeroed in on a reaction stitching two glycine molecules together.

At the heart is trimetaphosphate (TMP), which helps guide the reaction. TMP is especially interesting for prebiotic chemistry, and it was scarce on early Earth, explained the team, which makes its selective enrichment critical. A single chamber increased TMP levels when mixed with other chemicals.

Using a computer simulation, a TMP and glycine mix increased the final producta doubled glycineby five orders of magnitude.

These results show that otherwise challenging prebiotic reactions are massively boosted with heat flows that selectively enrich chemicals in different regions, wrote the team.

In all, they tested over 50 prebiotic molecules and found the fractures readily separated them. Because each crack can have a different mix of molecules, it could explain the rise of multiple life-sustaining building blocks.

Still, how lifes building blocks came together to form organisms remains mysterious. Heat flows and rock fissures are likely just one piece of the puzzle. The ultimate test will be to see if, and how, these purified prebiotics link up to form a cell.

Image Credit: Christof B. Mast

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Life's Origins: How Fissures in Hot Rocks May Have Kickstarted Biochemistry - Singularity Hub

Biochemistry

Professor Robert Cross awarded Biochemical Society Award for Sustained Excellence – University of Warwick

Professor Robert Cross, Warwick Medical School has been awarded the Biochemical Society Award for Sustained Excellence 2025.

The work and contribution of fifteen eminent bioscientists, outstanding educators and exceptional early career researchers has been acknowledged in the annual Biochemical Society Awards following a record year of nominations.

Each recipient has been recognised for excellence in their field as well as a strong commitment to build, support, and nurture future talent. Winners of the 2025 Awards represent a cross-section of the molecular biosciences ranging from redox biology and plant-microbe interactions to mechanochemistry and virology.

Professor Steve Busby, Professor of Biochemistry at the University of Birmingham, and Chair of the Biochemical Societys Awards Committee, says: "The list of the 2025 Biochemical Society award winners is impressive and, of course, we have a wonderful mix of awardees, since each prize is targeted to a different section of our community. This is due to great foresight by the Societys managers and funders, over many many years. As well as congratulating the winners, I want to say thanks for all the hard work put in by nominators, supporters, Biochemical Society staff and the Awards Panel during the current round, this scheme could not work without you and your efforts made my job easy!

Professor Cross said "The Biochemical Society is a national treasure and I am grateful for this recognition of my work. I like the idea of an award for sustained progress - for me, science is about finding a good problem, splitting it into smaller problems, and working to solve those, as best one can, for as long as it takes."

Professor Cross obtained his PhD in 1983 from the University of Nottingham and then won an EMBO long-term fellowship to work with J. Victor Small and Apolinary Sobieszek in Salzburg on the structure and mechanisms of smooth muscle myosin filaments. In 1986, he moved to MRC-LMB as an MDA fellow and alongside John Kendrick Jones, Clive Bagshaw and Mike Geeves, Rob was ultimately able to propose an explicit mechanism for myosin II self-assembly.

In 1991, he moved to the Marie Curie Research Institute (MCRI) and began work on kinesin, then newly-discovered. In 2005, Rob and Nick Carter found that kinesin can step processively backwards under load. This turned out to be key to its mechanochemical coupling, which, as they recently (2020) showed, combines tight-coupled forwards steps with loose-coupled backslips.

In 2009, the MCRI closed and Rob moved, with his colleagues Professor Andrew McAinsh and Professor Anne Straube, to Warwick Medical School, University of Warwick. At Warwick, Rob continues to interrogate the kinesin mechanism, but with an important paradigm shift, whereby the interlock between the mechanochemical mechanisms of kinesin and tubulin is paramount.

Find out more about the Awards here and find out more about Professor Rob Cross and his research here.

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Professor Robert Cross awarded Biochemical Society Award for Sustained Excellence - University of Warwick

Biochemistry

Study suggests that estrogen may drive nicotine addiction in women – EurekAlert

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Researchers discovered that estrogen induces the expression of olfactomedins (OLFM), proteins that are suppressed by nicotine in key areas of the brain involved in reward and addiction. The research could lead to new targeted therapies that help women control nicotine consumption.

Credit: Sally Pauss, University of Kentucky College of Medicine; created with BioRender.com

A newly discovered feedback loop involving estrogen may explain why women might become dependent on nicotine more quickly and with less nicotine exposure than men. The research could lead to new treatments for women who are having trouble quitting nicotine-containing products such as cigarettes.

Sally Pauss is a doctoral student at the University of Kentucky College of Medicine in Lexington. She led the project.

Studies show that women have a higher propensity to develop addiction to nicotine than men and are less successful at quitting, said Pauss, who is working under the supervision of Terry D. Hinds Jr., an associate professor. Our work aims to understand what makes women more susceptible to nicotine use disorder to reduce the gender disparity in treating nicotine addiction.

The researchers found that the sex hormone estrogen induces the expression of olfactomedins, proteins that are suppressed by nicotine in key areas of the brain involved in reward and addiction. The findings suggest that estrogennicotineolfactomedin interactions could be targeted with therapies to help control nicotine consumption.

Pauss will present the research at Discover BMB, the annual meeting of the American Society for Biochemistry and Molecular Biology, which will be held March 2326 in San Antonio.

Our research has the potential to better the lives and health of women struggling with substance use, she said. If we can confirm that estrogen drives nicotine seeking and consumption through olfactomedins, we can design drugs that might block that effect by targeting the altered pathways. These drugs would hopefully make it easier for women to quit nicotine.

For the new study, the researchers used large sequencing datasets of estrogen-induced genes to identify genes that are expressed in the brain and exhibit a hormone function. They found just one class of genes that met these criteria: those coding for olfactomedins. They then performed a series of studies with human uterine cells and rats to better understand the interactions between olfactomedins, estrogen and nicotine. The results suggested that estrogen activation of olfactomedins which is suppressed when nicotine is present might serve as a feedback loop for driving nicotine addiction processes by activating areas of the brains reward circuitry such as the nucleus accumbens.

The researchers are now working to replicate their findings and definitively determine the role of estrogen. This knowledge could be useful for those taking estrogen in the form of oral contraceptives or hormone replacement therapy, which might increase the risk of developing a nicotine use disorder.

The investigators also want to determine the exact olfactomedin-regulated signaling pathways that drive nicotine consumption and plan to conduct behavioral animal studies to find out how manipulation of the feedback loop affects nicotine consumption.

Sally Pauss will present this research during a poster session from 4:306:30 p.m. CDT on Monday, March 25, in the exhibit hall of the Henry B. Gonzlez Convention Center (Poster Board No. 152) (abstract). Contact the media team for more information or to obtain a free press pass to attend the meeting.

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About the American Society for Biochemistry and Molecular Biology (ASBMB)

The ASBMB is a nonprofit scientific and educational organization with more than 12,000 members worldwide. Founded in 1906 to advance the science of biochemistry and molecular biology, the society publishes three peer-reviewed journals, advocates for funding of basic research and education, supports science education at all levels, and promotes the diversity of individuals entering the scientific workforce. http://www.asbmb.org

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Study suggests that estrogen may drive nicotine addiction in women - EurekAlert

Biochemistry

Yale men’s basketball confused for university’s Molecular Biophysics and Biochemistry on Twitter – Sporting News

Yale men's basketball's recent success has had the masses flocking for a glimpse at the inner workings of the team. Any piece of content relating to the team is susceptible to being devoured by the public. Sometimes, that can even sweep up entities unrelated to the basketball team at hand.

Yale's Molecular Biophysics and Biochemistry program was the latest department to get caught in the Bulldogs' riches. The world-renowned institution has been largely overshadowed by its nouveau riche supernovas in recent days. The most glaring example of such a phenomenon? The number of Twitter replies directed toward the molecular biophysics and biochemistry department in the first place.

There's been a massive groundswell of Twitter users interested in contacting the storied research org over the past few days. The reason for such interest is because Yale's Molecular Biophysics and Biochemistry has a rather familiar Twitter username: @YaleMBB.

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Many seem to believe that @YaleMBB's Twitter account is the same as Yale men's basketball's Twitter account. That is not actually the case. The Bulldogs are represented by the Twitter account @YaleMBasketball.

Have no fear, though: Yale's Molecular Biophysics and Biochemistry made it clear that they are the original @YaleMBB, not the other way around.

MORE: Where is Yale located?

From their Twitter account:

The social media account even took the unprecedented step of adding an addendum to its Twitter bio, stating the following:

'Yale Molecular Biophysics and Biochemistry (not @YaleMBasketball)'

Whether that piece of context will appease the masses is anyone's guess. Misinformation is rife in today's age.

Nevertheless, those hoping to get their fix of all things molecular biophysics and biochemistry will surely be pleased with their beloved program's desire to stick up for themselves, even if it's at the expense of one of its host university's most-beloved institutes.

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Yale men's basketball confused for university's Molecular Biophysics and Biochemistry on Twitter - Sporting News

Biochemistry

Plants have an astonishing biochemical communication network – Earth.com

Researchers at Purdue University have made significant strides in understanding plant communication through chemical signals, revealing their intricate language.

Plants, incapable of movement, have evolved unique mechanisms for survival and communication, particularly through Volatile Organic Compounds (VOCs).

These compounds serve as distress signals, warning neighboring plants of potential dangers, such as insect attacks or diseases.

Natalia Dudareva, a Distinguished Professor at Purdue in the departments of Biochemistry and Horticulture and Landscape Architecture, emphasizes the importance of VOCs in plant communication.

She describes it as a form of immunization, where plants primed by these signals respond more vigorously to threats, despite showing no visible changes under normal conditions.

Plants inform neighboring plants about pathogen attacks. It looks almost like immunization. Under normal conditions, you dont see any changes in the receiver plant. But as soon as a receiver plant is infected, it responds much faster. Its prepared for response, explained Dudareva.

The concept of plants communicating through VOCs is not new to science, but the mechanisms behind this communication have remained largely unexplored due to the lack of identifiable markers.

However, recent discoveries by Dudareva and her team have shed light on this process. Their research has documented how petunias produce volatiles to sterilize parts of their flowers, protecting against microbial invasion.

This discovery, first published in 2019, also introduced stigma size as a reliable marker for studying inter-organ communication in plants.

Shannon Stirling, a Ph.D. student at Purdue and the studys lead author, has contributed significantly to this research.

Through meticulous analysis, including measurements of stigma size affected by exposure to VOCs, Stirlings work has helped establish a consistent trend in the communication process.

There are a lot of sugars on the stigma, especially in petunias. It means that bacteria will grow very nicely without these volatiles present, Dudareva explained.

But if the stigma does not receive tube-produced volatiles, its also smaller. This was interorgan communication. Now we had a good marker stigma size to study this communication process, she concluded.

This trend is further supported by genetic studies that pinpointed a karrikin-like signaling pathway as a crucial element in this communication.

Karrikins, interestingly, are compounds not produced by plants but are associated with smoke or fire exposure, raising intriguing questions about plant evolutionary biology.

The study also highlights the exceptional selectivity of plant receptors, particularly in recognizing specific sesquiterpene compounds.

Matthew Bergman, a postdoctoral researcher and co-author of the study, points out the receptors ability to differentiate between mirror images of compounds, emphasizing the precision of this signaling system in avoiding false triggers.

The plant produces many different volatile compounds and is exposed to plenty of others, Bergman said. Its quite remarkable how selective and specific this receptor is exclusively for this signal being sent from the tubes. Such specificity ensures that no other volatile signals are getting by. Theres no false signaling.

Stirlings expertise in protein manipulation has been pivotal in identifying the interactions between signaling molecules and receptors. The process involves delicate techniques to modify protein levels in petunia pistils, a challenging task given the small size of these organs.

Pistils and stigmas are small. Theyre a little difficult to work with because of their size, Stirling said. Even the sheer amount of stigmas you need to get enough sample for anything is quite large because they dont weigh much.

This methodological breakthrough could pave the way for further discoveries in plant signaling and communication.

Petunias, with their vivid colors and fragrances, are more than just a visual delight. As Bergman notes, their value extends into the realm of scientific research, serving as an effective model for understanding complex biological processes.

In summary, this fascinating research has peeled back the layers of mystery surrounding plant communication. These brilliant scientists discovered how petunias, through the sophisticated use of volatile organic compounds, communicate threats to their neighbors. This communication, in turn, effectively immunizes them against potential dangers.

This study highlights the intricacies of plant signaling pathways, particularly through the discovery of the karrikin-like signaling mechanism and the precise receptor specificity for sesquiterpene compounds, while setting the stage for future research in plant biology.

By advancing our understanding of these complex communication systems, scientists unlock new possibilities for enhancing plant resilience and health, paving the way for agricultural innovations and environmental conservation strategies.

As discussed above, Volatile Organic Compounds (VOCs) represent a vast group of chemicals that plants and other organisms naturally emit. These compounds easily evaporate at room temperature, making them a significant part of the air we breathe.

In the plant kingdom, VOCs serve as critical components in a sophisticated communication network. They play pivotal roles in attracting pollinators, deterring herbivores, and signaling neighboring plants about environmental stressors.

Plants utilize VOCs to convey vital information to their surroundings. This form of communication is especially crucial in responding to threats such as herbivore attacks or disease.

When a plant gets damaged, it releases specific VOCs into the air. These signals can directly repel pests or attract natural enemies of the pests, such as predators or parasitoids, effectively reducing the damage to the plant.

Moreover, VOCs are not just about defense. They are instrumental in forming symbiotic relationships and facilitating plant-to-plant interactions.

For example, when one plant is attacked, neighboring plants can detect the VOCs released and preemptively bolster their own defenses, a phenomenon known as priming. This capability suggests a level of interconnectedness and communal support among plant populations.

Beyond defense, plants produce VOCs to lure pollinators. These chemical signals can attract specific insects or animals, ensuring the plants reproductive success.

The diverse array of scents and odors produced by flowers is primarily due to VOCs, tailored to appeal to the plants pollinators, whether they be bees, birds, or bats.

Furthermore, VOCs facilitate symbiotic relationships between plants and microorganisms. Certain VOCs can attract beneficial microbes that help the plant absorb nutrients more efficiently or provide resistance against pathogens.

This interaction underscores the complexity of VOCs in plant ecology, extending beyond plant-to-plant communication to encompass a broader ecological network.

The exchange of VOCs among plants and between plants and other organisms significantly influences ecosystem dynamics. It affects plant competition, biodiversity, and the structure of plant communities.

VOCs can mediate the outcome of plant interactions, determining which species dominate in certain conditions and contributing to the overall health and resilience of ecosystems.

As discussed above, Volatile Organic Compounds are more than mere byproducts of plant metabolism. They are vital communicative tools that plants use to interact with their environment.

Through the release of VOCs, plants can defend against predators, attract pollinators, and communicate with neighboring flora, showcasing a sophisticated level of interaction that mirrors the complexity of animal communication networks.

As research in this field progresses, we continue to uncover the depth and breadth of plant communication, revealing an intricate world where plants are far from passive entities in their ecosystems.

This study, which appears in the March 22, 2024, issue of the journal Science, is a collaborative effort involving scientists from Purdue, Universit Jean Monnet Saint-Etienne in France, and the University of California-Davis.

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Plants have an astonishing biochemical communication network - Earth.com

Biochemistry

Study links long-term consumption of deep-fried oil with increased neurodegeneration – ASBMB Today

A new study found higher levels of neurodegeneration in rats that consumed reused deep fried cooking oils and their offspring compared to rats on a normal diet. Deep frying, which involves completely submerging food in hot oil, is a common method of food preparation around the world.

Results from the study also suggest that the increased neurodegeneration is tied to the oils effects on the bidirectional communication network between the liver, gut and brain. The livergutbrain axis plays a crucial role in regulating various physiological functions, and its dysregulation has been associated with neurological disorders.

All that oil could be going to your head. Research presented at Discover BMB in San Antonio found higher levels of neurodegeneration in rats that consumed reused deep fried cooking oils compared to rats on a normal diet.

Kathiresan Shanmugam, an associate professor from Central University of Tamil Nadu in Thiruvarur, led the research team.

Deep-frying at high temperatures has been linked with several metabolic disorders, but there have been no long-term investigations on the influence of deep-fried oil consumption and its detrimental effects on health, said Shanmugam, formerly at Madurai Kamaraj University, Madurai. To our knowledge we are first to report long-term deep-fried oil supplementation increases neurodegeneration in the first-generation offspring.

Sugasini Dhavamani, a research collaborator from the University of Illinois at Chicago, will present the research at Discover BMB, the annual meeting of the American Society for Biochemistry and Molecular Biology, which will be held March 2326 in San Antonio.

Deep frying food not only adds calories; reusing the same oil for frying, a common practice in both homes and restaurants, removes many of the oils natural antioxidants and health benefits. Oil that is reused also can contain harmful components such as acrylamide, trans fat, peroxides and polar compounds.

To explore the long-term effects of reused deep-fried frying oil, the researchers divided female rats into five groups that each received either standard chow alone or standard chow with 0.1 ml per day of unheated sesame oil, unheated sunflower oil, reheated sesame oil or reheated sunflower oil for 30 days. The reheated oils simulated reused frying oil.

Compared with the other groups, the rats that consumed reheated sesame or sunflower oil showed increased oxidative stress and inflammation in the liver. These rats also showed significant damage in the colon that brought on changes in endotoxins and lipopolysaccharides toxins released from certain bacteria. As a result, liver lipid metabolism was significantly altered, and the transport of the important brain omega-3 fatty acid DHA was decreased. This, in turn, resulted in neurodegeneration, which was seen in the brain histology of the rats consuming the reheated oil as well as their offspring.

Additional studies in which MSG was used to induce neurotoxicity in the offspring showed that the offspring that consumed the reheated oils were more likely to show neuronal damage than the control group receiving no oil or those that received unheated oil.

Although more studies are needed, the researchers say that supplementation with omega-3 fatty acids and nutraceuticals such as curcumin and oryzanol might be helpful in reducing liver inflammation and neurodegeneration. They added that clinical studies in humans are needed to evaluate the adverse effects of eating fried foods, especially those made with oil that is used repeatedly.

As a next step, the researchers would like to study the effects of deep-frying oil on neurodegenerative diseases such as Alzheimers and Parkinsons as well as on anxiety, depression and neuroinflammation. They would also like to further explore the relationship between gut microbiota and the brain to identify potential new ways to prevent or treat neurodegeneration and neuroinflammation.

Sugasini Dhavamani will present this research during a poster session from 4:30 to 6:30 p.m. CDT on Sunday, March 25, in the exhibit hall of the Henry B. Gonzlez Convention Center (Poster Board No. 326) (abstract).

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Study links long-term consumption of deep-fried oil with increased neurodegeneration - ASBMB Today

Biochemistry

New surfactant could improve lung treatments for premature babies – ASBMB Today

Scientists have developed a new lung surfactant that is produced synthetically rather than relying on the use of animal tissues. With further development, the formulation could provide a cheaper and more readily available alternative to Infasurf, a medication used to prevent and treat respiratory distress in premature babies.

Surfactants are substances that decrease surface tension where liquids interface with other liquids, gases or solids. In addition to their use in medicines, they are found in a wide range of products including detergents, cosmetics, motor oils and adhesives.

Scientists at Discover BMB in San Antonio reported a new lung surfactant that is produced synthetically rather than derived using animal tissues. It might eventually provide a cheaper and more accessible alternative to medication currently used to prevent and treat respiratory distress in premature babies.

Suzanne Farver Lukjan, a lecturer in chemistry at Troy University in Alabama, led the work.

A synthetic surfactant could potentially have a longer shelf life, lower production costs, have less batch variability and pose less risk of an immune response compared to animal-derived lung surfactants, she said. We hope our formulation will one day be used in hospitals.

Lukjan will present the research at Discover BMB, the annual meeting of the American Society for Biochemistry and Molecular Biology, which is being held March 2326 in San Antonio.

Lung surfactants help premature babies breathe while their lung cells finish developing. In addition to offering a potential alternative to replace Infasurf for babies, researchers say the new synthetic surfactant could be useful for treating adults with lung injuries as a result of diseases such as chronic obstructive pulmonary disorder, miners lung or emphysema.

Researchers have previously attempted to develop synthetic lung surfactants, but some have been removed from the market and others have not been able to lower surface tension as well as animal-derived formulations.

In the new work, Lukjans team created candidate surfactants from synthetic lipids (fats) and peptides (short chains of amino acids) and then tested their surface-tension-lowering capabilities. They aimed to mimic the composition, lipid phase behavior and biophysical function of Infasurf as closely as possible.

After tweaking a step in the sample preparation process, the researchers found a few formulations that showed particular promise. Although tests demonstrated that the chemical behavior of the synthetic surfactants was quite different from that of Infasurf, the new surfactants were able to mimic the drugs functionality in terms of lowering surface tension and seem to achieve the optimal range in terms of peptide concentration.

As a next step, Lukjan said, the group plans to continue to refine and test their formulation to further optimize the combination of lipids and peptides. The surfactant would also need to undergo safety testing before it could be used clinically.

This work was partially funded by ONY Biotech Inc., maker of Infasurf.

Suzanne Lukjan will present this research from 4:30 to 6:30 p.m. CDT on Monday, March 25, in the exhibit hall of the Henry B. Gonzlez Convention Center (Poster Board No. 210) (abstract).

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New surfactant could improve lung treatments for premature babies - ASBMB Today

Biochemistry

The Power and Promise of RNA – Duke University School of Medicine

The word messenger RNA, or mRNA for short, went from scientific jargon to everyday conversation during the pandemic because of the molecule's starring role in COVID-19 vaccines.

Messenger RNA contains blueprints for proteins that do all sorts of jobs in our bodies. In COVID-19 vaccines, it contains instructions to make proteins similar to the spikes on the coronavirus. This encourages the immune system to create antibodies to fight the virus if we encounter it in the future.

Vaccines are just the beginning of the therapeutic potential of RNA. Scientists at Duke University School of Medicine have long probed the mysteries of RNA, with an eye on harnessing its power for new and better therapies for cancer, diabetes, heart disease and more.

RNA translates our genetic code into action, using information in our genes to create a functioning organism. But the body has ways to modify RNA to change gene expression. These RNA modifications, crucial for normal development, sometimes go awry in disease states.

At Duke, several scientists study RNA modifications. Thats an area of strength for us, said cardiologist Christopher Holley, MD, PhD, associate professor of medicine and assistant research professor in Department of Molecular Genetics and Microbiology. We cant think of any other university in the world that has as large a group studying RNA modifications as there is here at Duke.

Unlike mRNA, not all RNA contains blueprints for proteins. Some types of RNA guide the modification of mRNA, essentially turning genes on or off without changing the genetic code itself.

In RNA, the genetic code is written in base chemicals referred to by the letters A, G, C, and U. Holley compares RNA modifications to an asterisk. These modifications dont change the letter sequence of RNA, he said. You still have the same word, but there is some extra information.

Holley studies a type of modification-guiding RNA called small nucleolar RNA, or snoRNA. While snoRNAs have a role in normal biology, they are also active in some unhealthy processes, including oxidative stress, which damages cells.

Holley has found that turning snoRNAs off in mice protects the mice from diabetes, atherosclerosis, and the symptoms of sickle cell disease, with no apparent side effects. There seems to be a beneficial effect of dialing down these snoRNAs, he said, because we think they really promote oxidative stress damage.

Holley, whose doctorate is in pharmacology, is designing a molecule that will attach itself to snoRNAs, causing them to self-destruct. With the help of Dukes Office of Technology and Commercialization, Holley and a colleague, launched a company called snoPanther to help bring the idea to market.

The dream is that we would be able to turn these into drugs for people, he said.

Hes especially interested in developing better treatments to help his patients avoid heart attacks. Hes actively pursuing snoRNA treatments for diabetes and sickle cell disease as well.

There are hundreds of snoRNAs, he said, and we think in general it could be a whole new class of molecules we could target for drug development.

One of the reasons Kate Meyer, PhD, assistant professor in biochemistry, came to Duke was the concentration of RNA researchers here. That was a big draw for me, Meyer said. Its great because we all study similar concepts but were different enough that we dont compete with each other; we complement each other.

Meyer studies a modification called m6A, in which a molecule called a methyl group gets added to a particular site on RNA. Proper regulation of m6A is required for cells and organisms to function and for animals to develop normally, she said. Dysregulation of m6A has been linked to a variety of different diseases, most notably several cancers.

When she was a postdoctoral researcher, Meyer helped develop the first technique to map m6A sites in cells. At Duke, she and her lab members have developed new methods which can detect m6A from very low amounts of RNA, allowing researchers to zoom in and identify sites in a single cell.

Single-cell m6A profiling has provided new insights into m6A biology, she said. The new technique revealed about 170,000 m6A sites throughout the body many more than scientists had imagined.

Meyer, who is particularly interested in neuroscience applications, studies the functions of m6A in the brain, where m6A is known to be active in response to axonal injury, neural diseases, and brain cancer.

The more we understand about methylation and how it is regulated in cells, she said, the better positioned we are to develop novel therapeutics.

Meyer recently served on the National Academies of Sciences, Engineering and Medicine committee that compiled a report providing a roadmap for achieving the complete sequencing of RNA molecules and their modifications from one end to the other. Meyer believes this feat will help enable researchers, clinicians, and the biotechnology sector to more fully harness the power of RNA.

Before Meyer joined the Duke faculty, Stacy Horner, PhD, associate professor in integrative immunobiology, came across Meyers postdoctoral paper mapping m6A sites. Horner decided to use the technique in her own lab, in a slightly different application.

Horner studies RNA in viruses and she wanted to look for m6A in viral RNA. I felt like we should look at this because no one was exploring this, she said, and then, with her work, we were able to do this.

She found that viral RNA, like our RNA, does contain m6A sites, a finding that is informing further research. We have been looking at how proteins in the body might sense a specific pattern in viral RNA that contains these modifications, she said.

Her overall goal is to understand how our bodies distinguish viral RNA (which the immune system should attack) from our own RNA (which the immune system should ignore).

In illuminating these biological mechanisms, Horners research could lead to treatments for autoimmune diseases in which the body's immune system attack its own RNA. You need to know the biochemical mechanisms that distinguish viral RNA from our own RNA so you know what to target, she said.

Her work will also be important in understanding how to design RNA therapeutics so that the body doesnt identify them as something to attack.

Horner, who also has appointments in the departments of cell biology, medicine, molecular genetics and microbiology, and the Duke Cancer Institute, now works alongside Meyer to co-direct the Center for RNA Biology, the intellectual home for RNA research at Duke.

We share what were learning and we share technology, she said. It really helps us push the envelope.

As a relative newcomer to RNA research, Josh Huang, PhD, the Duke School of Medicine Distinguished Professor of Neuroscience, appreciates the rich environment of Dukes in-house expertise, which has helped him get up to speed on RNA after years of studying neural circuitry.

Hes interested in using RNA as a tool to learn more about cell types and to manipulate cells to treat disease.

He has recently developed a technique he calls CellREADR to program engineered mRNA to bind to RNA in particular cells in the body and deliver instructions.

Imagine the target sequence is in RNA in a cancer cell. Once the engineered mRNA is attached to the cancer RNA, it issues instructions. Its a message that we want to deliver to the cancer cell, Huang said, to tell the cancer cell to die or to label the cancer cell so that immune cells will kill it.

READ MORE New RNA-based tool can illuminate brain circuits, edit specific cells

The technology has applications far beyond cancer. In Parkinsons disease patients, for example, engineered mRNA could locate cells involved in synthesizing dopamine, attach to the RNA in those cells, and deliver instructions to fix the malfunction.

Like Holley, Huang has started a company to bring his technology to market, called Doppler Bio, with help from Dukes Office of Technology and Commercialization.

RNA therapies are quicker and less expensive to manufacture than more traditional pharmaceuticals, which is one of the reasons the COVID-19 vaccines were designed and produced so quickly. They also have the potential to be easily tailored for different vaccines and disease treatments.

One of the most exciting benefits for patients is the possibility of increased effectiveness with fewer side effects.

In the case of cancer, say, RNA therapy could potentially destroy cancer cells without affecting other cells. This contrasts with currently available radiation and chemotherapy, which damage a broad swath of normal cells in the body.

Broadly speaking, that is the promise of RNA therapeutics precision and effectiveness, Huang said.

Mary-Russell Roberson is a freelance writer in Durham.

Eamon Queeney is assistant director of multimedia and creative at the Duke School of Medicine.

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The Power and Promise of RNA - Duke University School of Medicine