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Tag: American Society for Biochemistry and Molecular Biology (ASBMB)

  • ASBMB calls for student loan relief

    ASBMB calls for student loan relief

    Newswise — On June 20, the American Society for Biochemistry and Molecular Biology submitted public hearing testimony to the Department of Education expressing concerns about the growing burden of student loan debt. The society called for expanding debt-relief programs across all educational levels and allowing postdoctoral researchers to defer loan payments until after completion of their training.

    “We are in the midst of a student debt crisis, and it’s hurting the research enterprise and more importantly, the next generation of scientists,” Sarina Neote, ASBMB public affairs director, said. “The average student debt balance has more than doubled in the past two decades, and this increase is coming at the expense of inclusivity. Student debt disproportionately affects underrepresented groups like Black, Latinx and American Indian students; the scientific workforce and enterprise will narrow and suffer if relief doesn’t come soon.”

    Historically marginalized groups such as Black students take on more debt than white students and are more likely to default on their loans.

    Recent Ph.D. graduates and postdocs already struggle to cover basic living costs. The student debt burden causes them to delay important milestones, such as purchasing property, which stifles the national economy, the ASBMB noted.

    To alleviate these financial burdens and allow the scientific workforce to grow, the ASBMB called for the Education Department to expand public and private service programs similar to the successful National Institutes of Health loan-repayment program. This program aims to counteract “financial pressure by repaying up to $50,000 annually of a researcher’s qualified education debt in return for commitment to engage in NIH mission-relevant research.”

    Neote said: “Education attainment and fulfillment should not come with such an unattainably high price tag.”

    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. For more information about the ASBMB, visit www.asbmb.org.

    American Society for Biochemistry and Molecular Biology (ASBMB)

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  • New insights into an old drug: Scientists discover why aspirin works so well

    New insights into an old drug: Scientists discover why aspirin works so well

    Newswise — New research has revealed important information about how aspirin works. Even though this drug has been available commercially since the late 1800s, scientists have not yet fully elucidated its detailed mechanism of action and cellular targets. The new findings could pave the way to safer aspirin alternatives and might also have implications for improving cancer immunotherapies.

    Aspirin, which is a nonsteroidal anti-inflammatory drug, is one of the most widely used medications in the world. It is used to treat pain, fever and inflammation, and an estimated 29 million people in the U.S. take it daily to reduce the risk of cardiovascular diseases.

    Scientists know that aspirin inhibits the cyclooxygenase enzyme, or COX, which creates messenger molecules that are crucial in the inflammatory response. Researchers led by Subhrangsu Mandal, a professor of chemistry and biochemistry at the University of Texas at Arlington, have discovered more about this process.

    Prarthana Guha, a graduate student in Mandal’s lab, will present the team’s findings at Discover BMB, the annual meeting of the American Society for Biochemistry and Molecular Biology, March 25–28 in Seattle. Avisankar Chini also made significant contributions to the study.

    “Aspirin is a magic drug, but long-term use of it can cause detrimental side effects such as internal bleeding and organ damage,” Mandal said. “It’s important that we understand how it works so we can develop safer drugs with fewer side effects.”

    The team found that aspirin controls transcription factors required for cytokine expression during inflammation while also influencing many other inflammatory proteins and noncoding RNAs that are critically linked to inflammation and immune response. Mandal said this work has required a unique interdisciplinary team with expertise in inflammation signaling biology and organic chemistry.

    They also showed that aspirin slows the breakdown of the amino acid tryptophan into its metabolite kynurenine by inhibiting associated enzymes called indoleamine dioxygenases, or IDOs. Tryptophan metabolism plays a central role in the inflammation and immune response.

    “We found that aspirin downregulates IDO1 expression and associated kynurenine production during inflammation,” Mandal said. “Since aspirin is a COX inhibitor, this suggests potential interplay between COX and IDO1 during inflammation.”

    IDO1 is an important target for immunotherapy, a type of cancer treatment that helps the body’s immune system seek out and destroy cancer cells. Because COX inhibitors modulate the COX–IDO1 axis during inflammation, the researchers predict that COX inhibitors might also be useful as drugs for immunotherapy.

    Mandal and his team are now creating a series of small molecules that modulate COX–IDO1 and will explore their potential use as anti-inflammatory drugs and immunotherapeutic agents.

     

    Prarthana Guha will present this research from 4 to 5:30 p.m. PDT on Tuesday, March 28, in Exhibit Hall 4AB of the Seattle Convention Center (Poster Board No. 185) (abstract). Contact the media team for more information or to obtain a free press pass to attend the meeting.

     

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    Research in Mandal’s lab is funded by National Institute of Health grant R15 HL142032-01.

     

    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. www.asbmb.org

    Find more news briefs and tipsheets at: https://discoverbmb.asbmb.org/newsroom.

     

     

     

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  • Global analysis of coronavirus protein research reveals how countries respond to disease

    Global analysis of coronavirus protein research reveals how countries respond to disease

    Newswise — In a new study, researchers examined how a country’s number of published 3D protein structures for coronaviruses, including the one responsible for COVID-19, correlated with its economic output and population. The findings reveal important insights into how different countries’ research establishments respond to disease outbreaks and could be useful for planning responses to future pandemics.

    The study showed that countries with larger economies generated more 3D structure determinations for the protein components of coronaviruses, although there were many outliers. For example, some advanced and prosperous countries published few or no coronavirus structures while some countries strongly affected by COVID-19 published far more such structures than would be expected based on their populations and economies.

    Manfred Philipp, professor emeritus at the City University of New York, will present the new research at Discover BMB, the annual meeting of the American Society for Biochemistry and Molecular Biology, March 25–28 in Seattle.

    The 3D structures of proteins, such as those that make up coronaviruses, are determined using techniques such as X-ray crystallography and nuclear magnetic resonance. This information is then deposited into the Protein Data Bank (PDB) database so that it can be used to develop new drug treatments and new vaccines. Protein structure information is also key for understanding how viruses infect cells and interact with our immune system.

    “We asked ourselves how different countries respond to disease, not in terms of treatment and medical care, but in terms of the research needed to study those diseases and to develop new treatments,” said Philipp. “Structure determinations provide a clear metric in terms of research response without any vagaries of interpretation.”

    Although a great deal of research has examined levels of coronavirus research funding in various countries, most of this work has focused either on coronavirus-related patents or financial inputs. However, relating research to patents is complex, in part, because some nonprofits perform considerable amounts of research but rarely apply for patents while some patent-generating organizations don’t conduct a lot of research. Financial-based analyses don’t provide a complete picture because it is difficult to capture both public and private funds. Also, private research funds are not always publicly disclosed and some funds that are reported may be used for administrative and overhead costs instead of directly for research.

    “Because we did not look at levels research funding, we didn’t have to figure out how much research funding was devoted to disease and how much to something else,” said Philipp. “Our metric only sees research successes and provides a clear indication of the amount of research applied to this topic alone.”

    In the work, the researchers collected and cataloged 3D structure determinations for all proteins and nucleic acids that are components of coronaviruses. This included viruses from animal infections as well as those responsible for the 2003 SARS epidemic in Asia, the 2012 MERS epidemic in the Middle East, the worldwide COVID-19 pandemic and other coronaviruses that have been studied.

    Of the approximately 40 countries the researchers examined, the United States, United Kingdom and China had the highest number of protein structures. They found that population size contributed very little to the number of coronavirus protein deposits while countries with a higher GDP did tend to deposit more protein structures. The number of confirmed COVID-19 cases was positively associated with the number of PDB deposits per country, especially in the U.S. Although South Africa and Brazil are not in the top 10 research-producing countries, they had a high number of COVID-19 cases and PDB deposits, suggesting that the high number of cases experienced in these countries influenced their research output.

    “Our research on the country distribution of coronavirus-related structure determinations is intended to give research administrators in various countries the tools to redirect research funds in the most productive direction,” said Philipp. “For example, it can help countries with large research budgets but few if any structure determinations to redirect the focus of their research. This should not be the only such metric, but it is a key metric since it is independent of administrative and overhead costs.”

    Next, the researchers plan to examine whether the number of structure publications for coronaviruses will continue to increase as the COVID-19 pandemic subsides and whether the countries that have led in depositing coronavirus structures into the PDB will continue to lead. 

     

    Manfred Philipp will present this research from 4:30–6:30 p.m. PDT on Sunday, March 26, in Exhibit Hall 4AB of the Seattle Convention Center (Poster Board No. 177) (abstract). Contact the media team for more information or to obtain a free press pass to attend the meeting.

     

    Image available.

     

    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. www.asbmb.org

    Find more news briefs and tipsheets at: https://discoverbmb.asbmb.org/newsroom.

     

     

     

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  • Cancer cells with thicker glycocalyx barrier are better at evading immune cells

    Cancer cells with thicker glycocalyx barrier are better at evading immune cells

    Newswise — One of the ways that cancer cells hide from the body’s immune system is by forming a thin surface barrier called the glycocalyx. In a new study, researchers examined the material properties of this barrier with unprecedented resolution, revealing information that could help improve current cell-based cancer immunotherapies.

    Cancer cells often form the glycocalyx with high levels of cell-surface mucins, which are thought to help protect the cancer cell from immune cell attack. However, a physical understanding of this barrier has remained limited, especially as it relates to cell-based cancer immunotherapies, which involve removing immune cells from a patient, modifying them to seek and destroy cancer, and then putting them back into the patient’s body.

    “We found that changes in the thickness of the barrier that were as small as 10 nanometers could affect the antitumor activity of our immune cells or the engineered cells used for immunotherapy,” said Sangwoo Park, a graduate student in Matthew Paszek’s Lab at Cornell University in Ithaca, New York. “We used this information to engineer immune cells that can get through the glycocalyx, and we hope this approach could be used to enhance current cell-based immunotherapies.”

    Park will present the findings at Discover BMB, the annual meeting of the American Society for Biochemistry and Molecular Biology, March 25–28 in Seattle.

    “Our lab has advanced a powerful strategy called scanning angle interference microscopy (SAIM) for measuring the nanoscale dimensions of the cancer cell glycocalyx,” said Park. “This imaging technique allows us to understand the structural relationship of cancer-associated mucins to the biophysical properties of the glycocalyx.”

    The researchers generated a cellular model to precisely control the cell-surface mucin expression to mimic the cancer cell glycocalyx. They then combined SAIM with genetic approaches to study how the surface density, glycosylation and crosslinking of cancer-associated mucins affect the thickness of the barrier at the nanoscale. They also analyzed how the glycocalyx thickness affected a cell’s resistance to attack by immune cells.

    The study revealed that the thickness of cancer cells’ glycocalyx is one of the major parameters determining immune cell evasion and that engineered immune cells worked better if the glycocalyx was thinner.

    Based on this knowledge, the researchers engineered immune cells with special enzymes on their surface to allow them to attach to and interact with the glycocalyx. Experiments performed at the cellular level showed that these immune cells were able to overcome the glycocalyx armor of cancer cells.

    Next, the researchers plan to determine whether these findings can be replicated in the laboratory and, eventually, in clinical trials.

     

    Sangwoo Park will present this research during the Regulatory Glycosylation Spotlight Session from 2–3 p.m. PDT on Sunday, March 26, in Room 608 of the Seattle Convention Center (abstract). Contact the media team for more information or to obtain a free press pass to attend the meeting.

     

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    This investigation was supported by National Institute of Health New Innovator DP2 GM229133, National Cancer Institute (NCI) U54 CA210184, NCI R33 CA193043, National Institute of General Medical Sciences (NIGMS) R01 GM138692, NIGMS R01 GM137314, National Science Foundation 1752226, and Breast Cancer Coalition of Rochester 07.1922Research.

     

    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. www.asbmb.org

    Find more news briefs and tipsheets at: https://discoverbmb.asbmb.org/newsroom.

     

     

     

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  • The heart benefits of walnuts likely come from the gut

    The heart benefits of walnuts likely come from the gut

    Newswise — A new study examining the gene expression of gut microbes suggests that the heart-healthy benefits of walnuts may be linked to beneficial changes in the mix of microbes found in our gut. The findings could help identify other foods or supplements with similar nutritional benefits.

    Researchers led by Kristina S. Petersen from Texas Tech University in Lubbock found that introducing walnuts into a person’s diet may alter the gut’s mix of microbes — known as the microbiome — in a way that increases the body’s production of the amino acid L-homoarginine. Homoarginine deficiency has been linked to higher risk for cardiovascular disease.

    “Research has shown that walnuts may have heart-healthy benefits like lowering cholesterol levels and blood pressure,” said Mansi Chandra, an undergraduate researcher at Juniata College in Huntingdon, Pennsylvania. “This motivated us to look at how walnuts benefited the gut microbiome and whether those effects led to the potential beneficial effects. Our findings represent a new mechanism through which walnuts may lower cardiovascular disease risk.”

    Chandra will present the new findings at Discover BMB, the annual meeting of the American Society for Biochemistry and Molecular Biology, March 25–28 in Seattle.

    The researchers used an approach known as metatranscriptomics to study the gene expression of gut microbes. This recently developed technology can be used to quantify gene expression levels and monitor how these levels shift in response to various conditions such as dietary changes.

    “To our knowledge, this is the first study to use metatranscriptomics analysis for studying the impact of walnut consumption on the gut microbiota gene expression,” Chandra said. “These exploratory analyses contribute to our understanding of walnut-related modulation of gut microbiome, which could be very impactful in learning how gut health impacts our heart health in general.”

    The metatranscriptomics analysis used samples acquired from a previously performed controlled-feeding study in which 35 participants with high cardiovascular risk were put on a two-week standard Western diet and then randomly assigned to one of three study diets. The study participants followed each diet for six weeks with a break between each.

    The diets included one that incorporated whole walnuts, one that included the same amount of omega-3 fatty acid alpha-linolenic acid, or ALA, and polyunsaturated fatty acids as the walnut diet but without walnuts, and one that partially substituted another fatty acid known as oleic acid for the same amount of ALA found in walnuts but without consumption of any walnuts. The diets were designed to provide information about how walnuts affected cardiovascular health due to their bioactive compounds and ALA content and whether walnut ALA is the best substitute for dietary saturated fat compared to oleic acid.

    For the new work, researchers used metatranscriptomics to analyze gene expression and the bacteria in the gastrointestinal tract from fecal samples collected shortly before the participants finished the run-in diet and each of the three study diets.

    The analysis revealed higher levels of Gordonibacter bacteria in the gut of participants on the walnut diet. This bacterium converts the plant polyphenols ellagitannins and ellagic acid into metabolites that allow them to be absorbed by the body. Participants consuming the walnut diet also showed higher levels of expression for several genes that are involved in important metabolic and biosynthetic pathways, including ones that increase the body’s production of the amino acid L-homoarginine.

    Although more work is needed to confirm these observations, the research could eventually help inform dietary interventions based on walnuts. “Since a lot of people are allergic to nuts, these findings also suggest that other food supplements that boost the endogenous production of homoarginine may also be helpful,” Chandra said.

    Next, the researchers would like to apply metabolomic and proteomic analyses to identify the final products of the genes that showed higher levels of expression. This would allow them to better understand the biological mechanisms at work.

     

    Mansi Chandra will present this research during the Undergraduate Poster Competition from noon to 3:30 p.m. PDT on Saturday, March 25, and during the poster session from 4:30 to 6:30 p.m. PDT on Sunday, March 26, in Exhibit Hall 4AB of the Seattle Convention Center (Poster Board No. 25) (abstract). Contact the media team for more information or to obtain a free press pass to attend the meeting.

     

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    This release may include updated data or information that differs from the abstract submitted to the Discover BMB meeting.

     

    Kristina S. Petersen was previously affiliated with Pennsylvania State University.

     

    This study was funded by the California Walnut Commission. The research was also supported by the Penn State Clinical and Translational Research Institute, Pennsylvania State University Clinical and Translational Science Award and NIH/National Center for Advancing Translational Sciences (Grant UL1TR000127).

     

    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. www.asbmb.org

    Find more news briefs and tipsheets at https://discoverbmb.asbmb.org/newsroom.

     

     

     

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  • Reimagining drugs for rare brain disorder

    Reimagining drugs for rare brain disorder

    BYLINE: Marissa Locke Rottinghaus

    Newswise — A team of researchers has developed a new method to screen FDA-approved drugs to determine if they could be repurposed or improved to help patients with a rare, debilitating disease of the nervous system.

    Spinocerebellar ataxia type 5 causes cerebellar neurodegeneration. Loss of coordination, impaired gait and slurred speech are just a few of the debilitating symptoms, which usually emerge between the ages of 20 and 30. There is no cure or even a targeted therapy. SCA5 affects around 1,000 people in the U.S. but is a part of a group of diseases that plagues tens of thousands more.

    Despite the nature and broad reach of SCA5 and related diseases, few researchers are trying to find a cure. However, one ataxia-focused research group published a study on Jan. 30 detailing a new method to screen for drugs that might help.

    “Not only is there no known therapeutic to treat these diseases, but, to our knowledge, there is no other research campaign to identify potential therapies for a lot of these ataxias,” said Robyn Rebbeck, a postdoctoral researcher at the University of Minnesota and one of the lead authors on the study.

    SCA5 is inherited and is sometimes called “Lincoln’s ataxia” because it has been passed down over 10 generations in one family with traces to President Abraham Lincoln’s grandparents. It is caused by a mutation in the β-III-spectrin gene, which is critical for creating connections between neurons in the central nervous system.

    Adam Avery, the assistant professor at Oakland University who oversaw the work, said: “Our goal is to improve the conditions of these patients within the next 10­­ to 20 years. … (W)e are family people. We want to provide SCA5 patients and their families with the hope of an effective treatment.”

    The mutation studied by the researchers causes β-III-spectrin and a structural protein called actin to stick together. This abnormally tight interaction results in a traffic jam inside neurons, which prevents them from carrying out their normal functions, such as controlling speech and movement.

    The research team created a pipeline to screen FDA-approved drugs against the mutated β-III-spectrin protein to find out if any can restore its normal function. This assay uses cutting-edge spectroscopy to examine whether and how drugs change the interaction of mutant β-III-spectrin with actin and is at least five-times more sensitive than methods used previously. The drugs that dampen β-III-spectrin’s binding to actin initiate a unique florescent signal. This high-throughput screening method allows the team to evaluate 1,536 drugs in about six minutes.

    Of the 3,000 FDA-approved drugs analyzed, two immediately stood out to the researchers for their high efficacy and potency: ginsenoside Rb1 and micafungin. However, this is just the beginning. The researchers plan to screen thousands more compounds to get their best shot at finding an effective drug.

    Piyali Guhathakurta, an assistant professor at the University of Minnesota and a lead author, said the team is now “primed for screening much larger libraries for compounds that can lead us to drugs that have the potential to treat SCA5. Our assay is the start of the drug-discovery campaign, with collaborators preparing to test these compounds in systems more akin to the human patients that we hope to treat.”

    The researchers plan to develop a cell culture and mouse model to more definitively test their hits from the drug screen. If the hits are successful in ameliorating disease in future models, they would be that much closer to a drug specific for SCA5 patients.

    “Our study is proof that the binding of this mutant spectrin to actin is a druggable target,” Avery said. “This work establishes that we can modulate this interaction using small molecule drugs.”

    Though there is much work to be done, the team is optimistic about the prospects that this new pipeline presents for studying mutations in β-III-spectrin-related proteins that cause other rare diseases like muscular dystrophy.

    “Our findings may pave the way for the development of a new class of drugs that will provide relief to patients suffering from SCA5 and additional diseases due to mutations in spectrin-related proteins,” Avery explained. “Our technology is adaptable for drug discovery for treatment of other diseases associated with disrupted actin binding.”

    American Society for Biochemistry and Molecular Biology (ASBMB)

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