It’s possible that I shall make an ass of myself. But in that case one can always get out of it with a little dialectic. I have, of course, so worded my proposition as to be right either way (K.Marx, Letter to F.Engels on the Indian Mutiny)
Friday, January 19, 2024
The American Journal of Clinical Nutrition launches new article series to educate physicians and other health care professionals on nutrition
Rockville, MD (January 16, 2024) – To educate physicians and other health care professionals on the fundamentals of nutrition, The American Journal of Clinical Nutrition has launched a new article series titled Nutrition for the Clinician. The effort supports the White House National Strategy on Hunger, Nutrition, and Health and its directives to expand nutrition knowledge of health care providers, an effort long supported by the American Society for Nutrition. Nancy Krebs, MD, MS, Professor of Pediatrics, University of Colorado School of Medicine, is the Associate Editor for the series.
Through case-based learning, Nutrition for the Clinician provides continuing education that enhances clinical reasoning and use of the best nutrition evidence in practice. Each clinical case will feature a clearly identified nutrition problem and defined learning objectives. Cases will be published in the journal’s regular issues periodically throughout the year.
“Nutrition plays a pivotal role in health and disease,” stated Christopher Duggan, MD, MPH, Editor-in-Chief, The American Journal of Clinical Nutrition. “By presenting nutritional challenges seen in hospital and outpatient care and describing evidence-based treatment approaches, we hope physicians will gain a deeper understanding of how nutrition significantly impacts patient outcomes, as well as see firsthand the clinical reasoning process of top clinicians.”
Titled “A Perfect Storm in a Pandemic – A Child with Complex Medical History and Special Diet Encounters COVID,” the inaugural case highlights a six-year-old child with undernutrition and acute COVID-19 infection.
Authors Nancy Krebs, MD and Stephanie Waldrop, MD (University of Colorado) provide medical history, laboratory results, and clinical findings and offer commentary and questions to guide readers through the case. The authors analyze the differential diagnosis and treatment considerations at the outset and reassess them as new data emerges over the course of care.
The case is freely accessible at the following link: https://ajcn.nutrition.org/article/S0002-9165(23)66234-3/fulltext. The American Society for Nutrition is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education for physicians. The ASN designates this activity for a maximum of 1.00 AMA PRA Category 1 Credit™. For details on claiming CME credit for reading Nutrition for the Clinician, click here.
“Having knowledge of nutrition is important for all medical specialists, yet studies have shown that nutrition education and training in medical schools and residency programs is lacking,” expressed Kevin Schalinske, PhD, President, American Society for Nutrition. “We hope this new resource will pique the interest of physicians and advanced practice providers and inspire them to learn more about nutrition care in clinical practice.” Dietitians also may find interest in the range of medical scenarios and accompanying nutritional diagnostics and therapies presented.
The AJCN welcomes contributions to this new series from both individual providers and interprofessional teams. Prospective authors can direct pre-submission inquiries to ajcn.editorialoffice@jjeditorial.com.
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About The American Journal of Clinical Nutrition The American Journal of Clinical Nutrition, one of the most influential journals in biology and medicine, publishes research in human nutrition and fosters the application of science into clinical practice. Topics include high-impact clinical, observational, public health, and epidemiologic studies in all areas of nutrition including obesity and metabolism; micronutrients; body composition; and nutrition in clinical settings. Genetic and novel precision nutrition approaches are featured. Visit us online at ajcn.nutrition.org or follow us on X (formerly Twitter) @AJCNutrition #AJCN.
About the American Society for Nutrition (ASN) The American Society for Nutrition (ASN) is the preeminent professional organization for scientists and clinicians around the world. Founded in 1928, the society brings together the top nutrition researchers, medical practitioners, policy makers and industry leaders to advance the science, education, and practice of nutrition, reaching more than 55 million people annually. ASN publishes four peer-reviewed journals and provides education and professional development opportunities year-round. Since 2018, the American Society of Nutrition has presented NUTRITION, the leading global annual meeting for nutrition professionals. Visit us at www.nutrition.org.
Cryo-microscopy reveals nano-sized copy machine implicated in origin of life
RNA is thought to have sparked the origin of life by self-copying. Researchers reveal the atomic structure of an "RNA copy machine". This breakthrough sheds light on a primordial RNA world and fuels advancements in RNA nanotechnology and medicine
THE PICTURE SHOWS AN RNA POLYMERASE RIBOZYME THOUGHT TO BE IMPLICATED IN THE ORIGIN OF LIFE. THE RIBOZYME IS SHOWN FROZEN IN ICE TO SYMBOLIZE HOW IT WAS FROZEN IN TIME FOR IMAGING AND HOW IT WORKS BEST UNDER ICE-COLD CONDITIONS. THE ACTIVE SITE IS HIGHLIGHTED BY A YELLOW/RED LIGHT AND THE PROPOSED POSITION OF THE TEMPLATE-PRODUCT HELIX IS SHOWN IN TRANSPARENT.
How the intricate molecular machinery of life arose from simple beginnings has been a long-standing question. Several lines of evidence point towards a primordial"RNA world", where an "RNA copy machine" (a so-called replicase) started making copies of itself and other RNA molecules to kick-start evolution and life itself. However, the ancient replicase appears to have been lost in time and its role in modern biology has been taken over by more efficient protein machines. To support the RNA world hypothesis, researchers have been seeking to re-create an equivalent of the RNA replicase in the laboratory. While such molecular “Doppelgangers” of the ancient replicase have been discovered, both their detailed molecular structure and mode of action has remained elusive due to the difficulty of determining the structure of dynamic RNA molecules.
Structure of an ice-loving RNA replicase
In a research paper published in PNAS, a team of researchers now report the first atomic structure of an RNA replicase using cryogenic electron microscopy (cryo-EM). The RNA replicase being studied was developed by the Holliger lab (MRC LMB Cambridge, UK) to be efficient at copying long templates using nucleotide triplets in the eutectic ice phase (similar to slush-ice). Returning from postdoctoral studies in the Holliger lab, Emil L. Kristoffersen, currently assistant professor at Aarhus University, facilitated a collaboration with the Andersen lab (Aarhus University, Denmark) to determine the structure of the RNA replicase by cryo-EM. Interestingly, the structure shows striking similarities to protein-based polymerases with domains for template binding, polymerization, and substrate discrimination arranged in a molecular shape resembling an open hand.
"It was surprising to find that a ribozyme that we evolved artificially in the test tube would display features of naturally occurring protein polymerases. This indicates that evolution can discover convergent molecular solutions no matter if the material is RNA or protein", explains Philipp Holliger, program leader at MRC LMB Cambridge, UK.
Model for RNA synthesis in an RNA world
To better understand how the RNA replicase works, the researchers did a comprehensive mutational study to highlight the crucial elements of the RNA structure. This analysis confirmed features of the catalytic site but also revealed the importance of two so-called kissing-loop interactions, which bind the scaffolding and the catalytic subunits together, as well as the importance of a specific RNA domain for fidelity, that is the accuracy with which the replicase copies RNA strands. While the researchers could not determine the structure of the replicase “in-action” while actively copying RNA, it was possible to build a model for RNA-based RNA copying that is consistent with all experimental data.
"Cryo-EM is a powerful method for studying the structure and dynamical features of RNA molecules. By combing cryo-EM data with experiments, we were able to build a model of the inner workings of this complex RNA machine", tells Ewan McRae, who did the cryo-EM work as a postdoc in the Andersen lab at Aarhus University but has now started his own research group at Houston Methodist Research Institute, Texas, USA.
Inspiration for RNA nanotechnology and medicine
The study provides an exciting first glimpse of an RNA replicase thought to reside at the very root of the tree of life. The currently developed RNA-based replicases are however very inefficient (as compared to protein-based polymerases) and cannot yet sustain their own replication and evolution. The structural insight provided by the reported study may help in designing more efficient replication mechanisms and thus get us closer to developing RNA world scenarios in the test tube.
"The properties of RNA replicases may be further improved by using chemical modifications that could exist in an RNA world. In addition, research into the origin of life leads to the discovery of several novel RNA building blocks that may be used in the emerging field of RNA nanotechnology and medicine", explains Ebbe Sloth Andersen, associate professor at Aarhus University, Denmark.
About the research
External funding:
The research was funded by Independent Research Fund Denmark (9040-00425B), Novo Nordisk Foundation (NNF21OC0070452), Canadian Natural Sciences and Engineering Research Council (532417), Carlsberg Foundation (CF20-0635, CF17-0809), Lundbeck Foundation (R250-2017-1502), Medical Research Council, as part of United Kingdom Research and Innovation (also known as UK Research and Innovation (UKRI)) (MC_U105178804), Volkswagen Foundation (96 755), Herchel Smith studentship (2017), and Marie Curie fellowship (H2020-MSCA-IF-2018-845303).
Conflicts of interest: The researchers declare that there are no conflicts of interest in connection with this research.
Link to the scientific article:
Cryo-EM structure and functional landscape of an RNA polymerase ribozyme Ewan K. S. McRae, Christopher J. K. Wan, Emil L. Kristoffersen, Kalinka Hansen, Edoardo Gianni, Isaac Gallego, Joseph F. Curran, James Attwater, Philipp Holliger, and Ebbe S. Andersen Proceedings of the National Academy of Sciences (PNAS) Vol. 121, No. 2 (January 9, 2024) https://doi.org/10.1073/pnas.2313332121
ITHACA, N.Y. – People may form inaccurate impressions about us from our social media posts, finds new Cornell University research that is the first to examine perceptions of our personalities based on online posts.
An analysis of Facebook status updates found substantial discrepancies between how viewers saw the authors across a range of personality traits, and the authors’ self-perceptions. Viewers rated the Facebook users on average as having lower self-esteem and being more self-revealing, for example, than the users rated themselves.
Status updates containing photos, video or links in addition to text facilitated more accurate assessments than those with just text, the researchers found. Overall, they said, the study sheds light on the dynamic process by which a cyber audience tries to make sense of who we are from isolated fragments of shared information, jointly constructing our digital identity.
“The impression people form about us on social media based on what we post can differ from the way we view ourselves,” said Qi Wang, professor of psychology and director of the Culture & Cognition Lab. “A mismatch between who we are and how people perceive us could influence our ability to feel connected online and the benefits of engaging in social media interaction.”
Prior research has focused on perceptions of personality traits gleaned from personal websites, such as blogs or online profiles, finding that readers can assess them accurately. The Cornell researchers believe their study is the first to investigate audience perceptions of social media users through their posts, on platforms where users often don’t share cohesive personal narratives while interacting with “friends” they may know only a little or sometimes not at all.
Interestingly, the study found that Facebook status updates generated perceptions of users that were consistent with cultural norms in offline contexts concerning gender and ethnicity – even though viewers were blind to their identities. For example, female Facebook users were rated as more extraverted than male users, in line with general findings that women score higher on extraversion. White Facebook users were seen as being more extraverted and having greater self-esteem than Asian users, whose cultures place more emphasis on modesty, Wang said.
“We present ourselves in line with our cultural frameworks,” she said, “and others can discern our ‘cultured persona’ through meaning making of our posts.”
The scholars said future research should explore this “outsourced meaning-making process” with larger samples of posts, and on other popular platforms such as Instagram and X, formerly known as Twitter.
Wang said the findings could help developers design interfaces that allow people to express themselves most authentically. For users, misunderstandings about who they are on social media might not cause direct harm, she said, but could hinder their efforts to foster good communication and relationships.
“If people’s view of us is very different from who we actually are, or how we would like to be perceived,” Wang said, “it could undermine our social life and well-being.”
LIGHT PUBLISHING CENTER, CHANGCHUN INSTITUTE OF OPTICS, FINE MECHANICS AND PHYSICS, CAS
IMAGE:
A, SCHEMATIC OF THE PHOTONIC PROCESSOR. PIC, PHOTONIC INTEGRATED CIRCUIT. MRR, MICRORING RESONATOR. MOD, MODULATOR. BPD, BALANCED PHOTODETECTOR. TIA, TRANSIMPEDANCE AMPLIFIER. FPGA, FIELD-PROGRAMMABLE GATE ARRAY. SIGNAL PATHWAY STARTS AT MRR MOD AND ENDS AT BPD, COMPOSING AN ON-CHIP WAVEGUIDE WITH A LENGTH OF 1.6 MM, WHICH HAS AN INDEX OF REFRACTION NEAR 2.44. THE LATENCY IS, ACCORDINGLY, THE LIGHT PROPAGATION TIME, WHICH IS ABOUT 15 PS. B, PACKAGED PALM-SIZED PHOTONIC PROCESSOR. THE SETUP COMPRISES TWO PRINTED CIRCUITED BOARDS PILED TOGETHER AND CONNECTED BY A RIBBON CABLE. THE TOP BOARD MOUNTS THE PIC IS IMPEDANCE ENGINEERED FOR HANDLING HIGH-FREQUENCY SIGNALS. THE BOTTOM BOARD IS POPULATED WITH MULTICHANNEL DIGITAL-TO-ANALOGUE CONVERTERS (DACS), PROVIDING TUNING CURRENTS AND BIASING VOLTAGES FOR COMPONENTS ON THE PIC. C, ZOOMED-IN VIEW OF THE PACKAGED PIC, TIAS, AND FIBRE ARRAY
CREDIT: BY WEIPENG ZHANG, JOSHUA LEDERMAN, THOMAS FERREIRA DE LIMA, JIAWEI ZHANG, SIMON BILODEAU, LEILA HUDSON, ALEXANDER TAIT, BHAVIN SHASTRI, AND PAUL PRUCNAL
Radar altimeters are the sole indicators of altitude above a terrain. Spectrally adjacent 5G cellular bands pose significant risks of jamming altimeters and impacting flight landing and take-off. As wireless technology expands in frequency coverage and utilises spatial multiplexing, similar detrimental radio-frequency (RF) interference becomes a pressing issue. To address this interference, RF front-ends with exceptionally low latency are crucial for industries like transportation, healthcare, and the military, where the timeliness of transmitted messages is critical. Future generations of wireless technologies will impose even more stringent latency requirements on RF front-ends due to increased data rate, carrier frequency, and user count. Additionally, challenges arise from the physical movement of transceivers, resulting in time-variant mixing ratios between interference and signal-of-interest (SOI). This necessitates real-time adaptability in mobile wireless receivers to handle fluctuating interference, particularly when it carries safety-to-life critical information for navigation and autonomous driving, such as aircraft and ground vehicles.
In a new paper published in Light: Science & Applications, a team of scientists, led by Professor Paul Prucnal from Lightwave Lab, Department of Electrical and Computer Engineering, Princeton University, USA, and co-workers have introduced a system-on-chip (SoC) that employs silicon photonics to tackle dynamic radio-frequency (RF) interference, a growing issue in fields like transportation, healthcare, and military operations. This innovation is particularly crucial in light of the increased risk of radar altimeter jamming by adjacent 5G cellular bands, posing threats to aircraft safety.
The heart of this technological leap lies in photonic integrated circuits (PICs), which can process broadband information by converting radio frequencies into optical frequencies. Unlike traditional analogue RF components or digital electronics, PICs dramatically reduce latency through direct analogue processing, a critical feature as wireless technologies progress towards higher frequencies.
However, integrating a complete system on a chip for microwave processing has faced challenges in design, control, and packaging. Current PICs typically require bulky external devices for signal analysis and control, leading to impractical size, weight, and power metrics for real-world deployment.
Addressing these challenges, the research introduces a compact, palm-sized standalone photonic device. This device integrates modulators, microring resonator (MRR) weight banks, and photodetectors on a single chip, significantly reducing processing latency to less than 15 picoseconds. In addition, a field-programmable gate array (FPGA) with integrated peripherals handles high-throughput statistical analysis and high-level blind source separation (BSS) algorithms. This setup enables real-time execution at a refresh rate of 305 Hz, a marked improvement over previous systems.
The research team successfully tested this device in two dynamic interference scenarios - mobile communications and radar altimeters. The results were convincible, demonstrating error-free operation and maintaining signal-to-noise ratios over 15 dB. This breakthrough showcases the device's potential to address real-world interference challenges effectively.
This research marks a significant step forward in the development of photonic processors. It pioneered the development of a PIC capable of real-time online learning and rapid adjustment of photonic weights. As the research progresses, enhancements in form factor, performance, and online adaptiveness are anticipated. These advancements will broaden the applicability of photonic processors to a range of demanding tasks, including model predictive control and neuromorphic computing. The study marks a substantial step forward in the field of photonic signal processing, highlighting its potential in addressing complex, real-world challenges.
CHEMISTS AT UC DAVIS ARE USING CATALYSTS (SHOWN IN GRAY SPHERES) TO MAKE ORGANIC COMPOUNDS (BLUE STICKS) WITH A SPECIFIC CHIRALITY, OR “HANDEDNESS.” MOST BIOLOGICAL MOLECULES ARE CHIRAL, INCLUDING MANY PRESCRIPTION DRUGS. THE DISCOVERY COULD MAKE IT EASIER TO SYNTHESIZE PHARMACEUTICALS WITH THE CORRECT SYMMETRY.
In nature, organic molecules are either left- or right-handed, but synthesizing molecules with a specific “handedness” in a lab is hard to do. Make a drug or enzyme with the wrong “handedness,” and it just won’t work. Now chemists at the University of California, Davis, are getting closer to mimicking nature’s chemical efficiency through computational modeling and physical experimentation.
In a study appearing Jan. 10 in Nature, Professor Dean Tantillo, graduate students William DeSnoo and Croix Laconsay, and colleagues at the Max Planck Institute in Germany report the successful synthesis of specific chiral, or “handed,” molecules using rearrangements of simple hydrocarbons in the presence of complex organic catalysts. Most biological compounds, including many prescription drugs, are chiral.
Tantillo and colleagues hope the findings will enable scientists to better harness hydrocarbons for a variety of purposes, such as precursors to medicines and materials.
“The novelty of this paper is that this is really the first time, to my knowledge, that someone has been able to get a carbocation shift that makes one of the mirror image products rather than the other with high selectivity,” Tantillo said.
Little balls of grease
In chemistry, chirality is a property that refers to a pair of molecules that share atomic makeup but are mirror images of each other. Like your left and right hands, they can’t be superimposed on each other.
“Synthetic chemists often want to make molecules that come in mirror image forms, but they only want one of them,” Tantillo said. “For example, if you want to make a drug molecule, often you need one of the two chiral forms to bind selectively to a protein or enzyme target.”
Achieving this can be difficult in a lab setting because such molecules, according to Tantillo, are often like “little balls of grease with some positive charge smeared around them.”
The greasy-like nature of these molecules typically makes binding by a chemical catalyst in one orientation over another difficult due to the lack of charged groups for the catalyst to grab on to.
But the researchers found a solution. Using a chiral organic acid, imidodiphosphorimidate, as a catalyst, the team successfully performed rearrangements of achiral alkenyl cycloalkanes, producing chiral molecules of interest called cycloalkenes. Using computational methods, Tantillo and colleagues deduced how the catalyst selectively produces one chiral form over the other.
Similarities to nature
Tantillo said that the resulting reaction is similar to how enzymes that make hydrocarbon products called terpenes behave in nature. Part of Tantillo’s research concerns mapping terpene reaction pathways using quantum mechanical methods.
“If there are multiple possible pathways to a product, then every time you stop at an intermediate on that pathway, you have the possibility to get byproducts that come from that intermediate,” he said. “So it is important to know when and why a carbocation wants to stop en route to a given terpene if one wants to understand and ultimately re-engineer terpene-forming enzymes.”
The new method published in Naturecould in principle be harnessed to produce both natural molecules and nonnatural molecules.
“Whether these things will ever be done is hard to say, but petroleum is a source of a lot of hydrocarbons, and if you could catalytically turn those into molecules with defined chirality, you’ve increased the value of those molecules,” Tantillo said.
Additional co-authors are: Vijay Wakchaure, Markus Leutzsch and Benjamin List, Max Planck Institut für Kohlenforschung, Mülheim an der Ruhr, Germany; and Nobuya Tsuji, Hokkaido University, Sapporo, Japan.
The work was supported in part by the Max Planck Society, the Deutsche Forschungsgemeinschaft and the European Research Council, and the U.S. National Science Foundation.
Catalytic asymmetric cationic shifts of aliphatic hydrocarbons
ARTICLE PUBLICATION DATE
10-Jan-2024
COI STATEMENT
A patent on the synthesis of imino-imidodiphosphates catalysts has been filed (patent no. WO 2017/037141 A1, EP 3 138 845 A1). Furthermore, a patent on an improved synthesis of imidodiphosphoryl-derived catalysts using hexachlorophosphazonium salts has been filed (patent no. EP 3 981 775 A1).
Cheap substitute for expensive metal in an industrially common chemical reaction
Researchers from Osaka University and collaborating partners have developed an economical catalyst for an important chemical transformation, which might inspire additional efforts at lowering costs in the chemical industry
(A) THE PHOTO OF NANO-NI3C/AL2O3 CATALYST. (B) TRANSMISSION ELECTRON MICROSCOPE IMAGE OF NANO-NI3C/AL2O3. (C) HYDROGENATION OF NITRILE TO BENZYLAMINE USING NANO-NI3C OR NI NANOPARTICLE CATALYST, AND THE SUBSTRATE SCOPE FOR THE NITRILE HYDROGENATION CATALYZED BY NANO-NI3C/AL2O3.
CREDIT: 2024 YAMAGUCHI ET AL., NICKEL CARBIDE NANOPARTICLE CATALYST FOR SELECTIVE HYDROGENATION OF NITRILES TO PRIMARY AMINES, CHEMISTRY – A EUROPEAN JOURNAL
Osaka, Japan – The chemical industry commonly uses rare, expensive metals to produce pharmaceuticals and other essential substances. Replacing these metals whenever possible with more-abundant, cheaper substitutes would benefit environmental sustainability, lower costs, and minimize the risk of supply chain disruptions.
Now, in a study recently published in Chemistry – A European Journal, researchers from Osaka University and collaborating partners have met this need in their work on an industrially useful chemical transformation. The simple, gentle reaction conditions reported here might inspire researchers who are working to reduce use of expensive metals for as many chemical reactions as possible.
So-called noble metals are especially versatile materials. For example, palladium is a metal of choice for catalyzing a chemical transformation – converting nitriles into primary amines – that is a common step in nylon and plastics production. However, such metals are rare and costly. Substitutes based on common metals such as nickel could be cheaper catalysts. Unfortunately, many cheap metals require challenging experimental conditions, such as high pressures and temperatures, for the previously mentioned chemical transformation. Determining whether nickel carbide has the same limitations – and if not, evaluating the scope of the chemical transformations that are possible with this catalyst – was the goal of the research team’s study.
“In our work, we thoroughly study the reaction chemistry that underlies a novel nickel carbide nanoparticle heterogeneous catalyst for selective hydrogenation of nitriles into primary amines,” explains Sho Yamaguchi, lead author of the study. “The substrate scope is broad – many types of heteroaromatic and aliphatic nitriles can undergo this transformation.”
There are several advantages of the researchers’ catalyst. One, despite the mild required reaction conditions – 1 atmosphere pressure of hydrogen and a relatively low temperature of approximately 150°C – the catalyst still exhibited 4-times the activity of simple nickel nanoparticles. Two, the catalyst was reusable: at least 3-times. Three, the reaction yields were high: up to 99%.
“We’re excited because our research will help minimize the use of expensive metals for and simplifies the experimental setup of a common class of chemical syntheses,” says Tomoo Mizugaki, senior author. “Furthermore, our theoretical calculations provide insights that will help us optimize the catalyst for additional applications.”
This work is an important step forward in increasing the sustainability of a class of chemical reactions that are required for synthesizing pharmaceuticals and many other everyday products. Because the nickel catalyst is much cheaper than a noble metal, and the required experimental procedures are simple, feasible applications to further chemical transformations should be straightforward.
Hydrogenation of various nitriles using the nano-Ni3C/Al2O3 catalyst under 1 bar H2.
CREDIT
2024 Yamaguchi et al., Nickel Carbide Nanoparticle Catalyst for Selective Hydrogenation of Nitriles to Primary Amines, Chemistry – A European Journal
The article, “Nickel carbide nanoparticle catalyst for selective hydrogenation of nitriles to primary amines,” was published in Chemistry – A European Journal at DOI: https://doi.org/10.1002/chem.202303573
About Osaka University Osaka University was founded in 1931 as one of the seven imperial universities of Japan and is now one of Japan's leading comprehensive universities with a broad disciplinary spectrum. This strength is coupled with a singular drive for innovation that extends throughout the scientific process, from fundamental research to the creation of applied technology with positive economic impacts. Its commitment to innovation has been recognized in Japan and around the world, being named Japan's most innovative university in 2015 (Reuters 2015 Top 100) and one of the most innovative institutions in the world in 2017 (Innovative Universities and the Nature Index Innovation 2017). Now, Osaka University is leveraging its role as a Designated National University Corporation selected by the Ministry of Education, Culture, Sports, Science and Technology to contribute to innovation for human welfare, sustainable development of society, and social transformation. Website: https://resou.osaka-u.ac.jp/en
Copper is an essential trace element required to produce energy in the body and allows humans to live in our atmosphere. But research has found that increased accumulation of copper is associated with worse outcomes for patients with the most common type of kidney cancer called clear cell renal cell carcinoma (ccRCC).
The University of Cincinnati Cancer Center’s Maria Czyzyk-Krzeska, MD, PhD, has been awarded a five-year, $2.8 million grant from the National Institutes of Health to investigate how copper contributes to the advancement and recurrence of ccRCC.
Study background
Tobacco smoking is a risk factor for ccRCC. Czyzyk-Krzeska and collaborators, analyzing patient samples from UC, the Cincinnati VA Medical Center and the National Cancer Institute’s Urology Oncology branch, discovered that tumors from patients who were smokers had significantly higher levels of copper compared to nonsmokers. Follow-up studies
using several separate groups of patients showed increased copper accumulation in more advanced tumors and tumors that came back following surgical removal.
“That indicated to us that copper has a potential driving effect in tumor progression of clear cell renal cell carcinoma,” said Czyzyk-Krzeska, a University of Cincinnati Cancer Center researcher and professor in the Department of Cancer Biology in UC’s College of Medicine.
Study details
Czyzyk-Krzeska said the first aim of the study will seek to identify the mechanisms that allow ccRCC cells to take up more copper.The research team will also learn more about copper’s metabolic effects on the tumor cells, specifically the role it plays in the metabolism of mitochondria, the parts of the cell responsible for producing energy.
The third aim of the study will test whether any of the copper-specific features of the tumor cells have vulnerabilities that can open up new treatments for ccRCC.
“There are essentially two or three major lines of treatment for kidney cancer, but ultimately there’s always a group of tumors that are not responsive or recur” said Czyzyk-Krzeska. “We hope what we find is going to provide opportunities for new treatments.”
The data from the study may also shed light on the potential of copper as a biomarker for ccRCC, Czyzyk-Krzeska said.
“Because these levels of copper are higher in certain tumors, we think that copper could be used as a biomarker for evaluation of prognosis and potentially also for predicting which treatment could be appropriate for this specific group of tumors,” she said. “We think that this data will be important for personalized medicine in the treatment of ccRCC.”
Czyzyk-Krzeska said the ongoing research is a multidisciplinary effort between cancer biologists in her department including Tom Cunningham, David Plas and Krushna Patra; UC bioinformatics expert Jarek Meller; and former UC faculty member and analytical chemist Julio Landero, now at Icahn School of Medicine at Mount Sinai New York. The team also collaborates with urologic oncologists, urologists and pathologists at UC.
