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(1)s r e i t n o r F cience of S. Gordon Research Conferences. Advance Your Career at the Frontiers of Science! October-November 2021 I remember my ﬁrst GRC experience because the quality of science and “ depth of discussion were inspirational to me as a young graduate student. ” GEOFFREY VARGISH, Past Chair of the Inhibition in the CNS GRS. Alcohol-Induced End Organ Diseases OCTOBER 24 – 29, 2021 FOUR POINTS SHERATON / HOLIDAY INN EXPRESS, VENTURA, CA, US CHAIRS: Gyongyi Szabo and Bernd Schnabl VICE CHAIRS: Elizabeth Kovacs and Gavin Arteel. Biotherapeutics and Vaccines Development. Cell Biology of Metals. Medicinal Chemistry. OCTOBER 17 – 22, 2021 MOUNT SNOW, WEST DOVER, VT, US. OCTOBER 24 – 29, 2021 MOUNT SNOW, WEST DOVER, VT, US. CHAIRS: Caryn Outten and Mitchell Knutson VICE CHAIRS: Angela Wilks and Kerry Kornfeld. Central Nervous System Injury and Repair OCTOBER 17 – 22, 2021 JORDAN HOTEL AT SUNDAY RIVER, NEWRY, ME, US. NOVEMBER 14 – 19, 2021 VENTURA BEACH MARRIOTT, VENTURA, CA, US. CHAIRS: Yimin Zou and Simone Di Giovanni VICE CHAIRS: Elizabeth Bradbury and Yishi Jin. CHAIRS: Michael Tarlov and Linda Narhi VICE CHAIRS: Peter Tessier and Jessica Molek. Chronobiology. Cannabinoid Function in the CNS NOVEMBER 7 – 12, 2021 FOUR POINTS SHERATON / HOLIDAY INN EXPRESS, VENTURA, CA, US CHAIRS: Matthew Hill and Sachin Patel VICE CHAIRS: Miriam Melis and Mario Stelt. Carbon Capture, Utilization and Storage. OCTOBER 10 – 15, 2021 MOUNT SNOW, WEST DOVER, VT, US. CHAIR: Roger Aines VICE CHAIR: Andre Bardow. Cardiac Arrhythmia Mechanisms OCTOBER 17 – 22, 2021 FOUR POINTS SHERATON / HOLIDAY INN EXPRESS, VENTURA, CA, US CHAIRS: David Christini and Ursula Ravens VICE CHAIRS: Crystal Ripplinger and Edward Vigmond. Phagocytes OCTOBER 24 – 29, 2021 WATERVILLE VALLEY, WATERVILLE VALLEY, NH, US CHAIR: Michelle Lennartz VICE CHAIR: Sergio Catz. Physical Science of Cancer NOVEMBER 14 – 19, 2021 FOUR POINTS SHERATON / HOLIDAY INN EXPRESS, VENTURA, CA, US. CHAIR: Samer Hattar VICE CHAIR: Charlotte Helfrich-Forster. CHAIRS: Josef Käs and Sharon Gerecht VICE CHAIRS: David Odde and Jennifer Munson. Computer Aided Drug Design. Stochastic Physics in Biology. NOVEMBER 7 – 12, 2021 MOUNT SNOW, WEST DOVER, VT, US. OCTOBER 10 – 15, 2021 FOUR POINTS SHERATON / HOLIDAY INN EXPRESS, VENTURA, CA, US. CHAIR: Georgia McGaughey VICE CHAIR: Matthias Rarey. OCTOBER 24 – 29, 2021 JORDAN HOTEL AT SUNDAY RIVER, NEWRY, ME, US. CHAIR: Janeta Popovici-Muller VICE CHAIR: Cynthia Parrish. Lung Development, Injury and Repair NOVEMBER 7 – 12, 2021 WATERVILLE VALLEY, WATERVILLE VALLEY, NH, US CHAIRS: Anne-Karina Perl and Daniel Tschumperlin VICE CHAIRS: Rory Morty and Xin. Mammalian DNA Repair OCTOBER 31 – NOVEMBER 5, 2021 FOUR POINTS SHERATON / HOLIDAY INN EXPRESS, VENTURA, CA, US CHAIR: Lee Zou VICE CHAIR: Patricia Opresko. CHAIR: Yuhai Tu VICE CHAIR: Jie Xiao. Stress Proteins in Growth, Development and Disease NOVEMBER 7 – 12, 2021 JORDAN HOTEL AT SUNDAY RIVER, NEWRY, ME, US CHAIR: Brian Freeman VICE CHAIR: Harm Kampinga. Three Dimensional Electron Microscopy OCTOBER 31 – NOVEMBER 5, 2021 JORDAN HOTEL AT SUNDAY RIVER• NEWRY, ME, US CHAIR: Sharon Wolf VICE CHAIR: Daniela Nicastro. Apply now at www.grc.org!.

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(3) . Using physics to better understand and use materials Studying the characteristics of materials has captured the attention of many scientists, especially physicists. The knowledge that researchers gain from dissecting the properties of materials impacts the lives of people around the world. In three virtual physics presentations organized in April and May 2021 by the Hong Kong Institute for Advanced Study (HKIAS) at the City University of Hong Kong (CityU), expert scientists discussed the history and latest advances in understanding atomic-level interactions in glass, tuning quantum states, and raising the temperature of superconductivity, all part of the HKIAS Distinguished Lecture Series on Physics. This series is supported in part by the Kwang Hua Educational Foundation.. Exploring the grand challenge of glass On April 14, Xun-Li WangóHead and Chair Professor of the Department of Physics at CityUókicked off this series with a lecture titled ìStructure and Dynamics of Metallic GlassóAtomistic Insights from Neutron and Synchrotron Scattering Experiments.î Wang emphasized that understanding materials made of glass is one of the biggest challenges in science, leading the audience through his atomic-level findings about the structure of metallic glass and the dynamics of phonons (elementary heat particles) within it. Scattering is a powerful technique for studying the structure and dynamics of glass, Wang noted. ìThis is an important topic and there are plenty of opportunities in this field,î he said, while emphasizing the scientific prospects available in Dongguan, China.. PHOTOS: COURTESY OF HKIAS. Tuning the efficiency of quantum states Basing his lecture on the demand for information about low-dimensional physics theory, Ruiqin ZhangóChair Professor of Physics and Materials Science and Engineering at CityUódiscussed ìTuning of Confined Quantum Statesî on April 28. ìConfined quantum states open up many possibilities,î Zhang said. ìWe have been working on engineering these confined quantum states using different strategies,î he notedóstrategies that include surface engineering, stress or strain engineering, and excited-state engineering. Research in this area facilitates the development of miniaturized and efficient equipment that uses solar energy to produce hydrogen. Zhang added that this research can promote the application of low-dimensional materials in the fields of optoelectronics, nanoelectronics, environmental science, green energy, biology, and medicine.. Professor Xun-Li Wang Head of Department and Chair Professor of Physics, CityU Professor Ruiqin Zhang Chair Professor of Physics, CityU. Discovered in 1911, superconductivityóthe ability of a charge to move through a material with no electrical resistanceóappears in certain materials at extremely low temperatures. Bao explained how room-temperature superconductivity ìhas been a dream for us for many decades.î To find superconductivity at even higher temperatures, scientists like Bao are studying materials such as iron chalcogenides; these insulating cuprate ceramics created an Iron Age of superconductors and offer hope for realizing Baoís dream.. A commitment to a better world Xun-Li Wang. Ruiqin Zhang. Wei Bao. HKIAS is committed to advancing CityU and the worldís academic community by delivering groundbreaking research and encouraging talented young researchers. In recent years, the institute has provided a platform for preeminent visiting scholars to engage in pioneering research and contribute to postdoctoral and postgraduate training. To advance the frontiers of interdisciplinary research, HKIAS is creating research clusters. Three recent clustersóthe HKIAS Materials Science Cluster, the HKIAS Bioscience Cluster, and the HKIAS Mathematics Clusteróencourage collaboration and deliver high-quality research. Led by HKIAS senior fellows, each cluster addresses a significant problem or set of interrelated questions through individual and collective research. Serving as incubators for larger and longer-term collaborations, the clusters aim to attract external funding and generate significant results. They also enrich the instituteís distinctive intellectual community through partnerships that spark new approaches and findings, as well as facilitating the mentoring of junior scholars. To make the world a better place, HKIAS will keep delivering pioneering research and nurturing young, talented scholars across disciplinesódriving the development of CityU and of science education across the globe.. Warming up superconductors In the last lecture of this series on May 12, Wei BaoóChair Professor in the Department of Physics at CityUódelivered a talk entitled ìLattice, Charge, Spin and Orbital Aspects of the Iron Chalcogenide Superconductors.î. Professor Wei Bao Chair Professor of Physics, CityU. Hong Kong Institute for Advanced Study Phone: +852-3442-6611 Email: [email protected].

(4) Advertorial. Noster has launched its first postbiotics product based on decades of research on gut microorganisms including lactic acid bacteria and related lipid metabolites.. ìMankind has come a long way in understanding the causes and treatment of human ailments since Hippocrates proposed over 2,000 years ago that all disease begins in the gut,î says Kohey Kitao, CEO of Noster Inc., an innovative Kyoto-based company specializing in the development of therapeutic drugs to treat diseases by controlling and manipulating gut microorganisms and their metabolites. ìWe established Noster in May 2020 with the goal of ëconnecting life and the gut microbiome.í Our in-house expertise has evolved tremendously since my first chance encounter more than 10 years ago with gut microbes and fatty acid metabolites in the human gut. Now, in 2021, we have successfully launched HYA-50, our first postbiotic product under our CUMEC brand, which stands for ëcutting-edge microbiome care.í It is a functional supplement that is the direct result of Nosterís knowledge of the gut microbial lipid metabolite 10-hydroxy-cis-12-octadecenoic acid (10HOE, also called HYA) and is so named because it contains 50% HYA. Our research shows that taking three capsules of HYA-50 before meals improves insulin resistance and controls blood glucose levels. This treatment heralds the beginning of an exciting new chapter in our story of the benefits of gut microorganism for human health.î. Embracing serendipity, realizing potential, and overcoming challenges The scientific know-how accumulated by Noster is based on longterm, multidisciplinary collaborations with experts in academia. An interest in the health benefits of HYA is one thing, but turning that interest into a viable product is something quite different. The companyís first major challenge was establishing a process for mass-producing HYA. ìI first became aware of the potential health benefits of HYA during serendipitous meetings with two academics,î recalls Kitao. ìThe first was with Jun Ogawa, a professor at Kyoto University, who was excited by his groupís discovery that HYA is produced by gut microbes in the intestinal tract and transferred to the host (1). Next, I remember long conversations about HYA with Ikuo Kimura, now also a professor at Kyoto University, whose group made important fundamental contributions to our understanding of the potential role of HYA for the treatment of chronic type 2 diabetes, inflammatory bowel disease, and insulin resistance in mouse models (2, 3). I wanted to explore potential pharmaceutical applications of these scientific findings but realized that the first hurdle to overcome for drug discovery applications was producing HYA in large volumes. This was around 10 years ago. It was a daunting task, but we took up the challenge!î. PHOTOS: PROVIDED BY NOSTER.

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(8) PHOTOS: PROVIDED BY NOSTER. Produced by the Science

(9) . Large-scale production of HYA-50 and the launch of CUMEC Producing HYA for functional supplement applications necessitates that all the materials used must themselves be composed of foods. ìGiven the strict regulations for such products, our goal was to produce at least 50%-pure HYA in large quantities,î explains Kitao. ìWe used high-purity sources of linoleic acid, a form of seed oil, and cultivated lactic acid bacteria in-house for highefficiency conversion of this source oil into HYA, which is produced by gut microbial metabolism in the human digestive tract. It was a difficult task, but we managed to complete it successfully through a collaboration with Kyoto University.î For the mass production of HYA, the Noster R&D team decided to use highly pure (>70%) safflower oil as the source for the linoleic acid. Their next task was devising a procedure that would yield a high conversion rate of the linoleic acid into HYA. Their experiments revealed that it would be critical to protect the safflower oil from oxidation and optimize the emulsion of ingredients to enhance contact between the lactic acid bacteria and linoleic acid. ìOur process was anaerobic, with a highly efficient reaction in the emulsified state,î says Kitao. ìThe know-how for cultivating anaerobic bacteria in the laboratory is one of Nosterís key technologies. It is not a straightforward process, necessitating a deep understanding of the behavior of gut microorganisms. We can now extract many kinds of metabolites directly from gut microorganisms cultivated in-house.î The final step was to recover HYA from the reaction solution with a purity of more than 50%. Since it had emulsified in the reaction process, it could not be separated cleanly using normal centrifugation. The Noster team careful analyzed the effect of temperature on the physical characteristics of the fatty acidñwater emulsion, and determined an optimal temperature that led to highefficiency separation of 50% pure HYA from the emulsion. ìUsing this process, we went from being able to produce several grams of HYA-50 with a purity of 50% to synthesizing kilogram amounts,î says Kitao. ìThis production technology is at the heart of our HYA-50 CUMEC postbiotic product.î Boosting purity for clinical research The purity of HYA-50 was adequate in a consumer product, but much higher purityócloser to 99%ówas needed to perform advanced clinical studies. The most difficult step in producing. ultrapure HYA was developing a highly efficient refining process. The conversion of linoleic acid to HYA is a reversible enzymatic reaction and is therefore never 100% complete. To address this problem, the Noster team attempted to remove residual linoleic acid using a fractionation column after the reaction had run its course. However, this conventional approach did not yield complete separation, leaving too much linoleic acid residue in the refinement product. Nosterís solution was to find lactic acid bacteria strains that increased the conversion rate, thereby minimizing the amount of linoleic acid remaining after the reaction. Notably, even the best lactic acid bacteria strains selected from Nosterís library of about 400 strains for mass production of high-purity HYA yielded a maximum conversion rate of only 80%, leaving 20% linoleic acid remaining. To solve this problem, the project team turned to Escherichia coli, creating a strain of this bacteria that carried the conjugated linoleic acid hydrase (CLA-HY) enzyme, which converts linoleic acid to HYA. After testing numerous E. coli strains, transfection vectors, and culture conditions, the research team succeeded in generating a strain capable of converting close to 100% of linoleic acid to HYA. Another challenge was that conventional purification processes rely on diethyl ether. Production of large volumes of HYA would require large amounts of this ether, which is extremely flammable and can only be used safely in small amounts, severely limiting the production potential of pure HYA. Kitao explains the Noster teamís approach to this problem: ìWe experimentally found a solvent with low flammability that could efficiently separate HYA and linoleic acid. But then we hit another wall. This solvent led to the rapid deterioration of the fractionation column, and it was not a practical solution for a continuous purification process. So we still had work to do!î Eventually, the Noster team developed a customized fractionation column to efficiently separate HYA and linoleic acid using the new solvent, but with significantly less deterioration. ìThe combination of the new solvent and our new column enabled us to scale up the production of our ultrapure HYA product.î. Production of other lipid metabolites Over the last decade, Noster researchers have established procedures for producing other types of lipid metabolites in.

(10) Advertorial. Libraries for drug discovery Nosterís technology for cultivating gut microorganisms and related metabolites has enabled the company to establish two unique libraires: a microbial library of more than 1,600 strains and a lipid metabolite collection of more than 300 compounds. ìOur libraries offer a wealth of information on gut microorganisms and metabolites that can be candidates for drug discovery. They. have attracted attention from researchers working on therapeutics and drug discovery based on the gut microbiome. We continue to welcome collaborations.î For information about Nosterís gut microbiome libraires: Microbial library: www.noster.inc/products/microbial/. Lipid metabolite library: www.noster.inc/products/metabolite/.. The importance of standardization and sharing In 2016, Japan launched the Society 5.0 initiative as part of its national 5th Science and Technology Basic Plan, which builds on the four historical social infrastructures of hunting, agriculture, industry, and information, and hopes to create a new society where people and technology are increasingly linked, and where artificial intelligence helps us break previous barriers. Notably, molecular-level health careógenetic engineeringñbased medicine for the personalized treatment of chronic diseasesóis an important pillar of the plan. Noster believes that further advances in this field necessitate sharing accurate data on lipidomics as part of an openaccess, large-scale data platform. ìNoster is an active member of Japanís Council on Competitiveness-Nippon [COCN] and is providing full access to our library of microorganisms and gut microbial lipid metabolites,î says Kitao. ìWe fully support projects to standardize data on lipids and metabolites for use in lipidomics research.î. PHOTOS: PROVIDED BY NOSTER. recombinant bacteria. But it was not easy. For example, in the case of linoleic and oleic acids, the fatty acid conversion reaction occurs in multiple steps, and each step of the reaction is catalyzed by a different enzyme. Furthermore, these are reversible reactions exhibiting conversion rates of less than 100%, with the amount of the desired final product decreasing with each step. Noster researchers experimented with using multiple strains of recombinant bacteria to improve efficiency, but the reactions were difficult to control, and it was not possible to efficiently isolate target compounds. For instance, it was difficult to simultaneously separate and purify individual fatty acids from a solution containing a mixture of multiple fatty acids, because the structures and physical properties of each fatty acid were similar. ìAfter much experimentation we were able to improve our yield of a wide range of lipid metabolites from several milligrams to tens of milligrams,î says Kitao. ìThis was enough for cell-based experiments and animal tests, accelerating the drug discovery process.î.

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(12) . Notably, Noster has also been conducting its own research on standardization and lipid analysis with Makoto Arita, a professor at Keio University and team leader of the Laboratory for Metabolomics at the RIKEN Center for Integrative Medical Sciences. Arita is using the latest liquid chromatography-mass spectrometry-based lipidomics to standardize the properties of lipids, with the goal of elucidating the structure and function of endogenous lipid mediators that regulate inflammation and tissue homeostasis. COCN has formulated plans to establish next-generation health care systems centered on providing customized medical care for individuals at the molecular level. This year COCN proposed establishing a national lipids center, which is expected to be completed within the next 3 to 5 years.. Diabetes clinical trials with HYA One of Nosterís major goals is harnessing the power of metabolites produced by gut microorganisms to develop therapeutics to treat the underlying causes of chronic diseases such as diabetes and intestinal inflammation disorders. To achieve this goal, the first important milestone is initiating human clinical trials. ìWe have invested considerable time and effort into developing protocols to produce large volumes of high-purity HYA to enable us to initiate these trials,î says Kitao. ìIn November 2020, we started clinical trials with Wataru Ogawa at Kobe University on the efficacy of HYA on ëinsulin sensitivity in patients with impaired glucose tolerance or mild diabetes mellitus,í as stated in the Japan Registry of Clinical Trials. This trial is based on oral administration of 99%pure HYA capsulesóa minimally invasive approach compared with conventional highly invasive injection-based treatments.î Noster is also planning to launch clinical trials in 2021 on using HYA to treat individuals with a high body mass index (>30) and type 1 diabetes. The Noster & Science Microbiome Prize ìGlobal multidisciplinary research partnerships will be critical for further innovation and advances in microbiome research,î says Kitao. ìIn 2020, we launched the Noster & Science Microbiome Prize to support and inspire young scientists to find sustainable solutions to chronic diseases. We enjoyed meeting the 2020 recipients during the online awards ceremony held in September 2020 and are pleased to congratulate the 2021 winners.î The 2021 Grand Prize winner is Eran Blacher, postdoctoral research fellow in neurology and neurological sciences at Stanford University in California. The other finalists are Maria ZimmermannKogadeeva, a group leader at EMBL Heidelberg in Germany, and Erez Baruch, who is currently doing his internal medicine residency at The University of Texas Health Science Center in Houston, Texas.. Further information about the Noster & Science Microbiome Prize can be found at www.sciencemag.org/prizes/noster-sciencemicrobiome-prize. A summary of the proceedings of the 2020 Prize awards ceremony is available on the Microbiome Research X website: noster-mrx.net.. Microbiome Research Podcast (MRX Podcast) In April 2020, Noster launched the Microbiome Research X (MRX) website to highlight the latest research results in this field. ìInspired by the success of the MRX website, we decided to launch the MRX Podcast in the fall of 2020,î explains Kitao. ìThe podcast hosts conversations with scientists working on the gut microbiome. It is a highly effective way of connecting with people on a global scale.î The first three podcasts feature interviews with the grand winner and two finalists of the 2020 Noster & Science Microbiome Prize. They describe their research as well as how they prepared their essays for the prize.. You can listen to the MRX Podcasts here:. Apple Podcasts. Google Podcasts. A future of postbiotics-inspired pharma Over the last decade, Noster has made important contributions to the international understanding of the role of gut microorganisms in human health. ìOur journey to study the health benefits of gut microorganisms busily working away inside our bodies has only just started,î explains Kitao. ìI look forward to the day when postbioticbased therapeutics will be so widespread that we do not even think about it anymore. It will be just like breathing.î References 1. S. Kishino et al., Proc. Natl. Acad. Sci. U.S.A. 110, 17808ñ17813 (2013). 2. J. Miyamoto et al., J. Biol. Chem. 290, 2902ñ2918 (2015). 3. J. Miyamoto et al., Nat. Commun. 10, 4007 (2019).. Sponsored by.

(13) CALL FO R PAPERS. BioDesign Research is a Science Partner Journal published in afliation with Nanjing Agricultural University (NAU) and distributed by the American Association for the Advancement of Science (AAAS). BioDesign Research publishes high quality breakthrough research, reviews, editorials, and perspectives focusing on in silico biosystems design, genetic or epigenetic modifcations, and genome writing or rewriting in any organism.. Submit your research to BioDesign Research today! Learn more at spj.sciencemag.org/bdr The Science Partner Journals (SPJ) program was established by the American Association for the Advancement of Science (AAAS), the non-proft publisher of the Science family of journals. The SPJ program features high quality, online-only, editorially independent openaccess publications produced in collaboration with international research institutions, foundations, funders and societies. Through these collaborations, AAAS expands its eforts to communicate science broadly and for the beneft of all people by providing a top-tier international research organization with the technology, visibility, and publishing expertise that AAAS is uniquely positioned to ofer as the world’s largest general science membership society. Learn more at spj.sciencemag.org @SPJournals. @SPJournals. A RT I C L E P R O C E S S I N G C H A R G E S WA I V E D U N T I L 2 0 2 2.

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