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A Study Finds Neuropeptide Somatostatin Enhances Visual Processing
Researchers have confirmed that neuropeptide somatostatin can improve cognitive function in the brain. A research group of Professor Seung-Hee Lee from the Department of Biological Sciences at KAIST found that the application of neuropeptide somatostatin improves visual processing and cognitive behaviors by reducing excitatory inputs to parvalbumin-positive interneurons in the cortex.
This study, reported at Science Advances on April 22nd (EST), sheds a new light on the therapeutics of neurodegenerative diseases. According to a recent study in Korea, one in ten seniors over 65 is experiencing dementia-related symptoms in their daily lives such like memory loss, cognitive decline, and motion function disorders. Professor Lee believes that somatostatin treatment can be directly applied to the recovery of cognitive functions in Alzheimer’s disease patients.
Professor Lee started this study noting the fact that the level of somatostatin expression was dramatically decreased in the cerebral cortex and cerebrospinal fluid of Alzheimer’s disease patients
Somatostatin-expressing neurons in the cortex are known to exert the dendritic inhibition of pyramidal neurons via GABAergic transmission. Previous studies focused on their inhibitory effects on cortical circuits, but somatostatin-expressing neurons can co-release somatostatin upon activation. Despite the abundant expression of somatostatin and its receptors in the cerebral cortex, it was not known if somatostatin could modulate cognitive processing in the cortex.
The research team demonstrated that the somatostatin treatment into the cerebral cortex could enhance visual processing and cognitive behaviors in mice. The research team combined behaviors, in vivo and in vitro electrophysiology, and electron microscopy techniques to reveal how the activation of somatostatin receptors in vivo enhanced the ability of visual recognition in animals. Interestingly, somatostatin release can reduce excitatory synaptic transmission to another subtype of GABAergic interneurons, parvalbumin (PV)-expressing neurons.
As somatostatin is a stable and safe neuropeptide expressed naturally in the mammalian brain, it was safe to be injected into the cortex and cerebrospinal fluid, showing a potential application to drug development for curing cognitive disorders in humans.
Professor Lee said, “Our research confirmed the key role of the neuropeptide SST in modulating cortical function and enhancing cognitive ability in the mammalian brain. I hope new drugs can be developed based on the function of somatostatin to treat cognitive disabilities in many patients suffering from neurological disorders.”
This study was supported by the National Research Foundation of Korea.
Publication:
Song, Y. H et al. (2020) ‘Somatostatin enhances visual processing and perception by suppressing excitatory inputs to parvalbumin-positive interneurons in V1’, Science Advances, 6(17). Available online at https://doi.org/10.1126/sciadv.aaz0517
Profile:
Seung-Hee Lee
Associate Professor
shlee1@kaist.ac.kr
https://sites.google.com/site/leelab2013/
Sensory Processing Lab (SPL)
Department of Biological Sciences (BIO)
Korea Advanced Institute of Science and Technology (KAIST)
Profile:
You-Hyang Song
Researcher (Ph.D.)
dbgidtm17@kaist.ac.kr
SPL, KAIST BIO
Profile:
Yang-Sun Hwang
Researcher (M.S.)
hys940129@kaist.ac.kr
SPL, KAIST BIO
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2020.04.23 View 13313 -
Long Economic Depressions and Disparities Loom in the Wake of the COVID-19
"Global Cooperation for Managing Data Key to Mitigating the Impacts Around the World"
<Full recorded video of the GSI-IF2020>
The COVID-19 pandemic will lead to long economic depressions around the entire world. Experts predicted that the prevalent inequities among the countries, regions, and individuals will aggravate the economic crisis. However, crises always come with new opportunities and international cooperation and solidarity will help creating a new normal in the post-coronavirus era.
In a very basic but urgent step, global cooperation for managing data is the key to respond to COVID-19 since medicine and healthcare are intertwined with data science, said experts during an online international forum hosted by the Global Strategy Institute at KAIST on April 22.
KAIST launched its think-tank, the Global Strategy Institute (GSI), in February. The GSI aims to identify global issues proactively and help make breakthroughs well aligned with solid science-based policies.
The inaugural forum of the GSI focused on how the COVID-19 pandemic would impact socio-economic, scientific, and political landscapes, under the theme “Global Cooperation in the Coronavirus Era.”
In his opening remarks, KAIST President Sung-Chul Shin stressed that future global governance will be dominated by the power of science and technology. “If we can implement efficient policies together with troubleshooting technology for responding to future crises, we will emerge stronger than before,” he said.
President Shin said ‘the Korean model’, which is being recognized as a shining example for dealing with the pandemic, is the result of collaborations combining the creativity of the private sector, the public sector’s strong infrastructure, and the full support of the citizens. He added, “Without the technological prowess coming from the competent R&D power of Korea, we could not achieve these impressive results.”
“Creative collaboration among the private and public sectors, along with research universities from around the world, will help shore up global resilience against the epidemic. We should work together to build a world of growing prosperity,” President Shin said.
Prime Minister Sye-Kyun Chung, who is in charge of the Central Disaster and Safety Countermeasures Headquarters in Korea, stressed global solidarity in his welcoming remarks, saying that “We need to share information and rely on the strength of our connections, rather than retreating into nationalistic isolation.”
Peter Lee, Vice President of the Microsoft Healthcare, pointed out in his welcoming remarks three critical sectors for global cooperation: medicine and healthcare, public health and prevention, and life and the economy. He emphasized the rule of thumb for managing data, saying that data in these fields should be open, standardized, and shared among countries to combat this global pandemic.
During a keynote session, Director General of the International Vaccine Institute (IVI) Jerome Kim described the challenges that go along with developing a vaccine. Dr. Kim said that only 7% of vaccine candidates go through the clinical trial stages, and it will take five to 10 years to completely prove a new vaccine’s safety after completing three stages of clinical tests.
“It’s very challenging to develop the vaccine for COVID-19 within 12 to 15 months,” said Dr. Kim. He added that 78 out of 115 candidates are currently undergoing clinical trials around the world.
There are five groups, including Moderna, Inovio, Jenner Institute, CanSino, and the Beijing Institute of Biological Products, who are doing clinical trials in phases 1 and 2. “Given the fact that COVID-19 is a totally new type of virus, various stakeholders’ participation, such as the National Immunization Technical Advisory Groups, the WHO, and UNICEF, is needed to work together to benefit the entire world,” he pointed out.
Professor Edward Yoonjae Choi from the Graduate School of AI at KAIST shared how AI and data sciences are being utilized to interpret the major trends of the epidemic. His group mainly focuses on deep learning to model electronic health records (EHR) for disease predictions. Professor Choi said AI and machine learning would be crucial solutions and collaborative research projects will surely accelerate how quickly we can overcome the pandemic.
In addition, Dr. Kijung Shin’s group is interpreting the SIR (Susceptible, Infected, and Recovered) model in Korea to predict the number of infections and when people were infected. However, researchers noticed that they could not see the typical modeling in Korea for predicting the number of infections since the model disregarded the new variable of humans’ efforts to stop the spread the virus.
According to research by Professor Steven Whang’s group on social distancing and face mask distribution among vulnerable age groups, people in their 20s, 60s, and 70s followed the social distancing guidelines the most strictly. The research team analyzed the data provided by SK Telecom in the Gangnam district of Seoul. The data provided on people in their 70s, a group that accounted for half of all fatalities, showed that masks were generally well distributed nationwide.
Dr. Alexandros Papaspyrids, Tertiary Education Industry Director of the Asia region of Microsoft, said that despite all the disadvantages and problems related to remote education, we shouldn’t expect to return to the days before the COVID-19 any time soon. “We should accept the new normal and explore new opportunities in the new educational environment,” he said.
Hongtaek Yong, Deputy Minister at the Office of R&D Policy at the Ministry of Science and ICT presented the Korean government’s disease prevention and response policy and how they tried to mitigate the economic and social impact.
He stressed the government’s fast testing, tracing, and openness for successfully flattening the curve, adding that the government used an ICT-based approach in all aspects of their response. From early this year when the first patient was reported, the government aggressively encouraged the biotech industry to develop diagnostic kits and novel therapeutic medications.
As a result, five companies were able to produce genetic diagnostic reagents through the emergency approval. More notably, four of them are conducting massive R&D projects sponsored by the government and this is the result of the government’s continuous investment in R&D. Korea is the leader in R&D investment among the OECD countries.
According to Yong, the government’s big data project that was launched in 2017 continuously traces the trends of epidemics in Korea. The epidemiological studies based on the paths taken by suspected patients using credit card transaction made the difference in predicting the spread of the coronavirus and implementing countermeasures. The data has been provided to the Korea’s Center for Disease Control (CDC).
“In addition to the epidemics, we have so many other pending issues arising from digital and social equities, un-contact services, and job security. We are very open to collaborate and cooperate with other countries to deal with this global crisis,” Yong said.
During the subsequent panel discussions, David Dollar, a senior fellow at the Brookings Institution, said, “The global economy in the coronavirus era will not have a rapid V-shaped recovery, but rather will fall into a long depression for at least two years.” He pointed out that if countries practice protectionism like they did during the Great Depression, the recession will be even worse. Hence, he urged the international community, especially developed nations, to avoid protectionism, consider the economic difficulties of developing countries, and provide them with financial support.
Co-Director of the Center for Universal Education at the Brookings Institution Rebecca Winthrop raised concerns over the recent shift to online teaching and learning, claiming that insufficient infrastructures in low-income families in developing nations are already causing added educational disparities and provoking the inequity issue around the world. “The ways to provide quality education equally through faster and more effective means should be studied,” she said.
Professor Joungho Kim, the director of the KAIST GSI and the forum’s organizer, concluded the event by saying that this forum will be a valuable resource for everyone who is providing assistance to those in need, both during and after the COVID-19 pandemic.
(END)
2020.04.22 View 21535 -
Ultrathin but Fully Packaged High-Resolution Camera
- Biologically inspired ultrathin arrayed camera captures super-resolution images. -
The unique structures of biological vision systems in nature inspired scientists to design ultracompact imaging systems. A research group led by Professor Ki-Hun Jeong have made an ultracompact camera that captures high-contrast and high-resolution images. Fully packaged with micro-optical elements such as inverted micro-lenses, multilayered pinhole arrays, and gap spacers on the image sensor, the camera boasts a total track length of 740 μm and a field of view of 73°.
Inspired by the eye structures of the paper wasp species Xenos peckii, the research team completely suppressed optical noise between micro-lenses while reducing camera thickness. The camera has successfully demonstrated high-contrast clear array images acquired from tiny micro lenses. To further enhance the image quality of the captured image, the team combined the arrayed images into one image through super-resolution imaging.
An insect’s compound eye has superior visual characteristics, such as a wide viewing angle, high motion sensitivity, and a large depth of field while maintaining a small volume of visual structure with a small focal length. Among them, the eyes of Xenos peckii and an endoparasite found on paper wasps have hundreds of photoreceptors in a single lens unlike conventional compound eyes. In particular, the eye structures of an adult Xenos peckii exhibit hundreds of photoreceptors on an individual eyelet and offer engineering inspiration for ultrathin cameras or imaging applications because they have higher visual acuity than other compound eyes.
For instance, Xenos peckii’s eye-inspired cameras provide a 50 times higher spatial resolution than those based on arthropod eyes. In addition, the effective image resolution of the Xenos peckii’s eye can be further improved using the image overlaps between neighboring eyelets. This unique structure offers higher visual resolution than other insect eyes.
The team achieved high-contrast and super-resolution imaging through a novel arrayed design of micro-optical elements comprising multilayered aperture arrays and inverted micro-lens arrays directly stacked over an image sensor. This optical component was integrated with a complementary metal oxide semiconductor image sensor.
This is first demonstration of super-resolution imaging which acquires a single integrated image with high contrast and high resolving power reconstructed from high-contrast array images. It is expected that this ultrathin arrayed camera can be applied for further developing mobile devices, advanced surveillance vehicles, and endoscopes.
Professor Jeong said, “This research has led to technological advances in imaging technology. We will continue to strive to make significant impacts on multidisciplinary research projects in the fields of microtechnology and nanotechnology, seeking inspiration from natural photonic structures.”
This work was featured in Light Science & Applications last month and was supported by the National Research Foundation (NRF) of and the Ministry of Health and Welfare (MOHW) of Korea.
Image credit: Professor Ki-Hun Jeong, KAIST
Image usage restrictions: News organizations may use or redistribute this image, with proper attribution, as part of news coverage of this paper only.
Publication:
Kisoo Kim, Kyung-Won Jang, Jae-Kwan Ryu, and Ki-Hun Jeong. (2020) “Biologically inspired ultrathin arrayed camera for high-contrast and high-resolution imaging”. Light Science & Applications. Volume 9. Article 28. Available online at https://doi.org/10.1038/s41377-020-0261-8
Profile:
Ki-Hun Jeong
Professor
kjeong@kaist.ac.kr
http://biophotonics.kaist.ac.kr/
Department of Bio and Brain Engineering
KAIST
Profile:
Kisoo Kim
Ph.D. Candidate
kisoo.kim1@kaist.ac.kr
http://biophotonics.kaist.ac.kr/
Department of Bio and Brain Engineering
KAIST
(END)
2020.03.23 View 18136 -
‘OSK Rising Stars 30’ Recognizes Four KAISTians
Four KAISTians were selected as star researchers to brighten the future of optics in commemoration of the 30th anniversary of the Optical Society of Korea (OSK). As ‘OSK Rising Stars 30’, the OSK named 27 domestic researchers under the age of 40 who have made significant contributions and will continue contributing to the development of Korea’s optics academia and industry.
Professor YongKeun Park from the Department of Physics was selected in recognition of his contributions to the field of biomedical optics. Professor Park focuses on developing novel optical methods for understanding, diagnosing, and treating human diseases, based on light scattering, light manipulation, and interferometry. As a member of numerous international optics societies including the OSA and the SPIE and a co-founder of two start-up companies, Professor Park continues to broaden his boundaries as a leading opticist and entrepreneur.
Professor Jonghwa Shin from the Department of Materials Science and Engineering was recognized for blazing a trail in the field of broadband metamaterials. Professor Shin’s research on the broadband enhancement of the electric permittivity and refractive index of metamaterials has great potential in both academia and industry.
Professor Hongki Yoo from the Department of Mechanical Engineering is expected to create a significant ripple effect in the diagnosis of cardiovascular disorders through the development of new optical imaging techniques and applications.
Finally, Dr. Sejeong Kim, a KAIST graduate and a Chancellor’s postdoctoral research fellow at the University of Technology Sydney (UTS), was acknowledged for her optical device research utilizing two-dimensional materials. Dr. Kim’s research at UTS now focuses on the introduction of micro/nano cavities for new materials.
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2020.03.16 View 11429 -
A Single Biological Factor Predicts Distinct Cortical Organizations across Mammalian Species
-A KAIST team’s mathematical sampling model shows that retino-cortical mapping is a prime determinant in the topography of cortical organization.-
Researchers have explained how visual cortexes develop uniquely across the brains of different mammalian species. A KAIST research team led by Professor Se-Bum Paik from the Department of Bio and Brain Engineering has identified a single biological factor, the retino-cortical mapping ratio, that predicts distinct cortical organizations across mammalian species.
This new finding has resolved a long-standing puzzle in understanding visual neuroscience regarding the origin of functional architectures in the visual cortex. The study published in Cell Reports on March 10 demonstrates that the evolutionary variation of biological parameters may induce the development of distinct functional circuits in the visual cortex, even without species-specific developmental mechanisms.
In the primary visual cortex (V1) of mammals, neural tuning to visual stimulus orientation is organized into one of two distinct topographic patterns across species. While primates have columnar orientation maps, a salt-and-pepper type organization is observed in rodents.
For decades, this sharp contrast between cortical organizations has spawned fundamental questions about the origin of functional architectures in the V1. However, it remained unknown whether these patterns reflect disparate developmental mechanisms across mammalian taxa, or simply originate from variations in biological parameters under a universal development process.
To identify a determinant predicting distinct cortical organizations, Professor Paik and his researchers Jaeson Jang and Min Song examined the exact condition that generates columnar and salt-and-pepper organizations, respectively. Next, they applied a mathematical model to investigate how the topographic information of the underlying retinal mosaics pattern could be differently mapped onto a cortical space, depending on the mapping condition.
The research team proved that the retino-cortical feedforwarding mapping ratio appeared to be correlated to the cortical organization of each species. In the model simulations, the team found that distinct cortical circuitries can arise from different V1 areas and retinal ganglion cell (RGC) mosaic sizes. The team’s mathematical sampling model shows that retino-cortical mapping is a prime determinant in the topography of cortical organization, and this prediction was confirmed by neural parameter analysis of the data from eight phylogenetically distinct mammalian species.
Furthermore, the researchers proved that the Nyquist sampling theorem explains this parametric division of cortical organization with high accuracy. They showed that a mathematical model predicts that the organization of cortical orientation tuning makes a sharp transition around the Nyquist sampling frequency, explaining why cortical organizations can be observed in either columnar or salt-and-pepper organizations, but not in intermediates between these two stages.
Professor Paik said, “Our findings make a significant impact for understanding the origin of functional architectures in the visual cortex of the brain, and will provide a broad conceptual advancement as well as advanced insights into the mechanism underlying neural development in evolutionarily divergent species.”
He continued, “We believe that our findings will be of great interest to scientists working in a wide range of fields such as neuroscience, vision science, and developmental biology.”
This work was supported by the National Research Foundation of Korea (NRF).
Image credit: Professor Se-Bum Paik, KAIST
Image usage restrictions: News organizations may use or redistribute this image, with proper attribution, as part of news coverage of this paper only.
Publication:
Jaeson Jang, Min Song, and Se-Bum Paik. (2020). Retino-cortical mapping ratio predicts columnar and salt-and-pepper organization in mammalian visual cortex. Cell Reports. Volume 30. Issue 10. pp. 3270-3279. Available online at https://doi.org/10.1016/j.celrep.2020.02.038
Profile:
Se-Bum Paik
Assistant Professor
sbpaik@kaist.ac.kr
http://vs.kaist.ac.kr/
VSNN Laboratory
Department of Bio and Brain Engineering
Program of Brain and Cognitive Engineering
http://kaist.ac.kr
Korea Advanced Institute of Science and Technology (KAIST)
Daejeon, Republic of Korea
Profile:
Jaeson Jang
Ph.D. Candidate
jaesonjang@kaist.ac.kr
Department of Bio and Brain Engineering, KAIST
Profile:
Min Song
Ph.D. Candidate
night@kaist.ac.kr
Program of Brain and Cognitive Engineering, KAIST
(END)
2020.03.11 View 14030 -
Coordination Chemistry and Alzheimer’s Disease
It has become evident recently that the interactions between copper and amyloid-b neurotoxically impact the brain of patients with Alzheimer’s disease. KAIST researchers have reported a new strategy to alter the neurotoxicity in Alzheimer’s disease by using a rationally designed chemical reagent.
This strategy, developed by Professor Mi Hee Lim from the Department of Chemistry, can modify the coordination sphere of copper bound to amyloid-b, effectively inhibiting copper’s binding to amyloid-b and altering its aggregation and toxicity. Their study was featured in PNAS last month.
The researchers developed a small molecule that is able to directly interact with the coordination sphere of copper–amyloid-b complexes followed by modifications via either covalent conjugation, oxidation, or both under aerobic conditions. The research team simply utilized copper–dioxygen chemistry to design a chemical reagent.
Answering how peptide modifications by a small molecule occur remains very challenging. The system includes transition metals and amyloidogenic proteins and is quite heterogeneous, since they are continuously being changed. It is critical to carefully check the multiple variables such as the presence of dioxygen and the type of transition metal ions and amyloidogenic proteins in order to identify the underlying mechanisms and target specificity of the chemical reagent.
The research team employed various biophysical and biochemical methods to determine the mechanisms for modifications on the coordination sphere of copper–Aꞵ complexes. Among them, peptide modifications were mainly analyzed using electrospray ionization-mass spectrometry.
Mass spectrometry (MS) has been applied to verify such peptide modifications by calculating the shift in exact mass. The research team also performed collision-induced dissociation (CID) of the target ion detected by MS to pinpoint which amino acid residue is specifically modified. The CID fragmentizes the amide bond located between the amino acid residues. This fragmental analysis allows us to identify the specific sites of peptide modifications.
The copper and amyloid-b complexes represent a pathological connection between metal ions and amyloid-b in Alzheimer’s disease. Recent findings indicate that copper and amyloid-b can directly contribute toward neurodegeneration by producing toxic amyloid-b oligomers and reactive oxygen species.
Professor Lim said, “This study illustrates the first experimental evidence that the 14th histidine residue in copper–amyloid-b complexes can be specifically modified through either covalent conjugation, oxidation, or both. Considering the neurotoxic implications of the interactions between copper and amyloid-b, such modifications at the coordination sphere of copper in amyloid-b could effectively alter its properties and toxicity.”
“This multidisciplinary study with an emphasis on approaches, reactivities, and mechanisms looks forward to opening a new way to develop candidates of anti-neurodegenerative diseases,” she added. The National Research Foundation of Korea funded this research.
2020.03.03 View 7740 -
Professor Hojong Chang’s Research Team Wins ISIITA 2020 Best Paper Award
The paper written by Professor Hojong Chang’s research team from KAIST Institute for IT Convergence won the best paper award from the International Symposium on Innovation in Information Technology Application (ISIITA) 2020, held this month at Ton Duc Thang University in Vietnam.
ISIITA is a networking symposium where leading researchers from various fields including information and communications, biotechnology, and computer systems come together and share on the convergence of technology.
Professor Chang’s team won the best paper award at this year’s symposium with its paper, “A Study of Single Photon Counting System for Quantitative Analysis of Luminescence”. The awarded paper discusses the realization of a signal processing system for silicon photomultipliers.
The silicon photomultiplier is the core of a urinalysis technique that tests for sodium and potassium in the body using simple chemical reactions. If our bodily sodium and potassium levels exceed a certain amount, it can lead to high blood pressure, cardiovascular problems, and kidney damage.
Through this research, the team has developed a core technique that quantifies the sodium and potassium discharged in the urine. When the reagent is injected into the urine, a very small amount of light is emitted as a result of the chemical reaction. However, if there is a large amount of sodium and potassium, they interrupt the reaction and reduce the emission. The key to this measurement technique is digitizing the strength of this very fine emission of light. Professor Chang’s team developed a system that uses a photomultiplier to measure the chemiluminescence.
Professor Chang said, “I look forward for this signal processing system greatly helping to prevent diseases caused by the excessive consumption of sodium and potassium through quick and easy detection.”
Researcher Byunghun Han who carried out the central research for the system design added, “We are planning to focus on miniaturizing the developed technique, so that anyone can carry our device around like a cellphone.”
The research was supported by the Ministry of Science and ICT.
(END)
2020.02.27 View 10337 -
Professor Jong Chul Ye Appointed as Distinguished Lecturer of IEEE EMBS
Professor Jong Chul Ye from the Department of Bio and Brain Engineering was appointed as a distinguished lecturer by the International Association of Electrical and Electronic Engineers (IEEE) Engineering in Medicine and Biology Society (EMBS). Professor Ye was invited to deliver a lecture on his leading research on artificial intelligence (AI) technology in medical video restoration. He will serve a term of two years beginning in 2020.
IEEE EMBS's distinguished lecturer program is designed to educate researchers around the world on the latest trends and technology in biomedical engineering. Sponsored by IEEE, its members can attend lectures on the distinguished professor's research subject.
Professor Ye said, "We are at a time where the importance of AI in medical imaging is increasing.” He added, “I am proud to be appointed as a distinguished lecturer of the IEEE EMBS in recognition of my contributions to this field.”
(END)
2020.02.27 View 10697 -
New Catalyst Recycles Greenhouse Gases into Fuel and Hydrogen Gas
< Professor Cafer T. Yavuz (left), PhD Candidate Youngdong Song (center), and Researcher Sreerangappa Ramesh (right) >
Scientists have taken a major step toward a circular carbon economy by developing a long-lasting, economical catalyst that recycles greenhouse gases into ingredients that can be used in fuel, hydrogen gas, and other chemicals. The results could be revolutionary in the effort to reverse global warming, according to the researchers. The study was published on February 14 in Science.
“We set out to develop an effective catalyst that can convert large amounts of the greenhouse gases carbon dioxide and methane without failure,” said Cafer T. Yavuz, paper author and associate professor of chemical and biomolecular engineering and of chemistry at KAIST.
The catalyst, made from inexpensive and abundant nickel, magnesium, and molybdenum, initiates and speeds up the rate of reaction that converts carbon dioxide and methane into hydrogen gas. It can work efficiently for more than a month.
This conversion is called ‘dry reforming’, where harmful gases, such as carbon dioxide, are processed to produce more useful chemicals that could be refined for use in fuel, plastics, or even pharmaceuticals. It is an effective process, but it previously required rare and expensive metals such as platinum and rhodium to induce a brief and inefficient chemical reaction.
Other researchers had previously proposed nickel as a more economical solution, but carbon byproducts would build up and the surface nanoparticles would bind together on the cheaper metal, fundamentally changing the composition and geometry of the catalyst and rendering it useless.
“The difficulty arises from the lack of control on scores of active sites over the bulky catalysts surfaces because any refinement procedures attempted also change the nature of the catalyst itself,” Yavuz said.
The researchers produced nickel-molybdenum nanoparticles under a reductive environment in the presence of a single crystalline magnesium oxide. As the ingredients were heated under reactive gas, the nanoparticles moved on the pristine crystal surface seeking anchoring points. The resulting activated catalyst sealed its own high-energy active sites and permanently fixed the location of the nanoparticles — meaning that the nickel-based catalyst will not have a carbon build up, nor will the surface particles bind to one another.
“It took us almost a year to understand the underlying mechanism,” said first author Youngdong Song, a graduate student in the Department of Chemical and Biomolecular Engineering at KAIST. “Once we studied all the chemical events in detail, we were shocked.”
The researchers dubbed the catalyst Nanocatalysts on Single Crystal Edges (NOSCE). The magnesium-oxide nanopowder comes from a finely structured form of magnesium oxide, where the molecules bind continuously to the edge. There are no breaks or defects in the surface, allowing for uniform and predictable reactions.
“Our study solves a number of challenges the catalyst community faces,” Yavuz said. “We believe the NOSCE mechanism will improve other inefficient catalytic reactions and provide even further savings of greenhouse gas emissions.”
This work was supported, in part, by the Saudi-Aramco-KAIST CO2 Management Center and the National Research Foundation of Korea.
Other contributors include Ercan Ozdemir, Sreerangappa Ramesh, Aldiar Adishev, and Saravanan Subramanian, all of whom are affiliated with the Graduate School of Energy, Environment, Water and Sustainability at KAIST; Aadesh Harale, Mohammed Albuali, Bandar Abdullah Fadhel, and Aqil Jamal, all of whom are with the Research and Development Center in Saudi Arabia; and Dohyun Moon and Sun Hee Choi, both of whom are with the Pohang Accelerator Laboratory in Korea. Ozdemir is also affiliated with the Institute of Nanotechnology at the Gebze Technical University in Turkey; Fadhel and Jamal are also affiliated with the Saudi-Armco-KAIST CO2 Management Center in Korea.
<Newly developed catalyst that recycles greenhouse gases into ingredients that can be used in fuel, hydrogen gas and other chemicals.>
Publication:
Song et al. (2020) Dry reforming of methane by stable Ni–Mo nanocatalysts on single-crystalline MgO. Science, Vol. 367, Issue 6479, pp. 777-781. Available online at http://dx.doi.org/10.1126/science.aav2412
Profile: Prof. Cafer T. Yavuz, MA, PhD
yavuz@kaist.ac.kr
http://yavuz.kaist.ac.kr/
Associate Professor
Oxide and Organic Nanomaterials for the Environment (ONE) Laboratory
Graduate School of Energy, Environment, Water and Sustainability (EEWS)
Korea Advanced Institute of Science and Technology (KAIST)
http://kaist.ac.kr
Daejeon, Republic of Korea
Profile: Youngdong Song ydsong88@kaist.ac.kr
Ph.D. Candidate
Department of Chemical and Biomolecular Engineering
Korea Advanced Institute of Science and Technology (KAIST)
http://kaist.ac.kr
Daejeon, Republic of Korea
(END)
2020.02.17 View 17444 -
What Fuels a “Domino Effect” in Cancer Drug Resistance?
KAIST researchers have identified mechanisms that relay prior acquired resistance to the first-line chemotherapy to the second-line targeted therapy, fueling a “domino effect” in cancer drug resistance. Their study featured in the February 7 edition of Science Advances suggests a new strategy for improving the second-line setting of cancer treatment for patients who showed resistance to anti-cancer drugs.
Resistance to cancer drugs is often managed in the clinic by chemotherapy and targeted therapy. Unlike chemotherapy that works by repressing fast-proliferating cells, targeted therapy blocks a single oncogenic pathway to halt tumor growth. In many cases, targeted therapy is engaged as a maintenance therapy or employed in the second-line after front-line chemotherapy.
A team of researchers led by Professor Yoosik Kim from the Department of Chemical and Biomolecular Engineering and the KAIST Institute for Health Science and Technology (KIHST) has discovered an unexpected resistance signature that occurs between chemotherapy and targeted therapy. The team further identified a set of integrated mechanisms that promotes this kind of sequential therapy resistance.
“There have been multiple clinical accounts reflecting that targeted therapies tend to be least successful in patients who have exhausted all standard treatments,” said the first author of the paper Mark Borris D. Aldonza. He continued, “These accounts ignited our hypothesis that failed responses to some chemotherapies might speed up the evolution of resistance to other drugs, particularly those with specific targets.”
Aldonza and his colleagues extracted large amounts of drug-resistance information from the open-source database the Genomics of Drug Sensitivity in Cancer (GDSC), which contains thousands of drug response data entries from various human cancer cell lines. Their big data analysis revealed that cancer cell lines resistant to chemotherapies classified as anti-mitotic drugs (AMDs), toxins that inhibit overacting cell division, are also resistant to a class of targeted therapies called epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs).
In all of the cancer types analyzed, more than 84 percent of those resistant to AMDs, representatively ‘paclitaxel’, were also resistant to at least nine EGFR-TKIs. In lung, pancreatic, and breast cancers where paclitaxel is often used as a first-line, standard-of-care regimen, greater than 92 percent showed resistance to EGFR-TKIs. Professor Kim said, “It is surprising to see that such collateral resistance can occur specifically between two chemically different classes of drugs.”
To figure out how failed responses to paclitaxel leads to resistance to EGFR-TKIs, the team validated co-resistance signatures that they found in the database by generating and analyzing a subset of slow-doubling, paclitaxel-resistant cancer models called ‘persisters’.
The results demonstrated that paclitaxel-resistant cancers remodel their stress response by first becoming more stem cell-like, evolving the ability to self-renew to adapt to more stressful conditions like drug exposures. More surprisingly, when the researchers characterized the metabolic state of the cells, EGFR-TKI persisters derived from paclitaxel-resistant cancer cells showed high dependencies to energy-producing processes such as glycolysis and glutaminolysis.
“We found that, without an energy stimulus like glucose, these cells transform to becoming more senescent, a characteristic of cells that have arrested cell division. However, this senescence is controlled by stem cell factors, which the paclitaxel-resistant cancers use to escape from this arrested state given a favorable condition to re-grow,” said Aldonza.
Professor Kim explained, “Before this research, there was no reason to expect that acquiring the cancer stem cell phenotype that dramatically leads to a cascade of changes in cellular states affecting metabolism and cell death is linked with drug-specific sequential resistance between two classes of therapies.”
He added, “The expansion of our work to other working models of drug resistance in a much more clinically-relevant setting, perhaps in clinical trials, will take on increasing importance, as sequential treatment strategies will continue to be adapted to various forms of anti-cancer therapy regimens.”
This study was supported by the Basic Science Research Program of the National Research Foundation of Korea (NRF-2016R1C1B2009886), and the KAIST Future Systems Healthcare Project (KAISTHEALTHCARE42) funded by the Korean Ministry of Science and ICT (MSIT). Undergraduate student Aldonza participated in this research project and presented the findings as the lead author as part of the Undergraduate Research Participation (URP) Program at KAIST.
< Figure 1. Schematic overview of the study. >
< Figure 2. Big data analysis revealing co-resistance signatures between classes of anti-cancer drugs. >
Publication:
Aldonza et al. (2020) Prior acquired resistance to paclitaxel relays diverse EGFR-targeted therapy persistence mechanisms. Science Advances, Vol. 6, No. 6, eaav7416. Available online at http://dx.doi.org/10.1126/sciadv.aav7416
Profile: Prof. Yoosik Kim, MA, PhD
ysyoosik@kaist.ac.kr
https://qcbio.kaist.ac.kr/
Assistant Professor
Bio Network Analysis Laboratory
Department of Chemical and Biomolecular Engineering
Korea Advanced Institute of Science and Technology (KAIST)
http://kaist.ac.kr
Daejeon, Republic of Korea
Profile: Mark Borris D. Aldonza
borris@kaist.ac.kr
Undergraduate Student
Department of Biological Sciences
Korea Advanced Institute of Science and Technology (KAIST)
http://kaist.ac.kr
Daejeon, Republic of Korea
(END)
2020.02.10 View 14490 -
Blood-Based Multiplexed Diagnostic Sensor Helps to Accurately Detect Alzheimer’s Disease
A research team at KAIST reported clinically accurate multiplexed electrical biosensor for detecting Alzheimer’s disease by measuring its core biomarkers using densely aligned carbon nanotubes.
Alzheimer’s disease is the most prevalent neurodegenerative disorder, affecting one in ten aged over 65 years. Early diagnosis can reduce the risk of suffering the disease by one-third, according to recent reports. However, its early diagnosis remains challenging due to the low accuracy but high cost of diagnosis.
Research team led by Professors Chan Beum Park and Steve Park described an ultrasensitive detection of multiple Alzheimer's disease core biomarker in human plasma. The team have designed the sensor array by employing a densely aligned single-walled carbon nanotube thin films as a transducer.
The representative biomarkers of Alzheimer's disease are beta-amyloid42, beta-amyloid40, total tau protein, phosphorylated tau protein and the concentrations of these biomarkers in human plasma are directly correlated with the pathology of Alzheimer’s disease.
The research team developed a highly sensitive resistive biosensor based on densely aligned carbon nanotubes fabricated by Langmuir-Blodgett method with a low manufacturing cost.
Aligned carbon nanotubes with high density minimizes the tube-to-tube junction resistance compared with randomly distributed carbon nanotubes, which leads to the improvement of sensor sensitivity. To be more specific, this resistive sensor with densely aligned carbon nanotubes exhibits a sensitivity over 100 times higher than that of conventional carbon nanotube-based biosensors.
By measuring the concentrations of four Alzheimer’s disease biomarkers simultaneously Alzheimer patients can be discriminated from health controls with an average sensitivity of 90.0%, a selectivity of 90.0% and an average accuracy of 88.6%.
This work, titled “Clinically accurate diagnosis of Alzheimer’s disease via multiplexed sensing of core biomarkers in human plasma”, were published in Nature Communications on January 8th 2020. The authors include PhD candidate Kayoung Kim and MS candidate Min-Ji Kim.
Professor Steve Park said, “This study was conducted on patients who are already confirmed with Alzheimer’s Disease. For further use in practical setting, it is necessary to test the patients with mild cognitive impairment.” He also emphasized that, “It is essential to establish a nationwide infrastructure, such as mild cognitive impairment cohort study and a dementia cohort study. This would enable the establishment of world-wide research network, and will help various private and public institutions.”
This research was supported by the Ministry of Science and ICT, Human Resource Bank of Chungnam National University Hospital and Chungbuk National University Hospital.
< A schematic diagram of a high-density aligned carbon nanotube-based resistive sensor that distinguishes patients with Alzheimer’s Disease by measuring the concentration of four biomarkers in the blood. >
Profile:
Professor Steve Park
stevepark@kaist.ac.kr
Department of Materials Science and Engineering
http://steveparklab.kaist.ac.kr/
KAIST
Profile:
Professor Chan Beum Park
parkcb at kaist.ac.kr
Department of Materials Science and Engineering
http://biomaterials.kaist.ac.kr/
KAIST
2020.02.07 View 10898 -
Cancer cell reversion may offer a new approach to colorectal cancer treatment
A novel approach to reverse the progression of healthy cells to malignant ones may offer a more effective way to eradicate colorectal cancer cells with far fewer side effects, according to a team of researchers based in South Korea.
Colorectal cancer, or cancer of the colon, is the third most common cancer in men and the second most common in women worldwide. South Korea has the second highest incident rate of colorectal cancer in the world, topped only by Hungary, according to the World Cancer Research Fund.
Their results were published as a featured cover article on January 2 in Molecular Cancer Research, a journal of the American Association for Cancer Research.
Led by Kwang-Hyun Cho, a professor and associate vice president of research at KAIST , the researchers used a computational framework to analyze healthy colon cells and colorectal cancer cells. They found that some master regulator proteins involved in cellular replication helped healthy colon cells mature, or differentiate into their specific cell type, and remain healthy. One particular protein, called SETDB1, suppressed the helpful proteins, forcing new cells to remain in a state of immaturity with the potential to become cancerous.
“This suggests that differentiated cells have an inherent resistance mechanism against malignant transformation and indicates that cellular reprogramming is indispensable for malignancy,” said Cho. “We speculated that malignant properties might be eradicated if the tissue-specific gene expression is reinstated — if we repress SETDB1 and allow the colon cells to mature and differentiate as they would normally.”
Image credit: Kwang-Hyun Cho, KAIST
Image restriction: News organizations may use or redistribute this image, with proper attribution, as part of news coverage of this paper only.
Using human-derived cells, Cho and his team targeted the tissue-specific gene expression programs identified in their computational analysis. These are the blueprints for the proteins that eventually help immature cells differentiate into tissue-specific cell types, such as colon cells. When a person has a genetic mutation, or has exposure to certain environmental factors, this process can go awry, leading to an overexpression of unhelpful proteins, such as SEDTB1.
The researchers specifically reduced the amount of SEDTB1 in these tissue-specific gene expression programs, which allowed the cells to mature and fully differentiate into colon cells.
“Our experiment also shows that SETDB1 depletion combined with cytotoxic drugs might be potentially beneficial to anticancer treatment,” Cho said. Cytotoxic drugs are often used for cancer treatment because the type of medicine contains chemicals that are toxic to cancer cells which can prevent them from replicating or growing. He noted that this combination could be more effective in treating cancer by transforming the cancer cell state into a less malignant or resistant state. He eventually pursues a cancer reversion therapy alone instead of conventional cytotoxic drug therapy since the cancer reversion therapy can provide a much less painful experience for patients with cancer who often have severe side effects from treatments intended to kill off cancerous cells, such as chemotherapy.
The researchers plan to continue studying how to return cancer cells to healthier states, with the ultimate goal of translating their work to therapeutic treatment for patients with colorectal cancer.
“I think our study of cancer reversion would eventually change the current medical practice of treating cancer toward the direction of keeping the patient’s quality of life while minimizing the side effects of current anti-cancer therapies,” Cho said.
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This work was funded by KAIST and the National Research Foundation of Korea grants funded by the Korean government, the Ministry of Science and Information and Communication Technology.
Other authors include Soobeom Lee, Chae Young Hwang and Dongsan Kim, all of whom are affiliated with the Laboratory for Systems Biology and Bio-Inspired Engineering in the Department of Bio and Brain Engineering at KAIST; Chansu Lee and Sung Noh Hong, both with the Department of Medicine, and Seok-Hyung Kim of the Department of Pathology in the Samsung Medical Center at the Sungkyunkwan University School of Medicine.
-Profile
Professor Kwang-Hyun Cho
ckh@kaist.ac.kr
http://sbie.kaist.ac.kr/
Department of Bio and Brain Engineering
KAIST
https://www.kaist.ac.kr
2020.01.31 View 7497