Tech

Irvine, Calif., Jan. 11, 2021 - Often admired for their flawless appearance to the naked eye, crystals can have defects at the nanometer scale, and these imperfections may affect the thermal and heat transport properties of crystalline materials used in a variety of high-technology devices.

Employing newly developed electron microscopy techniques, researchers at the University of California, Irvine and other institutions have, for the first time, measured the spectra of phonons - quantum mechanical vibrations in a lattice - at individual crystalline faults, and they discovered the propagation of phonons near the flaws. The team's findings are the subject of a study published recently in Nature.

"Point defects, dislocations, stacking faults and grain boundaries are often found in crystalline materials, and these defects can have a significant impact on a substance's thermal conductivity and thermoelectric performance," said senior co-author Xiaoqing Pan, UCI's Henry Samueli Endowed Chair in Engineering, as well as a professor of materials science and engineering and physics & astronomy.

He said that there are ample theories to explain the interactions between crystal imperfections and phonons but little experimental validation due to the inability of earlier methods to view the phenomena at high enough space and momentum resolution. Pan and his collaborators approached the problem through the novel development of space- and momentum-resolved vibrational spectroscopy in a transmission electron microscope at UCI's Irvine Materials Research Institute.

With this technique, they were able to observe individual defects in cubic silicon carbide, a material with a wide range of applications in electronic devices. Pan and his colleagues were familiar with how imperfections in silicon carbide are manifested as stacking faults, and theoretical work has described the thermoelectric impacts, but now the team has produced direct experimental data to characterize phonon interactions with the individual defects.

"Our method opens up the possibility of studying the local vibrational modes at intrinsic and non-intrinsic defects in materials," said Pan, who is also director of IMRI and UCI's Center for Complex and Active Materials, funded by the National Science Foundation. "We expect it to find important applications in many different areas, ranging from the study of thermal resistance-inducing interfacial phonons to defect structures engineered to optimize a material's thermal properties."

CAMBRIDGE, MA -- When we experience a new event, our brain records a memory of not only what happened, but also the context, including the time and location of the event. A new study from MIT neuroscientists sheds light on how the timing of a memory is encoded in the hippocampus, and suggests that time and space are encoded separately.

In a study of mice, the researchers identified a hippocampal circuit that the animals used to store information about the timing of when they should turn left or right in a maze. When this circuit was blocked, the mice were unable to remember which way they were supposed to turn next. However, disrupting the circuit did not appear to impair their memory of where they were in space.

The findings add to a growing body of evidence suggesting that when we form new memories, different populations of neurons in the brain encode time and place information, the researchers say.

"There is an emerging view that 'place cells' and 'time cells' organize memories by mapping information onto the hippocampus. This spatial and temporal context serves as a scaffold that allows us to build our own personal timeline of memories," says Chris MacDonald, a research scientist at MIT's Picower Institute for Learning and Memory and the lead author of the study.

Susumu Tonegawa, the Picower Professor of Biology and Neuroscience at the RIKEN-MIT Laboratory of Neural Circuit Genetics at the Picower Institute, is the senior author of the study, which appears this week in the Proceedings of the National Academy of Sciences.

Time and place

About 50 years ago, neuroscientists discovered that the brain's hippocampus contains neurons that encode memories of specific locations. These cells, known as place cells, store information that becomes part of the context of a particular memory.

The other critical piece of context for any given memory is the timing. In 2011, MacDonald and the late Howard Eichenbaum, a professor of psychological and brain sciences at Boston University, discovered cells that keep track of time, in a part of the hippocampus called CA1.

In that study, MacDonald, who was then a postdoc at Boston University, found that these cells showed specific timing-related firing patterns when mice were trained to associate two stimuli -- an object and an odor -- that were presented with a 10-second delay between them. When the delay was extended to 20 seconds, the cells reorganized their firing patterns to last 20 seconds instead of 10.

"It's almost like they're forming a new representation of a temporal context, much like a spatial context," MacDonald says. "The emerging view seems to be that both place and time cells organize memory by mapping experience to a representation of context that is defined by time and space."

In the new study, the researchers wanted to investigate which other parts of the brain might be feeding CA1 timing information. Some previous studies had suggested that a nearby part of the hippocampus called CA2 might be involved in keeping track of time. CA2 is a very small region of the hippocampus that has not been extensively studied, but it has been shown to have strong connections to CA1.

To study the links between CA2 and CA1, the researchers used an engineered mouse model in which they could use light to control the activity of neurons in the CA2 region. They trained the mice to run a figure-eight maze in which they would earn a reward if they alternated turning left and right each time they ran the maze. Between each trial, they ran on a treadmill for 10 seconds, and during this time, they had to remember which direction they had turned on the previous trial, so they could do the opposite on the upcoming trial.

When the researchers turned off CA2 activity while the mice were on the treadmill, they found that the mice performed very poorly at the task, suggesting that they could no longer remember which direction they had turned in the previous trial.

"When the animals are performing normally, there is a sequence of cells in CA1 that ticks off during this temporal coding phase," MacDonald says. "When you inhibit the CA2, what you see is the temporal coding in CA1 becomes less precise and more smeared out in time. It becomes destabilized, and that seems to correlate with them also performing poorly on that task."

Memory circuits

When the researchers used light to inhibit CA2 neurons while the mice were running the maze, they found little effect on the CA1 "place cells" that allow the mice to remember where they are. The findings suggest that spatial and timing information are encoded preferentially by different parts of the hippocampus, MacDonald says.

"One thing that's exciting about this work is this idea that spatial and temporal information can operate in parallel and might merge or separate at different points in the circuit, depending on what you need to accomplish from a memory standpoint," he says.

MacDonald is now planning additional studies of time perception, including how we perceive time under different circumstances, and how our perception of time influences our behavior. Another question he hopes to pursue is whether the brain has different mechanisms for keeping track of events that are separated by seconds and events that are separated by much longer periods of time.

"Somehow the information that we store in memory preserves the sequential order of events across very different timescales, and I'm very interested in how it is that we're able to do that," he says.

CHICAGO (January 11, 2021): A new study of liver transplant centers confirms that non-Hispanic white patients get placed on liver transplant waitlists at disproportionately higher rates than non-Hispanic Black patients. However, researchers went a step further as they identified key reasons for that disparity: disproportionate access to private health insurance, travel distance to transplant centers, and a potential lack of knowledge among both practitioners and patients about available options. The study was selected for the 2020 Southern Surgical Association Program and published as an "article in press" on the website of the Journal of the American College of Surgeons in advance of print.

"We found that the Black population was underrepresented at the vast majority of centers, meaning that the percentage of the Black population in a donor service area (DSA)--the geographic area the center serves--was significantly higher than the percentage of the Black population on waitlists," said lead author Ali Zarrinpar, MD, PhD, FACS, a transplant and hepatobiliary surgeon at the University of Florida, Gainesville.

Dr. Zarrinpar and colleagues analyzed deceased donor liver transplant and waitlist data obtained from the Scientific Registry of Transplant Recipients for 109 high-volume liver transplant centers (250 or more transplant operations over a five-year period from 2013 to 2018), excluding Veterans Affairs centers and Hospital Auxilio Mutuo in San Juan, Puerto Rico, because of its nearly 100 percent Hispanic population. The researchers used five-year U.S. Census Bureau estimates from 2017 to calculate demographics of each center's DSA.

Of 30,353 patients on waitlists at the 109 centers, 69 percent were non-Hispanic white, 7.9 percent were non-Hispanic Black, 17 percent were Hispanic, and 6.1 percent were of other racial or ethnic categories. By comparison, the overall national racial/ethnic distribution from the 2017 Census update was 61.5 percent white, 12.3 percent Black, 17.6 percent Hispanic, and 8.6 percent other racial/ethnic groups.

The disparities shifted a bit when actual liver transplant operations were evaluated: 70.9 percent in whites, 9.4 percent in Blacks, 14 percent in Hispanics, and 5.7 percent in other racial/ethnic groups. Nonetheless, resolving disparities on transplant waitlists would go far toward a more equitable distribution of transplants, the researchers found.

"When we looked at the characteristics of each individual center that correlated with that difference, we found that the more each center transplanted people with private insurance, the less they were representative of the Black population in their donor service area," Dr. Zarrinpar said. "Further, the longer amount of time people traveled to that center for liver transplantation, the less the center was representative of the percentage of the Black population in their donor service area."

Other potential reasons the study evaluated but did not correlate with the disparity include DSA poverty rates, educational levels, the proportion of public and private insurance within the DSA, and whether the center was a public or private institution, Dr. Zarrinpar said.

The findings raise multiple questions about why Black patients are placed on liver transplant waitlists at a much lower rate. "Are underrepresented populations just not getting referred to the transplant centers?" Dr. Zarrinpar asked.

"Another issue is primary care access. Patients need to be made aware earlier on that transplantation is a potential solution for certain liver conditions. If aware, they next need to know what it takes to be placed on a waitlist. Also, we must address the false perception that patients may have that liver transplants aren't covered by insurance, specifically those covered by Medicaid."

In fact, Dr. Zarrinpar added, Medicaid covers liver transplant, and "the vast majority of transplant centers will take public insurance."

Although the study did not look at barriers to liver transplants for underserved populations, they could exist at any number of points along the care spectrum, Dr. Zarrinpar said, including transplant centers, referring centers, referring physicians, or even patients themselves. "The patients may not have insurance at the time they develop their liver disease, but it's possible for the transplant centers to obtain coverage for people who are not just underserved but don't have the means," he said. "Many publicly available insurances exist for these patients."

The authors conclude that increased awareness of these trends may promote equitable access to liver transplant waitlists. Strategies include targeting physicians who could potentially refer these patients, Dr. Zarrinpar said. "As long as a patient has medical need, the ability to undergo a transplant operation successfully, and a support system to ensure long-term success with the transplanted liver, being placed on a transplant waitlist is an option," he said. "We don't want people to rule themselves out before seeking help."

CORVALLIS, Ore. - Researchers in the Oregon State University College of Engineering have developed a battery anode based on a new nanostructured alloy that could revolutionize the way energy storage devices are designed and manufactured.

The zinc- and manganese-based alloy further opens the door to replacing solvents commonly used in battery electrolytes with something much safer and inexpensive, as well as abundant: seawater.

Findings were published today in Nature Communications.

"The world's energy needs are increasing, but the development of next-generation electrochemical energy storage systems with high energy density and long cycling life remains technically challenging," said Zhenxing Feng, a chemical engineering researcher at OSU. "Aqueous batteries, which use water-based conducting solutions as the electrolytes, are an emerging and much safer alternative to lithium-ion batteries. But the energy density of aqueous systems has been comparatively low, and also the water will react with the lithium, which has further hindered aqueous batteries' widespread use."

A battery stores power in the form of chemical energy and through reactions converts it to the electrical energy needed to power vehicles, cellphones, laptops and many other devices and machines. A battery consists of two terminals - the anode and cathode, typically made of different materials - as well as a separator and electrolyte, a chemical medium that allows for the flow of electrical charge.

In a lithium-ion battery, as its name suggests, a charge is carried via lithium ions as they move through the electrolyte from the anode to the cathode during discharge, and back again during recharging.

"Electrolytes in lithium-ion batteries are commonly dissolved in organic solvents, which are flammable and often decompose at high operation voltages," Feng said. "Thus there are obviously safety concerns, including with lithium dendrite growth at the electrode-electrolyte interface; that can cause a short between the electrodes."

Dendrites resemble tiny trees growing inside a lithium-ion battery and can pierce the separator like thistles growing through cracks in a driveway; the result is unwanted and sometimes unsafe chemical reactions.

Combustion incidents involving lithium-ion batteries in recent years include a blaze on a parked Boeing 787 jet in 2013, explosions in Galaxy Note 7 smartphones in 2016 and Tesla Model S fires in 2019.

Aqueous batteries are a promising alternative for safe and scalable energy storage, Feng said. Aqueous electrolytes are cost-competitive, environmentally benign, capable of fast charging and high power densities and highly tolerant of mishandling.

Their large-scale use, however, has been hindered by a limited output voltage and low energy density (batteries with a higher energy density can store larger amounts of energy, while batteries with a higher power density can release large amounts of energy more quickly).

But researchers at Oregon State, the University of Central Florida and the University of Houston have designed an anode made up of a three-dimensional "zinc-M alloy" as the battery anode - where M refers to manganese and other metals.

"The use of the alloy with its special nanostructure not only suppresses dendrite formation by controlling the surface reaction thermodynamics and the reaction kinetics, it also demonstrates super-high stability over thousands of cycles under harsh electrochemical conditions," Feng said. "The use of zinc can transfer twice as many charges than lithium, thus improving the energy density of the battery.

"We also tested our aqueous battery using seawater, instead of high purity deionized water, as the electrolyte," he added. "Our work shows the commercial potential for large-scale manufacturing of these batteries."

Feng and Ph.D. student Maoyu Wang used X-ray absorption spectroscopy and imaging to track the atomic and chemical changes of the anode in different operation stages, which confirmed how the 3D alloy was functioning in the battery.

"Our theoretical and experimental studies proved that the 3D alloy anode has unprecedented interfacial stability, achieved by a favorable diffusion channel of zinc on the alloy surface," Feng said. "The concept demonstrated in this collaborative work is likely to bring a paradigm shift in the design of high-performance alloy anodes for aqueous and non-aqueous batteries, revolutionizing the battery industry."

Rice is the staple food of about half the world's population. The cultivation of the rice plant is very water-intensive and, according to the German aid organization Welthungerhilfe, around 15 per cent of rice is grown in areas with a high risk of drought. Global warming is therefore becoming increasingly problematic for rice cultivation, leading more and more often to small harvests and hunger crises. Crop failures caused by plant pathogens further aggravate the situation. Here, conventional agriculture is trying to counteract this with pesticides, which are mostly used as a precautionary measure in rice cultivation. The breeding of resistant plants is the only alternative to these environmentally harmful agents - and currently only moderately successful. If the plants are resistant to one pathogen thanks to their breeding, they are usually more susceptible to other pathogens or are less robust under adverse environmental conditions.

Bacterium confers pathogen resistance

For this reason, an international research group which includes the Institute of Environmental Biotechnology at Graz University of Technology has been studying the microbiome of rice plant seeds for some time now in order to establish correlations between plant health and the occurrence of certain microorganisms. The group has now achieved a major breakthrough. They identified a bacterium inside the seed that can lead to complete resistance to a particular pathogen and is naturally transmitted from one plant generation to another. The findings published in the scientific journal Nature Plants provide a completely new basis for designing biological plant protection products and additionally reducing harmful biotoxins produced by plant pathogens.

The microbiome of rice

In conventional rice cultivation in the Chinese province of Zhejiang, it was observed that one genotype of rice plants (cultivar Zhongzao 39) sometimes develops resistance to the plant pathogen Burkholderia plantarii. This pathogen leads to crop failures and also produces a biotoxin that can cause organ damage and tumours in persistently exposed humans and animals. "Up to now, the sporadic resistance of rice plants to this pathogen could not be explained," says Tomislav Cernava from the Institute of Environmental Biotechnology at Graz University of Technology. Together with the luminary of microbiome research and Institute head, Gabriele Berg, and his institute colleague Peter Kusstatscher, Cernava has been investigating the microbiome of rice seeds from different cultivation regions in detail in the context of a collaboration with Zhejiang University (Hangzhou) and Nanjing Agricultural University in China as well as with the Japanese Hokkaido University in Sapporo.

Bacterial composition as a decisive factor

The scientists found that the resistant plants have a different bacterial composition inside the seeds than the disease-susceptible plants. The bacterial genus Sphingomonas in particular was found significantly more often in resistant seeds. The researchers therefore isolated bacteria of this genus from the seeds and identified the bacterium Sphingomonas melonis as the responsible agent for disease resistance. This bacterium produces an organic acid (anthranilic acid), which inhibits the pathogen and thereby renders it harmless. "This also works when the isolated Sphingomonas melonis is applied to non-resistant rice plants. This automatically makes them resistant to the plant pathogen Burkholderia plantarii," explains Tomislav Cernava. In addition, the bacterium establishes itself in certain rice genotypes and is then passed on naturally from one plant generation to the next. "The potential of this finding is enormous. In the future, we will be able to use this strategy to reduce pesticides in agriculture and at the same time achieve good crop yields," emphasizes Cernava.

All-solid-state batteries are the next-generation batteries that can simultaneously improve the stability and capacity of existing lithium batteries. The use of non-flammable solid cathodes and electrolytes in such batteries considerably reduces the risk of exploding or catching fire under high temperatures or external impact and facilitates high energy density, which is twice that of lithium batteries. All-solid-state batteries are expected to become a game changer in the electric vehicle and energy storage device markets. Despite these advantages, the low ionic conductivity of solid electrolytes combined with their high interfacial resistance and rapid deterioration reduce battery performance and life, thus limiting their commercialization.

The Korea Institute of Science and Technology (KIST) is proud to announce that the research team of Dr. Sang-baek Park at the Center for Energy Materials Research, in collaboration with the research team of Professor Hyun-jung Shin of Sungkyunkwan University, has developed a breakthrough material design strategy that can overcome the problem of high interfacial resistance between the solid electrolyte and the cathode, which is an obstacle to the commercialization of all-solid-state batteries.

Unique physical phenomena occur at the interface where two different substances meet. Unlike the atoms inside the bulk of a substance, which hold hands with other atoms around themselves and form stable bonds, the atoms at the interface, having no neighboring atom of the same substance on one side, are likely to form a different atomic arrangement.

In all-solid-state batteries having a solid electrode-solid electrolyte interface, a phenomenon occurs that disturbs the atomic arrangement and limits charge transfer, thereby increasing resistance and accelerating deterioration. Methods of coating an appropriate material on the surface of the cathode and the electrolyte or inserting an intermediate layer are currently being studied to solve the above-mentioned problem. However, this further increases the costs and lowers the overall activity and energy density of the batteries.

In order to solve these problems, the KIST-Sungkyunkwan University joint research team first systematically identified the crystal structure of the material that directly affects the solid interface. Using epitaxial film technology (a semiconductor manufacturing technology) to grow a thin film along the direction in which the crystals of the substrate were formed, cathode films having different exposed crystal planes were obtained under varying conditions. The effect of the exposed crystal plane on the interface between the solid electrolyte and the cathode material was analyzed in detail, disregarding other factors such as particle size and contact area that could affect the result.

The results indicated that the leakage of the transition metal from the cathode material into the electrolyte was suppressed by the closely-packed structure of the exposed crystal plane, which improved the stability of the all-solid-state battery. In addition, when the interface of the crystals was arranged in parallel with the direction of movement of the electrons, the movement of ions and electrons along the crystals was not hindered, resulting in reduced resistance and improved output.

"This means that improving the cathode material itself by increasing the density of the crystal plane and adjusting the direction of the interface between the crystals can ensure high performance and stability," said Dr. Sang-baek Park, KIST. "We plan to accelerate the development of all-solid-state battery materials by overcoming the instability of the solid electrolyte and solid cathode interface and imparting improved ion-charge exchange characteristics through this study, which has investigated the mechanism of all-solid-state battery degradation."

Special Issue: Tumor Microenvironment and Drug Delivery
Guest Editors: Huile Gao, West China School of Pharmacy, Sichuan University, Chengdu, China; Zhiqing Pang, Fudan University, Shanghai, China and Wei He, China Pharmaceutical University, Nanjing, China

The Journal of the Institute of Materia Medica, the Chinese Academy of Medical Sciences and the Chinese Pharmaceutical Association, Acta Pharmaceutica Sinica B (APSB) is a monthly journal, in English, which publishes significant original research articles, rapid communications and high quality reviews of recent advances in all areas of pharmaceutical sciences -- including pharmacology, pharmaceutics, medicinal chemistry, natural products, pharmacognosy, pharmaceutical analysis and pharmacokinetics.

Acta Pharmaceutica Sinica B Volume 10, Issue 11 is a special issue on tumor microenvironment and drug delivery. Several drug delivery systems to treat cancer are available to the market with many other promising candidates currently under investigation. The complex tumor microenvironment greatly influences drug delivery efficiency of these systems to tumors, while the tumor microenvironment can be leveraged to design smart drug delivery systems for improving tumor drug delivery. Knowledge about tumor microenvironment and its impact to tumor drug delivery are critically important for improving the drug delivery efficiency to tumors.

Featured papers in this issue are:

The role of tumor-associated macrophages (TAMs) in tumor progression and relevant advance in targeted therapy by authors Qiyao Yang, Ningning Guo, Yi Zhou, Jiejian Chen, Qichun Wei and Min Han. Tumor-associated macrophages (TAMs) as a major part in the tumor environment (TME) are associated with the progression of tumor. In this review article, the authors summarize the roles TAMs play and some TAM targeting strategies. The article provides some perspectives about drug targets for TAMs and some potential combination therapies.

Dual-targeting nanovesicles enhance specificity to dynamic tumor cells in vitro and in vivo via manipulation of ?v?3-ligand binding by authors Yang Song, Xiangfu Guo, Jijun Fu, Bing He Xueqing Wang, Wenbing Dai, Hua Zhang and Qiang Zhang. The authors investigated a doxorubicin-loaded lipid vesicle targeted to dynamic tumor cells in flowing blood system. RGDm7 and DT4, helped lipid vesicle bind with ?v?3 on the surface of tumor cell in a "fast-binding/slow-unbinding" way. Meanwhile, DT4 led the lipid vesicle to dissolve near nucleus and promoted the cytotoxicity of doxorubicin.

Precise delivery of obeticholic acid via nanoapproach for triggering natural killer T cell-mediated liver cancer immunotherapy by authors Guofeng Ji, Lushun Ma, Haochen Yao, Sheng Ma, Xinghui Si, Yalin Wang, Xin Bao, Lili Ma, Fangfang Chen, Chong Ma, Leaf Huang, Xuedong Fang and Wantong Song. The authors discuss how nanoemulsion-loaded obeticholic acid (OCA-NE) accumulates in liver sinusoidal endothelial cells (LSECs) and triggers robust natural killer T (NKT) cell-mediated liver cancer therapy.

Other articles published in the issue include:

Editorial

Editorial of Special Issue on Tumor Microenvironment and Drug Delivery
Huile Gao, Zhiqing Pang, Wei He

Review articles

Manipulation of immune?vascular crosstalk: new strategies towards cancer treatment
Yang Zhao, Xiangrong Yu, Jia Li

The progress and perspective of nanoparticle-enabled tumor metastasis treatment
Wei Zhang, Fei Wang, Chuan Hu, Yang Zhou, Huile Gao, Jiang Hu

Nanomedicines modulating tumor immunosuppressive cells to enhance cancer immunotherapy
Yuefei Zhu, Xiangrong Yu, Soracha D. Thamphiwatana, Ying Zheng, Zhiqing Pang

Small interfering RNA for cancer treatment: overcoming hurdles in delivery
Nitin Bharat Charbe, Nikhil D. Amnerkar, B. Ramesh, Murtaza M. Tambuwala, Hamid A. Bakshi, Alaa A.A. Aljabali, Saurabh C. Khadse, Rajendran Satheeshkumar, Saurabh Satija, Meenu Metha, Dinesh Kumar Chellappan, Garima Shrivastava, Gaurav Gupta, Poonam Negi, Kamal Dua, Flavia C. Zacconi

Nanomedicine-based drug delivery towards tumor biological and immunological microenvironment
Jin Li, Diane J. Burgess

Novel agents targeting leukemia cells and immune microenvironment for prevention and treatment of relapse of acute myeloid leukemia after allogeneic hematopoietic stem cell transplantation
Wei Shi, Weiwei Jin, Linghui Xia, Yu Hu

Natural products remodel cancer-associated fibroblasts in desmoplastic tumors
Rujing Chen, Leaf Huang, Kaili Hu

Original Articles

Tailored core?shell dual metal-organic frameworks as a versatile nanomotor for effective synergistic antitumor therapy
Biyuan Wu, Jintao Fu, Yixian Zhou, Sulan Luo, Yiting Zhao, Guilan Quan, Xin Pan, Chuanbin Wu

Molecular engineering of antibodies for site-specific conjugation to lipid polydopamine hybrid nanoparticles
Hobin Yang, Quoc-Viet Le, Gayong Shim, Yu-Kyoung Oh, Young Kee Shin

Injectable thermo-responsive nano-hydrogel loading triptolide for the anti-breast cancer enhancement via localized treatment based on "two strikes" effects
Yaoyao Luo, Jingjing Li, Yichen Hu, Fei Gao, George Pak-Heng Leung, Funeng Geng, Chaomei Fu, Jinming Zhang

Short Communication

Phospholipid membrane-decorated deep-penetrated nanocatalase relieve tumor hypoxia to enhance chemo-photodynamic therapy
Junjing Yin, Haiqiang Cao, Hong Wang, Kaoxiang Sun, Yaping Li, Zhiwen Zhang

Researchers from Trinity College Dublin have discovered a key mechanism underlying bacterial skin colonisation in atopic dermatitis, which affects millions around the globe.

Atopic dermatitis (AD, also called commonly eczema) is the most common chronic inflammatory skin disorder in children, affecting 15-20% of people in childhood. During disease flares, patients experience painful inflamed skin lesions accompanied by intense itch and recurrent skin infection.

The bacterium Staphylococcus aureus (S. aureus) thrives on skin affected by AD, increasing inflammation and worsening AD symptoms. Although a small number of therapies are available at present for patients with moderate to severe AD, it is vital that we understand how S. aureus colonises AD skin so that we can develop new treatments that directly target the bacterium.

The researchers, from Trinity's School of Genetics and Microbiology and School of Clinical Medicine, set out to identify the human and bacterial factors that enable S. aureus to interact with skin by studying the attachment of the bacterium to "corneocytes", which are dead, flattened skin cells in the outer layer of the skin.

The findings, recently published in the prestigious journal Proceedings of the National Academy of Sciences of the USA, show that S. aureus binds to a specific region of human corneodesmosin, a protein located on the surface of AD patient corneocytes.

Bacterial binding to corneocytes in the lab is reduced if the relevant region of corneodesmosin is blocked with an antibody, indicating the importance of this interaction during S. aureus attachment to human skin.

In lab experiments, Dr Aisling Towell, PhD graduate in Microbiology at Trinity, showed that bacterial interaction with corneodesmosin relies on two proteins attached to the surface of S. aureus, FnBPB and ClfB.

Explaining the significance, Dr Joan Geoghegan, Associate Professor of Microbiology in Trinity's Department of Microbiology, said:

"Our findings provide new insights into how S. aureus bacteria attach to corneocytes at the skin surface, which is a crucial step during colonisation. Specifically, our discovery of an interaction between bacterial proteins and corneodesmosin on AD patient corneocytes is a key advance that could pave the way towards developing targeted approaches for preventing S. aureus skin colonisation in AD."

Alan Irvine, Professor of Dermatology at Trinity, added:

"AD is both a common and incredibly uncomfortable condition that has a massive impact on quality of life in both children and adults. Colonisation of the skin with S. aureus is a major driver of AD and a cause of disease flares. By identifying a major mechanism through which S aureus binds to the skin of patients with AD we have opened the possibility of targeting this pathway as a therapeutic option in AD.

"Targeting S. aureus binding to human skin by using small molecules would be a welcome addition to our therapeutic options. This is especially important in an era where antimicrobial resistance is an emerging global threat."

Diets rich in healthy and plant-based foods encourages the presence of gut microbes that are linked to a lower risk of common illnesses including heart disease, research has found.

A large-scale international study using metagenomics and blood chemical profiling has uncovered a panel of 15 gut microbes associated with lower risks of common conditions such as obesity and type 2 diabetes. The study has been published today in Nature Medicine from researchers at King's College London, Massachusetts General Hospital (MGH), Harvard T.H. Chan School of Public Health, the University of Trento, Italy, and health start-up company ZOE.

The PREDICT 1 (Personalized Responses to Dietary Composition Trial 1) analyzed detailed data on the composition of participants' gut microbiomes, their dietary habits, and cardiometabolic blood biomarkers. It uncovered strong links between a person's diet, the microbes in their gut (microbiome) and their health.

Researchers identified microbes that positively or negatively correlate 'good' and 'bad' with an individual's risk of certain serious conditions such as diabetes, heart disease and obesity. Surprisingly, the microbiome has a greater association to these markers than other factors, such as genetics. Some of the identified microbes are so novel that they have not yet been named.

The researchers defined a "healthy" diet as one that contained a mix of foods associated with a lower risk of chronic disease. They found that trial subjects who ate such a diet, or one rich in plants, were more likely to have high levels of specific 'good' gut microbes which are associated with a low risk of common illnesses. The researchers also found microbiome-based biomarkers of obesity as well as markers for cardiovascular disease and impaired glucose tolerance, which are key risk factors for COVID. These findings can be used to help create personalized eating plans designed specifically to improve one's health.

Dr. Sarah Berry, Reader in Nutrition Sciences at King's College London said, "As a nutritional scientist, finding novel microbes that are linked to specific foods, as well as metabolic health, is exciting. Given the highly personalised composition of each individuals' microbiome, our research suggests that we may be able to modify our gut microbiome to optimize our health by choosing the best foods for our unique biology."

For example, the findings reveal that having a microbiome rich in Prevotella copri and Blastocystis species was associated with maintaining a favorable blood sugar level after a meal. Other species were linked to lower post-meal levels of blood fats and markers of inflammation.

Professor Tim Spector, Epidemiologist from King's College London, who started the PREDICT study program and is scientific founder of ZO, said: "When you eat, you're not just nourishing your body, you're feeding the trillions of microbes that live inside your gut."

Nicola Segata, PhD, professor and principal investigator of the Computational Metagenomics Lab at the University of Trento, Italy and leader of the microbiome analysis in the study, said: "We were surprised to see such large, clear groups of what we informally call 'good' and 'bad' microbes emerging from our analysis. It is also exciting to see that microbiologists know so little about many of these microbes that they are not even named yet. This is now a big area of focus for us, as we believe they may open new insights in the future into how we could use the gut microbiome as a modifiable target to improve human metabolism and health."

PREDICT is the largest in-depth nutritional study in the world. PREDICT 1 was an international collaboration to study links between diet, the microbiome, and biomarkers of cardiometabolic health. The researchers gathered microbiome sequence data, detailed long-term dietary information, and results of hundreds of cardiometabolic blood markers from just over 1,100 participants in the U.S. and the U.K. PREDICT 2 completed its primary investigations in 2020 with a further 1,000 U.S participants, and PREDICT 3 launched a few months ago.

Researchers have for the first time identified the way viruses like the poliovirus and the common cold virus 'package up' their genetic code, allowing them to infect cells.

The findings, published in the journal PLOS Pathogens by a team from the Universities of York and Leeds, open up the possibility that drugs or anti-viral agents can be developed that would stop such infections.

Once a cell is infected, a virus needs to spread its genetic material to other cells. This is a complex process involving the creation of what are known as virions - newly -formed infectious copies of the virus. Each virion is a protein shell containing a complete copy of the virus's genetic code. The virions can then infect other cells and cause disease.

What has been a mystery until now is a detailed understanding of the way the virus assembles these daughter virions.

Professor Reidun Twarock, from the University of York's Department of Mathematics, said: "Understanding in detail how this process works, and the fact that it appears conserved in an entire family of viral pathogens, will enable the pharmaceutical industry to develop anti-viral agents that can block these key interactions and prevent disease."

The study focuses on a harmless bovine virus that is non-infectious in people, Enterovirus-E, which is the universally adopted surrogate for the poliovirus. The poliovirus is a dangerous virus that infects people, causing polio and is the target of a virus eradication initiative by the World Health Organization.

The enterovirus group also includes the human rhinovirus, which causes the common cold.

Professor Peter Stockley, former Director of the Astbury Centre for Structural Molecular Biology at Leeds, said: "This study is extremely important because of the way it shifts our thinking about how we can control some viral diseases. If we can disrupt the mechanism of virion formation, then there is the potential to stop an infection in its tracks.

"Our analysis suggests that the molecular features that control the process of virion formation are genetically conserved, meaning they do not mutate easily - reducing the risk that the virus could change and make any new drugs ineffective."

The study details the role of what are called RNA packaging signals, short regions of the RNA molecule which together with proteins from the virus's casing ensure accurate and efficient formation of an infectious virion.

Using a combination of molecular and mathematical biology, the researchers were able to identify possible sites on the RNA molecule that could act as packaging signals. Using advanced electron microscopes, scientists were able to directly visualise this process - the first time that has been possible with any virus of this type.

With the Proof of Concept funding line, the ERC grants recipients of ERC frontier research funds (Starting, Consolidator, Advanced or Synergy grants) with 150.000 Euro to develop promising ideas with commercial or societal potential to the proof of concept stage. With this funding, Olaf Groß and his team in the Metabolism and Inflammation Group at the Institute of Neuropathology of the Medical Center - University of Freiburg will test whether a new class of immune activating drugs they discovered can boost the effectiveness of cancer immunotherapies or vaccines against infectious diseases.

Groß studies a protein complex called the inflammasome within macrophages, specialized cells of the body's defense system that patrol tissues for signs of danger. When their inflammasome is activated, macrophages sound the alarm by releasing of potent factors called cytokines. These cytokines alert other cells in the body, initiating an inflammatory response that helps other immune cells attack cancer cells or infections, explains Groß. Within the context of his ERC Starting Grant, he and his team discovered a new class of small molecules that potently and specifically activate the inflammasome, acting like turbo boosters for the immune system.

"There has been great excitement surrounding the development of inflammasome inhibitors for the treatment of inflammatory diseases", Groß explains. "But we think that in the right clinical setting inflammasome activators might be just as valuable", he adds. During the proof of concept phase, Groß and his team will test whether his IMMUNOSTIM compounds improve the efficacy of cancer treatment and vaccines. "We will also be looking for commercial partners for further development of this promising new class of immunotherapeutics", says Groß.

Groß received his doctorate at Technical University of Munich in 2008. Following postdoctoral research at the University of Lausanne in Switzerland he established an independent research group focused on the inflammasome at Klinikum rechts der Isar in Munich. Since 2017, Groß is Professor at the University of Freiburg in the Institute of Neuropathology of the University Medical Center. He is a Speaker of the University of Freiburg's Emerging Field in Metabolism Research and member of the Cluster of Excellence CIBSS - the Centre for Integrative Biological Signalling Studies. Within CIBSS he studies the signalling mechanisms responsible for inflammasome activation by the IMMUNOSTIM compounds and screens for new molecules that modulate metabolic and immune signalling processes.

CHAMPAIGN, Ill. -- For years, researchers have worked to repurpose excess atmospheric carbon dioxide into new chemicals, fuels and other products traditionally made from hydrocarbons harvested from fossil fuels. The recent push to mitigate the climactic effects of greenhouse gases in the atmosphere has chemists on their toes to find the most efficient means possible. A new study introduces an electrochemical reaction, enhanced by polymers, to improve CO2-to-ethylene conversion efficiency over previous attempts.

The results of the study led by University of Illinois Urbana-Champaign chemistry professor Andrew Gewirth and graduate student Xinyi (Stephanie) Chen are published in the journal Natural Catalysis.

Allowing CO2 gas to flow through a reaction chamber fitted with copper electrodes and an electrolyte solution is the most common method researchers use to convert CO2 to useful carbon-containing chemicals, the study reports.

"Copper metal is highly selective toward the type of carbon that forms ethylene," Gewirth said. "Different electrode materials will produce different chemicals like carbon monoxide instead of ethylene, or a mix of other carbon chemicals. What we have done in this study is to design a new kind of copper electrode that produces almost entirely ethylene."

Previous studies have used other metals and molecular coatings on the electrode to help direct the CO2-reduction reactions, the study reports. However, these coatings are not stable, often break down during the reaction process and fall away from the electrodes.
"What we did differently in this study was to combine the copper ions and polymers into a solution, then apply that solution to an electrode, entraining the polymer into the copper," Chen said.

In the lab, the team found that the new polymer-entrained electrodes were less likely to break down and produced more stable chemical intermediates, resulting in more efficient ethylene production. "We were able to convert CO2 to ethylene at a rate of up to 87%, depending on the electrolyte used," Chen said. "That is up from previous reports of conversion rates of about 80% using other types of electrodes."

"With the development of economic sources of electricity, combined with the increased interest in CO2-reduction technology, we see great potential for commercialization of this process," Gewirth said.

Nothing in biology is static. Biological processes fluctuate over time, and if we are to put together an accurate picture of cells, tissues, organs etc., we have to take into account their temporal patterns. In fact, this effort has given rise to an entire field of study known as "chronobiology".

The liver is a prime example. Everything we eat or drink is eventually processed there to separate nutrients from waste and regulate the body's metabolic balance. In fact, the liver as a whole is extensively time-regulated, and this pattern is orchestrated by the so-called circadian clock, our body's internal metronome, as well as biochemical signals and eating rhythms.

But the liver is actually divided into small repeating units called "lobules", in which distinct zones perform different functions. This intricate spatial organization is known as "liver zonation". For example, the breakdown of sugars during digestion takes place preferentially on one side of the lobule, the so-called central zone, while the production of glucose while we rest from stores such as fat, occurs on the other side of the liver, at the portal side.

So far, liver zonation has only been studied statically, looking into what each zone does independently of time, and vice-versa. And given how central the liver is in mammalian physiology, the two research approaches have to join efforts to understand how temporal and spatial liver programs interact.

In a first ever study, scientists at EPFL and the Weizmann Institute of Science, led by Professors Felix Naef at EPFL's School of Life Sciences and Shalev Itzkovitz at the Weizmann, have been able to monitor the spatial shifts of gene expression within liver lobules in relationship to the circadian clock. Studying this link is a focus of Naef's research, which has previously uncovered connections between the circadian clock and the liver's proteins, our cell cycles, and even the 3D structure of chromatin, the tightly packaged DNA in the cell nucleus.

The study came out of a EPFL-Weizmann joint grant from the Rothschild Caesarea Foundation.

By exploiting the ability to analyze liver tissue in every individual cell, the researchers studied approximately 5000 genes in liver cells at several timepoints throughout the 24-hour day. They then statistically classified the space-time patterns they uncovered with a model that can capture both spatial and temporal variations in the levels of messenger RNA (mRNA), a marker of gene expression.

The study revealed that many of the liver's genes seem to be both zonated and rhythmic, meaning that they are regulated by both their location in the liver and the time of the day. These dually regulated genes are mostly linked to key functions of the liver, e.g. the metabolism of lipids, carbohydrates, and amino acids, but also include a few genes that have never been associated with metabolism, e.g. genes related to chaperone proteins, which help other biomolecules change their 3D structure or even assemble and disassemble.

"The work reveals a richness of space-time gene expression dynamics of the liver, and shows how compartmentalization of liver function in both space and time is hallmark of metabolic activity in the mammalian liver," says Felix Naef.

Russian researchers have proposed a new method for synthesizing high-quality graphene nanoribbons -- a material with potential for applications in flexible electronics, solar cells, LEDs, lasers, and more. Presented in The Journal of Physical Chemistry C, the original approach to chemical vapor deposition, offers a higher yield at a lower cost, compared with the currently used nanoribbon self-assembly on noble metal substrates.

Silicon-based electronics are steadily approaching their limits, and one wonders which material could give our devices the next big push. Graphene, the 2D sheet of carbon atoms, comes to mind but for all its celebrated electronic properties, it does not have what it takes: Unlike silicon, graphene does not have the ability to switch between a conductive and a nonconductive state. This defining characteristic of semiconductors like silicon is crucial for creating transistors, which underlie all of electronics.

However, once you cut graphene into narrow ribbons, they gain semiconducting properties, provided that the edges have the right geometry and there are no structural defects. Such nanoribbons have already been used in experimental transistors with reasonably good characteristics, and the material's elasticity means the devices can be made flexible. While it is technologically challenging to integrate 2D materials with 3D electronics, there are no fundamental reasons why nanoribbons could not replace silicon.

A more practical way to obtain graphene nanoribbons is not by cutting up graphene sheets or nanotubes but the other way around, by growing the material atom by atom. This approach is known as bottom-up synthesis, and unlike its top-down counterpart, it yields structurally perfect, and therefore technologically useful, nanoribbons. The currently dominant method for bottom-up synthesis, known as self-assembly, is costly and difficult to scale up for industrial production, so materials scientists are seeking alternatives to it.

"Graphene nanoribbons are a material whose properties are of interest to fundamental science and hold a promise for applications in all sorts of futuristic devices. However, the standard technique for its synthesis has some drawbacks," explained Pavel Fedotov, a senior researcher at the MIPT Laboratory of Nanocarbon Materials. "Maintaining ultrahigh vacuum and using a gold substrate is very costly, and the output of material is comparatively low."

"My colleagues and I have proposed an alternative way to synthesize atomically flawless nanoribbons. Not only does it work under normal vacuum and with the much cheaper nickel substrate, the yield increases by virtue of the nanoribbons being produced as multilayer films, rather than individually. To separate these films into monolayer ribbons, they are put in suspension," the researcher went on. "Importantly, none of that compromises the quality of the material. We confirmed the absence of defects by obtaining the appropriate Raman scattering profiles and observing photoluminescence of our nanoribbons."

Graphene nanoribbons come in different types, and the ones that the Russian scientists manufactured using their original chemical vapor deposition technique have the structure depicted on the right in Figure 1. They are seven atoms wide and have edges someone found reminiscent of an armchair, hence the name: 7-A graphene nanoribbons. This type of nanoribbons has the semiconducting properties valuable for electronics, unlike its 7-Z cousin with zigzag edges (shown on the left), which behaves like a metal.

The synthesis occurs in an airtight glass tube evacuated to one-millionth the standard atmospheric pressure, which is still 10,000 times higher than the ultrahigh vacuum normally required for nanoribbon self-assembly. The initial reagent used is a solid substance containing carbon, hydrogen, and bromine and known as DBBA. It is placed in the tube with a nickel foil, pre-annealed at 1,000 degrees Celsius to remove oxide film. The glass tube with DBBA is then subjected to heat treatment for several hours in two stages: first at 190 C, then at 380 C. The first heating leads to the formation of long polymer molecules, and during the second stage, they transform into nanoribbons with atomically precise structure, densely packed into films that are up to 1,000 nanometers thick.

After obtaining the films, the researchers suspended them in a solution and exposed them to ultrasound, breaking up the multilayer "stacks" into one-atom-thick carbon nanoribbons. The solvents used were chlorobenzene and toluene. Prior experiments showed these chemicals to be optimal for suspending nanoribbons in a stable manner, preventing aggregation back into stacks and the appearance of structural defects. Nanoribbon quality control was also done in suspension, via optical methods: The analysis of Raman scattering and photoluminescence data confirmed that the material had no significant defects.

Because the new synthesis technology for manufacturing defectless multilayer 7-A carbon nanoribbons is comparatively cheap and easy to scale up, it is an important step toward introducing that material into the large-scale production of electronic and optical devices that would eventually vastly outperform the ones existing today.

"Experience shows that once a new carbon material is discovered, that means new properties and new applications. And graphene nanoribbons were no different," the head of the MIPT Laboratory of Nanocarbon Materials, Elena Obraztsova recalled. "Initially, nanoribbons were synthesized inside single-walled carbon nanotubes, which served to constrain ribbon width. It was on these embedded nanoribbons that luminescence was originally demonstrated, with its parameters varying with nanotube geometry."

"Our new approach -- bottom-up chemical vapor deposition -- enables ultranarrow graphene ribbons to be produced in large amounts and under fairly mild conditions: moderate vacuum, nickel substrate. The resulting material exhibits bright excitonic photoluminescence. It is promising for many applications in nonlinear optics, which we are going to pursue," the researcher added.

Moms are not more likely than other women to support gun control efforts. In fact, a new study finds that parenthood doesn't have a substantial effect on the gun control views of men or women.

"Everybody 'knows' that moms are more politically liberal on gun control issues," says Steven Greene, corresponding author of the study and a professor of political science at North Carolina State University. "We wanted to know if that's actually true. And, as it turns out, it's not true - which was surprising."

To explore the impact of parenthood on people's gun control views, the researchers drew on data collected by the Pew Center for Research in 2017 as part of Pew's nationally representative American Trends Panel. The researchers then used statistical models to account for various confounding variables, such as political affiliation, allowing them to focus specifically on the effect that parenthood has on one's beliefs regarding gun control.

The Pew surveys had examined a range of issues pertaining to gun control. Across the board, men were substantially more politically conservative than women on questions related to gun laws and regulations. In other words, men were more likely to favor fewer regulations and laxer legal requirements when it comes to guns.

On four of the gun control issues, parenthood had no statistical impact at all - meaning that the positions of moms were no different from the positions of women who weren't parents, and the positions of dads were no different from the positions of men who weren't parents. Those four issues pertained to: gun ownership, or how permissive gun ownership laws should be; home safety, or laws pertaining to how guns and ammunition are stored or secured in the home; teachers and guns, or whether school personnel should carry firearms; and whether stricter gun laws would reduce mass shootings.

However, parenthood did have a small - but statistically significant - impact on two other gun control issues.

Mothers were actually more politically conservative than other women on the issue of gun strictness - meaning that moms were slightly more likely to support less restrictive gun laws.

And fathers were more politically conservative than other men on the issue of gun prevalence - meaning they were slightly more likely to believe that more people should be allowed to own guns, and guns should be allowed in more places.

"When we talk about political movements and efforts to change laws, it's important to have a clear, accurate sense of where people stand on the relevant issues," Greene says. "Using the potent symbolism of motherhood in America in order advance a political agenda, in this case, is actually ignoring the fact that positions on gun control are virtually identical for women across the board. There is some minor variation, but even there, it actually suggests that mothers are less supportive of restrictive gun laws.

"To be clear, most women - including most moms - support more restrictive gun laws. But it's not because they're parents."