Study Finds Structural Changes in the SARS-CoV-2 Alpha and Beta Variants (Medicine)

Changes to the ‘spike’ protein explain Alpha’s faster spread, and how the Beta variant evades immune responses, suggesting the need for a booster with an updated vaccine

New SARS-CoV-2 variants are spreading rapidly, and there are fears that current COVID-19 vaccines won’t protect against them. The latest in a series of structural studies of the SARS-CoV-2 variants’ “spike” protein, led by Bing Chen, PhD, at Boston Children’s Hospital, reveals new properties of the Alpha (formerly U.K.) and Beta (formerly South Africa) variants. Of note, it suggests that current vaccines may be less effective against the Beta variant.

Spike proteins, on the surface of SARS CoV-2, are what enable the virus to attach to and enter our cells, and all current vaccines are directed against them. The new study, published in Science on June 24, used cryo-electron microscopy (cryo-EM) to compare the spike protein from the original virus with that the Alpha and Beta variants.

The structural findings indicate that mutations in the Beta variant (also known as B.1.351) change the shape of the spike surface at certain locations. As a result, neutralizing antibodies induced by current vaccines are less able to bind to the Beta virus, which may allow it to evade the immune system even when people are vaccinated.

“The mutations make antibodies stimulated by the current vaccine less effective,” says Chen, in the division of Molecular Medicine at Boston Children’s. “The Beta variant is somewhat resistant to the current vaccines, and we think a booster with the new genetic sequence can be beneficial for protecting against this variant.”

However, the study also found that mutations in the Beta variant make the spike less effective in binding to ACE2 — suggesting that this variant is less transmissible than the Alpha variant.

Reassurance on the Alpha variant; more variant studies underway

As for the Alpha variant (B.1.1.7), the study confirms that a genetic change in the spike (a single amino acid substitution) helps the virus bind better to ACE2 receptors, making it more infectious. However, testing indicates that antibodies elicited by existing vaccines can still neutralize this variant.

To be a heightened threat, the researchers say, a SARS-CoV-2 variant would need to do three things: spread more easily, evade the immune system in vaccinated people or those previously exposed to COVID-19, and cause more severe disease. Fortunately, the Alpha and Beta variants do not meet all these criteria.

“Our data suggest that the most problematic combination of such mutations is not yet present in the existing variants examined here,” the researchers write.

Chen’s team also plans to report the structures of other variants of concern, including the Delta variant (B.1.617.2), in the near future. Those investigations are still under way.

Yongfei Cai, PhDJun Zhang, PhD, and Tianshu Xiao, PhD of Boston Children’s Hospital were co-first authors on the paper. The study was funded by Emergent Ventures, the Massachusetts Consortium on Pathogen Readiness, and the National Institutes of Health (grants AI147884, AI141002, and AI127193).

Featured image: Mutations in the SARS-CoV-2 variants cause changes in the electrostatic potential (electric charge at rest) on the spike surface. Here, positively charged areas are shown in blue and negatively charged areas in red. In the Beta variant, the receptor-binding domain (RBD) and N-terminal domain (NTD) have changed substantially, affecting the ability of antibodies to bind to and neutralize the virus. © Bing Chen, PhD, Boston Children’s Hospital


Provided by Boston Children’s Hospital

Conductive 2D Phthalocyanine-based Metal-organic Framework Nanosheets Developed for Efficient Electroreduction of CO2 (Chemistry)

The electrocatalytic conversion of CO2 into value-added chemicals using renewable electricity is a promising approach to reduce atmospheric CO2 concentration and realize carbon-energy balance. However, the low current density still limits CO2 electroreduction reaction (CO2RR) for commercial application.Crystalline porous metal-organic frameworks (MOFs) are one class of promising alternatives for CO2RR due to their high CO2 adsorption uptakes and periodically arranged isolated metal active sites. However, the poor conductivity and slow electron-transfer capability of the traditional MOFs usually result in low current density in CO2RR.

In a study published in Angew. Chem. Int. Ed., Prof. CAO Rong and Prof. HUANG Yuanbiao from Fujian Institute of Research on the Structure of Matter of the Chinese Academy of Sciences constructed one type of conductive two-dimensional (2D) phthalocyanine-based MOF nanosheets (NiPc-NiO4).

The researchers heated nickel phthalocyanin-2,3,9,10,16,17,23,24-octaol (NiPc-OH) and Ni(OAc)2·4H2O in water at 85 °C for 24 h, and fabricated ultrathin 2D NiPc-NiO4 nanosheets by exfoliating from its bulk via high-frequency sonication at room temperature.

As expected, the researchers found that the electrical conductivity of NiPc-NiO4 has a high value of 4.8 × 10-5 S m-1 measured at room temperature using a two-contact probe method. Such good electrical conductivity would be beneficial for the electron transfer to the active sites during CO2RR, thereby improving energy conversion efficiency and electrochemical activity.

The as-prepared 2D NiPc-NiO4 nanosheets showed outstanding activity towards CO2 electroreduction with nearly 100% CO selectivity, large CO partial current density up to 34.5 mA cm-2, high turnover frequency up to 2603 h-1, and excellent long-term durability. Such high turnover frequency (TOF) and CO partial current density is higher than any state-of-the-art MOF catalysts.

The density functional theory calculation proved that the nickel of phthalocyanine center is the active sites and NiPc-NiO4 performs better activity than the phthalocyanine molecules due to the fast electron transfer capacity and excellent reducibility, which is consistent with the experiment results.

This study provides an effective way to improve the CO2 electroreduction performance by designing conductive crystalline frameworks with uniformly distributed phthalocyanine active sites. It also builds a bridge between the homogeneous molecule catalysts and heterogeneous porous catalysts.


Reference: Yi, J.-D., Si, D.-H., Xie, R., Yin, Q., Zhang, M.-D., Wu, Q., Chai, G.-L., Huang, Y.-B. and Cao, R. (2021), Conductive Two-Dimensional Phthalocyanine-based Metal–Organic Framework Nanosheets for Efficient Electroreduction of CO2. Angew. Chem. Int. Ed.. https://doi.org/10.1002/anie.202104564


Provided by Chinese Academy of Sciences

Surface Oxygenate Species Enhance Cobalt-catalyzed Fischer-Tropsch Synthesis (Chemistry)

Carbide-supported metal catalysts are promising due to the special properties of metal carbide and the interactions between metals and the carbide supports. However, surface oxide species are inevitable in carbide materials, and their roles in metal-carbide interaction still remain unclear.

Recently, Assoc. Prof. LIU Yuefeng’s group from the Dalian Institute of Chemical Physics (DICP) of the Chinese Academy of Sciences (CAS), in collaboration with Prof. LIU Xi from Shanghai Jiao Tong University, observed the migration of TiOx species to metallic cobalt surface during the reduction process employing the in situ environmental scanning transmission electron microscopy (ESTEM).

This work was published in ACS Catalysis on June 19.

Co/TiC-SiC catalysts presented higher Fischer-Tropsch Synthesis (FTS) activity than Co/SiC owing to the stronger metal support interaction that resulted in the better dispersion of Co NPs as well as the improved turnover frequency (TOF).

The researchers achieved direct structural observation at nanoscopic scale for the metal-support interaction and revealed that the migration of surface TiOx species on the metallic active site significantly involved in the modulation of the interaction between metal and TiC substrate.

The formation of Co-TiOx-TiC heterojunction structure over Co/TiC-SiC catalyst not only benefited the dispersion of Co NPs, but also rendered the superior intrinsic FTS activity.

“This work paves the way for the future rational design of advanced catalysts through moderate metal-support interaction by employing surface oxide species on carbide materials,” said Prof. LIU.

This work was supported by the National Natural Science Foundation of China, Liaoning Revitalization Talents Program, and China Postdoctoral Science Foundation.

Featured image: The reduction process for cobalt species and the origin for the improved intrinsic activity (Image by JIANG Qian) 


Provided by Chinese Academy of Sciences

Researchers Fabricate Bio-friendly X-ray Detectors based on Metal-free Perovskite Single Crystals

Metal-free halide perovskites are novel candidates for ferroelectrics and X-ray detection. However, the molecular self-assembly of these perovskites and its influence remain unexplored.

Recently, a research group led by Prof. LIU Shengzhong from the Dalian Institute of Chemical Physics (DICP) of the Chinese Academy of Sciences (CAS) fabricated halide-modulated self-assembly of metal-free perovskite single crystals for bio-friendly X-ray detection.

This study was published in Matter on June 14.

Molecular self-assembly plays a critical role in crystal engineering for the design and fabrication of novel metal-free perovskite compounds.

After preparing DABCO-NH4X3 (X = Cl, Br, I) single crystals, the researchers investigated halide-modulated molecular assembly via hydrogen bonding in metal-free perovskites and its influence on their crystal packing, band nature, mechanical and electrical properties, as well as final optoelectronic performance.

They found that the crystal DABCO-NH4I3 with superior in-plane charge transport and lower charge effective mass exhibited higher carrier mobility. Therefore, it presented better X-ray detection sensitivity, reaching 567 μC Gyair-1 cm–2. Meanwhile, they demonstrated the feasibility of X-ray imaging had a well-defined ‘heart’ image.

A variety of non-metallic and organic groups readily were available for the A, B and X in crystal DABCO-NH4I3, resulting in fine-tuned properties and free of associated toxicity.

“This work benefited the understanding of molecular self-assembly behavior and was intended to inspire activities to study an assortment of novel ABX3 perovskite materials for potential biological and therapeutic applications,” said Prof. LIU.

This work was supported by the National Key Research and Development Program of China, the Key Program project of the National Natural Science Foundation of China, and the National Natural Science Foundation of China.

The study, “Halide-modulated self-assembly of metal-free perovskite single crystals for bio-friendly X-ray detection”, Matter, 2021. DOI:https://doi.org/10.1016/j.matt.2021.05.018

Featured image: Metal-free perovskite series, DABCO-NH4X3 (X = Cl, Br, I), exhibit a remarkable variety of perovskite-type structures through halide modulation, therefore their single crystals grown at the same condition show different crystal morphology (Image by DUAN Lianjie)  


Provided by Chinese Academy of Sciences

Researchers Resolve Magnetic Structures of Different Topological Semimetals (Physics)

Topological semimetals are one of the major discoveries in condensed-matter physics in recent years. The magnetic Weyl semimetal, in which the Weyl nodes can be generated and modulated by magnetization, provides an ideal platform for the investigation of the magnetic field-tunable link between Weyl physics and magnetism. But due to the lack of appropriate or high quality specimens, most of the theoretically expected magnetic topological semimetals have not been experimentally confirmed. Therefore, exploration of new magnetic topological semimetals is of great importance.

Recently, researchers from the High Magnetic Field Laboratory of the Hefei Institutes of Physical Science (HFIPS), in collaboration with researchers from Huazhong University of Science and Technology and Anhui University, resolved magnetic structures of different topological semimetals with the help of Resistive Magnet of China’s Steady High Magnetic Field Facility (SHMFF) of HFIPS.

The team performed an investigation on high-quality single crystals of PrAlGe and DySb. For PrAlGe, the intrinsic ferromagnetic ordering acts as a Zeeman coupling to split the spin-up and spin-down bands, but the whole band structure is still kept. The study of magnetism suggested that the magnetic interaction in PrAlGe is of a 2D Ising type, revealing a uniaxial magnetic interaction along the c axis. However, the ordering moments are tilted from the c axis, which causes antiferromagnetism in the ab plane.

As for DySb, a field-induced tricritical phenomenon is revealed. Based on the magnetization analysis, a detailed H-T phase diagram around the phase transition is constructed when the magnetic field is applied along [001] direction.

This phase diagram is indicative of delicate competition and balance between multiple magnetic interactions in these systems and lays a solid foundation for future research in topological transition and criticality.

Figure 1. (a) Crystal and magnetic structures of PrAlGe; (b) M(H) curves up to high magnetic field of 30T; (c) angular-dependent magnetization; (d) critical isothermal analysis under high magnetic field.(Image by ZHANG Lei) 

Featured image. H-T phase diagram for DySb. (Image by ZHANG Lei)


References: Wei Liu, Dandan Liang, Fanying Meng, Jun Zhao, Wenka Zhu, Jiyu Fan, Li Pi, Changjin Zhang, Lei Zhang, and Yuheng Zhang, “Field-induced tricritical phenomenon and multiple phases in DySb”, Phys. Rev. B 102, 174417 – Published 10 November 2020. Link to paper (2) Wei Liu, Jun Zhao, Fanying Meng, Azizur Rahman, Yongliang Qin, Jiyu Fan, Li Pi, Zhaoming Tian, Haifeng Du, Lei Zhang, and Yuheng Zhang, “Critical behavior of the magnetic Weyl semimetal PrAlGe”, Phys. Rev. B 103, 214401 – Published 1 June 2021. Link to paper


Researchers Deepen Understanding of Disruption Physics in EAST (Physics)

The thermal and magnetic energies stored in the plasma are released in a very short time during the disruption and deposited on the device, which can cause damages to the integrity of plasma-facing components. In China Fusion Engineering Test Reactor (CFETR) and International Thermonuclear Experimental Reactor (ITER) with high stored energy and large plasma current, damages could be severer.

Recently, a research group from the Institute of Plasma Physics (ASIPP) of the Hefei Institutes of Physical Science (HFIPS) reported a series of new progresses in disruption physics including runaway electron and disruption prediction, which deepened the understanding on Experimental Advanced Superconducting Tokamak (EAST) disruption.

The researchers studied the general characteristics of disruption halo currents in EAST tokamak with ‘W-Like’ graphite divertor and ‘ITER-Like’ tungsten divertor, which provided with more physics information on the ITER divertor. As a result, halo currents decreased with the decrease of vertical displacement, and therefore obtained a lower limit of halo fraction versus Toroidal Peaking Factor.

They further investigated the runaway electron generation and loss in EAST disruption, aiming at elaborating contribution of wave resonant supra-thermal electrons by lower hybrid waves on runaway seeds, and the effects of magnetohydrodynamics instabilities on runaway electron (RE) loss are analyzed in detail.

Fig. 1 Halo current versus Toroidal Peaking Factor. (Image by CHEN Dalong) 

Besides, experimentally observation demonstrated two threshold electric fields, characterizing a lower field required for significant seed RE generation and sustainment and a higher field required for the RE avalanche onset in the flattop. These results also open a possibility for RE suppression before the RE avalanche onset.

In another experiment, to classify disruptive discharges and distinguish them from non-disruptive discharges, a full convolutional neural network was trained on a large database of experimental EAST data. The true positive rate of the model increases up to 0.875, while the false rate decreases to 0.061. The proposed data-driven predicted model exhibits immense potential for application in long pulse fusion device such as ITER.

 Fig. 2 Behaviors of runaway electron during EAST disruption. (Image by TANG Tian) 

They also applied a real-time disruption predictor using a random forest (DPRF) for high-density disruptions to the plasma control system of the EAST tokamak.

The result confirmed the viability of DPRF to trigger the mitigation system, and can be more valuable when its interpretability is preserved to aid physics-based strategies.

The studies serve as solid basis for future development on disruption mitigation and prediction.

The studies were supported by the National Key R&D Program of China, Youth Innovation Promotion Association o Chinese Academy of Science and the National Natural Science Foundation of China.

Featured image: the disruption prediction category implemented in the real-time computer of EAST PCS. (Image by HU Wenhui)


References


Provided by Chinese Academy of Sciences

Throwing An ‘Axion Bomb’ Into A Black Hole Challenges Fundamental Law of Physics (Planetary Science)

New research shows how the fundamental law of conservation of charge could break down near a black hole.

Singularities, such as those at the centre of black holes, where density becomes infinite, are often said to be places where physics ‘breaks down’. However, this doesn’t mean that ‘anything’ could happen, and physicists are interested in which laws could break down, and how.

“We take aim at one of the most cherished laws of physics: the conservation of charge.”

— Professor Martin McCall

Now, a research team from Imperial College London, the Cockcroft Institute and Lancaster University have proposed a way that singularities could violate the law of conservation of charge. Their theory is published in Annalen der Physik.

Co-author Professor Martin McCall, from the Department of Physics at Imperial, said: “’Physics breaks down at a singularity’ is one of the most famous statements in pop-physics. But by showing how this might actually happen, we take aim at one of the most cherished laws of physics: the conservation of charge.”

Destroying charge

The conservation of charge says that the total electric charge of any isolated system – including the Universe as a whole – never changes. This means that if negatively or positively charged particles move into one area, the same amount of respectively charged particles must move out.

This has been shown at the very smallest scales: when different particles are created or eliminated in experiments such as the Large Hadron Collider, the same amount of negatively and positively charged particles are always produced or destroyed, respectively.

Now, by modifying classic physics equations to include axions, a candidate for dark matter, the team have been able to show that temporary singularities – such as black holes that appear and then later evaporate – could destroy charge when they come to the end of their life.

Ring of red layers surrounded by perpendicular rings of blue layers
Coupled axion and electromagnetic field © University College London

Axions are hypothetical particles that may explain dark matter – the ‘missing’ 85 percent of the matter of the Universe. Their predicted properties could form a field that would interact with the kind of fields physicists have known about for centuries – electromagnetic fields, which are described by a set of equations called Maxwell’s equations.

Using a branch of mathematics called differential geometry, the team found out how to create or destroy charge, violating the charge conservation of the Universe.

Philosophical implications

Co-author Dr Jonathan Gratus, from the Department of Physics at Lancaster University, said: “You can imagine creating an ‘axion bomb’ that holds charge by combining coupled axion and magnetic fields; and then dropping it into an evaporating black hole. As the construction shrinks and disappears into the singularity, it takes electrical charge with it.   It is the combination of a temporary singularity and a newly proposed type of axion field that is crucial to its success.”

Co-author Dr Paul Kinsler, from the Department of Physics at Imperial, said: “There are also philosophical implications. Although people often like to say that physics ‘breaks down’, here we show that although exotic phenomena might occur, what actually happens is nevertheless constrained by the still-working laws of physics around the singularity.”

The team say the axion phenomenon would only occur under extreme conditions that currently cannot be created in a lab, but that future advances in intense laser fields might allow the theory to be tested in a terrestrial environment.

Temporary Singularities and Axions: An Analytic Solution that Challenges Charge Conservation’ by Jonathan Gratus, Paul Kinsler and Martin W. McCall is published in Annalen der Physik.

Top image: This artist’s conception illustrates one of the most primitive supermassive black holes known (central black dot) at the core of a young, star-rich galaxy. Credit: NASA/JPL-Caltech


Provided by Imperial College London

Antacids May Improve Blood Sugar Control in People With Diabetes (Medicine)

Antacids improved blood sugar control in people with diabetes but had no effect on reducing the risk of diabetes in the general population, according to a new meta-analysis published in the Endocrine Society’s Journal of Clinical Endocrinology & Metabolism.

Type 2 diabetes is a global public health concern affecting almost 10 percent of people worldwide. Doctors may prescribe diet and lifestyle changes, diabetes medications, or insulin to help people with diabetes better manage their blood sugar, but recent data points to common over the counter antacid medicines as another way to improve glucose levels.

“Our research demonstrated that prescribing antacids as an add-on to standard care was superior to standard therapy in decreasing hemoglobin A1c (HbA1c) levels and fasting blood sugar in people with diabetes,” said study author Carol Chiung-Hui Peng, M.D., of the University of Maryland Medical Center Midtown Campus in Baltimore, Md.

“For people without diabetes, taking antacids did not significantly alter their risk of developing the disease,” said study author, Huei-Kai Huang, M.D., of the Hualien Tzu Chi Hospital in Hualien, Taiwan.

The researchers performed a meta-analysis on the effects of proton pump inhibitors (PPIs)—a commonly used type of antacid medication—on blood sugar levels in people with diabetes and whether these medications could prevent the new onset of diabetes in the general population. The analysis included seven studies (342 participants) for glycemic control and 5 studies (244, 439 participants) for risk of incident diabetes. The researchers found antacids can reduce HbA1c levels by 0.36% in people with diabetes and lower fasting blood sugar by 10 mg/dl based on the results from seven clinical trials. For those without diabetes, the results of the five studies showed that antacids had no effect on reducing the risk of developing diabetes.

“People with diabetes should be aware that these commonly used antacid medications may improve their blood sugar control, and providers could consider this glucose-lowering effect when prescribing these medications to their patients,” said study author Kashif Munir, M.D., associate professor in the division of endocrinology, diabetes and nutrition at the University of Maryland School of Medicine in Baltimore, Md.

Other authors of the study include: Yuting Huang and Khulood Bukhari of the University of Maryland Medical Center Midtown Campus in Baltimore, Md.; Yu-Kang Tu of the National Taiwan University and the Taipei Medical University in Taipei, Taiwan; Gin Yi Lee of the Danbury Hospital in Danbury, Conn.; Rachel Huai-En Chang of the Johns Hopkins Bloomberg School of Public Health in Baltimore, Md.; Yao-Chou Tsai of the Taipei Medical University; Yunting Fu of the University of Maryland in Baltimore, Md.

The manuscript received no external funding.

The manuscript, “Effects of Proton Pump Inhibitors on Glycemic Control and Incident Diabetes: A Systematic Review and Meta-analysis,” was published online, ahead of print


Provided by Endocrine Society

Bigger May Not Always Be Better: Density Not Size Governs Receptor Activation on Immune Cells (Medicine)

Scientists from within the Antibody and Vaccine Group at the University of Southampton have gained novel insights into how an important class of immune receptors called tumour necrosis factor receptors (TNFR) are activated.

The work, published in the journal Communications Biology on 23rd June 2021, investigates a class of receptors present on immune cells called TNFR. These receptors, such as CD40, 4-1BB and OX40, are key in helping the immune system fight pathogens and cancer cells. Accordingly, antibody drugs which are designed to specifically target and activate these receptors (called agonists) have been developed for cancer treatment.

The mechanism by which these receptors are activated on the cell surface is important for designing optimal drug formats; however, to date it is not fully understood. Previous work showed that receptor clustering, redistribution of receptors dispersed over the cell surface into localised clusters, is essential for TNF receptor activation, and it is commonly believed that larger clusters induce more potent activation.

The current study, led by Dr Ben Yu and Professor Mark Cragg at the Centre for Cancer Immunology, with colleagues across the University and at ONI UK, employed a set of unique reagents developed at Southampton targeting CD40, 4-1BB and OX40, as well as a new super-resolution microscopy acquired through funding from from the Mark Benevolent Fund, to address how differential receptor clustering mediates receptor activity.

Graphical abstract. © University of Southampton

Results from the study confirmed that TNF receptor activation absolutely requires receptor clustering but interestingly, disproved the commonly held belief that larger clusters induce more receptor activation. Rather, the study finds that agonists that induced smaller clusters – but with higher receptor density – mediated better TNF receptor activity than those which induced larger clusters.

In addition to receptor size, the study reveals that one of the most potent antibody agonists targeting CD40 induced a novel rod-shaped clustering structure, which could potentially explain the super-agonistic nature of that antibody. These findings add significant insight into how TNF receptors cluster to mediate immune activation and will help guide future development of therapeutic antibodies targeting TNF receptors.

The study was funded by Cancer Research UK.


Reference: Yu, X., James, S., Felce, J.H. et al. TNF receptor agonists induce distinct receptor clusters to mediate differential agonistic activity. Commun Biol 4, 772 (2021). https://doi.org/10.1038/s42003-021-02309-5


Provided by University of Southampton