Lack of detailed knowledge of SARS-CoV-2 infection has been hampering the development of treatments for coronavirus disease 2019 (COVID-19). Here, we report that RNA triggers the liquid-liquid phase ...separation (LLPS) of the SARS-CoV-2 nucleocapsid protein, N. By analyzing all 29 proteins of SARS-CoV-2, we find that only N is predicted as an LLPS protein. We further confirm the LLPS of N during SARS-CoV-2 infection. Among the 100,849 genome variants of SARS-CoV-2 in the GISAID database, we identify that ~37% (36,941) of the genomes contain a specific trio-nucleotide polymorphism (GGG-to-AAC) in the coding sequence of N, which leads to the amino acid substitutions, R203K/G204R. Interestingly, N
exhibits a higher propensity to undergo LLPS and a greater effect on IFN inhibition. By screening the chemicals known to interfere with N-RNA binding in other viruses, we find that (-)-gallocatechin gallate (GCG), a polyphenol from green tea, disrupts the LLPS of N and inhibits SARS-CoV-2 replication. Thus, our study reveals that targeting N-RNA condensation with GCG could be a potential treatment for COVID-19.
Cyclic GMP‐AMP synthase (cGAS) functions as a key sensor for microbial invasion and cellular damage by detecting emerging cytosolic DNA. Here, we report that GTPase‐activating protein‐(SH3 ...domain)–binding protein 1 (G3BP1) primes cGAS for its prompt activation by engaging cGAS in a primary liquid‐phase condensation state. Using high‐resolution microscopy, we show that in resting cells, cGAS exhibits particle‐like morphological characteristics, which are markedly weakened when G3BP1 is deleted. Upon DNA challenge, the pre‐condensed cGAS undergoes liquid–liquid phase separation (LLPS) more efficiently. Importantly, G3BP1 deficiency or its inhibition dramatically diminishes DNA‐induced LLPS and the subsequent activation of cGAS. Interestingly, RNA, previously reported to form condensates with cGAS, does not activate cGAS. Accordingly, we find that DNA – but not RNA – treatment leads to the dissociation of G3BP1 from cGAS. Taken together, our study shows that the primary condensation state of cGAS is critical for its rapid response to DNA.
Synopsis
Host cell encoded cGAS is a critical DNA sensor to detect invading pathogens. The stress‐granule protein G3BP1 engages cGAS in a primary condensation state to enable a rapid response to free DNA.
G3BP1 primes cGAS for its prompt activation.
G3BP1 engages cGAS in a primary condensation state.
DNA‐ but not RNA‐interaction leads to the dissociation of G3BP1 from cGAS.
Green tea compound epigallocatechin gallate (EGCG) inhibits G3BP1‐promoted cGAS phase condensation and activation.
Host cell encoded cGAS is a critical DNA sensor to detect invading pathogens. The stress‐granule protein G3BP1 engages cGAS in a primary condensation state to enable a rapid response to free DNA.
Engineering the band gap chemically by organic molecules is a powerful tool with which to optimize the properties of inorganic 2D materials. The obtained materials are however still limited by ...inhomogeneous compositions and properties at nanoscale and small adjustable band gap ranges. To overcome these problems in the traditional exfoliation and then organic modification strategy, an organic modification and then exfoliation strategy was explored in this work for preparing 2D organic metal chalcogenides (OMCs). Unlike the reported organically modified 2D materials, the inorganic layers of OMCs are fully covered by long-range ordered organic functional groups. By changing the electron-donating ability of the organic functional groups and the electronegativity of the metals, the band gaps of OMCs were varied by 0.83 eV and their conductivities were modulated by 9 orders of magnitude, which are 2 and 10
times higher than the highest values observed in the reported chemical methods, respectively.
Hyperuricaemia (increased serum urate concentration) occurs mainly in higher primates, including in humans, because of inactivation of the gene encoding uricase during primate evolution. Individuals ...with hyperuricaemia might develop gout - a painful inflammatory arthritis caused by monosodium urate crystal deposition in articular structures. Hyperuricaemia is also associated with common chronic diseases, including hypertension, chronic kidney disease, type 2 diabetes and cardiovascular disease. Many mouse models have been developed to investigate the causal mechanisms for hyperuricaemia. These models are highly diverse and can be divided into two broad categories: mice with genetic modifications (genetically induced models) and mice exposed to certain environmental factors (environmentally induced models; for example, pharmaceutical or dietary induction). This Review provides an overview of the mouse models of hyperuricaemia and the relevance of these models to human hyperuricaemia, with an emphasis on those models generated through genetic modifications. The challenges in developing and comparing mouse models of hyperuricaemia and future research directions are also outlined.
Abstract
To understand the parameter degeneracy of M subdwarf spectra at low resolution, we assemble a large number of spectral features in the wavelength range 0.6–2.5
μ
m with band strength ...quantified by narrowband indices. Based on the index trends of BT-Settl model sequences, we illustrate how the main atmospheric parameters (
T
eff
, log
g
, M/H, and
α
/Fe) affect each spectral feature differently. Furthermore, we propose a four-step process to determine the four parameters sequentially, which extends the basic idea proposed by Jao et al. Each step contains several spectral features that break the degeneracy effect when determining a specific stellar parameter. Finally, the feasibility of each spectroscopic diagnostic with different spectral quality is investigated. The result is resolution-independent down to
R
∼ 200.
Adjuvants are important components in vaccines to increase the immunogenicity of proteins and induce optimal immunity. In this study, we designed a novel ternary adjuvant system Alum + c-GAMP + ...poly(I:C) with STING agonist 3,3'-c-GAMP (c-GAMP) and TLR3 agonist poly(I:C) co-adsorbed on the conventional adjuvant aluminum gel (Alum), and further constructed an S1 protein vaccine. Two doses of vaccination with the ternary adjuvant vaccine were sufficient to induce a balanced Th1/Th2 immune response and robust humoral and cellular immunity. Additionally, the ternary adjuvant group had effective neutralizing activity against live virus SARS-CoV-2 and pseudovirus of all variants of concern (alpha, beta, gamma, delta and omicron). These results indicate that the ternary adjuvants have a significant synergistic effect and can rapidly trigger potent immune responses; the combination of the ternary adjuvant system with S1 protein is a promising COVID-19 vaccine candidate.
Safe and effective vaccines are the best method to defeat worldwide SARS-CoV-2 and its circulating variants. The SARS-CoV-2 S protein and its subunits are the most attractive targets for the ...development of protein-based vaccines. In this study, we evaluated three lipophilic adjuvants, monophosphoryl lipid A (MPLA), Toll-like receptor (TLR) 1/2 ligand Pam3CSK4, and α-galactosylceramide (α-GalCer), in liposomal and nonliposomal vaccines. The immunological results showed that the MPLA-adjuvanted liposomal vaccine induced the strongest humoral and cellular immunity. Therefore, we further performed a systematic comparison of S-trimer, S-ECD, S1, and RBD as antigens in MPLA-adjuvanted liposomes and found that, although these four vaccines all induced robust specific antibody responses, only S-trimer, S1, and RBD liposomes, but not S-ECD, elicited potent neutralizing antibody responses. Moreover, RBD, S-trimer, and S1 liposomes effectively neutralized variants (B.1.1.7/alpha, B.1.351/beta, P.1/gamma, B.1.617.2/delta, and B.1.1.529/omicron). These results provide important information for the subunit vaccine design against SARS-CoV-2 and its variants.
Abstract
In this paper, we report 591 high-velocity star candidates (HiVelSCs) selected from over 10 million spectra of Data Release 7 (DR7) of the Large Sky Area Multi-object Fiber Spectroscopic ...Telescope and the second Gaia data release, with three-dimensional velocities in the Galactic rest frame larger than 445 km s
−1
. We show that at least 43 HiVelSCs are unbound to the Galaxy with escape probabilities larger than 50%, and this number decreases to eight if the possible parallax zero-point error is corrected. Most of these HiVelSCs are metal-poor and slightly
α
-enhanced inner halo stars. Only 14% of them have Fe/H > −1, which may be the metal-rich “in situ” stars in the halo formed in the initial collapse of the Milky Way or metal-rich stars formed in the disk or bulge but kinematically heated. The low ratio of 14% implies that the bulk of the stellar halo was formed from the accretion and tidal disruption of satellite galaxies. In addition, HiVelSCs on retrograde orbits have slightly lower metallicities on average compared with those on prograde orbits; meanwhile, metal-poor HiVelSCs with Fe/H < −1 have an even faster mean retrograde velocity compared with metal-rich HiVelSCs. To investigate the origins of HiVelSCs, we perform orbit integrations and divide them into four types, i.e., hypervelocity stars, hyper-runaway stars, runaway stars and fast halo stars. A catalog for these 591 HiVelSCs, including radial velocities, atmospheric parameters, Gaia astrometric parameters, spatial positions, and velocities, etc., is available in the China-VO PaperData Repository at doi:
10.12149/101038
.
A novel sulfonate–carboxylate ligand of biphenyl-3,3′-disulfonyl-4,4′-dicarboxylic acid (H4–BPDSDC) and its lanthanide–organic frameworks {LnK(BPDSDC)(DMF)(H2O)·x(solvent)} n (JXNU-2, where JXNU ...denotes Jiangxi Normal University, DMF indicates dimethylformamide, and Ln = Sm3+, Eu3+, and Pr3+) were synthesized and structurally characterized. The three isomorphous lanthanide compounds feature three-dimensional frameworks constructed from one-dimensional (1D) rod-shaped heterometallic Ln–K secondary building units and are an illustration of a Kagome-like lattice with large 1D hexagonal channels and small 1D trigonal channels. The porous material of the representive JXNU-2(Sm) has an affinity to quadrupolar molecules such as CO2 and C2H2. In addition, the JXNU-2(Sm) compound exhibits humidity- and temperature-dependent proton conductivity with a large value of 1.11 × 10–3 S cm–1 at 80 °C and 98% relative humidity. The hydrophilic sulfonate group on the surface of channels facilitates enrichment of the solvate water molecules in the channels, which enhances the proton conductivity of this material. Moreover, the JXNU-2(Eu) material with the characteristic bright red color shows the potential for recognition of K+ and Fe3+ ions. The enhancing Eu3+ luminescence with the K+ ion and quenching Eu3+ luminescence with the Fe3+ ion can be associated with the functional groups of the organic ligand.
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