Sliding van der Waals polytypes
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Ginsenoside Rg3 enriches SCFA-producing commensal bacteria to confer protection against enteric viral infection via the cGAS-STING-type I IFN axis
The microbiota-associated factors that influence host susceptibility and immunity to enteric viral infections remain poorly defined. We identified that the herbal monomer ginsenoside Rg3 (Rg3) can shape the gut microbiota composition, enriching robust short-chain fatty acid (SCFA)-producing Blautia spp. Colonization by representative Blautia coccoides and Blautia obeum could protect germ-free or vancomycin (Van)-treated mice from enteric virus infection, inducing type I interferon (IFN-I) responses in macrophages via the MAVS-IRF3-IFNAR signaling pathway. Application of exogenous SCFAs (acetate/propionate) reproduced the protective effect of Rg3 and Blautia spp. in Van-treated mice, enhancing intracellular Ca2+– and MAVS-dependent mtDNA release and activating the cGAS-STING-IFN-I axis by stimulating GPR43 signaling in macrophages. Our findings demonstrate that macrophage sensing of metabolites from specific commensal bacteria can prime the IFN-I signaling that is required for antiviral functions.
Translocation-specific polymerase chain reaction in preimplantation genetic testing for recurrent translocation carrier
It is occasionally necessary to distinguish balanced reciprocal translocations from normal diploidy since balanced carriers can have reproductive problems or manifest other disease phenotypes. It is challenging to do this however using next generation sequencing (NGS) or microarray-based preimplantation genetic testing (PGT). In this study, discarded embryos were harvested from balanced reciprocal translocation carriers intending PGT that were determined to be unsuitable for transfer due to unbalanced translocations or translocation-unrelated aneuploidy. Two trophoectoderm biopsy samples were obtained from each single embryo. Whole genome amplification (WGA) was performed either by looping-based amplification (LBA) or multiple displacement amplification (MDA). NGS-based copy number variation (CNV) analysis as well as translocation-specific PCR was performed for each. We used embryo samples from t(8;22)(q24.13;q11.2) and t(11;22)(q23;q11.2) carriers since they are recurrent constitutional translocations that have nearly identical breakpoints even among independent unrelated families. CNV analysis was generally consistent between the two WGA methods. Translocation-specific PCR allowed us to detect each derivative chromosome in the MDA WGA samples but not with the LBA method, presumably due to coverage bias or the shorter sized WGA products. We successfully distinguished balanced reciprocal translocations from normal diploidy in normal samples with CNV analysis. A combination of CNV analysis and translocation-specific PCR using MDA-amplified WGA product can distinguish between balanced reciprocal translocation and normal diploidy in preimplantation genetic testing for structural rearrangements (PGT-SR).
Imaging molecular structures and interactions by enhanced confinement effect in electron microscopy
Atomic imaging of molecules and intermolecular interactions are of great significance for a deeper understanding of the basic physics and chemistry in various applications, but it is still challenging in electron microscopy due to their thermal mobility and beam sensitivity. Confinement effect and low-dose imaging method may efficiently help us achieve stable high-resolution resolving of molecules and their interactions. Here, we propose a general strategy to image the confined molecules and evaluate the strengths of host-guest interactions in three material systems by low-dose electron microscopy. Then, we change the guest molecules to analyze how each kind of interaction strength influences the imaging quality of these molecules by using a same parameter, the aspect ratios of imaged molecular projections. In the material systems of perovskites (ionic) and zeolites with adsorbed molecules (van der Waals), we can obtain a clear image of molecular configurations by enhancing host-guest interactions. Even in metal organic framework (coordination) system, the atomic structures and bonds of aromatics can be achieved. These results provide a general description on the relation between molecular images and interactions, making it possible to study more molecular behaviors in wide applications by real-space imaging.
KorB switching from DNA-sliding clamp to repressor mediates long-range gene silencing in a multi-drug resistance plasmid
Examples of long-range gene regulation in bacteria are rare and generally thought to involve DNA looping. Here, using a combination of biophysical approaches including X-ray crystallography and single-molecule analysis for the KorB–KorA system in Escherichia coli, we show that long-range gene silencing on the plasmid RK2, a source of multi-drug resistance across diverse Gram-negative bacteria, is achieved cooperatively by a DNA-sliding clamp, KorB, and a clamp-locking protein, KorA. We show that KorB is a CTPase clamp that can entrap and slide along DNA to reach distal target promoters up to 1.5 kb away. We resolved the tripartite crystal structure of a KorB–KorA–DNA co-complex, revealing that KorA latches KorB into a closed clamp state. DNA-bound KorA thus stimulates repression by stalling KorB sliding at target promoters to occlude RNA polymerase holoenzymes. Together, our findings explain the mechanistic basis for KorB role switching from a DNA-sliding clamp to a co-repressor and provide an alternative mechanism for long-range regulation of gene expression in bacteria.
Twist–torsion coupling in beating axonemes
Motile cilia and flagella produce regular bending waves that enable single-cell navigation due to non-planar waveforms with characteristic torsion. However, it is not known how torsion, a geometric property of the three-dimensional waveform, relates to mechanical twist deformations of the axoneme, the conserved cytoskeletal core of cilia and flagella. Here we show that axoneme twisting and torsion are coupled and that twist waves propagate along the beating axoneme of Chlamydomonas reinhardtii algae. We resolve the three-dimensional shapes of the axonemal waveform with nanometre precision at millisecond timescales using defocused dark-field microscopy and beat-cycle averaging, observing regular hetero-chiral torsion waves propagating base to tip. To investigate whether the observed torsion results from axonemal twist, we attach gold nanoparticles to axonemes and measure their cross-section rotation during beating. We find that, locally, the axonemal cross-section co-rotates with the bending plane, evidencing twist–torsion coupling. Our results demonstrate the link between shape and mechanical deformation in beating axonemes and can inform models of the dynamics of motor proteins inside the axoneme responsible for shaping the beat of motile cilia.
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