120 research outputs found

    Cryo-electron tomography of periplasmic flagella in Borrelia burgdorferi reveals a distinct cytoplasmic ATPase complex.

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    Periplasmic flagella are essential for the distinct morphology and motility of spirochetes. A flagella-specific type III secretion system (fT3SS) composed of a membrane-bound export apparatus and a cytosolic ATPase complex is responsible for the assembly of the periplasmic flagella. Here, we deployed cryo-electron tomography (cryo-ET) to visualize the fT3SS machine in the Lyme disease spirochete Borrelia burgdorferi. We show, for the first time, that the cytosolic ATPase complex is attached to the flagellar C-ring through multiple spokes to form the “spoke and hub� structure in B. burgdorferi. This structure not only strengthens structural rigidity of the round-shaped C-ring but also appears to rotate with the C-ring. Our studies provide structural insights into the unique mechanisms underlying assembly and rotation of the periplasmic flagella and may provide the basis for the development of novel therapeutic strategies against several pathogenic spirochetes

    Histone Peptide Recognition by KDM5B-PHD1: A Case Study

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    A detailed understanding of the energetic contributions to histone peptide recognition would be valuable for a better understanding of chromatin anchoring mechanisms and histone diagnostic design. Here, we probed the energetic contributions to recognize the same unmodified histone H3 by three different plant homeodomain (PHD) H3K4me0 <i>readers</i>: hKDM5B-PHD1 (first PHD finger of hKDM5B), hBAZ2A-PHD, and hAIRE-PHD1. The energetic contributions of residues differ significantly from one complex to the next. For example, H3K4A substitution completely aborts the formation of the hAIRE–histone peptide complex, while it has only a small destabilizing effect on binding of the other readers, even though H3K4 methylation disrupts all three complexes. Packing density suggests that methylation of more tightly packed Lys/Arg residues can disrupt binding, even if the energetic contribution is small. The binding behavior of hKDM5B-PHD1 and hBAZ2A-PHD is similar, and like PHD H3R2 <i>readers</i>, both possess a pair of Asp residues in the treble clef for interaction with H3R2. PHD subtype sequences, especially the tandem PHD–PHD fingers, show enrichment in the treble clef Asp residues, suggesting that it is a subtype-specific property. These Asp residues make significant energetic contributions to the formation of the hKDM5B–histone peptide complex, suggesting that there are interactions in addition to those reported in the recent NMR structure. However, the presence of the treble clef Asp in PHD sequences may not always be sufficient for histone peptide binding. This study showcases <i>reader</i>–histone peptide interactions in the context of residue conservation, energetic contributions, interfacial packing, and sequence-based <i>reader</i> subtype predictability

    Table_1_Higher serum selenium concentration is associated with lower risk of all-cause and cardiovascular mortality among individuals with chronic kidney disease: A population-based cohort study of NHANES.docx

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    BackgroundSelenium is an essential nutrient and trace element required for human health and plays an important role in antioxidative and anti-inflammatory processes. However, the long-term impact of selenium levels on the health of patients with chronic kidney disease remains unclear.MethodParticipants in this study were 3,063 CKD adults from the Third National Health and Nutrition Examination Survey (NHANES 1999–2000, 2003–2004, and 2011–2018). The mortality status and the cause of death of the study participants were obtained from the National Death Index records. For all-cause and cardiovascular disease (CVD) mortality, the models employed to estimate hazard ratios (HRs) and 95% CI were Cox proportional hazard models and competing risk models, respectively.ResultDuring the follow-up period, 884 deaths occurred, including 336 heart-disease-associated deaths. The median (IQR) concentration of serum selenium was 181.7 (156.1, 201.5) μg/L. After full adjustment, serum selenium levels were associated with a decreased risk of mortality in patients with CKD, including all-cause and CVD mortality (P trend trend ConclusionHigher serum selenium concentration was independently associated with a decreased risk of all-cause and CVD mortality in patients with CKD.</p

    Multicomponent Assembly of Supramolecular Coordination Polygons on a Au(111) Surface

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    We have studied the self-assembly of a series of multicomponent cyclic supramolecular polygons on a Au(111) surface using scanning tunneling microscopy and kinetic Monte Carlo simulations. Our results indicate that while closed polygons or cages efficiently self-assemble in three dimensions at appropriate temperatures and concentrations, chain structures are formed predominantly and the yield of cyclic polygon structures is very low in two dimensions independent of temperature and concentration. This substantial shift in the ring–chain equilibrium can be attributed to subtle competition between kinetic and thermodynamic controls. Simulations suggest that on a surface, where the translational and rotational freedom of the molecules are restricted and intramolecular bond flipping is hindered, the low-energy reaction pathways that are essential for the formation of cyclic structures are blocked. In addition, microscopy images suggest that surface defects provide kinetic traps that further reduce the yield of cyclic structures. Our findings reveal the striking differences between the on-surface self-assembly and solution self-assembly of discrete supramolecular systems

    Results of segmentation on images with a single object.

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    <p>Results of segmentation on images with a single object.</p

    Normalized aesthetic and ecological landscape value coefficients.

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    <p>Normalized aesthetic and ecological landscape value coefficients.</p

    Aesthetic landscape value scores (P, point<sub>*</sub>hm<sup>2</sup>) of five landscape types.

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    <p>Aesthetic landscape value scores (P, point<sub>*</sub>hm<sup>2</sup>) of five landscape types.</p

    Results of segmentation on images with complex backgrounds.

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    <p>Results of segmentation on images with complex backgrounds.</p

    Results of segmentation using different values of <i>m</i> (the number of cluster regions).

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    <p>Results of segmentation using different values of <i>m</i> (the number of cluster regions).</p
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