Notes

Effect of toothbrush bristle firmness and also toothbrushing force on the harsh dentine wear.
In two cases with diagnostic tissue on CT-guided biopsy, an open biopsy was still recommended based on the clinical scenario; in both cases the open biopsy results matched those of the CT-guided biopsy. Among 18 patients who required surgery, there was a 100% correlation between percutaneous needle biopsy and final pathological diagnosis. There were no biopsy-induced complications or extra-spinal seeding of tumor. CONCLUSIONS CT-guided biopsy is a safe and effective technique. It represents a critical component of the diagnostic algorithm given the diverse pathology of primary sacral lesions and dramatic differences in treatment. Eight undescribed quinolone alkaloids, pesimquinolones A-H, as well as six known compounds, were isolated from the solid culture broth of the fungus Penicillium simplicissimum. Their chemical structures were characterized by combined analyses of NMR spectroscopy and single-crystal X-ray crystallography. Pesimquinolones A-G are the first examples of naturally occurring quinolone alkaloids possessing a limonene moiety. Their anti-inflammatory activities on LPS-induced nitric oxide (NO) production in adherent cells were evaluated. Pesimquinolones A, E, G, and H showed promising suppressive effect on the production of NO with IC50 values of 1.94, 1.29, 1.20, and 1.23 μM, respectively. BACKGROUND Telomeres are chromosome end structures important in the maintenance of genome homeostasis. They are replenished by the action of telomerase and associated proteins, such as the OB (oligonucleotide/oligosaccharide-binding)-fold containing telomere-end binding proteins (TEBP) which plays an essential role in telomere maintenance and protection. The nature of TEBPs is well known in higher and some primitive eukaryotes, but it remains undetermined in trypanosomatids. Previous in silico searches have shown that there are no homologs of the classical TEPBs in trypanosomatids, including Leishmania sp. However, Replication Protein A subunit 1 (RPA-1), an OB-fold containing DNA-binding protein, was found co-localized with trypanosomatids telomeres and showed a high preference for the telomeric G-rich strand. METHODS AND RESULTS We predicted the absence of structural homologs of OB-fold containing TEBPs in the Leishmania sp. genome using structural comparisons. We demonstrated by molecular docking that the ssDNA binding mode of LaRPA-1 shares features with the higher eukaryotes POT1 and RPA-1 crystal structures ssDNA binding mode. Using fluorescence spectroscopy, protein-DNA interaction assays, and FRET, we respectively show that LaRPA-1 shares some telomeric functions with the classical TEBPs since it can bind at least one telomeric repeat, protect the telomeric G-rich DNA from 3'-5' Exonuclease I digestion, and unfold telomeric G-quadruplex. CONCLUSIONS Our results suggest that RPA-1 emerges as a TEBP in trypanosomatids, and in this context, we present two possible evolutionary landscapes of trypanosomatids RPA-1 that could reflect upon the evolution of OB-fold containing TEBPs from all eukaryotes. BACKGROUND Ammonia lyases are enzymes of industrial and biomedical interest. Knowledge of structure-dynamics-function relationship in ammonia lyases is instrumental for exploiting the potential of these enzymes in industrial or biomedical applications. METHODS We investigated the conformational changes in the proximity of the catalytic pocket of a 3-methylaspartate ammonia lyase (MAL) as a model system. At this scope, we used microsecond all-atom molecular dynamics simulations, analyzed with dimensionality reduction techniques, as well as in terms of contact networks and correlated motions. RESULTS We identify two regulatory elements in the MAL structure, i.e., the β5-α2 loop and the helix-hairpin-loop subdomain. These regulatory elements undergo conformational changes switching from 'occluded' to 'open' states. The rearrangements are coupled to changes in the accessibility of the active site. The β5-α2 loop and the helix-hairpin-loop subdomain modulate the formation of tunnels from the protein surface to the catalytic site, making the active site more accessible to the substrate when they are in an open state. CONCLUSIONS Our work pinpoints a sequential mechanism, in which the helix-hairpin-loop subdomain of MAL needs to break a subset of intramolecular interactions first to favor the displacement of the β5-α2 loop. The coupled conformational changes of these two elements contribute to modulate the accessibility of the catalytic site. MDV3100 GENERAL SIGNIFICANCE Similar molecular mechanisms can have broad relevance in other ammonia lyases with similar regulatory loops. Our results also imply that it is important to account for protein dynamics in the design of variants of ammonia lyases for industrial and biomedical applications. Free nitrous acid (FNA) has been recently reported to be an effective and eco-friendly inactivator for waste activated sludge (WAS), while the limited decomposition of the extracellular polymeric substance (EPS) matrix hampers resource recovery from WAS. This work employed peracetic acid (PAA) to assist FNA and explored the contribution of co-pretreatment to hydrogen recovery in a prefermentation-bioelectrolysis cascading system. The results showed that co-pretreatment led to approximately 8.8% and 20.4% increases in the exfoliation of particulate proteins and carbohydrates, respectively, from tightly bound EPS (TB-EPS) over that of sole FNA pretreatment. Electron paramagnetic resonance analysis verified that the synergistic effect of FNA, PAA and various generated free radicals was the essential process. This effect further promoted the accumulation of volatile fatty acids (VFAs) after 96 h of prefermentation, and the peak concentration in co-pretreated WAS (AD-FPWAS) was approximately 2.5-fold that in sole reducing bacteria and methanogens were explored by molecular ecological network analysis. From an environmental and economic perspective, this promising FNA and PAA co-pretreatment approach provides new insight for energy recovery from WAS biorefineries. Sulfate radical-based advanced oxidation processes (SR-AOPs) show a good prospect for effective elimination of organic contaminants in water due to the powerful oxidation capability and good adaptability of sulfate radical (SO4•-). However, great concerns have been raised on occurrence of the carcinogenic byproduct bromate (BrO3-) in SR-AOPs. The present article aims to provide a critical review on BrO3- formation during bromine (Br)-containing water oxidation by various SR-AOPs. Potential reaction mechanisms are elaborated, mainly involving the sequential oxidation of bromide (Br-) by SO4•- to Br-containing radicals (e.g., bromine atom (Br•)) and then to hypobromous acid/hypobromite (HOBr/OBr-), which acts as the requisite intermediate for BrO3- formation. Some key influencing factors on BrO3- formation are discussed. Particularly, dissolved organic matter (DOM) as a component ubiquitously present in aquatic environments shows a significant suppression effect on BrO3- formation, primarily attributed to the reduction of Br• by DOM to Br-.
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