-
Glenn Saunders posted an update 7 months ago
DFT calculations are employed to quantify the influence of the presence, number, nature, and position of posttranscriptional methylation on stacking strength of RNA bases. We carry out detailed potential energy scans of the variation in stacking energies with characteristic geometrical parameters in three categories of forty stacked dimers – canonical base homodimers (N||N), methylated base homodimers (mN||mN) and heterodimers of canonical bases and methylated counterparts (N||mN). Our analysis reveals that neutral methylation invariably enhances the stacking of bases. Further, N||mN stacking is stronger than mN||mN stacking and charged N||mN exhibit strongest stacking among all dimers. Fludarabine purchase This indicates that methylations greatly enhance stacking when dispersed in RNA sequences containing identical bases. Comparison of stacks involving singly- and doubly-methylated purines reveal that incremental methylation enhances the stacking in neutral dimers. Although methylation at the carbon position of neutral pyrimidine dimers greatly enhances the stacking, methylation on the 5-membered ring imparts better stacking compared to methylation on the 6-membered ring in adenine dimers. However, methylation at the ring nitrogen (N1 ) provides better stacking than the amino group (N2 ) in guanine dimers. Our results thus highlight subtle structural effects of methylation on RNA base stacking and will enhance our understanding of the physicochemical principles of RNA structure and dynamics.Ochratoxin A (OTA) is a fungal toxin that causes serious threat to human health. OTA could lead to the injury of various tissues, especially kidney injury. However, the toxic effects of OTA on human kidney tubular epithelial cell (HK-2) and the possible mechanism remains poorly understood. This study was to investigate the toxic effects of OTA on HK-2 and elucidate the molecular mechanism. HK-2 cells were treated OTA to evaluate the effect of OTA on cell viability and apoptosis. OTA inhibited the growth of HK-2 in a concentration-dependent manner. With the concentration increased, OTA significantly lead to the apoptosis of HK-2. OTA could increase the levels of reactive oxygen species (ROS) and Malondialdehyde (MDA). Superoxide dismutase (SOD) and glutathione (GSH) activities were decreased by OTA. Furthermore, OTA increased Caspase-3 and Bax expression and decreased BCL2 expression. Compared to the control group, the expression of PTEN was increased and the expression of PI3K and AKT were decreased in OTA treated groups. In addition, we found OTA could disrupt the formation of lipid raft by attenuating sphingomyelin and cholesterol levels. In conclusion, our results indicated that OTA induces apoptosis in HK-2 through regulating PTEN/AKT signaling pathway via disrupting lipid raft formation.The synthesis of phenalenyl-endcapped cumulene as a cumulene-based singlet biradical and the spin correlation changes of one-dimensional aggregates are described. The high propensity for self-aggregation of phenalenyl rings and the introduction of bulky substituents into the appropriate positions led to the formation of a one-dimensional chain assembly. Single-crystal X-ray structural analysis indicated that the bond length alternation of the cumulene chain increased with decreasing temperature, along with improved overlapping of the phenalenyl rings. Variable-temperature Raman spectroscopy and magnetic susceptibility measurements revealed that a localized spin pair within the molecule decouples at low temperatures and a continuum spin system involving intra- and inter-molecular spin-spin interactions emerges in the one-dimensional chain.Sulfur chemistry based on solid-liquid dissolution-deposition route inevitably encounters shuttle of lithium polysulfides, its parasitic interaction with lithium (Li) anode and flood electrolyte environment. The sulfurized pyrolyzed poly(acrylonitrile) (S@pPAN) cathode favors solid-solid conversion mechanism in carbonate ester electrolytes but fails to pair high-capacity Li anode. Herein, we rationally design a cation-solvent fully coordinated ether electrolyte to simultaneously resolve the problems of both Li anode and S@pPAN cathode. Raman spectroscopy reveals a highly suppressed solvent activity and a cation-solvent fully coordinated structure (molar ratio 11). Consequently, Li electrodeposit evolves into round-edged morphology, LiF-rich interphase, and high reversibility. Moreover, S@pPAN cathode inherits a neat solid-phase redox reaction and fully eliminated the dissolution of lithium polysulfides. Finally, we harvest a long-life Li-S@pPAN pouch cell with slight Li metal excessive (0.4 time) and ultra-lean electrolyte design (1 μL mgS -1 ), delivering 394 Wh kg-1 energy density based on electrodes and electrolyte mass.African trypanosomes cause disease in humans and livestock, avoiding host immunity by changing the expression of variant surface glycoproteins (VSGs); the major glycosylphosphatidylinositol (GPI) anchored antigens coating the surface of the bloodstream stage. Proper trafficking of VSGs is therefore critical to pathogen survival. The valence model argues that GPI anchors regulate progression and fate in the secretory pathway and that, specifically, a valence of two (VSGs are dimers) is critical for stable cell surface association. However, recent reports that the MITat1.3 (M1.3) VSG N-terminal domain (NTD) behaves as a monomer in solution and in a crystal structure challenge this model. We now show that the behavior of intact M1.3 VSG in standard in vivo trafficking assays is consistent with an oligomer. Nevertheless, Blue Native Gel electrophoresis and size exclusion chromatography-multiangle light scattering chromatography of purified full length M1.3 VSG indicates a monomer in vitro. However, studies with additional VSGs show that multiple oligomeric states are possible, and that for some VSGs oligomerization is concentration dependent. These data argue that individual VSG monomers possess different propensities to self-oligomerize, but that when constrained at high density to the cell surface, oligomeric species predominate. These results resolve the apparent conflict between the valence hypothesis and the M1.3 NTD VSG crystal structure.