Riosbeyer1038

Osmotic pressure (Π) induces membrane tension in cell membranes and the lipid bilayers of vesicles and plays an important role in the functions and physical properties of these membranes. We recently developed a method to determine quantitatively the membrane tension of giant unilamellar vesicles (GUVs) under Π and applied it to GUVs comprising electrically neutral dioleoylphosphatidylcholine (DOPC). Here, we examined the effect of Π on GUVs composed of DOPC and negatively charged dioleoylphosphatidylglycerol (DOPG) in a buffer containing a physiological concentration of ions. First, we examined the rate constant, kr, for constant tension (σex)-induced rupture of DOPG/DOPC (4/6)-GUVs under Π and obtained the dependence of kr on σex in GUVs for various values of Π. Comparing this dependence in the absence of Π provided values for membrane tension due to Π, σosm, which agree with the theoretical values within the experimental error. The values of σosm for DOPG/DOPC-GUVs were smaller than those for DOPC-GUVs under the same Π. Two factors, that is, the solute concentration in a GUV suspension and the elastic modulus of the GUV membrane, can reasonably explain this difference based on the theory of σosm. check details We also examined the effect of Π on the rate constant, kFF, for the transbilayer movement of lipid molecules in single GUVs. The values of kFF increased with increasing Π, indicating that kFF increased with σosm. This result supports the existence of prepores in stretched lipid bilayers. Based on these results, we discuss the membrane tension of DOPG/DOPC-GUVs under Π.Development of antidotes against botulism requires understanding of the enzymatically active conformations of Botulinum neurotoxin serotype A (BoNT/A) light chain (LCA). We performed small angle X-ray scattering (SAXS) to characterize the solution structures of truncated light chain (tLCA). The 34-37 Å radius of gyration of tLCA was 1.5-times greater than the averaged 22-23-Å radius from the crystal structures. The bimodal distribution of interatomic distances P(r) indicated the two-domain tLCA structure with 129-133 Å size, and Kratky plots indicated the tLCA partial unfolding in the 25-37 °C temperature range. To interpret these data, we employed molecular dynamics simulations and machine learning. Excellent agreement between experimental and theoretical P(r) profiles helped to resolve conformational subpopulations of tLCA in solution. Partial unfolding of the C-terminal portion of tLCA (residues 339-425) results in formation of extended conformations with the larger globular domain (residues 2-298) and the smaller unstructured domain (339-425). The catalytic domain, buried 20 Å-deep inside the crystal structure, becomes accessible in extended solution conformations (8-9 Å deep). The C- and N-termini containing different functional sequence motifs are maximally separated in the extended conformations. Our results offer physical insights into the molecular basis of BoNT/A function and stress the importance of reversible unfolding-refolding transitions and hydrophobic interactions.Breast cancer is one of the most common cancers in women worldwide. In the past decades, many advances have been made in understanding and treating breast cancer. However, due to the highly heterogeneous nature of this disease, a precise characterization of breast cancer on the molecular level is of great importance but not yet readily available. In the present study, we systematically profiled proteomes and N-glycoproteomes of cancerous, paracancerous, and distal noncancerous tissues from patients with breast cancer. The data revealed distinct proteomic and N-glycoproteomic landscapes between different tissues, showing biological insights obtained from the two data sets were complementary. Specifically, the complement and angiogenesis pathways in the paracancerous tissues were activated. Taken together, the changes that occurred in paracancer tissue and N-glycoproteomics are important complements to the conventional proteomic analysis of cancer tissue. Their combination provides more precise and sensitive molecular correlates of breast cancer. Our data and strategy shed light on precisely defining breast cancer, providing valuable information for individual patient diagnosis and treatment. The MS data of this study have been deposited under the accession number IPX0001924000 at iProX.A visible-light-mediated radical Smiles rearrangement has been achieved using neutral eosin Y as a direct hydrogen atom transfer (HAT) photocatalyst. Novel N-heterocycles as single diastereomers featuring an isothiazolidin-3-one 1,1-dioxide moiety are directly accessed by this method. A wide range of functional groups can be incorporated in the products by employing diverse aldehydes and N-(hetero)arylsulfonyl propiolamides. The transformation proceeds through a cascade of visible-light-induced HAT, 1,4-addition, Smiles rearrangement, 5-endo-trig cyclization, and a reverse HAT process. Preliminary biological studies of the highly functionalized heterocyclic compounds suggest potential anticancer activity with some of the synthesized compounds.Gout and hyperuricemia can seriously affect the quality of life; at present, however, existing medicines are unable to meet all clinical needs. In the current study, a novel peptide (i.e., rice-derived-peptide-3 (RDP3), AAAAMAGPK-NH2, 785.97 Da) in water extract obtained from shelled Oryza sativa fruits was identified. Testing revealed that RDP3 (minimum effective concentration 100 μg/kg) did not show both hemolytic and acute toxicity, and reduced uric acid levels in the serum of hyperuricemic mice by inhibiting xanthine oxidase activity and decreasing urate transporter 1 expression. RDP3 also alleviated renal injury in hyperuricemic mice by decreasing NLRP3 inflammasome expression. Furthermore, RDP3 alleviated formalin-induced paw pain and reduced monosodium urate crystal-induced paw swelling and inflammatory factors in mice. Thus, this newly identified peptide reduced uric acid levels and renal damage in hyperuricemic mice and showed anti-inflammatory and analgesic activities, indicating the potential of RDP3 as an antigout medicine candidate.