Stretch-activated composite ion channels in Bacillus subtilis.

The presence of ion-conducting pores in the membrane of Bacillus subtilis giant protoplasts was discovered using the patch-clamp technique. Membrane stretch caused the activation of several conductances with values in the nS range. The observations indicate the presence of substate levels and of aggregates of channels behaving in a cooperative manner. Following repeated stretch cycles, the channels exhibited spontaneous activity. The characteristics of the electrical phenomena afterwards changed in time in a manner suggesting the decay of the giant channels into lower-conductance species, presumably corresponding to building blocks of the giant stretch-activated channels.     

Probing binding mechanism of interleukin-6 and olokizumab: in silico design of potential lead antibodies for autoimmune and inflammatory diseases

Computer-aided antibody engineering has been successful in the design of new biologics for disease diagnosis and therapeutic interventions. Interleukin-6 (IL-6), a well-recognized drug target for various autoimmune and inflammatory diseases such as rheumatoid arthritis, multiple sclerosis, and psoriasis, was investigated in silico to design potential lead antibodies. Here, crystal structure of IL-6 along with monoclonal antibody olokizumab was explored to predict antigen–antibody (Ag???Ab)-interacting residues using DiscoTope, Paratome, and PyMOL. Tyr56, Tyr103 in heavy chain and Gly30, Ile31 in light chain of olokizumab were mutated with residues Ser, Thr, Tyr, Trp, and Phe. A set of 899 mutant macromolecules were designed, and binding affinity of these macromolecules to IL-6 was evaluated through Ag???Ab docking (ZDOCK, ClusPro, and Rosetta server), binding free-energy calculations using Molecular Mechanics/Poisson Boltzman Surface Area (MM/PBSA) method, and interaction energy estimation. In comparison to olokizumab, eight newly designed theoretical antibodies demonstrated better result in all assessments. Therefore, these newly designed macromolecules were proposed as potential lead antibodies to serve as a therapeutics option for IL-6-mediated diseases.     

Effects of exogenous fatty acids on calcium uptake by brush-border membrane vesicles from rabbit small intestine

The uptake of a variety of fatty acids by isolated brush-border membranes from rabbit small intestine was studied. This uptake increased with acyl chain-length and was not diminished by washing of the lipid-treated membranes with 0.25 M CsBr. The binding of fatty acid was not accompanied by a decrease in endogenous acyl groups or of cholesterol and therefore corresponded to a net uptake accountable qualitatively and quantitatively by the fatty acid added to the membranes. The uptake of Ca2+ was stimulated by treatment of the membranes with low concentrations of unsaturated fatty acids (0.05 mM) as well as with various concentrations of caprylic acid (0.10-3.00 mM) and inhibited by treatment with higher concentrations of unsaturated fatty acids (0.20-0.60 mM). Saturated fatty acids had no marked effects on Ca2+ uptake. The stimulatory concentrations of unsaturated fatty acids did not change the Ca2+-binding characteristics of the membranes, whereas the higher concentrations decreased equilibrium binding of Ca2+ and very probably the number of high-affinity binding sites. The results of this study are assessed in terms of the effects of normal fatty acids found in the diet on the absorptive properties of the brush-border membranes.     

Aneurysms after microvascular anastomoses. Incidence and pathogenesis in experimental animals.

This study has demonstrated that aneurysms occur in about 50 percent of the rat femoral arteries subjected to microvascular anastomosis. These aneurysms are consistent histologically--being characterized by medial necrosis, loss of elastic lamellae, and subintimal hyperplasia. Mechanical trauma is implicated as a factor in their pathogenesis, though further study in necessary to define the exact etiology.     

Dimorphism inYarrowia lipolytica: Filament formation is suppressed by nitrogen starvation and inhibition of respiration

In contrast toSaccharomyces cerevisiae, nitrogen starvation inhibited formation of hyphae in liquid cultures ofY. lipolytica, while carbon source did not seem to be important for filament formation. Inhibitors of mitochondrial respiration strongly suppressed the development of hyphae, indicating that energy conversion processes, and thus carbon metabolism, may be involved. pH of the medium also strongly affected the morphology, but only in the presence of a complex nitrogen source, implying that the cells respond to altered nutrition in media with different pH rather than to pH itself. The results suggest that theXPR2 gene encodingY. lipolytica alkaline extracellular proteinase is involved in the regulation of dimorphism in this species.