Ribosome inhibiting proteins, RIPs, are a widespread family of toxic enzymes. Ricin is a plant toxin used as a poison and biological warfare agent; shiga toxin is a homologue expressed by pathogenic strains of E. coli. There is interest in creating effective antidote inhibitors to this class of enzymes. RIPs act by binding and hydrolyzing a specific adenine base from rRNA. Previous virtual screens revealed that pterins could bind in the specificity pocket of ricin and inhibit the enzyme. In this paper we explore a range of compounds that could serve as better platforms for inhibitor design. This establishes the importance of key hydrogen bond donors and acceptors for active-site complementarity. 8-Methyl-9-oxoguanine is a soluble compound that has the best inhibitory properties of any platform tested. The X-ray structure of this complex revealed that the inhibitor binds in an unexpected way that provides insight for future design. Several inhibitors of ricin were also shown to be inhibitors of shiga toxin, suggesting this program has the potential to develop effective antidotes to an important form of food poisoning.

Inspired by the turbinate structure in the olfaction system of a dog, a biomimetic artificial nose based on 3D porous laser-induced graphene (LIG) decorated with palladium (Pd) nanoparticles (NPs) has been developed for room-temperature hydrogen (H2) detection. A 3D porous biomimetic turbinate-like network of graphene was synthesized by simply irradiating an infrared laser beam onto a polyimide substrate, which could further be transferred onto another flexible substrate such as polyethylene terephthalate (PET) to broaden its application. The sensing mechanism is based on the catalytic effect of the Pd NPs on the crystal defect of the biomimetic LIG turbinate-like microstructure, which allows facile adsorption and desorption of the nonpolar H2 molecules. The sensor demonstrated an approximately linear sensing response to H2 concentration. Compared to chemical vapor-deposited (CVD) graphene-based gas sensors, the biomimetic turbinate-like microstructure LIG-gas sensor showed ∼1 time higher sensing performance with much simpler and lower-cost fabrication. Furthermore, to expand the potential applications of the biomimetic sensor, we modulated the resistance of the biomimetic LIG sensor by varying laser sweeping gaps and also demonstrated a well-transferred LIG layer onto transparent substrates. Moreover, the LIG sensor showed good mechanical flexibility and robustness for potential wearable and flexible device applications.

The f lavin-containing monooxygenase from yeast (yFMO) catalyzes the O 2 -and NADPH-dependent oxidations of biological thiols, including oxidation of glutathione to glutathione disulfide (GSSG). Glutathione and GSSG form the principle redox buffering system in the cell, with the endoplasmic reticulum (ER) being more oxidizing than the cytoplasm. Proper folding of disulfide-bonded proteins in the ER depends on an optimum redox buffer ratio. Here we show that yFMO is localized to the cytoplasmic side of the ER membrane. We used a gene knockout strain and expression vectors to show that yFMO has a major effect on the generation of GSSG transported into the ER. The enzyme is required for the proper folding, in the ER, of test proteins with disulfide bonds, whereas those without disulfide bonds are properly folded independently of yFMO in the ER or in the cytoplasm.

The postoperative drainage volumes varied greatly because of differences in the outer membrane permeability of CSDH, and such variation seems to be related to the findings on the CT scans obtained preoperatively. Patients with CSDH in whom there is less postoperative drainage than expected should be carefully observed, with special attention paid to the possibility of recurrence.

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