Membrane lipids are both the substrates and a mechanistically responsive environment of TMEM16 scramblase proteins

Recent discoveries about functional mechanisms of proteins in the TMEM16 family of phospholipid scramblases have illuminated the dual role of the membrane as both the substrate and a mechanistically responsive environment in the wide range of physiological processes and genetic disorders in which they are implicated. This is highlighted in the review of recent findings from our collaborative investigations of molecular mechanisms of TMEM16 scramblases that emerged from iterative functional, structural, and computational experimentation. In the context of this review, we present new MD simulations and trajectory analyses motivated by the fact that new structural information about the TMEM16 scramblases is emerging from cryo-EM determinations in lipid nanodiscs. Because the functional environment of these proteins in in vivo and in in vitro is closer to flat membranes, we studied comparatively the responses of the membrane to the TMEM16 proteins in flat membranes and nanodiscs. We find that bilayer shapes in the nanodiscs are very different from those observed in the flat membrane systems, but the function-related slanting of the membrane observed at the nhTMEM16 boundary with the protein is similar in the nanodiscs and in the flat bilayers. This changes, however, in the bilayer composed of longer-tail lipids, which is thicker near the phospholipid translocation pathway, which may reflect an enhanced tendency of the long tails to penetrate the pathway and create, as shown previously, a nonconductive environment. These findings support the correspondence between the mechanistic involvement of the lipid environment in the flat membranes, and the nanodiscs. © 2019 Wiley Periodicals, Inc.     

Initiation of Protein Synthesis with Non-Canonical Amino Acids In Vivo

By transplanting identity elements into E. coli tRNA^fMet, we have engineered an orthogonal initiator tRNA (itRNA^Ty2) that is a substrate for Methanocaldococcus jannaschii TyrRS. We demonstrate that itRNA^Ty2 can initiate translation in vivo with aromatic non-canonical amino acids (ncAAs) bearing diverse sidechains. Although the initial system suffered from low yields, deleting redundant copies of tRNA^fMet from the genome afforded an E. coli strain in which the efficiency of non-canonical initiation equals elongation. With this improved system we produced a protein containing two distinct ncAAs at the first and second positions, an initial step towards producing completely unnatural polypeptides in vivo. This work provides a valuable tool to synthetic biology and demonstrates remarkable versatility of the E. coli translational machinery for initiation with ncAAs in vivo.     

Spectroscopic and Morphological Study of Irradiated PVC Films Doped with Polyphosphates Containing 4,4'-Methylenedianiline

Russian Journal of Applied Chemistry - Polyphosphates containing 4,4'-methylenedianiline moiety were synthesized and their use as polyvinyl chloride (PVC) additives to enhance PVC...     

Initiation of Protein Synthesis with Non‐Canonical Amino Acids In Vivo

By transplanting identity elements into E. coli tRNA^fMet, we have engineered an orthogonal initiator tRNA (itRNA^Ty2) that is a substrate for Methanocaldococcus jannaschii TyrRS. We demonstrate that itRNA^Ty2 can initiate translation in vivo with aromatic non‐canonical amino acids (ncAAs) bearing diverse sidechains. Although the initial system suffered from low yields, deleting redundant copies of tRNA^fMet from the genome afforded an E. coli strain in which the efficiency of non‐canonical initiation equals elongation. With this improved system we produced a protein containing two distinct ncAAs at the first and second positions, an initial step towards producing completely unnatural polypeptides in vivo. This work provides a valuable tool to synthetic biology and demonstrates remarkable versatility of the E. coli translational machinery for initiation with ncAAs in vivo.     

Nephroprotective Effects of Alhagi camelorum against Cisplatin-Induced Nephrotoxicity in Albino Wistar Rats

Alhagi camelorum (AC) is an old plant with a significant therapeutic value throughout Africa, Asia, and Latin America. The overuse of cisplatin (Cis > 50 mg/m²) is associated with observed nephrotoxicity, ototoxicity, gastrotoxicity, myelosuppression, and allergic reactions. Remedial measures are needed for the protection of nephrotoxicity against cisplatin. Thus, we investigated the nephroprotective effects of AC plant extract to prevent cisplatin-induced nephrotoxicity in albino Wistar rats. The presence of polyphenols, phenolic compounds, tannins, and saponins was revealed during phytochemical investigation, and a significantly intense antioxidant activity was recorded. There were no toxicological symptoms in the treated rats, and no anatomical, physiological, or histological abnormalities were found compared to the control rats. The results of correcting cisplatin-induced nephrotoxicity revealed that the extract has a significant ability to treat kidney damage, with most parameters returning to normal after only three weeks of therapy. It is concluded that co-administration of cisplatin with AC extract showed exceptional nephroprotective effects at a dose of 600 mg/kg for Cis-induced nephrotoxicity.     

Decomposition of triacetone triperoxide is an entropic explosion

Both X-ray crystallography and electronic structure calculations using the cc-pVDZ basis set at the DFT B3LYP level were employed to study the explosive properties of triacetone triperoxide (TATP) and diacetone diperoxide (DADP). The thermal decomposition pathway of TATP was investigated by a series of calculations that identified transition states, intermediates, and the final products. Counterintuitively, these calculations predict that the explosion of TATP is not a thermochemically highly favored event. It rather involves entropy burst, which is the result of formation of one ozone and three acetone molecules from every molecule of TATP in the solid state.     

Simple bounds for closed queueing networks

Consider a closed Jackson type network in which each queue has a single exponential server. Assume that N customers are moving among k queues. We establish simple closed form bounds on the network throughput (both lower and upper), which are sharper than those that are currently available. Numerical evaluation indicates that the improvements are significant.     

Reduction electrochimique des oxydes de fer: Confrontation des caracteristiques electrochimiques et crist allographiques

Electrochemical properties of iron oxides, crystallographic data and examination of etching pits by scanning electron microscopy, suggest that ferric iron has electrochemical reactivity which differs according to its crystallographic position in the solid.     

Time-of-flight flow imaging using NMR remote detection

A time-of-flight imaging technique is introduced to visualize fluid flow and dispersion through porous media using NMR. As the fluid flows through a sample, the nuclear spin magnetization is modulated by rf pulses and magnetic field gradients to encode the spatial coordinates of the fluid. When the fluid leaves the sample, its magnetization is recorded by a second rf coil. This scheme not only facilitates a time-dependent imaging of fluid flow, it also allows a separate optimization of encoding and detection subsystems to enhance overall sensitivity. The technique is demonstrated by imaging gas flow through a porous rock.     

Role of copper species in the oxidative dimerization of arylboronic acids: synthesis of symmetrical biaryls

Certain Cu(I) and Cu(II) salts are able to mediate the dimerization of arylboronic acids in DMF. They provide the corresponding symmetrical biaryls in moderate to very good yields. It is possible to run the reaction catalytically under an oxygen atmosphere without a significant loss of yields.