A DFT study of the structure–property relationships of bistetrazole-based high-nitrogen energetic metal complexes

In this work, six series of new energetic metal complexes were designed. Each complex contained a large, high-energy, high-nitrogen, anionic chelating ligand (either the 5,5′-bistetrazolate anion, the 5,5′-azobistetrazolate anion, or the 5,5′-(hydrazine-1,2-diyl)bis-[1H-tetrazol-1-ide] anion—each of which has a different bridging group), Cu or Ni as the metal atom, and two small complexing agent ligands (NH₃ and/or NH₂NO₂). The molecular and electronic structures, heats of formation, densities, detonation properties, and impact sensitivities of the novel complexes were studied using density functional theory. Furthermore, the effects of varying the large chelating ligand (and thus the bridging group), the small complexing agents, and the metal atom on the structure and properties of the complex were investigated and analyzed in depth. The results show that the particular metal, bridging group, and complexing agents included in the energetic complex influence its structure and properties, but the effects of varying the constituents of the complex are complicated or unclear, and these effects are sometimes intertwined. In addition, the detonation pressures, detonation velocities, and impact sensitivities of the novel complexes ranged from 25.9 to 38.6 GPa, from 7.21 to 8.80 km s^?1, and from 17 to 48 cm, respectively. Five of the complexes (B3, C3, D3, E3, and F3) appear to possess comparable performance to the famous and widely used high explosive 1,3,5-trinitro-1,3,5-triazinane, making these new complexes attractive to energetic materials experimentalists.     

Enhancement of the thermal and alkaline pH stability of <Emphasis Type="Italic">Escherichia coli</Emphasis> lysine decarboxylase for efficient cadaverine production

Objective

To enhance the thermal and alkaline pH stability of the lysine decarboxylase from Escherichia coli (CadA) by engineering the decameric interface and explore its potential for industrial applications.

Results

The mutant T88S was designed for improved structural stability by computational analysis. The optimal pH and temperature of T88S were 7.0 and 55 °C (5.5 and 50 °C for wild-type). T88S showed higher thermostability with a 2.9-fold increase in the half-life at 70 °C (from 11 to 32 min) and increased melting temperature (from 76 to 78 °C). Additionally, the specific activity and pH stability (residual activity after 10 h incubation) of T88S at pH 8.0 were increased to 164 U/mg and 78% (58 U/mg and 57% for wild-type). The productivity of cadaverine with T88S (284 g l-lysine L^?1 and 5 g DCW L^?1) was 40 g L^?1 h^?1, in contrast to 28 g L^?1 h^?1 with wild-type.

Conclusion

The mutant T88S showed high thermostability, pH stability, and activity at alkaline pH, indicating that this mutant is a promising biocatalyst for industrial production of cadaverine.

     

Mediator mechanisms involved in TRPV1 and P2X receptor-mediated, ROS-evoked bradypneic reflex in anesthetized rats.

Inhalation of H2O2 is known to evoke bradypnea followed by tachypnea, which are reflexes resulting from stimulation by reactive oxygen species of vagal lung capsaicin-sensitive and myelinated afferents, respectively. This study investigated the pharmacological receptors and chemical mediators involved in triggering these responses. The ventilatory responses to 0.2% aerosolized H2O2 were studied before and after various pharmacological pretreatments in anesthetized rats. The initial bradypneic response was reduced by a transient receptor potential vanilloid 1 (TRPV1) receptor antagonist [capsazepine; change (Delta) = -53%] or a P2X purinoceptor antagonist [iso-pyridoxalphosphate-6-azophenyl-2',5'-disulphonate (PPADS); Delta = -47%] and was further reduced by capsazepine and iso-PPADS in combination (Delta = -78%). The initial bradypneic response was reduced by a cyclooxygenase inhibitor (indomethacin; Delta = -48%), ATP scavengers (apyrase and adenosine deaminase in combination; Delta = -50%), or capsazepine and indomethacin in combination (Delta = -47%), was further reduced by iso-PPADS and indomethacin in combination (Delta = -75%) or capsazepine and ATP scavengers in combination (Delta = -83%), but was not affected by a lipoxygenase inhibitor (nordihydroguaiaretic acid) or by any of the various vehicles. No pretreatment influenced delayed tachypnea. We concluded that 1) the initial bradypneic response to H2O2 results from activation of both TRPV1 and P2X receptors, possibly located at terminals of vagal lung capsaicin-sensitive afferent fibers; 2) the functioning of the TRPV1 and P2X receptors in triggering the initial bradypnea is, in part, mediated through the actions of cyclooxygenase metabolites and ATP, respectively; and 3) these mechanisms do not contribute to the H2O2-evoked delayed tachypnea.     

The Cancer Mutation D83V Induces an α-Helix to β-Strand Conformation Switch in MEF2B

MEF2B is a major target of somatic mutations in non-Hodgkin lymphoma. Most of these mutations are non-synonymous substitutions of surface residues in the MADS-box/MEF2 domain. Among them, D83V is the most frequent mutation found in tumor cells. The link between this hotspot mutation and cancer is not well understood. Here we show that the D83V mutation induces a dramatic α-helix to β-strand switch in the MEF2 domain. Located in an α-helix region rich in β-branched residues, the D83V mutation not only removes the extensive helix stabilization interactions but also introduces an additional β-branched residue that further shifts the conformation equilibrium from α-helix to β-strand. Cross-database analyses of cancer mutations and chameleon sequences revealed a number of well-known cancer targets harboring β-strand favoring mutations in chameleon α-helices, suggesting a commonality of such conformational switch in certain cancers and a new factor to consider when stratifying the rapidly expanding cancer mutation data.     

Characterization of a Novel Intestinal Glycerol-3-phosphate Acyltransferase Pathway and Its Role in Lipid Homeostasis

Dietary triglycerides (TG) are absorbed by the enterocytes of the small intestine after luminal hydrolysis into monacylglycerol and fatty acids. Before secretion on chylomicrons, these lipids are reesterified into TG, primarily through the monoacylglycerol pathway. However, targeted deletion of the primary murine monoacylglycerol acyltransferase does not quantitatively affect lipid absorption, suggesting the existence of alternative pathways. Therefore, we investigated the role of the glycerol 3-phosphate pathway in dietary lipid absorption. The expression of glycerol-3-phosphate acyltransferase (GPAT3) was examined throughout the small intestine. To evaluate the role for GPAT3 in lipid absorption, mice harboring a disrupted GPAT3 gene (Gpat3^−/−) were subjected to an oral lipid challenge and fed a Western-type diet to characterize the role in lipid and cholesterol homeostasis. Additional mechanistic studies were performed in primary enterocytes. GPAT3 was abundantly expressed in the apical surface of enterocytes in the small intestine. After an oral lipid bolus, Gpat3^−/− mice exhibited attenuated plasma TG excursion and accumulated lipid in the enterocytes. Electron microscopy studies revealed a lack of lipids in the lamina propria and intercellular space in Gpat3^−/− mice. Gpat3^−/− enterocytes displayed a compensatory increase in the synthesis of phospholipid and cholesteryl ester. When fed a Western-type diet, hepatic TG and cholesteryl ester accumulation was significantly higher in Gpat3^−/− mice compared with the wild-type mice accompanied by elevated levels of alanine aminotransferase, a marker of liver injury. Dysregulation of bile acid metabolism was also evident in Gpat3-null mice. These studies identify GPAT3 as a novel enzyme involved in intestinal lipid metabolism.     

Diploid hybrid origin of Hippophaë gyantsensis (Elaeagnaceae) in the western Qinghai–Tibet Plateau

Homoploid hybrid speciation, the origin of a hybrid species without change in chromosome number, is currently considered to be a rare form of speciation. In the present study, we examined the phylogenetic origin of Hippophaë gyantsensis, a diploid species occurring in the western Qinghai–Tibet Plateau. Some of its morphological and molecular traits suggest a close relationship to H. rhamnoides ssp. yunnanensis while others indicate H. neurocarpa. We conducted phylogenetic analyses of sequence data of two maternally inherited chloroplast (cp) DNA fragments and the bi‐parentally inherited nuclear ribosomal internal transcribed spacer (ITS) from 17 populations of H. gyantsensis, 15 populations of H. rhamnoides ssp. yunnanensis and 27 populations of H. neurocarpa across their distributional ranges, and modelled the niche differentiation of the three taxa. Multiple lines of evidence suggested that H. gyantsensis is a morphologically stable, genetically independent and ecologically distinct species. The inconsistent phylogenetic placements of the H. gyantsensis clade that comprised the dominant cpDNA haplotypes and ITS ribotypes suggested a probable diploid hybrid origin from multiple crosses between H. rhamnoides ssp. yunnanensis and H. neurocarpa. This tentative hypothesis is more parsimonious than alternative explanations according to the data available, although more evidence based on further testing is needed.     

Didymodon liae sp. nov. (Pottiaceae) from Tibet,China

Didymodon liae J. Kou, X.‐M. Shao & C. Feng sp. nov., is described and illustrated from Dagzê County in south central Tibet, China. The new species is most similar to Didymodon australasiae (Hook. & Grev.) R. H. Zander, but differs in plants growing loosely in a thin turf, stems without hyalodermis and sclerodermis, margins recurved from just above the base nearly to the apex, laminal cells strongly bulging, mammillose, covered with simple or forked papillae, and costa with a layer of ventral substereids. The new species is contrasted with other similar species of the genus. Information on its distribution and ecology is also provided.     

Dynamic reprogramming of histone acetylation and methylation in the first cell cycle of cloned mouse embryos

Epigenetic reprogramming is thought to play an important role in the development of cloned embryos reconstructed by somatic cell nuclear transfer (SCNT). In the present study, dynamic reprogramming of histone acetylation and methylation modifications was investigated in the first cell cycle of cloned embryos. Our results demonstrated that part of somatic inherited lysine acetylation on core histones (H3K9, H3K14, H4K16) could be quickly deacetylated following SCNT, and reacetylation occurred following activation treatment. However, acetylation marks of the other lysine residues on core histones (H4K8, H4K12) persisted in the genome of cloned embryos with only mild deacetylation occurring in the process of SCNT and activation treatment. The somatic cloned embryos established histone acetylation modifications resembling those in normal embryos produced by intracytoplasmic sperm injection through these two different programs. Moreover, treatment of cloned embryos with a histone deacetylase inhibitor, Trichostatin A (TSA), improved the histone acetylation in a manner similar to that in normal embryos, and the improved histone acetylation in cloned embryos treated with TSA might contribute to improved development of TSA-treated clones. In contrast to the asymmetric histone H3K9 tri- and dimethylation present in the parental genomes of fertilized embryos, the tri- and dimethylations of H3K9 were gradually demethylated in the cloned embryos, and this histone H3K9 demethylation may be crucial for gene activation of cloned embryos. Together, our results indicate that dynamic reprogramming of histone acetylation and methylation modifications in cloned embryos is developmentally regulated.