Transmembrane region of N-methyl-D-aspartate receptor (NMDAR) subunit is required for receptor subunit assembly

N-Methyl-D-aspartate receptors (NMDARs), one of three main classes of ionotropic glutamate receptors, play major roles in synaptic plasticity, synaptogenesis, and excitotoxicity. Unlike non-NMDA receptors, NMDARs are thought to comprise obligatory heterotetrameric complexes mainly composed of GluN1 and GluN2 subunits. When expressed alone in heterogenous cells, such as HEK293 cells, most of the NMDAR subunits can neither leave the endoplasmic reticulum (ER) nor be expressed in the cell membrane because of the ER retention signals. Only when NMDARs are heteromerically assembled can the ER retention signals be masked and NMDARs be expressed in the surface membrane. However, the mechanisms underlying NMDAR assembly remain poorly understood. To identify regions in subunits that mediate this assembly, we made a series of truncated or chimeric cDNA constructs. Using FRET measurement in living cells combined with immunostaining and coimmunoprecipitation analysis, we examined the assembly-determining domains of NMDAR subunits. Our results indicate that the transmembrane region of subunits is necessary for the assembly of NMDAR subunits, both for the homodimer and the heteromer.     

Biosynthesis of docosahexaenoic acid (DHA, 22:6-4, 7,10,13,16,19): two distinct pathways

Docosahexaenoic acid (DHA) has long been recognized for its beneficial effect in humans, but its biosynthetic pathway has not been clearly established until recently. According to Sprecher, in mammals, DHA is synthesized via a retro-conversion process in peroxisomes-the aerobic delta4 desaturation-independent pathway. Recent identification of a Thraustochytrium delta4 desaturase indicates that delta4 desaturation is indeed involved in DHA synthesis in Thraustochytrium. More interestingly, an alternative pathway for DHA biosynthesis-the anaerobic polyketide synthase pathway was also reported recently to occur in Schizochytrium, another member of the Thraustochytriidae. This mini-review attempts to assess the latest research on these distinct pathways for DHA biosynthesis.     

Quinoline-carboxylic acids are potent inhibitors that inhibit the binding of insulin-like growth factor (IGF) to IGF-binding proteins

4-benzylquinolines 5, based on a series of isoquinolines 1, were prepared and tested as inhibitors of the IGF/IGFBP-3 complex based on their ability to displace IGF-I from its binding to IGF-binding protein-3. SAR studies on the 6,7-dihydroxy moiety of the quinoline 5a showed that the catecol moiety could be replaced with other functional groups. Computational modeling of the 5a/mini-IGFBP-5 complex revealed the possible binding site of 5a on IGFBP-5.     

1,4-Disubstituted imidazoles are potential antibacterial agents functioning as inhibitors of enoyl acyl carrier protein reductase (FabI)

1,4-Disubstituted imidazole inhibitors of Staphylococcus aureus and Escherichia coli enoyl acyl carrier protein reductase (FabI) have been identified. Crystal structure data shows the inhibitor 1 bound in the enzyme active site of E. coli FabI.     

The toxicity of cerium nitrate to Elodea canadensis: subcellular distribution,chemical forms and physiological effects

The rare earth elements are increasingly being used as trace supplements in different fields. In this study, subcellular distribution, the chemical forms and toxicity of cerium (Ce) were evaluated for Elodea canadensis. The effect of Ce (5–20 mg L^?1) applied for 7 days was assessed by measuring changes in the nutrient elements, photosynthetic pigments, malondialdehyde and antioxidant systems. Ce accumulation was greatest in the cell walls, followed by the organelles and the soluble fraction. Ce levels were higher in cellulose and pectin than in other biomacromolecules. The toxic effects caused by Ce were shown by a reduction in photosynthetic pigments, disruption of nutrient elements, and increases in MDA content. E. canadensis shows Ce-induced oxidative stress by modulating antioxidant enzymes, such as guaiacol peroxidase and catalase. Elevated Ce levels may represent a potential risk for aquatic ecosystems.     

Functions of EDS1-like and PAD4 genes in grapevine defenses against powdery mildew

The molecular interactions between grapevine and the obligate biotrophic fungus Erysiphe necator are not understood in depth. One reason for this is the recalcitrance of grapevine to genetic modifications. Using defense-related Arabidopsis mutants that are susceptible to pathogens, we were able to analyze key components in grapevine defense responses. We have examined the functions of defense genes associated with the salicylic acid (SA) pathway, including ENHANCED DISEASE SUSCEPTIBILITY 1 (EDS1), EDS1-LIKE 2 (EDL2), EDL5 and PHYTOALEXIN DEFICIENT 4 (PAD4) of two grapevine species, Vitis vinifera cv. Cabernet Sauvignon, which is susceptible to E. necator, and V. aestivalis cv. Norton, which is resistant. Both VaEDS1 and VvEDS1 were previously found to functionally complement the Arabidopsis eds1-1 mutant. Here we show that the promoters of both VaEDS1 and VvEDS1 were induced by SA, indicating that the heightened defense of Norton is related to its high SA level. Other than Va/VvEDS1, only VaEDL2 complemented Arabidopsis eds1-1, whereas Va/VvPAD4 did not complement Arabidopsis pad4-1. Bimolecular fluorescence complementation results indicated that Vitis EDS1 and EDL2 proteins interact with Vitis PAD4 and AtPAD4, suggesting that Vitis EDS1/EDL2 forms a complex with PAD4 to confer resistance, as is known from Arabidopsis. However, Vitis EDL5 and PAD4 did not interact with Arabidopsis EDS1 or PAD4, correlating with their inability to function in Arabidopsis. Together, our study suggests a more complicated EDS1/PAD4 module in grapevine and provides insight into molecular mechanisms that determine disease resistance levels in Vitis species native to the North American continent.     

Maslinic acid protects vascular smooth muscle cells from oxidative stress through Akt/Nrf2/HO-1 pathway

Maslinic acid (MA) is a natural triterpenoid widely distributed in edible and medicinal plants and has been demonstrated to possess bioactivity. However, its effect on vascular smooth muscle cells (VSMC) has not been explored yet. In this study, we found that heme oxygenase-1 (HO-1) expression was increased in VSMCs treated with MA. Furthermore, MA was found to induce Akt activation in a dose- and time-dependent manner. Wortmannin suppression of Akt was able to abolish HO-1 upregulation in VSMCs, suggesting the requirement of Akt activation for MA effect on HO-1. Further investigation indicated that Akt activation resulted in the elevated expression of Nrf2, a HO-1 promoter, in MA-treated VMSCs. Finally, we found that MA was able to protect VSMCs from oxidative stress induced by H₂O₂. Blocking the activation of Akt/Nrf2/HO-1 was able to compromise the protective effect of MA on VSMCs. Collectively, we provided evidence that MA protected VMSCs from oxidative stress through Akt/Nrf2/HO-1 pathway.     

First Report of Dragon Fruit (Hylocereus undatus) Anthracnose Caused by Colletotrichum truncatum in China

Anthracnose disease was detected from dragon fruit (Hylocereus undatus) at a market of Yuanjiang County, Yunnan Province, China. The results of pathogenicity test, morphology studies and sequence analyses based on ITS and β‐tubulin loci indicated that the disease was caused by Colletotrichum truncatum. The pathogen produced elliptic, yellow spots with chlorotic halos on the surface of the fruit, and the lesion become depressed gradually. Grey to black acervuli appeared on the lesion surface in concentric circles later. This is the first report of dragon fruit anthracnose caused by this pathogen in China.