Structural analysis of the intracellular domain of (pro)renin receptor fused to maltose-binding protein

In Synechocystis sp. PCC 6803, the loop domain (aa 1–70) of the phycobilisome core-membrane linker, L_CM, was found to interact with the glycosyl transferase homolog, Sll1466. Growth of a Sll1466 knock-out mutant was slightly faster in low light, but strongly inhibited in high light; the phenotype is discussed in relation to the regulation of light energy transfer to photosystem II. At the molecular level, the mutant shows the following changes compared to the wild type: (1) a smaller size and higher mobility of phycobilisomes on the thylakoid membrane, and (2) a changed lipid composition of the thylakoid membrane, especially decreased amounts of digalactosyl diacylglycerol. These results indicate a profound regulatory role for Sll1466 in regulating photosynthetic energy transfer.     

Influence of organic co-solvents on the activity and substrate specificity of feruloyl esterases

Organic co-solvents can expand the use of enzymes in lignocellulose deconstruction through making substrates more soluble and thus more accessible. In choosing the most adequate co-solvent for feruloyl esterases, hydrolysis of methyl p-hydroxycinnamates by three pure enzymes (and a multi-enzyme preparation) was evaluated. Low concentrations of dimethylsulfoxide (DMSO) enhanced hydrolysis by two of the enzymes while at levels >20%, activity was reduced. DMSO also enhanced acetyl esterase-type activity of the enzymes. The co-solvent effect was different for each enzyme-substrate couple, indicating that other factors are also involved. Kinetic studies with a Talaromyces stipitatus feruloyl esterase showed low concentrations of dimethylsulfoxide enhanced the hydrolytic rate while K_m also increased. Moreover, long-term incubation (96 h) of an Aspergillus niger feruloyl esterase in dimethylsulfoxide:water provided to the enzyme the ability to hydrolyze methyl p-coumarate, suggesting an active-site re-arrangement. Dimethylsulfoxide (10-30%) is proposed as an adequate co-solvent for feruloyl esterase treatment of water-insoluble substrates.     

The inhibitory action of exo- and endocannabinoids on [³H]GABA release are mediated by both CB₁and CB₂receptors in the mouse hippocampus

Exogenous and endogenous cannabinoids play an important role in modulating the release of neurotransmitters in hippocampal excitatory and inhibitory networks, thus having profound effect on higher cognitive and emotional functions such as learning and memory. In this study we have studied the effect of cannabinoid agonists on the potassium depolarization-evoked [(3)H]GABA release from hippocampal synaptosomes in the wild-type (WT) and cannabinoid 1 receptor (CB(1)R)-null mutant mice. All tested cannabinoid agonists (WIN55,212-2, CP55,940, HU-210, 2-arachidonoyl-glycerol, 2-AG; delta-9-tetra-hydrocannabinol, THC) inhibited [(3)H]GABA release in WT mice with the following rank order of agonist potency: HU-210>CP55,490>WIN55,212-2>2-AG>THC. By contrast, 2-AG and THC displayed the greatest efficacy eliciting almost complete inhibition of evoked [(3)H]GABA efflux, whereas the maximal inhibition obtained by HU-210, CP55,490, and WIN55,212-2 were less, eliciting not more than 40% inhibition. The inhibitory effect of WIN55,212-2, THC and 2-AG on evoked [(3)H]GABA efflux was antagonized by the CB(1) receptor inverse agonist AM251 (0.5 μM) in the WT mice. In the CB(1)R knockout mice the inhibitory effects of all three agonists were attenuated. In these mice, AM251 did not antagonize, but further reduced the [(3)H]GABA release in the presence of the synthetic agonist WIN55,212-2. By contrast, the concentration-dependent inhibitory effects of THC and 2-AG were partially antagonized by AM251 in the absence of CB(1) receptors. Finally, the inhibition of evoked [(3)H]GABA efflux by THC and 2-AG was also partially attenuated by AM630 (1 μM), the CB(2) receptor-selective antagonist, both in WT and CB(1) knockout mice. Our data prove the involvement of CB(1) receptors in the effect of exo- and endocannabinoids on GABA efflux from hippocampal nerve terminals. In addition, in the effect of the exocannabinoid THC and the endocannabinoid 2-AG, non-CB(1), probably CB(2)-like receptors are also involved.     

New organic bases from amazonian Banisteriopsis caapi

Three new bases were isolated from Banisteriopsis caapi; they are harmine N-oxide, harmic acid methyl ester (methyl 7-methoxy-β-carboline 1-carboxylate) and harmalinic acid (7-methoxy-3,4-dihydro-β-carboline 1-carboxylic acid).     

Synthesis,evaluation and CoMFA/CoMSIA study of nitrofuranyl methyl N-heterocycles as novel antitubercular agents

A series of novel nitrofuranyl methyl N-heterocycles based on the structure of IIIM-MCD-211 were designed and synthesized. Compounds 6d, 8b and 12a show excellent activity against MTB H37Rv strain (MIC: 0.031–0.062?μg/mL) roughly comparable to INH and IIIM-MCD-211. In addition, a three-dimensional quantitative structure-activity relationship (3D-QSAR) study was performed on the above mentioned chemical series employing comparative molecular field analysis (CoMFA) and comparative molecular similarity index analysis (CoMSIA) techniques. The developed CoMFA and CoMSIA models display high external predictability (r²_pred of 0.954 and 0.935, respectively) and good statistical robustness. More importantly, the newly designed compounds 16a and 16b (MIC: <0.016?μg/mL) based on the two models, as expected, were found to be more active than 12a and IIIM-MCD-21. Design and synthesis of more potent nitrofuranyl methyl N-heterocycles as anti-TB agents are currently in progress.     

Endogenous reductions in N-methyl-d-aspartate receptor activity inhibit nitric oxide production in the anoxic freshwater turtle cortex

Increased nitric oxide (NO) production from hypoxic mammalian neurons increases cerebral blood flow (CBF) but also glutamatergic excitotoxicity and DNA fragmentation. Anoxia-tolerant freshwater turtles have evolved NO-independent mechanisms to increase CBF; however, the mechanism(s) of NO regulation are not understood. In turtle cortex, anoxia or NMDAR blockade depressed NO production by 27+/-3% and 41+/-5%, respectively. NMDAR antagonists also reduced the subsequent anoxic decrease in NO by 74+/-6%, suggesting the majority of the anoxic decrease is due to endogenous suppression of NMDAR activity. Prevention of NO-mediated damage during the transition to and from anoxia may be incidental to natural reductions of NMDAR activity in the anoxic turtle cortex.     

Over-expression of Roquin aggravates T cell mediated hepatitis in transgenic mice using T cell specific promoter

Chronic hepatitis is a major cause of liver cancer, so earlier treatment of hepatitis might be reducing liver cancer incidence. Hepatitis can be induced in mice by treatment with Concanavalin A (Con A); the resulting liver injury causes significant CD4⁺ T cell activation and infiltration. In these T cells, Roquin, a ring-type E3 ubiquitin ligase, is activated. To investigate the role of Roquin, we examined Con A-induced liver injury and T cell infiltration in transgenic (Tg) mice overexpressing Roquin specifically in T cells. In Roquin Tg mice, Con A treatment caused greater increases in both the levels of liver injury enzymes and liver tissue apoptosis, as revealed by TUNEL and H&E staining, than wild type (WT) mice. Further, Roquin Tg mice respond to Con A treatment with greater increases in the T cell population, particularly Th17 cells, though Treg cell counts are lower. Roquin overexpression also enhances increases in pro-inflammatory cytokines, including IFN-γ, TNF-α and IL-6, upon liver injury. Furthermore, Roquin regulates the immune response and apoptosis in Con A induced hepatitis via STATs, Bax and Bcl2. These findings suggest that over-expression of Roquin exacerbates T-cell mediated hepatitis.     

Rhodococcus aetherivorans sp. nov., a new species that contains methyl t-butyl ether-degrading actinomycetes

The taxonomic positions of two actinomycetes, strains Bc663 and 10bc312T, provisionally assigned to the genus Rhodococcus were determined using a combination of genotypic and phenotypic properties. The organisms have phenotypic properties typical of members of the genus Rhodococcus and were assigned to the 16S rRNA subgroup which contains Rhodococcus rhodochrous and closely related species. The two strains, which have many phenotypic features in common, belong to the same genomic species albeit one readily separated from Rhodococcus ruber with which they form a distinct phyletic line. The organisms were also distinguished from all of the species classified in the R. rhodochrous subgroup, including R. ruber, using a combination of phenotypic properties. The genotypic and phenotypic data show that strains Bc663 and 10bc312T merit recognition as a new species of Rhodococcus. The name proposed for the new species is Rhodococcus aetherivorans (10bc312T = DSM 44752T = NCIMB 13964T).     

茉莉酸甲酯对花生幼苗生长和抗旱性的影响

经过茉莉酸甲酯处理的花生幼苗,在形态、解剖和生理上都发生变化,其中以１２５ｍｇ／Ｌ处理最显著。处理后的植株幼苗矮化,叶小而厚,叶片贮水细胞大、蒸腾减弱、内源脱落酸和脯氨酸含量增多、过氧化物酶活性加大。由于水分的丧失减少,叶片水分的贮存增加,从而提高幼苗的抗旱性。     

Cytotoxic Constituents and Mechanism from Peganum harmala

Peganum harmala L. is a traditional Chinese and Uygur medicine used to treat cancer. Bioactivity‐guided fractionation was applied to determine the cytotoxic constituents from P. harmala. A novel triterpenoid and a phenolic glycoside were isolated and identified, as well as seven known compounds. The novel metabolites were elucidated to be 3α‐acetoxy‐27‐hydroxyolean‐12‐en‐28‐oic acid methyl ester ( 1 , OA) and N‐acetyl‐9‐syringinoside ( 9 ). Some compounds exhibited potent cytotoxicity against human tumor cells. Among them, OA showed the highest cytotoxicity against human lung cancer cells A549 with an IC₅₀ value of 8.03 ± 0.81 μm . OA had a potent anti‐NSCLC cell activity by interfering with the epidermal growth factor receptor (EGFR) activation and its downstream signaling, and could exert an antiproliferative effect by inactivation of EGFR‐driven antiapoptotic pathway followed by the release of mitochondrial cytochrome c, which might prove to be a promising leading compound for the development of an anti‐lung cancer drug.