A previously uncharacterized two-component signaling system in uropathogenic Escherichia coli coordinates protection against host-derived oxidative stress with activation of hemolysin-mediated host cell pyroptosis

Uropathogenic Escherichia coli (UPEC) deploy an array of virulence factors to successfully establish urinary tract infections. Hemolysin is a pore-forming toxin, and its expression correlates with the severity of UPEC infection. Two-component signaling systems (TCSs) are a major mechanism by which bacteria sense environmental cues and respond by initiating adaptive responses. Here, we began this study by characterizing a novel TCS (C3564/C3565, herein renamed orhK/orhR for oxidative resistance and hemolysis kinase/regulator) that is encoded on a UPEC pathogenicity island, using bioinformatic and biochemical approaches. A prevalence analysis indicates that orhK/orhR is highly associated with the UPEC pathotype, and it rarely occurs in other E. coli pathotypes tested. We then demonstrated that OrhK/OrhR directly activates the expression of a putative methionine sulfoxide reductase system (C3566/C3567) and hemolysin (HlyA) in response to host-derived hydrogen peroxide (H₂O₂) exposure. OrhK/OrhR increases UPEC resistance to H₂O₂ in vitro and survival in macrophages in cell culture via C3566/C3567. Additionally, OrhK/OrhR mediates hemolysin-induced renal epithelial cell and macrophage death via a pyroptosis pathway. Reducing intracellular H₂O₂ production by a chemical inhibitor impaired OrhK/OrhR-mediated activation of c3566-c3567 and hlyA. We also uncovered that UPEC links the two key virulence traits by cotranscribing the c3566-c3567 and hlyCABD operons. Taken together, our data suggest a paradigm in which a signal transduction system coordinates both bacterial pathogen defensive and offensive traits in the presence of host-derived signals; and this exquisite mechanism likely contributes to hemolysin-induced severe pathological outcomes.     

Two-dimensional Cu and first Pb coordination polymers based on a flexible 1,4-cyclohexanedicarboxylate ligand displaying different conformations and coordination modes

Two novel metal-organic hybrid coordination polymers {[Cu(bpo)(chdc)(H₂O)](H₂O)_0.5}_n (1) and [Pb(chdc)(H₂O)]_n (2) have been synthesized under different conditions and structurally characterized by single-crystal X-ray diffraction technique, where H₂chdc refers to a flexible 1,4-cyclohexanedicarboxylic acid ligand and bpo is 2,5-bis(4-pyridyl)-1,3,4-oxadiazole. Complex 1 has a two-dimensional (2-D) grid-like [11.28 × 13.63 Å²] framework in which the Cu^II centers are extended via bidentate bridging ligands bpo and e,e-trans-chdc along two directions, exhibiting large porous cavities. Coordination polymer 2 represents the first Pb^II complex of H₂chdc in which the larger Pb^II centers are connected by e,a-cis-chdc anions to afford a 2-D close-knit structure.     

Effects of sap velocity on the daytime increase of stem CO2 efflux from stems of Schima superba trees

Stem CO₂ efflux (E _s) has been estimated from a temperature-related equation, but sap flux often affects measurements of E _s, which leads to misunderstanding real stem respiration. In order to observe the relationship between E _s and stem temperature and to analyze the effect of sap velocity on E _s, stem temperature, E _s and sap flux were measured from a subtropical Schima superba plantation in South China on three trees for consecutive 3 days in July and October 2009. Stem temperature, E _s and sap velocity were significantly higher in July than in October. Stem temperature could explain 17–41 and 54–75% variations of E _s in July and October, respectively. A negative relationship between E _s and stem temperature was found during 1800–2300 hours in July. The daytime E _s was 9.2, 4.3 and 2.4% higher than the predicted for three trees in July, and this occurred only on Tree 1 in October. Sap velocity was positively correlated with E _s for three trees in July, and the increase of E _s with the increase of sap velocity was only observed on Tree 1 in October. These results demonstrated that the occurrence of sap flux could account for the increase of daytime E _s, and the effect of sap velocity on E _s varied with the seasons from the S. superba stem.     

Over-expression of OSRIP18 increases drought and salt tolerance in transgenic rice plants

Both drought and high salinity stresses are major abiotic factors that limit the yield of agricultural crops. Transgenic techniques have been regarded as effective ways to improve crops in their tolerance to these abiotic stresses. Functional characterization of genes is the prerequisite to identify candidates for such improvement. Here, we have investigated the biological functions of an Oryza sativa Ribosome-inactivating protein gene 18 (OSRIP18) by ectopically expressing this gene under the control of CaMV 35S promoter in the rice genome. We have generated 11 independent transgenic rice plants and all of them showed significantly increased tolerance to drought and high salinity stresses. Global gene expression changes by Microarray analysis showed that more than 100 probe sets were detected with up-regulated expression abundance while signals from only three probe sets were down-regulated after over-expression of OSRIP18. Most of them were not regulated by drought or high salinity stresses. Our data suggested that the increased tolerance to these abiotic stresses in transgenic plants might be due to up-regulation of some stress-dependent/independent genes and OSRIP18 may be potentially useful in further improving plant tolerance to various abiotic stresses by over-expression.     

Regio- and stereo-selective synthesis of vinyl glucose ester catalyzed by an alkaline protease of Bacillus subtilis

The transesterification of -d-glucose with divinylsuccinate, divinyladipate and divinylsebacate in pyridine at 55 °C for 3 days was catalyzed by an alkaline protease from Bacillus subtilis to give corresponding 6-O-vinyl glucose esters at 30%, 53% and 35% yield, respectively. The stereo-selectivity of the alkaline protease toward the -anomer was affected by the acyl donor chain length. 6-O-Vinylsuccinyl-d-glucose was mixture of - and -anomers (/=44/56), the other two products were the pure -d-glucose derivatives.     

Variations in sexual and asexual reproduction of Scirpus mariqueter along an elevational gradient

In order to assess the importance of sexual and asexual reproduction during the life history of Scirpus mariqueter, its reproductive and growth characters were concurrently examined along an elevational gradient (from low elevation to high elevation). The proportions of flowering shoot and inflorescence mass, seed : flower ratio and seed weight were used to quantify the investment in sexual reproduction. The proportions of current-year shoot and rhizome mass were used to quantify the investment in asexual reproduction, and the proportion of corm mass was used for growth, respectively. It was found that vegetative propagation predominated at low elevation, whereas sexual reproduction predominated at high elevation; and that sexual reproduction increased with declining asexual reproduction along the gradient. The results suggest that asexual reproduction is relatively favored in the early life stage, whereas sexual reproduction is favored when the population becomes mature and aged, probably because of the functional differentiation between the two reproductive types. Sexual productive characters (i.e. the proportions of flowering shoot and inflorescence mass) were negatively correlated to both growth and asexual reproductive characters along the gradient, indicating there might exist some trade-offs among growth, sexual and asexual reproduction during the life history. However, no obvious pattern was found between asexual reproductive characters and growth characters along the elevational gradient, possibly because of the varied relationships between them at different life stages. The variations in sexual and asexual reproduction in the species and the relationship between them are thought to be of great significance for local population growth, species persistence and evolution.     

Design,synthesis and biological evaluation of hypolipidemic compounds based on BRD4 inhibitor RVX-208

Bromodomain-containing protein 4 (BRD4) is a new therapeutic target for the treatment of diseases including cardiovascular diseases, cancer, inflammation and central nervous system (CNS) disorders. In this study, we introduced the pharmacophore of fibrates to a BRD4 inhibitor, RVX-208, to design dual-active hypolipidemic compounds, and found that some of new analogues showed favorable hypolipidemic activities. Synthetic accessibility towards this class of compounds optimized RVX-208 as well as would supply more thoughts on hypolipidemic drugs.     

Drug resistance‐related microRNAs in osteosarcoma: Translating basic evidence into therapeutic strategies

Although the application of multiple chemotherapy brought revolutionary changes to improve overall survival of osteosarcoma patients, the existence of multidrug resistance (MDR) has become a great challenge for successful osteosarcoma treatment in recent decades. Substantial studies have revealed various underlying mechanisms of MDR in cancers. As for osteosarcoma, evidence has highlighted that microRNAs (miRNAs) can mediate in the processes of DNA damage response, apoptosis avoidance, autophagy induction, activation of cancer stem cells, and signal transduction. Besides, these drug resistance‐related miRNAs showed much promise for serving as candidates for predictive biomarkers of poor outcomes and shorter survival time, and therapeutic targets to reverse drug resistance and overcome treatment refractoriness. This review aims to demonstrate the potential molecular mechanisms of miRNAs‐regulated drug resistance in osteosarcoma, and provide insight in translating basic evidence into therapeutic strategies.     

Discovery of genomic regions and candidate genes controlling shelling percentage using QTL‐seq approach in cultivated peanut (Arachis hypogaea L.)

Cultivated peanut (Arachis hypogaea L.) is an important grain legume providing high‐quality cooking oil, rich proteins and other nutrients. Shelling percentage (SP) is the 2nd most important agronomic trait after pod yield and this trait significantly affects the economic value of peanut in the market. Deployment of diagnostic markers through genomics‐assisted breeding (GAB) can accelerate the process of developing improved varieties with enhanced SP. In this context, we deployed the QTL‐seq approach to identify genomic regions and candidate genes controlling SP in a recombinant inbred line population (Yuanza 9102 × Xuzhou 68‐4). Four libraries (two parents and two extreme bulks) were constructed and sequenced, generating 456.89–790.32 million reads and achieving 91.85%–93.18% genome coverage and 14.04–21.37 mean read depth. Comprehensive analysis of two sets of data (Yuanza 9102/two bulks and Xuzhou 68‐4/two bulks) using the QTL‐seq pipeline resulted in discovery of two overlapped genomic regions (2.75 Mb on A09 and 1.1 Mb on B02). Nine candidate genes affected by 10 SNPs with non‐synonymous effects or in UTRs were identified in these regions for SP. Cost‐effective KASP (Kompetitive Allele‐Specific PCR) markers were developed for one SNP from A09 and three SNPs from B02 chromosome. Genotyping of the mapping population with these newly developed KASP markers confirmed the major control and stable expressions of these genomic regions across five environments. The identified candidate genomic regions and genes for SP further provide opportunity for gene cloning and deployment of diagnostic markers in molecular breeding for achieving high SP in improved varieties.