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Overeating disorders largely contribute to worldwide incidences of obesity. Available treatments are limited. Here, we discovered that long-term chemogenetic activation of ventrolateral periaqueductal gray (vlPAG) GABAergic cells rescue obesity of high-fat diet-induced obesity (DIO) mice. Thiswas associated with the recovery of enhanced mIPSCs, decreased food intake, increased energy expenditure, and inguinal white adipose tissue (iWAT) browning. In vivo calcium imaging confirmed vlPAG GABAergic suppression for DIO mice, with corresponding reduction in intrinsic excitability. Single-nucleus RNA sequencing identified transcriptional expression changes in GABAergic cell subtypes in DIO mice, highlighting Cacna2d1 as of potential importance. Overexpressing CACNA2D1 in vlPAG GABAergic cells of DIO mice rescued enhanced mIPSCs and calcium response, reversed obesity, and therefore presented here as a potential target for obesity treatment. [ABSTRACT FROM AUTHOR]

The aim of this study was to investigate the antitumor activity of exopolysaccharide (EPS) isolated from Lactobacillus helveticus MB2-1. Crude EPS from L. helveticus MB2-1 (LHEPS) was divided into three fractions (LHEPS-1, LHEPS-2, and LHEPS-3). Compared with LHEPS-2 and LHEPS-3, LHEPS-1 exhibited stronger growth inhibition against HepG-2 cells. Thus, the antitumor mechanism of LHEPS-1 with 100 and 600 μg/mL on the HepG-2 cells was evaluated, and we found that LHEPS-1 could enhance the release of lactate dehydrogenase (LDH) in cell culture medium and the amount of reactive oxygen species (ROS). Morphological analysis was performed and indicated that LHEPS-1 could promote HepG-2 cell apoptosis. Additionally, flow cytometric analysis showed that LHEPS-1 exerted a stimulatory effect on apoptosis of HepG-2 cells and induced the cell-cycle arrest at the G2/M phase. Moreover, caspase-3 and caspase-9 could be activated by LHEPS-1, and the results indicated that the induction of caspase-3 and caspase-9 activities may be involved in LHEPS-1-induced apoptosis. [ABSTRACT FROM AUTHOR]

Recently, we published the extraction, purification, and characterization of exopolysaccharide (EPS) from Lactobacillus helveticus MB2-1. In this study, the selective cytotoxic effects of LHEPS-3 fraction isolated from EPS of L. helveticus MB2-1 against human HepG-2 liver cancer cells and human HT29 colon cancer cells were evaluated. Results indicated that LHEPS-3 could significantly inhibit the proliferation of HepG-2 and HT29 cells in a dose- and time-dependent manner, and the inhibitory effects on HepG-2 cells were better than HT29 cells. In addition, with the increase of LHEPS-3 concentration (0–600 μg/mL), the incubation time (0–48 h), and the migration rate of HepG-2 cells gradually decreased. LHEPS-3 could also inhibit the neovascularization of chicken embryo chorioallantoic membrane (CAM) in a dose-dependent manner. Furthermore, the structure of LHEPS-3 was clarified by methylated analysis, one- and two-dimensional nuclear magnetic resonance (1D and 2D NMR), thereby the repeating units of LHEPS-3 were predicted. [ABSTRACT FROM AUTHOR]

In this paper, based on the statistical data, we investigate the effects of long-term exposure to ambient particulate air pollution on the transmission dynamics of tuberculosis (TB) in Jiangsu, China by studying the threshold dynamics of the TB epidemic model via the statistical data analytically and numerically. The basic reproduction number R0 > 1 reveals that TB in Jiangsu, China is an endemic disease and will persist for a long time. And the numerical results show that, in order to control the TB in Jiangsu effectively, we must decrease the depuration coefficient of PM10 in the body, the proportion of TB symptomatic infectious by direct transmission, the reactivation rate of the pre-symptomatic infectious and the effect coefficient of PM10 and MTB inhaled of TB transmission, and increase the uptake coefficient, the recovery rate of the symptomatic/pre-symptomatic infectious and the influence coefficient of PM10 on the body of mortality. Our study shows that PM10 is closely related to the incidence of TB, and the effective control efforts are suggested to focus on increasing close-contact distance and wearing protective mask to decrease the influence of PM10 on the TB transmission, which may shed a new light on understanding the environmental drivers to TB. [ABSTRACT FROM AUTHOR]

Many scholars have explored the treatment effect of biofilters with different packing media. However, there is little report on the microbial communities of the packing media. Therefore, this paper attempts to disclose the differences between two popular packing media of biofilter, namely, volcanic rock and ceramiste, in terms of the attached bacteria. Firstly, two multi-layer biofilters (MBFs) were designed, and respectively packed with volcanic rock and ceramiste. The packing media were collected after the MBFs entered stable operation. The DNA was extracted from the media and pyro-sequenced. After that, the community structure and diversity of the microorganisms were analyzed in details. The main results are as follows: The values of ACE estimator, Chao1 estimator, and Simpson's diversity show that volcanic rock had the higher bacterial diversity. The libraries with volcanic rock and ceramsite respectively consist of 1,810 and 1,352 operational taxonomic units (OTUs). Surprisingly, the Venn diagram of OTUs indicates that the two-packing media only share 13.2 % OTUs. The volcanic rock contained sequences in 16 phyla while ceramiste only covered sequences in 11 phyla. Among all phyla, Tenericutes was unique to ceramiste, while Chloroflexi, GN02, NKB19, Thermi, Chlorobi and TM7 were only observed in volcanic rock. Ceramiste contained more Proteobacteria (67.06 % vs. 64.12 %), Bacteroidetes (25.11 % vs. 22.72 %) andFirmicutes (6.20 % vs. 4.55 %) than volcanic rock. The research findings clarify the research direction and provide the theoretical basis for improving ceramiste technology and developing alternatives for volcanic rock. [ABSTRACT FROM AUTHOR]

In this paper, a novel method using conformal technique of finite-difference method (FDM) is proposed to capacitance extraction of microstrip lines. Instead of deriving the average dielectric constant e, this method uses electric field numerical weights to process the inhomogeneous cells, and takes the discontinuous effects of both inhomogeneous Ampere cell and Faraday cell into account. Besides, a new boundary condition is proposed, where the cells obeying exponential distribution are added at boundary. The new method shows good agreement with the measurement and traditional methods. [ABSTRACT FROM AUTHOR]

Microbial polyphosphate (polyP) production is vital to the removal of phosphate from wastewater. However, to date, engineered polyP synthesis using genetically accessible environmental bacteria remains a challenge. This study develops a simple solo medium-copy plasmid-based polyphosphate kinase (PPK1) overexpression strategy for achieving maximum intracellular polyphosphate accumulation by environmental bacteria. The polyP content of the subsequently engineered Citrobacter freundii (CPP) could reach as high as 12.7% of its dry weight. The biomass yield of CPP was also guaranteed because of negligible metabolic burden effects resulting from the medium plasmid copy number. Consequently, substantial removal of phosphate (Pi) from the ambient environment was achieved simultaneously. Because of the need for exogenous Pi for in vivo ATP regeneration, CPP could thoroughly remove Pi from synthetic municipal wastewater when it was applied for the "one-step" removal of Pi with a bench-scale sequence batch membrane reactor. Almost all the phosphorus except for that assimilated by CPP for cellular growth could be recovered in the form of more concentrated Pi. Overall, engineering environmental bacteria to overexpress PPK1 via a solo medium-copy plasmid strategy may represent a valuable general option for not only biotechnological research based on sufficient intracellular polyP production but also removal of Pi from wastewater and Pi enrichment. [ABSTRACT FROM AUTHOR]

To overcome inadequate functional integration, irregular pits, and insufficient agricultural machinery and agronomy in tobacco seedling transplanting equipment under film, a digging transplanting integrated machine was built. The machine uses parallel four-bar mechanism. The excavation equipment uses conical spiral blades. Using the trajectory approach, the four bar mechanism's fundamental parameters can be reversed. This method meets the requirements for coordinated excavation and transplantation. Mechanical study of soil units determines upward movement characteristics. Additionally, spiral angle, spiral blade outer diameter, and spiral blade speed are quantified to affect soil movement. The range of factors is derived. Based on three factors binary regression orthogonal combination simulated optimization experiment, a discrete element analysis was performed to enhance parameters. Experimental factors optimized include a spiral angle of 19°, a spiral blade diameter of 378 mm, and a rotational speed of 258 rpm. The two optimized test indicators are: a 193 mm hole depth and 350 mm hole diameter. The improved results were verified by field validation studies using a 191 mm hole depth and 347 mm hole diameter. The simulation optimization results and field validation experiment results are very similar. This study provides a technical basis for tobacco farming concurrent drilling and transplanting research. [ABSTRACT FROM AUTHOR]

Since the parameters of transmission line can affect the signal integrity and electromagnetic compatibility directly in high frequency circuit, and there is lack of researches in the field of solving the inductance parameter of nonuniform transmission line in anisotropic dielectric, a novel method has been proposed in this paper to solve this problem. The new method uses filament division to establish the dispersion model of nonuniform transmission line, and formulates the filament division principle based on Biot-Savart Law and skin effect. Then it develops the Ampere loop integral dyadic equations and the closed circuit dyadic impedance matrix equation with direction factor in frequency domain based on electromagnetic quasi-static (EMQS). To obtain the corresponding magnetic field direction factor, the relative position of filaments in geometric space is analyzed. Finally, the inductance parameters are obtained by the impedance matrix equation. The correctness of proposed method is verified by applying to uniform transmission line model. Then the new method is applied to the calculation of two nonuniform transmission line models which filled in free space and anisotropic dielectric respectively. The inductance parameters and frequency dependency solved by different methods are compared, showing accuracy and validity of the proposed method. Besides, the new method can be applied to various transmission line structures and different anisotropic dielectric. [ABSTRACT FROM AUTHOR]

Water-soluble polymers have been used in many applications in the oil sand and heavy oil industries, including drilling, enhanced oil recovery, tailings treatment, and water treatment. Because they are water soluble, residual polymer can remain with the aqueous phase, potentially leading to environmental impacts. Investigating the environmental fate of these water-soluble polymers is particularly important as they may be toxic to aquatic biota or terrestrial animal life. However, since polymers are somewhat complex because of their high molecular weight, there are many challenges in their measurement, especially in complex matrices. In this paper, polymers used in oilfield applications, particularly in the oil sand or heavy oil industries, are reviewed and various analytical methods for polymer characterization are compared. [ABSTRACT FROM AUTHOR]

The nontoxicity of titanium (Ti) and the potential to produce valuable photocatalysts from the final coagulated sludge constitute the main advantages of Ti-based coagulants over conventional ones. However, the low effluent pH and the too-fast hydrolysis limit the wide application of Ti-salt coagulants. Prehydrolysis, to some extent, is helpful to improve the coagulation performance of Ti-salt coagulants. However, the prehydrolyzed polytitanium chloride (PTC) still suffers from narrow applicable dose/pH range. A novel and efficient Ti-based coagulant, denoted as titanium xerogel coagulant (TXC), was successfully prepared by the sol-gel method with TiCl4 as the precursor and acetylacetone as a modifying agent. Compared with TiCl4, a PTC, and a commercial polyferric sulfate, the resulting TXC possessed a larger floc size, better settling property, and wider applicable coagulant dose/pH range. Moreover, the effluent pH after TXC coagulation was not significantly reduced, avoiding the corrosion problem sometimes caused by the low effluent pH. TXC exhibited good coagulation performance for several real wastewaters, especially for the wastewaters of low turbidity. These results demonstrate that gelation was a more effective strategy than prehydrolysis to overcome the inherent weaknesses of Ti salts as a type of promising coagulants. [ABSTRACT FROM AUTHOR]

This paper describes the design, working principle, as well as calibration of an air-floating six-axis force measurement platform, where the floating plate and nozzles were connected without contact, preventing inter-dimensional coupling and increasing precision significantly. The measurement repeatability error of the force size in the platform is less than 0.2% full scale (FS), which is significantly better than the precision of 1% FS in the six-axis force sensors on the current market. We overcame the difficulties of weight loading device in high-precision calibration by proposing a self-calibration method based on the floating plate gravity and met the calibration precision requirement of 0.02% FS. This study has general implications for the development and calibration of high-precision multi-axis force sensors. In particular, the air-floating six-axis force measurement platform could be applied to the calibration of some special sensors such as flexible tactile sensors and may be used as a micro-nano mechanical assembly platform for real-time assembly force testing. [ABSTRACT FROM AUTHOR]

The 2008 Wenchuan earthquake destroyed large areas of vegetation in the Baisha River and Longxi River basins, in Dujiangyan County, China. There were several debris flow events in these mountainous river basins after 2008. Currently, these damaged vegetation areas are in various stages of recovery. This recovery vegetation improves the resistance of slopes to both surficial erosion and mass wasting. We introduce a probabilistic approach to determining the relationships between damaged vegetation and slope materials' stability, and model the sediment and flow (hydrological) connectivity index to detect the hydrological changes in a given river basin, using the multi-temporal (1994-2014) remote-sensing images to monitor the vegetation recovery processes. Our results demonstrated that the earthquake-damaged vegetation areas have coupling relationships with topographic environment and slope material properties, and can be used to assess the slope material stability. Further, our analysis results showed that the areas with horizontal distance to river streams <500 m are areas that actively contribute sediment to the stream channel network, and are main material sources for debris flow processes in one given mountainous basin. [ABSTRACT FROM AUTHOR]

The eutrophication of three small lakes in the aquatic zones at the Huainan coal mine subsidence areas, designated as east site (ES), central site (CS), and west site (WS), were studied. Nutrient content, species, and nitrogen (N) to phosphorus (P) ratios were obtained through water quality analyses. Nutrient limitation was evaluated by nutrient enrichment bioassays (NEBs) in the autumn of 2012 and spring of 2013. Average annual concentrations of total phosphorus (TP) were 0.05, 0.08, and 0.10 mg/L, and total nitrogen (TN) concentrations were 0.77, 1.95, and 2.06 mg/L in the water column at CS, ES, and WS, respectively. All of the three lakes exhibited 'meso-eutrophic' states and the TN:TP ratio ranged from 25:1 to 74:1 with variability between seasons and sites. NEBs verified that primary productivity in the lakes at ES and WS were mainly limited by P, while N limitation or N and P co-limitation was present in the aquatic zones at CS due to unavailable dissolved inorganic nitrogen. In the studied lakes, the blue-green algae, which comprised 70% of all identified species, was the predominant taxa, while the micro-zooplankton taxa was dominant, indicating a typical trophic structure of eutrophic lakes. [ABSTRACT FROM AUTHOR]

Plywood samples treated with ammonium polyphosphate (APP) and 4A zeolite were prepared to investigate the effect of zeolite on wood's burning behavior using a cone calorimeter under a heat flux of 35 kW/m2. Results showed that APP decreased the heat release rate (HRR), total heat release (THR), and mass loss rate (MLR) of treated plywood. However, APP significantly increased the total smoke release (TSR) and carbon monoxide (CO) yield. The addition of 4A zeolite reduced the HRR, peak HRR, and THR of the plywood treated with only APP. The second HRR peak in a typical plywood curve diminished with the addition of as little as 2% 4A zeolite. The average specific extinction area (ASEA) and CO yield decreased significantly with the presence of zeolite in the APP. The ignition time did not change significantly and the TSR increased when zeolite was present. Thus, a suitable amount of 4A zeolite works synergistically with APP in promoting flame retardancy in flame retardant plywood. [ABSTRACT FROM AUTHOR]

HrpNEa is a harpin protein produced by the bacterial plant pathogen Erwinia amylovora. When applied to aerial parts of plants, the protein induces systemic acquired resistance in a variety of plant species. Here, we report that treating Chinese cabbage roots with HrPNEa induces resistance of the plant to Pectobacterium carotovora subsp. carotovora, the pathogen that invades roots and causes bacterial soft rot in cruciferous plants. Treating Chinese cabbage roots with HI-pNEa significantly decreased seventies of soft rot symptoms on the plant. The root treatment decreased the number of P carotovora subsp. carotovora cells attached to root surfaces and inhibited the ability of P carotovora subsp. carotovora to produce quorum-sensing signals, which regulate pathogenicity in a bacterial population-dependent manner. The inhibitory effects of HrPNE. on the root attachment and quorum-sensing signals accompanied the induced expression of several defense response genes. These results suggest that HrPNEa induces Chinese cabbage resistance to bacterial soft rot by inhibiting the bacterial attachment to root surfaces. [ABSTRACT FROM AUTHOR]

Dorsal–ventral patterning in vertebrate and invertebrate embryos is mediated by a conserved system of secreted proteins that establishes a bone morphogenetic protein (BMP) gradient. Although the Drosophila embryonic Decapentaplegic (Dpp) gradient has served as a model to understand how morphogen gradients are established, no role for the extracellular matrix has been previously described. Here we show that type IV collagen extracellular matrix proteins bind Dpp and regulate its signalling in both the Drosophila embryo and ovary. We provide evidence that the interaction between Dpp and type IV collagen augments Dpp signalling in the embryo by promoting gradient formation, yet it restricts the signalling range in the ovary through sequestration of the Dpp ligand. Together, these results identify a critical function of type IV collagens in modulating Dpp in the extracellular space during Drosophila development. On the basis of our findings that human type IV collagen binds BMP4, we predict that this role of type IV collagens will be conserved. [ABSTRACT FROM AUTHOR]

The attachment of rat aortic smooth muscle cells to various surfaces has been monitored by a thickness shear mode acoustic wave device incorporated into an on-line configuration. Using the total injection analysis method, laminin and fibronectin were adsorbed to the device surface, to be followed by introduction of cells into the system. The results of these experiments in terms of frequency and motional resistance measurements were also compared with those for cell attachment to the bare gold electrode of the sensor. The responses of the surface-bound cells to the introduction of various ions, depolarisation events and damage subsequent to exposure to hydrogen peroxide were also observed. Morphological changes in the cells, as confirmed by scanning electron microscopy, are correlated with results of the acoustic wave measurements. [ABSTRACT FROM AUTHOR]

Abstract??Intelligent data analysis has gained increasing attention in business and industry environments. Many applications are looking not only for solutions that can automate and de-skill the data analysis process, but also methods that can deal with vague information and deliver comprehensible models. Under this consideration, we present an automatic data analysis platform, in particular, we investigate fuzzy decision trees as a method of intelligent data analysis for classification problems. We present the whole process from fuzzy tree learning, missing value handling to fuzzy rules generation and pruning. To select the test attributes of fuzzy trees we use a generalized Shannon entropy. We discuss the problems connected with this generalization arising from fuzzy logic and propose some amendments. We give a theoretical comparison on the fuzzy rules learned by fuzzy decision trees with some other methods, and compare our classifiers to other well-known classification methods based on experimental results. Moreover, we show a real-world application for the quality control of car surfaces using our approach. [ABSTRACT FROM AUTHOR]

Oil spills and industrial wastewater discharge have inflicted severe damage upon the ecological environment and human health. Therefore, the development of an environmentally friendly and pollution-free membrane material for oil-water separation is imperative. This study presents the development of a novel oil-water separation material (PP-PPy-pHR) that is environmentally benign and capable of switching between wetting properties. The material was synthesised by dopamine modification, treatment with a pH-responsive polymer and the use of a high-efficiency photothermal layer composed of self-assembled polypyrrole (PPy), and it not only separates incompatible oil-water mixtures but also efficiently separates oil-water emulsions under different pH conditions. Due to the good photothermal effect of PPy, the evaporation rate of PP-PPy-pHR composite membrane loaded with PPy was 3.95 times higher than that of pure water for oily wastewater. In addition, the PPy-pHR composite membrane exhibited excellent durability and high stability in extremely acidic and alkaline solutions, showing remarkable potential for oil-water separation applications. [ABSTRACT FROM AUTHOR]

Eukaryotes evolved various strategies to coordinate their development and metabolism in response to harsh environments. However, it remains unknown whether fungi increase their resistance to stress from fungivorous arthropods by altering phenotype and metabolite composition. In this study, we investigated the coordinated regulation of sensor histidine kinase (SLN1) and acetyl-CoA carboxylase (ACC1) on sporulation and metabolite accumulation in Neurospora crassa, particularly upon the springtail Sinella curviseta (Collembola: Entomobryidae) attack. The mutants Δsln1, Δacc1, and double mutant Δsln1::Δacc1 exhibited reduced conidia number and defective sexual reproduction in contrast to the wild type. Intriguingly, double deletion of sln1 and acc1 results in failure of beak formation and, consequently, inhibits ascospores ejection which helps Δsln1::Δacc1 to escape the predation by S. curviseta. Furthermore, sln1 and/or acc1 play critical roles in metabolic processes in N. crassa. Compared with the control, the cultures exposed to S. curviseta produced more trehalose, carotenoids, folic acid, and fatty acids, especially in the asexual stage. The deletion of sln1 and acc1 affecte d the trehalose content, thereby reducing the resistance of Δsln1, Δacc1, and Δsln1::Δacc1 to S. curviseta. Null of sln1 and/or acc1 altered the lipid composition and thus carotenoids synthesis. Chemical analysis showed that N. crassa formed more fatty acids and carotenoids upon the attack of S. curviseta. Taken together, our data suggest that acc1 and sln1 work together to protect N. crassa from the stress of S. curviseta. SLN1 and ACC1 compose a regulatory system that coordinates the conidiation, perithecial formation, and metabolism, especially upon fungivores stress. IMPORTANCE Understanding the regulatory pathways by which fungi respond to environmental signals through interlinked genes provides insights into the interactions between fungi and insects. The coordinated optimization of the regulatory networks is necessary for fungi to adapt to their habitats. We demonstrated that the synergistic regulation of sensor histidine kinase (SLN1) and acetyl-CoA carboxylase (ACC1) plays a critical role in regulating the fungal response to Sinella curviseta stress. Furthermore, we found that the enhanced production of trehalose, carotenoids, and 5-MTHF plays crucial role in the resistance to the fungivore. Our results provide insights into the understanding of the adaptation of N. crassa to environmental stimuli. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • The degradation efficiency of TC over the 0.3-p-Ag 2 S/n-BiVO 4 can be achieved 90.2%. • Ten intermediate products for TC degradation were verified by the GC-MS. • The enhancing photocatalysis mechanism was attributed to the facilitated charge transfer. Abstract Three-dimensional microsphere p-Ag 2 S/n-BiVO 4 p-n heterojunction photocatalyst was successfully fabricated via depositing p-type Ag 2 S on n-type BiVO 4 , which showed excellent photocatalytic performance, compared with BiVO 4 and Ag 2 S, for the photocatalytic degradation of tetracycline under visible light irradiation. The enhancing photocatalytic performance can be attributed to the facilitated charge transfer, and the increased lifetime of the charge carriers confirmed by the results of time-resolved fluorescence spectra and photoelectrochemical measures. Moreover, 10 photocatalytic degradation intermediates and products were also identified by the gas chromatography-mass spectrometer. Finally, the photocatalytic enhancement mechanism over p-Ag 2 S/n-BiVO 4 was discussed. The strategy to form three-dimensional microspheres p-n heterojunction photocatalyst may open a new opportunity to design highly efficient photocatalyst for environmental treatment to control pollution. [ABSTRACT FROM AUTHOR]

China's higher education is facing a structural excess capacity crisis. Duopoly models that consist of two universities are constructed in attempt to investigate the impacts of demand price elasticity, product differentiation, subsidies, and cost efficiency on excess capacity. In doing so, it turns out that the ownership of capacity decision power in higher education will exert an effect on the extent of excess capacity and the impact on the product differentiation on excess capacity. The higher the subsidies granted to universities or the lower the cost, the more the excess capacity in one university, but the less in the other university. When universities have the capacity decision power, the demand price elasticity and excess capacity constitute a Type U relationship. While the government owns the capacity decision power, both are positively correlated to each other. These conclusions have a certain realistic significance for the higher education reform in China. [ABSTRACT FROM AUTHOR]

An atmospheric-pressure plasma sustained by an ac power supply was generated using electrolyte solution as one of the electrodes. By altering the power supply, ring-like patterns, double-ring patterns and plasma-spot patterns were observed at the electrolyte–electrode surface. Synchronous current–voltage characteristics and time-resolved images were measured. Important factors for the self-organized patterns, including the electrode gap, power, frequency and electrolyte concentration, were explored. The optical spectrum characteristics of the device were investigated. The pH of the solution after discharge was also explored and the results show that the pH of the solution is evidently reduced after the discharge, implying that acidic components are produced in the solution. This study provides an alternative discharge method for producing patterns on a water surface. [ABSTRACT FROM AUTHOR]

It has previously been demonstrated that nicotinamide adenine dinucleotide phosphate‑oxidase (NADPH) oxidase 4 (Nox4), is important in the pathogenesis of diabetic nephropathy (DN), however the exact mechanisms remain to be elucidated. The present study aimed to examine the effect of Nox4 on the alteration of the Notch pathway and cell apoptosis in the renal tubular epithelial cell line, HKC, under conditions of high glucose (HG; 30 mmol/l glucose). Nox4 and the Notch pathway were inhibited by N‑acetylcysteine (NAC), diphenylene iodonium (DPI) or γ‑secretase inhibitor (DAPT). The protein levels of Nox4, Notch1, Notch intracellular domain 1 (NICD1), phosphorylated (p) Ras‑related C3 botulinum toxin substrate 1 (Rac1), Rac1, B‑cell lymphoma 2 apoptosis regulator (Bcl‑2), Bcl‑2 associated protein X apoptosis regulator (Bax) and cleaved caspase‑3 were determined by western blotting. The Nox4 and Notch1 mRNA levels were detected by reverse transcription‑quantitative polymerase chain reaction. Intracellular reactive oxygen species (ROS) levels were detected via chloromethyl‑2',7'‑dichlorodihydrofluorescein diacetate. Apoptotic cells were determined using an Annexin V/propidium iodide apoptosis detection kit. HG upregulated Nox4, Notch1, NICD1, p‑Rac1, Bax and cleaved caspase‑3 expression levels and downregulated Bcl‑2 expression in cultured HKC cells, compared with cells cultured in normal glucose levels. Inhibition of the Notch pathway via DAPT increased Bcl‑2 expression, decreased Bax and cleaved caspase‑3 levels and prevented HKC cell apoptosis. Inhibition of Nox4 by NAC and DPI inhibited the Notch signaling pathway and ROS generation, which prevented HKC cell apoptosis. These findings indicated that Nox4 potentially mediates HG‑induced HKC cell apoptosis via the Notch pathway, and may be involved in renal tubular epithelial cell injury in DN. [ABSTRACT FROM AUTHOR]

Cystic fibrosis (CF) is caused by mutations that disrupt the plasma membrane expression, stability, and function of the cystic fibrosis transmembrane conductance regulator (CFTR) Cl- channel. Two small molecules, the CFTR corrector lumacaftor and the potentiator ivacaftor, are now used clinically to treat CF, although some studies suggest that they have counteracting effects on CFTR stability. Here, we investigated the impact of these compounds on the instability of F508del-CFTR, the most common CF mutation. To study individual CFTR Cl- channels, we performed single-channel recording, whereas to assess entire CFTR populations, we used purified CFTR proteins and macroscopicCFTRCl-currents. At 37 °C, low temperature-rescued F508del-CFTR more rapidly lost function in cell-free membrane patches and showed altered channel gating and current flow through open channels. Compared with purified wildtype CFTR, the full-length F508del-CFTR was about 10 °C less thermostable. Lumacaftor partially stabilized purified fulllength F508del-CFTR and slightly delayed deactivation of individual F508del-CFTR Cl- channels. By contrast, ivacaftor further destabilized full-length F508del-CFTR and accelerated channel deactivation. Chronic (prolonged) co-incubation of F508del-CFTR-expressing cells with lumacaftor and ivacaftor deactivated macroscopic F508del-CFTR Cl- currents. However, at the single-channel level, chronic co-incubation greatly increased F508del-CFTR channel activity and temporal stability in most, but not all, cell-free membrane patches. We conclude that chronic lumacaftor and ivacaftor co-treatment restores stability in a small subpopulation of F508del-CFTR Cl- channels but that the majority remain destabilized. A fuller understanding of these effects and the characterization of the small F508del-CFTR subpopulation might be crucial for CF therapy development. [ABSTRACT FROM AUTHOR]

The article presents an enzyme-derived clicking proteolysis-targeting chimeras (PROTACs) (ENCTACs) capable of orthogonally cross-linking two disparate small-molecule warhead ligands that recognize BET bromodomain-containing protein 4 (BRD4) protein and E3 ligase within tumors only upon hypoxia-induced activation of nitroreductaase enzyme. Topics include rational design and formations of nitroreductase (NTR)-activatable ENCTACs and ENCTAC activity in mice with solid tumors.

Background: Tuberculosis (TB) is an infectious disease of major public health concern. The disease has demonstrated large space-time variations. This study aims to explore the space-time dynamics of TB cases in an economically and geographically dynamic province in China with specific references of TB control for policy makers. Methods: Data on all reported TB cases from 2009 to 2012 were collected from the TB program at the Zhejiang Provincial Center for Disease Control and Prevention. We employed time series and exploratory spatial data analyses, including Moran's I, Local Getis's Gi*, and Kulldorff's space-time scan statistics, to identify the temporal trends and spatial patterns of TB at a county level. Results: A total of 147,941 TB cases were reported during 2009-2012 in Zhejiang. A higher proportion of TB cases were younger, male, and registered permanent residents among all TB cases notified in the province. TB cases were reported most frequently in April with small peaks in June, July, and October. This disease was spatially clustering with Moran's I values ranged from 0.29 to 0.32 (p < 0.001). A most likely cluster and ten secondary clusters were identified, mainly concentrated in the southeast and west counties of the province. Conclusions: This study identified seasonal patterns and significant space-time clusters of TB cases in Zhejiang, China. Poverty, migration, and seasonal effects may play important roles in potential clusters. [ABSTRACT FROM AUTHOR]

The harpin protein HrpN induces Arabidopsis resistance to the green peach aphid by activating the ethylene signalling pathway and by recruiting EIN2, an essential regulator of ethylene signalling, for a defence response in the plant. We investigated 37 ethylene-inducible Arabidopsis transcription factor genes for their effects on the activation of ethylene signalling and insect defence. Twenty-eight of the 37 genes responded to both ethylene and HrpN, and showed either increased or inhibited transcription, while 18 genes showed increased transcription not only by ethylene but also by HrpN. In response to HrpN, transcription levels of 22 genes increased, with AtMYB44 being the most inducible, six genes had decreased transcript levels, and nine remained unchanged. When Arabidopsis mutants previously generated by mutagenicity at the 37 genes were surveyed, 24 mutants were similar to the wild type plant while four mutants were more resistant and nine mutants were more susceptible than wild type to aphid infestation. Aphid-susceptible mutants showed a greater susceptibility for atmyb15, atmyb38 and atmyb44, which were generated previously by T-DNA insertion into the exon region of AtMYB15 and the promoter regions of AtMYB38 and AtMYB44. The atmyb44 mutant was the most susceptible to aphid infestation and most compromised in induced resistance. Resistance accompanied the expression of PDF1.2, an ethylene signalling marker gene that requires EIN2 for transcription in wild type but not in atmyb15, atmyb38, and atmyb44, suggesting a disruption of ethylene signalling in the mutants. However, only atmyb44 incurred an abrogation in induced EIN2 expression, suggesting a close relationship between AtMYB44 and EIN2. [ABSTRACT FROM AUTHOR]

Although stroke is a major human neurological disease, there is a paucity of effective neuroprotectants that can improve its treatment. Casticin is a natural monomer drug with many biological effects such as anti-inflammatory and anti-tumor actions. However, it is not clear whether it has a neuroprotective effect in ischemic stroke. In this study, the neuroprotective effect of casticin in a rat middle cerebral artery occlusion (MCAO) model was investigated. Results showed that casticin reduced the volume of the cerebral infarction, mNSS scores, swimming distance, time to find the submerged platform, and serum concentrations of TNF-α, TGF-β, IL-6 in MCAO rats. Moreover, casticin also decreased the expression of TLR4, NF-κB p65, and NF-κB p50 proteins and reversed the reduced expression of IκB protein in the brain tissue of MCAO rats. The in vitro study revealed that casticin decreased apoptosis of OGD/ R-PC12 cells, reduced the expression of TLR4, NF-κB p65, and NF-κB p50, while increased IκB protein expression. In conclusion, casticin improved the neurological functions of MCAO rats via inhibiting the TLR4/NF-κB pathway and might have the potential to be developed into a neuroprotective agent for stroke patients. [ABSTRACT FROM AUTHOR]

Tubulin-targeted chemotherapy has proven to be a successful and wide spectrum strategy against solid and liquid malignancies. Therefore, new ways to modulate this essential protein could lead to new antitumoral pharmacological approaches. Currently known tubulin agents bind to six distinct sites at α/β-tubulin either promoting microtubule stabilization or depolymerization. We have discovered a seventh binding site at the tubulin intradimer interface where a novel microtubule-destabilizing cyclodepsipeptide, termed gatorbulin-1 (GB1), binds. GB1 has a unique chemotype produced by a marine cyanobacterium. We have elucidated this dual, chemical and mechanistic, novelty through multidimensional characterization, starting with bioactivity-guided natural product isolation and multinuclei NMR-based structure determination, revealing the modified pentapeptide with a functionally critical hydroxamate group; and validation by total synthesis. We have investigated the pharmacology using isogenic cancer cell screening, cellular profiling, and complementary phenotypic assays, and unveiled the underlying molecular mechanism by in vitro biochemical studies and high-resolution structural determination of the α/β-tubulin-GB1 complex. [ABSTRACT FROM AUTHOR]

The article informs about how temporal pressure enhanced topical drug delivery through micropore formation. Topics discussed include report an innovative methodology based on temporal pressure to enhance the penetration of all kinds of drugs; and the delivery of insulin through topical application after the pressure treatment yields upto drop in blood glucose in diabetic mice.

β-Cells respond to peripheral insulin resistance by first increasing circulating insulin during diabetes. Islet remodeling supports this compensation, but its drivers remain poorly understood. Infiltrating macrophages have been implicated in late-stage type 2 diabetes, but relatively little is known on islet resident macrophages, especially during compensatory hyperinsulinemia. We hypothesized that islet resident macrophages would contribute to islet vascular remodeling and hyperinsulinemia during diabetes, the failure of which results in a rapid progression to frank diabetes. We used chemical (clodronate), genetics (CD169-diphtheria toxin receptor mice), or antibody-mediated (colony-stimulating factor 1 receptor α) macrophage ablation methods in diabetic (db/db) and diet-induced models of compensatory hyperinsulinemia to investigate the role of macrophages in islet remodeling. We transplanted islets devoid of macrophages into naïve diabetic mice and assessed the impact on islet vascularization. With the use of the above methods, we showed that macrophage depletion significantly and consistently compromised islet remodeling in terms of size, vascular density, and insulin secretion capacity. Depletion of islet macrophages reduced VEGF-A secretion in both human and mouse islets ex vivo, and this functionally translated to delayed revascularization upon transplantation in vivo. We revealed that islet resident macrophages were associated with islet remodeling and increased insulin secretion during diabetes. This suggests utility in harnessing islet macrophages during this phase to promote islet vascularization, remodeling, and insulin secretion. [ABSTRACT FROM AUTHOR]

Angiogenesis is a highly regulated process for formation of new blood vessels from pre-existing ones. Angiogenesis is dysregulated in various pathologies, including age-related macular degeneration, arthritis, and cancer. Inhibiting pathological angiogenesis therefore represents a promising therapeutic strategy for treating these disorders, highlighting the need to study angiogenesis in more detail. To this end, identifying the genes essential for blood vessel formation and elucidating their function are crucial for a complete understanding of angiogenesis. Here, focusing on potential candidate genes for angiogenesis, we performed a morpholino-based genetic screen in zebrafish and identified Cavin-2, a membrane-bound phosphatidylserine-binding protein and critical organizer of caveolae (small microdomains in the plasma membrane), as a regulator of angiogenesis. Using endothelial cells, we show that Cavin-2 is required for in vitro angiogenesis. [ABSTRACT FROM AUTHOR]

Matrix metalloproteinases (MMPs) and tissue inhibitors of matrix metalloproteinases (TIMPs) serve an important role in chondrosarcoma. The present study investigated whether the expression of MMPs was dependent on the activity of mitogen-activated protein kinase (MAPK) in chondrosarcoma. Surgical pathological specimens were collected to detect MMP-1, MMP-13, TIMP-1, type II collagen and phosphorylated MAPK levels in normal cartilage, enchondroma and chondrosarcoma tissues. The expression of MMP-1, MMP-13, TIMP-1 and type II collagen was investigated utilizing MAPK inhibitors in chondrosarcoma cells. It was noted that the expression levels of MMP-1, MMP-13 and TIMP-1 were increased in chondrosarcoma with the activity of MAPK. After chondrosarcoma cells were pretreated with MAPK inhibitors, the levels of MMP-1, MMP-13 and TIMP-1 were inhibited. Furthermore, MMP-1 and MMP-13 are essential in regulating the degradation of type II collagen and decomposing cartilage matrix major. The high expression levels of MMP-1 and MMP-13 in chondrosarcoma expedite the invasion by chondrosarcoma cells and their expression can be depressed by MAPK inhibitors. [ABSTRACT FROM AUTHOR]

The clinical efficacy and safety of different combinations of non-bio artificial liver in the treatment of acute liver failure was examined. A total of 61 cases were selected under blood purification treatment from the patients with severe acute liver failure admitted to the severe disease department of the hospital from December, 2010 to December, 2015. Three types of artificial liver combinations were observed, i.e., plasma exchange plus hemoperfusion plus continuous venovenous hemodiafiltration (PE+HP+CVVHDF), PE+CVVHDF and HP+CVVHDF. The heart rate (HR), mean arterial pressure (MAP), respiratory index (PaO2/FiO2), liver and kidney function indicator, as well as platelet and coagulation function were compared. A comparison before and after the treatment using the three methods, showed improvement in the HRs, MAPs, PaO2/FiO2, total bilirubins (TBIL) and alanine aminotransferases (ALT) (P<0.05), of which TBIL and ALT were decreased more significantly (P<0.01) in the PE+CVVHDF and PE+HP+CVVHDF groups. Only changes in the PE+HP+CVVHDF and PE+CVVHDF groups were statistically significant after prothrombin time and albumin treatment (P<0.05). The difference between the decrease in TBIL in the PE+HP+CVVHDF group and that in the HP+CVVHDF group was statistically significant (P<0.05). Treatment of the 61 patients using the artificial liver support system yielded a survival rate of 62.3% (38/61), and a viral survival rate of 35.0% (7/20); with the non-viral survival rate being 75.6% (31/41). In conclusion, following the treatment of three types of artificial livers, the function was improved to varying degrees, with the PE+HP+CVVHDF and the PE+CVVHDF method being better. By contrast, after the treatment of non-viral liver failure, the survival rate was significantly higher than the patients with viral liver failure. [ABSTRACT FROM AUTHOR]

Objectives: The objective of this study is to assess the social support received by patients diagnosed with multidrug-resistant tuberculosis (MDR-TB) in Zhejiang Province, People's Republic of China and the factors that may have influenced it. Methods: A total of 220 MDR-TB patients participated in the questionnaire-based survey, and the data from 212 valid questionnaires were analyzed. The respondents reported their sociodemographic status, disease features, and attitudes toward the disease. The social support rating scale was used to measure the patients' social support scores. An Independent Samples t-test, one-way analysis of variance, and a multiple linear regression model were used to analyze the related factors for the social support scores. Result: The average social support score of each MDR-TB patient was 32.56±7.86. Participants who were single, widowed or divorced, retired, and had fewer family members and lower family income were found to have lower social support scores. Participants unwilling to disclose their disease tended to have less social support (31.59,34.23, P=0.010). Participants who perceived great help from health care workers reported higher social support rating scale scores than those who perceived no help (35.36.29.89, P=0.014). Conclusion: MDR-TB patients in Zhejiang Province were shown to have a low level of social support. Patients who were not married, had smaller families, and lower family income received less social support, suggesting that family harmony could be an important source of social support. Patients' self-isolation may contribute to a decrease in the amount of support they receive from their surroundings. Health care organizations need to offer more social support to MDR-TB patients. [ABSTRACT FROM AUTHOR]

The binding interaction between gallic acid (GA) and lysozyme (LYS) was investigated and compared by molecular dynamics (MD) simulation and spectral techniques. The results from spectroscopy indicate that GA binds to LYS to generate a static complex. The binding constants and thermodynamic parameters were calculated. MD simulation revealed that the main driving forces for GA binding to LYS are hydrogen bonding and hydrophobic interactions. The root-mean-square deviation verified that GA and LYS bind to form a stable complex, while the root-mean-square fluctuation results showed that the stability of the GA-LYS complex at 298 K was higher than that at 310 K. The calculated free binding energies from the molecular mechanics/Poisson-Boltzmann surface area method showed that van der Waals forces and electrostatic interactions are the predominant intermolecular forces. The MD simulation was consistent with the spectral experiments. This study provides a reference for future study of the pharmacological mechanism of GA. [ABSTRACT FROM AUTHOR]

The interaction between zinc ion and human serum albumin (HSA) was investigated by nano-Watt- scale isothermal titration calorimetry (ITC). From the analysis of the ITC data, the binding characteristics and thermodynamic properties of the system were obtained and the binding mechanism was discussed. It was found that the experimental data fit well with the Langmuir's binding theory and the system behaved as a system with two classes of binding sites (high-affinity and low-affinity binding site). The binding number of high-affinity binding site (N1) is 1.40 and the binding constant (K1) is 2.72×105 L/mol. For the low-affinity binding site, the binding number (N2) is 1.55 and the binding constant (K2) is 3.78×103 L/mol. Moreover, it was indicated by the thermodynamic analysis that the binding processes of both types of binding sites were exothermic and spontaneous. The high-affinity binding was an enthalpy-entropy synergically driven process and the electrostatic interaction was the main force, while the low-affinity binding was an enthalpydriven process and this process was mainly driven by the van der Waals forces. [ABSTRACT FROM AUTHOR]

ε-Poly-L-lysine (ε-PL), showing a wide range of antimicrobial activity, is now industrially produced as a food additive by a fermentation process. A new strain capable of producing ε-PL was isolated from a soil sample collected from Gutian, Fujian Province, China. Based on its morphological and biochemical features and phylogenetic similarity with 16S rRNA gene, the strain was identified as Streptomyces albulus and named NK660. The yield of ε-PL in 30 l fed-batch fermentation with pH control was 4.2 g l-1 when using glycerol as the carbon source. The structure of ε-PL was determined by nuclear magnetic resonance (NMR) and matrix-assisted laser desorption/ ionization-time of flight mass spectrometry (MALDITOF MS). Previous studies have shown that the antimicrobial activity of ε-PL is dependent on its molecular size. In this study, the polymerization degree of the ε-PL produced by strain NK660 ranged from 19 to 33 L-lysine monomers, with the main component consisting of 24-30 L-lysine monomers, which implied that the ε-PL might have higher antimicrobial activity. Furthermore, the ε-PL synthetase gene (pls) was cloned from strain NK660 by genome walking. The pls gene with its native promoter was heterologously expressed in Streptomyces lividans ZX7, and the recombinant strain was capable of synthesizing ε-PL. Here, we demonstrated for the first time heterologous expression of the pls gene in S. lividans. The heterologous expression of pls gene in S. lividans will open new avenues for elucidating the molecular mechanisms of ε-PL synthesis. [ABSTRACT FROM AUTHOR]

Background: Data on effect of regular liver function monitoring during anti-TB treatment is limited in China. This study aimed to evaluate the effects of scheduled liver function monitoring on identification of asymptomatic liver damage and anti-TB treatment outcomes during anti-TB treatment. Methods: A retrospective analysis was performed based on a national-level cohort study. A total of 273 patients developing liver dysfunction were divided into two groups, 111 patients who were diagnosed through scheduled liver function test within two months after initiation of anti-TB treatment formed scheduled monitoring group, others who were diagnosed due to developing symptoms formed passive detection group (n = 162). The two groups were compared through clinical features, prognosis of liver dysfunction and impact on anti-TB treatment using propensity score weighting analysis. Results: 33.3% of 273 patients did not have any clinical symptoms, including 8 with severe hepatotoxicity. 1.8% in scheduled monitoring group and 11.1% in passive detection group required hospitalization (P = 0.004). Regarding the prognosis of liver dysfunction, most patients recovered, no death happened in scheduled monitoring group while 3 died in passive detection group. In terms of impact on anti-TB treatment, 35.1% in scheduled monitoring group and 56.8% in passive detection group changed their anti-TB treatment (P = 0.001). Conclusions: Scheduled monitoring is effective in identifying asymptomatic liver damage, reducing hospitalization rate and improving compliance of anti-TB treatment. [ABSTRACT FROM AUTHOR]

Background: Anti-tuberculosis drug induced liver injury (ATLI) is emerging as a significant threat to tuberculosis control in China, though limited data is available about the burden of ATLI at population level. This study aimed to estimate the incidence of ATLI, to better understand its clinical features, and to evaluate its impact on anti-tuberculosis (TB) treatment in China. Methodology/Principal Findings: In a population-based prospective study, we monitored 4,304 TB patients receiving directly observed treatment strategy (DOTS) treatment, and found that 106 patients developed ATLI with a cumulative incidence of 2.55% (95% Confidence Interval [CI], 2.04%-3.06%). Nausea, vomiting and anorexia were the top three most frequently observed symptoms. There were 35 (33.02%) ATLI patients with no symptoms, including 8 with severe hepatotoxicity. Regarding the prognosis of ATLI, 84 cases (79.25%) recovered, 18 (16.98%) improved, 2 (1.89%) failed to respond to the treatment with continued elevation of serum alanine aminotransferase, and 2 (1.89%) died as result of ATLI. Of all the ATLI cases, 74 (69.81%) cases changed their anti-TB treatment, including 4 (3.77%) cases with medication administration change, 21 (19.81%) cases with drugs replacement, 54 (50.94%) cases with therapy interruption, and 12 (11.32%) cases who discontinued therapy. In terms of treatment outcomes, 53 (51.46%) cases had TB cured in time, 48 (46.60%) cases had therapy prolonged, and 2 (1.94%) cases died. Compared with non-ATLI patients, ATLI patients had a 9.25-fold (95%CI, 5.69-15.05) risk of unsuccessful anti-TB treatment outcomes and a 2.11-fold (95%CI,1.23-3.60) risk of prolonged intensive treatment phase. Conclusions/Significance: ATLI could considerably impact the outcomes of anti-TB treatment. Given the incidence of ATLI and the size of TB population in China, the negative impact is substantial. Therefore, more research and efforts are warranted in order to enhance the diagnosis and the prevention of ATLI. [ABSTRACT FROM AUTHOR]

In Arabidopsis thaliana ( Arabidopsis) treated with the harpin protein HrpN, resistance to the green peach aphid Myzus persicae, a generalist phloem-feeding insect, develops with induced expression of the AtMYB44 gene. Special GLUCAN SYNTHESIS-LIKE ( GSL) genes and β-1,3-glucan callose play an important role in plant defence responses to attacks by phloem-feeding insects. Here we report that AtGLS5 and AtMYB44 are both required for HrpN-induced repression of M. persicae feeding from the phloem of Arabidopsis leaves. In 24 h successive surveys on large-scale aphid populations, the proportion of feeding aphids was much smaller in HrpN-treated plants than in control plants, and aphids preferred to feed from the 37 tested atgsl mutants rather than the wild-type plant. The atgsl mutants were generated previously by mutagenesis in 12 identified AtGSL genes ( AtGSL1 through AtGSL12); in the 24 h survey, both atgsl5 and atgsl6 tolerated aphid feeding, and atgsl5 was the most tolerant. Consistently, atgsl5 was also most inhibitive to the deterrent effect of HrpN on the phloem-feeding activity of aphids as monitored by the electrical penetration graph technique. These results suggested an important role of the AtGSL5 gene in the effect of HrpN. In response to HrpN, AtGSL5 expression and callose deposition were induced in the wild-type plant but not in atgsl5. In response to HrpN, moreover, the AtMYB44 gene known to be required for repression of aphid reproduction on the plant was also required for repression of the phloem-feeding activity. Small amounts of the AtGSL5 transcript and callose deposition were detected in the atmyb44 mutant, as in atgsl5. Both mutants performed similarly in tolerating the phloem-feeding activity and impairing the deterrent effect of HrpN, suggesting that AtGSL5 and AtMYB44 both contributed to the effect. [ABSTRACT FROM AUTHOR]

Background: Treatment of plants with HrpNEa, a protein of harpin group produced by Gram-negative plant pathogenic bacteria, induces plant resistance to insect herbivores, including the green peach aphid Myzus persicae, a generalist phloem-feeding insect. Under attacks by phloem-feeding insects, plants defend themselves using the phloem-based defense mechanism, which is supposed to involve the phloem protein 2 (PP2), one of the most abundant proteins in the phloem sap. The purpose of this study was to obtain genetic evidence for the function of the Arabidopsis thaliana (Arabidopsis) PP2-encoding gene AtPP2-A1 in resistance to M. persicae when the plant was treated with HrpNEa and after the plant was transformed with AtPP2-A1. Results: The electrical penetration graph technique was used to visualize the phloem-feeding activities of apterous agamic M. persicae females on leaves of Arabidopsis plants treated with HrpNEa and an inactive protein control, respectively. A repression of phloem feeding was induced by HrpNEa in wild-type (WT) Arabidopsis but not in atpp2-a1/E/142, the plant mutant that had a defect in the AtPP2-A1 gene, the most HrpNEa-responsive of 30 AtPP2 genes. In WT rather than atpp2-a1/E/142, the deterrent effect of HrpNEa treatment on the phloem-feeding activity accompanied an enhancement of AtPP2-A1 expression. In PP2OETAt (AtPP2-A1-overexpression transgenic Arabidopsis thaliana) plants, abundant amounts of the AtPP2-A1 gene transcript were detected in different organs, including leaves, stems, calyces, and petals. All these organs had a deterrent effect on the phloem-feeding activity compared with the same organs of the transgenic control plant. When a large-scale aphid population was monitored for 24 hours, there was a significant decrease in the number of aphids that colonized leaves of HrpNEatreated WT and PP2OETAt plants, respectively, compared with control plants. Conclusions: The repression in phloem-feeding activities of M. persicae as a result of AtPP2-A1 overexpression, and as a deterrent effect of HrpNEa treatment in WT Arabidopsis rather than the atpp2-a1/E/142 mutant suggest that AtPP2-A1 plays a role in plant resistance to the insect, particularly at the phloem-feeding stage. The accompanied change of aphid population in leaf colonies suggests that the function of AtPP2-A1 is related to colonization of the plant. [ABSTRACT FROM AUTHOR]

Lumazine synthase (LS) catalyzes the penultimate reaction in the multistep riboflavin biosynthesis pathway, which is involved in plant defenses. Plant defenses are often subject to synergistic effects of jasmonic acid and ethylene whereas LS is a regulator of jasmonic acid signal transduction. However, little is known about whether the enzyme contributes to defense responses. To study the role of LS in plant pathogen defenses, we generated transgenic tobacco expressing the rice (Oryza sativa) LS gene, OsLS. OsLS was cloned and found to have strong identity with its homologues in higher plants and less homology to microbial orthologues. The OsLS protein localized to chloroplasts in three OsLS-expressing transgenic tobacco (LSETT) lines characterized as enhanced in growth and defend. Compared with control plants, LSETT had higher content of both riboflavin and the cofactors flavin mononucleotide and flavin adenine dinucleotide. In LSETT, jasmonic acid and ethylene were elevated, the expression of defense-related genes was induced, levels of resistance to pathogens were enhanced, and resistance was effective to viral, bacterial, and oomycete pathogens. Extents of OsLS expression correlated with increases in flavin, jasmonic acid, and ethylene content, and correlated with increases in resistance levels, suggesting a role for OsLS in defense responses. [ABSTRACT FROM AUTHOR]

Leaf trichomes serve as a physical barrier and can also secrete antimicrobial compounds to protect plants from attacks by insects and pathogens. Besides the use of the physical and chemical mechanisms, leaf trichomes might also support plant responses by communicating the extrinsic cues to plant intrinsic signalling pathways. Here we report a role of leaf trichomes in tobacco (Nicotiana tabacum) hypersensitive cell death (HCD) induced by ParA1, an elicitin protein from a plant-pathogenic oomycete. After localized treatment with ParA1, reactive oxygen species were produced first in the leaf trichomes and then in mesophylls. Reactive oxygen species are a group of intracellular signals that are crucial for HCD to develop and for cells to undergo cell death subsequent to chromatin condensation, a hallmark of HCD. These events were impaired when the production of hydrogen peroxide (H2O2) was inhibited by catalase or a NADPH-oxidase inhibitor applied to trichomes, suggesting the importance of H2O2 in the pathway of HCD signal transduction from the trichomes to mesophylls. This pathway was no longer activated when leaf trichomes were treated with C51S, a ParA1 mutant protein defective in its interaction with N. tabacum TTG1 (NtTTG1), which is a trichome protein that binds ParA1, rather than C51S, in vitro and in trichome cells. The ParA1-NtTTG1 interaction and the HCD pathway were also abrogated when NtTTG1 was silenced in the trichomes. These observations suggest that NtTTG1 plays an essential role in HCD signal transduction from leaf trichomes to mesophylls [ABSTRACT FROM AUTHOR]