AO Activity Research Articles

The flaring activity of blazar AO 0235+164 in 2021

Context. The blazar AO 0235+164, located at redshift z = 0.94, has displayed interesting and repeating flaring activity in the past, with recent episodes in 2008 and 2015. In 2020, the source brightened again, starting a new flaring episode that peaked in 2021. Aims. We study the origin and properties of the 2021 flare in relation to previous studies and the historical behavior of the source, in particular the 2008 and 2015 flaring episodes. Methods.We analyzed the multiwavelength photo-polarimetric evolution of the source. From Very Long Baseline Array images, we derived the kinematic parameters of new components associated with the 2021 flare. We used this information to constrain a model for the spectral energy distribution of the emission during the flaring period. We propose an analytical geometric model to test whether the observed wobbling of the jet is consistent with precession. Results. We report the appearance of two new components that are ejected in a different direction than previously, confirming the wobbling of the jet. We find that the direction of ejection is consistent with that of a precessing jet. Our derived period agrees with the values commonly found in the literature. Modeling of the spectral energy distribution further confirms that the differences between flares can be attributed to geometrical effects.

Repeating flaring activity of the blazar AO 0235+164

Context. Blazar AO 0235+164, located at a redshift of z = 0.94, has undergone several sharp multi-spectral-range flaring episodes over recent decades. In particular, the episodes that peaked in 2008 and 2015, which were subject to extensive multi-wavelength coverage, exhibited an interesting behavior. Aims. We study the actual origin of these two observed flares by constraining the properties of the observed photo-polarimetric variability as well as of the broadband spectral energy distribution and the observed time-evolution behavior of the source. We use ultra-high-resolution total-flux and polarimetric very-long-baseline interferometry (VLBI) imaging. Methods. The analysis of VLBI images allowed us to constrain kinematic and geometrical parameters of the 7 mm jet. We used the discrete correlation function to compute the statistical correlation and the delays between emission at different spectral ranges. The multi-epoch modeling of the spectral energy distributions allowed us to propose specific models of the emission; in particular, with the aim to model the unusual spectral features observed in this source in the X-ray region of the spectrum during strong multi spectral-range flares. Results. We find that these X-ray spectral features can be explained by an emission component originating in a separate particle distribution than the one responsible for the two standard blazar bumps. This is in agreement with the results of our correlation analysis, where we did not find a strong correlation between the X-ray and the remaining spectral ranges. We find that both external Compton-dominated and synchrotron self-Compton-dominated models are able to explain the observed spectral energy distributions. However, the synchrotron self-Compton models are strongly favored by the delays and geometrical parameters inferred from the observations.

Phytochemical profile and anti-inflammatory effect of Artemisia annua L. essential oil

Plant-derived natural compounds are desired for their anti-inflammatory properties. We investigated the chemical composition and the anti-inflammatory effects of the essential oil obtained from leaves of the Chinese medicinal plant Artemisia annua L. Artemisia annua L. essential oil (AO) was obtained by hydrodistillation; the extraction yield was approximately 1.2%. Gas chromatography–mass spectrometry (GC–MS) revealed the presence of 13 compounds in AO; the major compounds were caryophyllene (32.16%), eucalyptol (28.62%), α-pinene (19.08%), and β-pinene (14.72%). Cell counting kit-8 (CCK8) assay revealed that AO did not show in vitro cytotoxicity toward RAW264.7 cells and suppressed the expression of nitric oxide (NO), tumor necrosis factor-alpha (TNF-α), and interleukin-6 (IL-6) in lipopolysaccharide (LPS)-induced RAW264.7 cells. Pretreatment with AO significantly reduced xylene-induced inflammation in the ears of Kunming mice. AO inhibited inflammatory cell infiltration, decreased epidermis thickness in the ear, and suppressed expression of TNF-α in the serum. The in vivo anti-inflammatory activity of AO was similar to that of the positive control compound Di Song Zhang Bo Cream. Overall, AO was observed to be an effective anti-inflammatory agent. These results provide an experimental basis for commercializing AO-derived external preparations for pharmacological and cosmetic industries.

A near magnetic-to-kinetic energy equipartition flare from the relativistic jet in AO 0235 + 164 during 2013–2019

ABSTRACT We present the multiwavelength flaring activity of the blazar AO 0235 + 164 during its recent active period from 2013 to 2019. From a discrete correlation function analysis, we find a significant ($\gt 95~{{\ \rm per\ cent}}$) correlation between radio and gamma-ray light curves with flares at longer wavelengths following flares at shorter wavelengths. We identify a new jet component in 43 GHz Very Long Baseline Array data that was ejected from the radio core on MJD $57246^{+26}_{-30}$ (2015 August 12), during the peak of the 2015 radio flare. From the analysis of the jet component, we derived a Doppler factor of δvar = 28.5 ± 8.4, a bulk Lorentz factor of $\Gamma =16.8^{+3.6}_{-3.1}$, and an intrinsic viewing angle of $\theta _{\rm v}=1.42^{+1.07}_{-0.52}\textrm {~degrees}$. Investigation of the quasi-simultaneous radio data revealed a partially absorbed spectrum with the turnover frequency varying in the range of 10−70 GHz and the peak flux density varying in the range of 0.7−4 Jy. We find the synchrotron self-absorption magnetic field strength to be $B_{\rm SSA}=15.3^{+12.6}_{-14.0}\textrm {~mG}$ at the peak of the 2015 radio flare, which is comparable to the equipartition magnetic field strength of $B_{\rm EQ}=43.6^{+10.6}_{-10.4}\textrm {~mG}$ calculated for the same epoch. Additional analysis of the radio emission region in the relativistic jet of AO 0235 + 164 suggests that it did not significantly deviate from equipartition during its recent flaring activity.

Extraction of Faloak Stem Bark (Sterculia quadrifida R. Br) Using Microwave-Assisted Extraction Method And LC-HRMS Profiling of the Extract

The extraction of bioactive plants is an essential step in isolating the targeted bioactive compounds. Microwave-assisted extraction (MAE) offers a green technology extraction that can minimize energy, time, and solvent and is a suitable method for extracting thermolabile plant bioactive compounds. The study aims to find out the optimal time and temperature for isolating the total phenolic content (TPC), total flavonoid (TF), and antioxidant activity (AO) of faloak stem bark (FSB) (Sterculia quadrifida R. Br) and to profile the phytochemicals in the FSB extract using sophisticated of LC-HRMS (Liquid Chromatography High-Resolution Mass Spectrometry). The research used the Randomized Block Design (RBD) method with two factors. The factors were the extraction time (5, 15, and 25 min) and temperature variation (50, 60, and 70°C). The data of observed parameters were calculated using Analysis of Variance (ANOVA) and followed by a further test with a 95% confidence interval. The results showed an interaction between temperature and time of extraction on TPC, TF, and AO activity. The best MAE condition for extracting FSB was achieved at 60°C for 25 min. The FSB extract had a TPC of 81.2 mg GAE/g, TF of 70.30 mg QE/g, and AO activity of 67.8%. LC-HRMS revealed the newly identified phenolic compounds such as methyl cinnamate, vanillin, apocynin, scopoletin, L(-)-pipecolinic acid, arecoline, δ-valerolactam, 3,4-dihydroxybenzaldehyde, 4-hydroxybenzaldehyde; flavonoids such as epicatechin and rutin and some fatty acids and its derivatives. Future research could focus on developing new therapies for promoting human health using extract FSB.

In Vitro and In Vivo Protective Effects of Agaro-Oligosaccharides against Hydrogen Peroxide-Stimulated Oxidative Stress.

In our previous research, we investigated the anti-inflammatory activity of the agaro-oligosaccharides prepared from the agar of Gracilaria lemaneiformis (AO). In the present study, in order to further explore the bioactivities of AO, the antioxidant activity of AO was investigated in vitro in Vero cells and in vivo in zebrafish. AO scavenged alkyl, 1,1-diphenyl-2-picrylhydrazyl, and hydroxyl radicals at the IC50 value of 4.86 ± 0.13, 3.02 ± 0.44, and 1.33 ± 0.05 mg/mL, respectively. AO significantly suppressed hydrogen peroxide (H2O2)-stimulated oxidative damage by improving cell viability. This happened via suppressing apoptosis by scavenging intracellular reactive oxygen species (ROS). Furthermore, the in vivo results displayed that AO protected zebrafish against H2O2-stimulated oxidative damage by reducing the levels of intracellular ROS, cell death, and lipid peroxidation in a dose-dependent manner. These results indicate that AO effectively alleviated in vitro and in vivo oxidative damage stimulated by H2O2, and suggest the potential of AO in the cosmetic and functional food industries.

Application of a synthetic phenol-type antioxidant for cryopreservation of Russian sturgeon (Acipenser gueldenstaedtii) sperm

Antioxidative and cryoprotective effects of a novel synthetic antioxidant–1,1'-(piperazine-1,4-diyl)bis(2-(2-hydroxyphenylthio)ethanone (AO) is presented in comparison with commonly known antioxidant butylated hydroxytoluene (BHT). Superoxide anion radical scavenging activity of new AO and the increase in superoxide dismutation activity of the Russian sturgeon’s (Acipenser gueldenstaedtii) sperm were established in the presence of this compound. It was shown that the new phenol agent reduces level of carbonyl oxidation by-products, which can react with thiobarbituric acid (TBARS), in Russian sturgeon’s native and frozen/thawed sperm, which indicates the manifestation of antioxidant properties by this compound including under the action of damaging factors during cryopreservation. A beneficial effect of this phenol derivative on the activity indicators (the percentage of motile sperm cells and total period of sperm movement) of the Russian sturgeon’s frozen/thawed sperm was shown, which indicates the cryoprotective effect of a novel synthetic antioxidant. The efficiency of the AO exceeds the effect of BHT under cryopreservation conditions of Russian sturgeon sperm in the presence of the modified Stein’s medium, but further studies are needed on the effect of a new phenol agent on the fertilizing capacity of Russian sturgeon’s sperm.

Osa-miR528 promotes seedling growth by enhancing nitrate uptake under nitrogen deficiency in rice

Nitrogen (N) is required for a plant’s normal growth and development. It has been shown that miRNAs play a vital role in N uptake, assimilation and translocation in plants. However, there are few studies, so far, showing a single miRNA regulating seedling growth under varying N concentrations from different sources. Here, we showed that the expression of rice miR528 was higher when induced by NO 3 - -N than that by NH 4 + -N. Further analysis indicated that overexpression of miR528 (OE) increased seedling biomass and roots total N content up to 82.70% and 133.31%, respectively, under NO 3 - -N deficiency. Conversely, mir528 exhibited an opposite phenotype compared with the OE plants, that is, a large margin of decrease of seedling biomass and roots’ total N content up to 21.60% and 22.45%, respectively. In addition, short-term 15 NO 3 - influx rates and mean net NO 3 - influx rates were increased in OE plants, which was consistent with the upregulated expression of OsNRT2s family member genes under NO 3 - -N deficiency condition. What’s more, OsAO was identified as the downstream target in response to NO 3 - -N and reduced AO activity in OE plants was found under NO 3 - -N starvation. Our data established that miR528 plays a positive role in regulating rice seedling growth in response to N deficiency, illustrating its capacity for engineering biomass improvement in crops. • osa-miR528 was the first miRNA regulating nitrate (NO 3 - ) uptaking in rice. • Overexpression of miR528 (OE) significantly improves dry weight and roots total N content by enhancing NO 3 - -N up-taking. • AO activity is induced by miR528- OsAO module under NO 3 - -N deficiency.

Changes of quality and free radical scavenging activity of strawberry and raspberry frozen under different conditions

The effects of different freezing methods and long-term frozen storage on quality of strawberry and raspberry were investigated, that is, the retention of initial property and free radical scavenging (AO) activity after individual quick freezing (IQF) and conventional (discontinuous) freezing. The physicochemical properties, vitamin C, and AO activity were more affected by long-term frozen storage than by freezing itself; however, their better retention was obtained after IQF. Moreover, AO activity was found to be higher in frozen samples compared to fresh fruits, but significant decrease was detected after 8 months of frozen storage. Despite the significantly higher initial content of vitamin C in strawberry, it demonstrated a lower AO activity than raspberry. Sensory attributes were significantly affected by freezing; the most considerable changes were recorded on their texture/firmness, especially after conventional (slow) freezing. Therefore, IQF can generally be suggested as a more suitable method of preserving these delicate fruits than slow freezing. Practical applications Nowadays, consumers are increasingly interested in foods that possess not only good nutritional value but also health-promoting property. Berries are known as rich sources of micronutrients and antioxidant compounds, but consumption of fresh strawberry and raspberry fruits may be limited because of seasonal and market availability; therefore, they must be preserved commonly by freezing. Frozen food industry is of crucial importance for developing countries, in which the fast freezing industry is rapidly developed. Investigation of the effect of industrial freezing and frozen storage on retention of the quality-related property and antioxidant activity is important for providing the best quality for consumers and health benefits, as well as international fruit trade. In addition, the results obtained in this study could provide best practice and guidance for the frozen fruit industry.

Experimental testing of hypotheses for temperature- and pH-based niche specialization of ammonia oxidizing archaea and bacteria.

Investigation of niche specialization in microbial communities is important in assessing consequences of environmental change for ecosystem processes. Ammonia oxidizing bacteria (AOB) and archaea (AOA) present a convenient model for studying niche specialization. They coexist in most soils and effects of soil characteristics on their relative abundances have been studied extensively. This study integrated published information on the influence of temperature and pH on AOB and AOA into several hypotheses, generating predictions that were tested in soil microcosms. The influence of perturbations in temperature was determined in pH 4.5, 6 and 7.5 soils and perturbations in pH were investigated at 15°C, 25°C and 35°C. AO activities were determined by analysing changes in amoA gene and transcript abundances, stable isotope probing and nitrate production. Experimental data supported major predictions of the effects of temperature and pH, but with several significant discrepancies, some of which may have resulted from experimental limitations. The study also provided evidence for unpredicted activity of AOB in pH 4.5 soil. Other discrepancies highlighted important deficiencies in current knowledge, particularly lack of consideration of niche overlap and the need to consider combinations of factors when assessing the influence of environmental change on microbial communities and their activities.

Silencing of ascorbate oxidase results in reduced growth, altered ascorbic acid levels and ripening pattern in melon fruit

Ascorbate oxidase (AO, EC 1.10.3.3) is a copper-containing enzyme localized at the apoplast, where it catalyzes the oxidation of ascorbic acid (AA) to dehydroascorbic acid (DHA) via monodehydroascorbic acid (MDHA) intermediate. Despite it has been extensively studied, no biological roles have been definitively ascribed. To understand the role of AO in plant metabolism, fruit growth and physiology, we suppressed AO expression in melon (Cucumis melo L.) fruit. Reduction of AO activity increased AA content in melon fruit, which is the result of repression of AA oxidation and simultaneous induction of certain biosynthetic and recycling genes. As a consequence, ascorbate redox state was altered in the apoplast. Interestingly, transgenic melon fruit displayed increased ethylene production rate coincided with elevated levels of 1-aminocyclopropane-1-carboxylic acid (ACC) oxidase (ACO, EC 1.14.17.4) activity and gene expression, which might contribute to earlier ripening. Moreover, AO suppressed transgenic melon fruit exhibited a dramatic arrest in fruit growth, due to a simultaneous decrease in fruit cell size and in plasmalemma (PM) ATPase activity. All the above, support for the first time, the in vivo AO participation in the rapid fruit growth of Cucurbitaceae and further suggest an alternative route for AA increase in ripening fruit.

Evaluation of novel green walnut liqueur as a source of antioxidants: Multi-method approach.

In this study, a novel green walnut liqueur (GWL) based on green walnuts, as the main ingredient, with the addition of fruits, aromatic plants, chocolate and honey, was produced at the pilot-scale. Antioxidant activity (AO) of the obtained GWL was determined using multiple AO assays in parallel, standard spectrophotometric (FC, DPPH and FRAP) and recently developed electrochemical ones, HydroxoPerhydroxoMercury(II) Complex and Mercury Reduction Antioxidant Power, and compared to similar commercial alcoholic beverages. Characterization of the GWL in terms of volatile and polyphenolic components was performed using SPE-GC-MS and HPLC-DAD-MS/MS, respectively. Sensory quality assessment was performed by experts in the field of sensory analysis of alcoholic beverages, using a scoring method. According to all AO assays applied, AO activity and total phenolics content of GWL were superior in comparison to commercial spirits considered. The volatile fraction of GWL was mainly composed of eugenol, α-terpineol and vanillin, while the most prevalent phenolic compounds were gallic (5.054mg/L) and chlorogenic acid (1.307mg/L) and flavonoids such as catechine (0.882mg/L), quercetin (0.499mg/L) and its sugar-conjugated derivatives, quercetin 3-O-glucoside (0.774mg/L) and quercetin-3-O-rhamnoside (0.614mg/L). Gallic acid is the major contributor to total AO activity, especially determined by DPPH and FRAP, followed by catechine, quercetin and chlorogenic acid. Among the terpenoids, contribution of eugenol to total AO activity is estimated as the highest. Excellent sensory quality (18.52 of maximum 20 scores) was ascribed to GWL. Consequently, the presence of bioactive compounds and high AO activity of GWL, in addition to high sensory quality score, indicates a high market potential for this high-value product.

Changes in tissue oxidative enzymes in rats exposed to red bull energy drink and alcohol

There is increase in combined ingestion of alcoholic beverages and energy drinks, but studies on their combined effects on tissue oxidative enzymes are limited. Hence, the present study examined the changes in tissue oxidative enzymes (aldehyde oxidase, AO, EC 1.2.3.1; xanthine oxidase, XO, EC 1.17.3.2; sulphite oxidase, SO, EC 1.8.3.1; and monoamine oxidase, MO, EC 1.4.3.4) in the liver, kidney, heart, brain and testes of rats exposed to red bull energy drink and ethanol. Twenty eight Wistar rats (190±5g) were used for the study. The animals were divided into four groups. Group 1 which was fed with only grower’s mash and water served as control. In addition to the normal dietand water rats in Group 2 receivedRed bull energy drink (3.5ml/kg body weight), while those in Group 3 received Ethanol (1.25g/kg body weight) by intubation. Rats in Group 4 received bothred bull and ethanol as in Groups 2 and 3.Consumption of red bull significantly (P<0.05) decreased liver AO activity as compared to control. The results showed that red bull, ethanol or their combination had variable effects on tissue oxidative enzymes as alteration was observed in the activity of the oxidative enzymes. The effect of a combination of red bull and ethanol was more pronounced in the liver MO, kidney AO, liver XO and liver SO than either red bull or ethanol alone. In conclusion the present study has shown that consumption of red bull, ethanol or their combination may alter the ability of tissue oxidative enzymes to metabolize zenobiotics.Keywords: Oxidative enzymes, Energy drinks, Alcohol, Red Bull, Rat

Transcriptional Regulation of miR528 by OsSPL9 Orchestrates Antiviral Response in Rice

Many microRNAs (miRNAs) are critical regulators of plant antiviral defense. However, little is known about how these miRNAs respond to virus invasion at the transcriptional level. We previously show that defense against Rice stripe virus (RSV) invasion entailed a reduction of miR528 accumulation in rice, alleviating miR528-mediated degradation of L-Ascorbate Oxidase (AO) mRNA and bolstering the antiviral activity of AO. Here we show that the miR528-AO defense module is regulated by the transcription factor SPL9. SPL9 displayed high-affinity binding to specific motifs within the promoter region of miR528 and activated the expression of miR528 gene in vivo. Loss-of-function mutations in SPL9 caused a significant reduction in miR528 accumulation but a substantial increase of AO mRNA, resulting in enhanced plant resistance to RSV. Conversely, transgenic overexpression of SPL9 stimulated the expression of miR528 gene, hence lowering the level of AO mRNA and compromising rice defense against RSV. Importantly, gain in RSV susceptibility did not occur when SPL9 was overexpressed in mir528 loss-of-function mutants, or in transgenic rice expressing a miR528-resistant AO. Taken together, the finding of SPL9-mediated transcriptional activation of miR528 expression adds a new regulatory layer to the miR528-AO antiviral defense pathway.

Differential influence of molybdenum and tungsten on the growth of barley seedlings and the activity of aldehyde oxidase under salinity

The influence of molybdenum, tungsten on germination and growth of barley Hordeum vulgare L. was studied. Results of this study revealed the differential effect of heavy metals on seedlings growth. Exogenous molybdenum treatment stimulated the growth of seedlings. The addition of the metal significantly stimulated root elongation. Contrastingly, the addition of tungsten resulted in increased seed germination and inhibits the growth of seedlings. The negative effect of tungsten on the growth of barley was more profound for roots of plants. In addition, the influence of metals on the growth of plants was also tested in saline conditions. It is shown that under salinity stress plant growth drastically decreased in presence of tungsten. Results of this study showed that activity of molybdenum-containing aldehyde oxidase (AO; EC 1.2.3.1) was also significantly affected by metals. The activity of AO in leaves and roots enhanced with increasing concentrations of molybdate, while tungstate treatment inhibited the enzyme activity. Perhaps, the differential influence of molybdenum and tungsten on the growth of barley is a direct effect of metals on aldehyde oxidase activity in plants. Moreover, the intense negative effect of tungsten treatment on barley growth under salinity conditions emphasizes an important role of aldehyde oxidase in plant resistance to stress factors.

Aromadendrene oxide 2, induces apoptosis in skin epidermoid cancer cells through ROS mediated mitochondrial pathway

AimsAromadendrene oxide 2 (AO-(2)) is an oxygenated sesquiterpene naturally found as a chemical component of essential oils. In the present study anticancer activity of AO-(2) has been investigated on A431 human epidermoid cancer and precancerous HaCaT cells. Material and methodsCell viability was used to detect cytotoxic activity. Mechanism of cell death induced by AO-(2) treatments was studied using Annexin V-FITC/PI binding, cell cycle analysis, measurement of MMP and ROS generation by flow cytometry. Expression of apoptosis related proteins was investigated by western blot. Key findingsAO-(2) inhibited the growth and colony formation ability of A431 and HaCaT cells in concentration dependent manner. It induced cell cycle arrest at G0/G1 phase and apoptosis through intracellular ROS accumulation. Inhibition of intracellular ROS by ascorbic acid and N-acetyl cysteine treatment completely blocked apoptotic effect. N-acetyl cysteine treatment significantly reversed G0/G1 arrest induced by AO-(2). AO-(2) treatment caused loss of mitochondrial membrane potential (ΔΨm), increase in Bax/Bcl-2 ratios, cytochrome c release, activation of caspases (cleaved caspase-3 and caspase-9) and PARP cleavage. AO-(2) also significantly inhibited the growth of multicellular tumor spheroids of A431 and HaCaT cells. SignificanceThe results of the present study reveals that AO-(2) a chemical component of essential oils induces apoptosis in A431 and HaCaT cells.

Nitric oxide acts downstream of abscisic acid in molybdenum-induced oxidative tolerance in wheat.

Our study first reveals that Mo mediates oxidative tolerance through ABA signaling. Moreover, NO acts downstream of ABA signaling in Mo-induced oxidative tolerance in wheat under drought stress. Nitric oxide (NO) is related to the improvement of molybdenum (Mo)-induced oxidative tolerance. While the function of Mo in abscisic acid (ABA) synthesis and in mediating oxidative tolerance by the interaction of ABA and NO remain to be studied. The -Mo and +Mo treatment-cultivated wheat was separated and subsequently was pretreated with AO inhibitor, ABA synthesis inhibitor, exogenous ABA, NO scavenger, NO donor or their combinations under polyethylene glycol 6000 (PEG)-stimulated drought stress (PSD). The AO activity and ABA content were increased by Mo in wheat under PSD, however, AO inhibitor decreased AO activity, correspondingly reduced ABA accumulation, suggesting that AO involves in the regulation of Mo-induced ABA synthesis. Mo enhanced activities andexpressions of antioxidant enzyme, while these effects of Mo were reversed by AO inhibitor and ABA synthesis inhibitor due to the decrease of ABA content, but regained by exogenous ABA, indicating that Mo induces oxidative tolerance through ABA. Moreover, NO scavenger inhibited activities of antioxidant enzyme caused by Mo and exogenous ABA, but the inhibitions were eliminated by NO donor, indicating that NO is involved in ABApathway in the regulation of Mo-induced oxidative tolerance in wheat under PSD. Finally, we proposed a scheme for the mechanism of Mo-induced oxidative tolerance.

Role of Biotic Elicitors as Potent Inducer of Defence Mechanism against Salt-Stress in Wheat (Triticum aestivum L.)

Wheat (Triticum aestivum L.) known as bread wheat (hexaploid), is an important cereal for millions around the world. Excessive salts in soil affect growth, development and productivity of crop plants and have been major constraints to agriculture. Plants, being sessile in nature, have developed mechanisms to cope with high salt concentrations in soil. To understand salt-tolerance in crop plant and its improvement, Total Phenolic Content (TPC), Lipid Peroxidation (LP), total Antioxidant activity (AO) and high affinity potassium transporters (HKTs) in shoot and root regions of contrasting wheat genotype WH 542 (salt-susceptible) and KRL 210 (salt-tolerant) were studied on seed priming with two different biotic elicitors-Salicylic Acid (SA) and Methyl Jasmonate (MJ). Primed seeds were sown in pots under controlled conditions in phytotron and were exposed to 150 mM NaCl stress after 14 days of germination. Expression pattern of HKT genes in the root and shoot of the primed and unprimed as well as stressed and unstressed seedlings were also studied using semi-quantitative and quantitative analysis. Higher levels of TPC, LP and AO activity were observed in the contrasting wheat genotypes under salt stressed condition. Both HKT1 and HKT3 genes were involved in regulating ion homeostasis. Up and down regulation of expression of HKT genes in shoot and root, respectively, provide resistance against salt uptake. Biotic elicitors (SA and MJ) were found to mitigate the effect of salt-stress by affecting expression of HKT genes as well their biochemical-processes. MJ showed better response than that of SA, and can be utilized to improve defense responses of crop plant against salt stress. The regulation of gene expressions and signaling cascades that regulate Na+ transporters remain to be elucidated and these studies will help in understanding the mechanism of ion homeostasis during salt stress to improve crop yield.

ROS accumulation and antiviral defence control by microRNA528 in rice.

MicroRNAs (miRNAs) are key regulators of plant-pathogen interactions. Modulating miRNA function has emerged as a new strategy to produce virus resistance traits1-5. However, the miRNAs involved in antiviral defence and the underlying mechanisms remain largely elusive. We previously demonstrated that sequestration by Argonaute (AGO) proteins plays an important role in regulating miRNA function in antiviral defence pathways6. Here we reveal that cleavage-defective AGO18 complexes sequester microRNA528 (miR528) upon viral infection. We show that miR528 negatively regulates viral resistance in rice by cleaving L-ascorbate oxidase (AO) messenger RNA, thereby reducing AO-mediated accumulation of reactive oxygen species. Upon viral infection, miR528 becomes preferentially associated with AGO18, leading to elevated AO activity, higher basal reactive oxygen species accumulation and enhanced antiviral defence. Our findings reveal a mechanism in which antiviral defence is boosted through suppression of an miRNA that negatively regulates viral resistance. This mechanism could be manipulated to engineer virus-resistant crop plants.

Discovery of Imidazoquinolines as a Novel Class of Potent, Selective, and in Vivo Efficacious Cancer Osaka Thyroid (COT) Kinase Inhibitors.

Cancer Osaka thyroid (COT) kinase is an important regulator of pro-inflammatory cytokines in macrophages. Thus, pharmacologic inhibition of COT should be a valid approach to therapeutically intervene in the pathogenesis of macrophage-driven inflammatory diseases such as rheumatoid arthritis. We report the discovery and chemical optimization of a novel series of COT kinase inhibitors, with unprecedented nanomolar potency for the inhibition of TNFα. Pharmacological profiling in vivo revealed a high metabolism of these compounds in rats which was demonstrated to be predominantly attributed to aldehyde oxidase. Due to the very low activity of hepatic AO in the dog, the selected candidate 32 displayed significant blood exposure in dogs which resulted in a clear prevention of inflammation-driven lameness. Taken together, the described compounds both potently and selectively inhibit COT kinase in primary human cells and ameliorate inflammatory pathologies in vivo, supporting the notion that COT is an appropriate therapeutic target for inflammatory diseases.