Differential Proteomic Analysis of Arabidopsis thaliana Genotypes Exhibiting Resistance or Susceptibility to the Insect Herbivore,Plutella xylostella

A proteomic study was conducted to investigate physiological factors affecting feeding behaviour by larvae of the insect, Plutella xylostella, on herbivore-susceptible and herbivore-resistant Arabidopsis thaliana. The leaves of 162 recombinant inbred lines (Rils) were screened to detect genotypes upon which Plutella larvae fed least (P. xylostella-resistant) or most (P. xylostella-susceptible). 2D-PAGE revealed significant differences in the proteomes between the identified resistant and susceptible Rils. The proteomic results, together with detection of increased production of hydrogen peroxide in resistant Rils, suggest a correlation between P. xylostella resistance and the production of increased levels of reactive oxygen species (ROS), in particular H₂O₂, and that this was expressed prior to herbivory. Many of the proteins that were more abundant in the Plutella-resistant Rils are known in other biological systems to be involved in limiting ROS damage. Such proteins included carbonic anhydrases, malate dehydrogenases, glutathione S-transferases, isocitrate dehydrogenase-like protein (R1), and lipoamide dehydrogenase. In addition, patterns of germin-like protein 3 isoforms could also be indicative of higher levels of reactive oxygen species in the resistant Rils. Consistent with the occurrence of greater oxidative stress in the resistant Rils is the observation of greater abundance in susceptible Rils of polypeptides of the photosynthetic oxygen-evolving complex, which are known to be damaged under oxidative stress. The combined results suggest that enhanced production of ROS may be a major pre-existing mechanism of Plutella resistance in Arabidopsis, but definitive corroboration of this requires much further work.     

Piroxicam confer neuroprotection in Cerebral Ischemia by inhibiting Cyclooxygenases,Acid- Sensing Ion Channel-1a and Aquaporin-4: an in silico comparison with Aspirin and Nimesulide

Cerebral ischemia (CI), caused by the deprivation of oxygen and glucose to the brain, is the leading cause of permanent disability.Neuronal demise in CI has been linked to several pathways which include cyclooxygenases (COX) − mediated production ofprostaglandins (PGs) and subsequently reactive oxygen species (ROS), aquaporin-4 (AQ-4) − mediated brain edema and acidsensingion channel-1a (ASIC-1a) − mediated acidotoxicity, matrix remodeling, in addition to others. Several non-steroidal antiinflammatorydrugs (NSAIDs) are presently in use to prevent these pathways. However, owing to the large number of processesinvolved, there is high drug load. So, identifying drugs with multimodal role has always been a frequently sought venture. Thepresent in silico study has been performed to find out the relative efficacy of three different NSAIDs (Piroxicam, Aspirin andNimesulide) in preventing neurodegeneration in CI, with respect to their inhibitory potential on COXs, AQ-4 and ASIC-1a. We findthat piroxicam is the most potent inhibitor of these receptors as compared to the NSAIDs under investigation. Since piroxicam hasalready been reported to inhibit N-methyl-D-aspartate (NMDA) receptor and matrix metalloproteinases (MMPs), which are alsolinked to CI-induced neurodegeneration, we hereby propose piroxicam to be a gold-standard drug in preventingneurodegeneration in CI.     

Effects of fluoxetine and LY 367265 on tolerance to the analgesic effect of morphine in rats

Morphine is widely used to treat chronic pain, however its utility is hindered by the development of tolerance to its analgesic effects. The aim of this study was to investigate effects of fluoxetine, a specific serotonin (5-HT) reuptake inhibitor, and LY 367265, an inhibitor of the 5-HT transporter and 5-HT2A receptor antagonist, on tolerance induced to the analgesic effect of morphine in rats. The study was carried out on male Wistar Albino rats (weighing 170-190 g). To constitute morphine tolerance, animals received morphine (50 mg/kg; s.c.) once daily for 3 days. After last dose of morphine, injected on day 4, morphine tolerance was evaluated. The analgesic effects of fluoxetine (10 mg/ kg; i.p.), LY 367265 (3 mg/kg; i.p.) and morphine were considered at 30-min intervals by tail-flick and hot-plate tests. The results showed that fluoxetine and LY 367265 significantly attenuated the development and expression of morphine tolerance. The maximal antinociceptive effects were obtained 30 min after administration of fluoxetine and 60 min after administration of LY 367265. In conclusion, we observed that co-injection of morphine with fluoxetine and LY 367265 increased the analgesic effects of morphine and delayed development of tolerance to morphine analgesia.     

Hypodipsic-hypernatremia syndrome in an adult with polycythemia: a case report

Background

Hypernatremia is a very common electrolyte disorder and is frequently encountered in out-patient as well as in-hospital settings. We describe an adult who was found to have unexplained relative polycythemia and episodic hypernatremia. A diagnosis of idiopathic hypodipsic-hypernatremia syndrome was made and the patient was managed with a water-drinking schedule.

Case presentation

A 24-year-old South African-Indian man was found to have polycythemia in association with episodes of hypernatremia. Investigations indicated that he had relative polycythemia. He experienced no thirst at a time when his serum sodium concentration was found to be 151?mmol/L. Further testing indicated that his renal response to arginine vasopressin was intact and magnetic resonance imaging of his brain revealed no hypothalamic lesions. A diagnosis of idiopathic hypodipsic-hypernatremia syndrome was made and he was managed with a water-drinking schedule that corrected his hypernatremia.

Conclusion

Hypodipsia should always be considered when a patient without physical or cognitive disability presents with unexplained episodic hypernatremia or with relative polycythemia.

     

Effects of oral L-arginine supplementation on blood pressure and asymmetric dimethylarginine in stress-induced preeclamptic rats

This study was carried out to elucidate the role of asymmetric dimethylarginine (ADMA) and nitric oxide (NO) in preeclampsia development, and to investigate the effect of L-arginine supplementation in rats. Preeclampsia was induced in pregnant rats using a stress model. L-arginine was administered orally and ADMA, urinary nitrate, and protein levels were measured on the 20th day of pregnancy. Compared with the group of rats that are normally pregnant, the levels of blood pressure (BP), protein excretion, and ADMA were significantly increased in preeclampsia which returned to normal levels following the supplementation of L-arginine. Both group of rats had similar urine nitrate levels. Arginine-ADMA-NO pathway is affected in preeclampsia. L-arginine supplementation decreased hypertension (HT), proteinuria, and ADMA levels indicating that taking L-arginine may be beneficial in preeclampsia treatment.     

Edgetic perturbation models of human inherited disorders

Cellular functions are mediated through complex systems of macromolecules and metabolites linked through biochemical and physical interactions, represented in interactome models as ‘nodes’ and ‘edges’, respectively. Better understanding of genotype‐to‐phenotype relationships in human disease will require modeling of how disease‐causing mutations affect systems or interactome properties. Here we investigate how perturbations of interactome networks may differ between complete loss of gene products (‘node removal’) and interaction‐specific or edge‐specific (‘edgetic’) alterations. Global computational analyses of ～50 000 known causative mutations in human Mendelian disorders revealed clear separations of mutations probably corresponding to those of node removal versus edgetic perturbations. Experimental characterization of mutant alleles in various disorders identified diverse edgetic interaction profiles of mutant proteins, which correlated with distinct structural properties of disease proteins and disease mechanisms. Edgetic perturbations seem to confer distinct functional consequences from node removal because a large fraction of cases in which a single gene is linked to multiple disorders can be modeled by distinguishing edgetic network perturbations. Edgetic network perturbation models might improve both the understanding of dissemination of disease alleles in human populations and the development of molecular therapeutic strategies.     

Phosphorylation of a reinitiation supporting protein,RISP, determines its function in translation reinitiation

Reinitiation supporting protein, RISP, interacts with 60S (60S ribosomal subunit) and eIF3 (eukaryotic initiation factor 3) in plants. TOR (target-of-rapamycin) mediates RISP phosphorylation at residue Ser267, favoring its binding to eL24 (60S ribosomal protein L24). In a viral context, RISP, when phosphorylated, binds the CaMV transactivator/ viroplasmin, TAV, to assist in an exceptional mechanism of reinitiation after long ORF translation. Moreover, we show here that RISP interacts with eIF2 via eIF2β and TOR downstream target 40S ribosomal protein eS6. A RISP phosphorylation knockout, RISP-S267A, binds preferentially eIF2β, and both form a ternary complex with eIF3a in vitro. Accordingly, transient overexpression in plant protoplasts of RISP-S267A, but not a RISP phosphorylation mimic, RISP-S267D, favors translation initiation. In contrast, RISP-S267D preferentially binds eS6, and, when bound to the C-terminus of eS6, can capture 60S in a highly specific manner in vitro, suggesting that it mediates 60S loading during reinitiation. Indeed, eS6-deficient plants are highly resistant to CaMV due to their reduced reinitiation capacity. Strikingly, an eS6 phosphomimic, when stably expressed in eS6-deficient plants, can fully restore the reinitiation deficiency of these plants in cellular and viral contexts. These results suggest that RISP function in translation (re)initiation is regulated by phosphorylation at Ser267.     

Analysis of G6PD enzyme deficiency in Saudi population

The evolutionary conservation of a housekeeping gene such as G6PD is greater than that of tissue-specific genes, presumably because the latter may require more specific adaptation to the physiology of individual organisms. The abundance of distinct mutation sites and their clinical manifestations make G6PD ideal for structure-function analysis. Therefore, it is of interest to screen of G6PD deficiency in the blood donors in Kingdom of Saudi Arabia. We report the mean and variation of enzyme activity in a huge set of Suadi to non-Saudi population with reference to the entire population. The sequence level conservation of G6PD among distant species is demonstrated using phylogenetic trees. These observations have implications in the sequence-structure-function understanding of G6PD with reference to its association to several human diseases.     

Oven,Temperature-Controlled Microwave,and Shade Drying Effects on Drying Kinetics,Bioactive Compounds and Antioxidant Activity of Knotweed (Polygonum cognatum Meissn.)

In this study, the plant node was dried in an oven (40, 50 and 60 °C), shade and temperature-controlled microwave (40, 50 and 60 °C) methods. Statistically (p<0.05), the values closest to the color values of fresh grass were determined in an oven at 40 °C drying temperature. Effective diffusion values varied between 8.85×10⁻⁸–5.65×10⁻⁶ m² s⁻¹. While the activation energy was 61.28 kJ mol⁻¹ in the oven, it was calculated as 85.24 kJ mol⁻¹ in the temperature-controlled microwave. Drying data was best estimated in the Midilli-Küçük (R² 0.9998) model oven at 50 °C. The highest SMER value was calculated as 0.0098 kg kWh⁻¹ in the temperature-controlled microwave drying method. The lowest SEC value in the temperature-controlled microwave was determined as 24.03 kWh kg⁻¹. It was determined that enthalpy values varied between −2484.66/−2623.38 kJ mol⁻¹, entropy values between −162.04/−122.65 J mol⁻¹ and Gibbs free energy values between 453335.22–362581.40 kJ mol⁻¹. Drying rate values were calculated in the range of 0.0127–0.9820 g moisture g dry matter⁻¹ in the temperature-controlled microwave, 0.0003–0.0762 g dry matter⁻¹ in the oven, and 0.001–0.0058 g moisture g dry moisture matter⁻¹ in the shade. Phenolic content 6957.79 μg GAE g⁻¹ fw - 48322.27 μg GAE g⁻¹ dw, flavonoid content 3806.67 mg KE L⁻¹ fw - 22200.00 mg KE L⁻¹ dw and antioxidant capacity 43.35 μmol TE g⁻¹ fw - 323.47 μmol TE g⁻¹ dw. The highest chlorophyll values were obtained from samples dried in an oven at 40 °C. According to the findings, it is recommended to dry the knotweed (Polygonum cognatum Meissn.) plant in a temperature-controlled microwave oven at low temperatures. In this study, in terms of drying kinetics and energy parameters, a temperature-controlled microwave dryer of 60 °C is recommended, while in terms of quality characteristics, oven 40 °C and shade methods are recommended.