Metabolic changes in leaves of <i>O. kilimandscharicum</i> following <i>H. armigera</i> infestation.

<p>Heat map representing relative expression of a sub-set of volatiles elicited in leaf tissue during <i>O. kilimandscharicum</i>-<i>H. armigera</i> interaction; comparison between metabolite profiles of local (L) and systemic (S) leaf tissue in <i>O. kilimandscharicum</i>, 12 h and 24 h after feeding by <i>H. armigera</i>, and also on days 3 (D3) and 6 (D6), compared to control (C) plants.</p

Two way analysis of variance for growth inhibition and percentage mortality of <i>H. armigera</i> upon exposure to <i>O. kilimandscharicum</i> leaf extract and selected metabolites on various days.

<p>DF = Degrees of freedom, SS = Sum of squares, MS = Mean square, n = numerator, d = denominator, p = probability of significance, α = 0.05.</p

Insecticidal Potential of Defense Metabolites from <i>Ocimum kilimandscharicum</i> against <i>Helicoverpa armigera</i>

<div><p>Genus <i>Ocimum</i> contains a reservoir of diverse secondary metabolites, which are known for their defense and medicinal value. However, the defense-related metabolites from this genus have not been studied in depth. To gain deeper insight into inducible defense metabolites, we examined the overall biochemical and metabolic changes in <i>Ocimum kilimandscharicum</i> that occurred in response to the feeding of <i>Helicoverpa armigera</i> larvae. Metabolic analysis revealed that the primary and secondary metabolism of local and systemic tissues in <i>O. kilimandscharicum</i> was severely affected following larval infestation. Moreover, levels of specific secondary metabolites like camphor, limonene and β-caryophyllene (known to be involved in defense) significantly increased in leaves upon insect attack. Choice assays conducted by exposing <i>H. armigera</i> larvae on <i>O. kilimandscharicum</i> and tomato leaves, demonstrated that <i>O. kilimandscharicum</i> significantly deters larval feeding. Further, when larvae were fed on <i>O. kilimandscharicum</i> leaves, average body weight decreased and mortality of the larvae increased. Larvae fed on artificial diet supplemented with <i>O. kilimandscharicum</i> leaf extract, camphor, limonene and β-caryophyllene showed growth retardation, increased mortality rates and pupal deformities. Digestive enzymes of <i>H. armigera -</i> namely, amylase, protease and lipase- showed variable patterns after feeding on <i>O. kilimandscharicum,</i> which implies striving of the larvae to attain required nutrition for growth, development and metamorphosis. Evidently, selected metabolites from <i>O. kilimandscharicum</i> possess significant insecticidal activity.</p></div

Placental Proteomics Provides Insights into Pathophysiology of Pre-Eclampsia and Predicts Possible Markers in Plasma

Pre-eclampsia is a hypertensive disorder characterized by the new onset of hypertension >140/90 mmHg and proteinuria after the 20th week of gestation. The disorder is multifactorial and originates with abnormal placentation. Comparison of the placental proteome of normotensive (<i>n</i> = 25) and pre-eclamptic (<i>n</i> = 25) patients by gel-free proteomic techniques identified a total of 2145 proteins in the placenta of which 180 were differentially expressed (>1.3 fold, <i>p</i> < 0.05). Gene ontology enrichment analysis of biological process suggested that the differentially expressed proteins belonged to various physiological processes such as angiogenesis, apoptosis, oxidative stress, hypoxia, and placental development, which are implicated in the pathophysiology of pre-eclampsia. Some of the differentially expressed proteins were monitored in the plasma by multiple reaction monitoring analysis, which showed an increase in apolipoproteins A-I and A-II in gestational weeks 26–30 (2-fold, <i>p</i> < 0.01), while haptoglobin and hemopexin decreased in gestational weeks 26–30 and week 40/at delivery (1.8 fold, <i>p</i> < 0.01) in pre-eclamptic patients. This study provides a proteomic insight into the pathophysiology of pre-eclampsia. Identified candidate proteins can be evaluated further for the development of potential biomarkers associated with pre-eclampsia pathogenesis

Two way analysis of variance for performance of <i>H. armigera</i> on various days feeding on tomato and <i>O. kilimandscharicum</i> leaves.

<p>DF = Degrees of freedom, SS = Sum of squares, MS = Mean square, n = numerator, d = denominator, p = probability of significance, α = 0.05.</p

Digestive enzymes of <i>H. armigera</i> larvae fed on <i>O. kilimandscharicum</i> leaves.

<p>Changes in the levels of <b>A.</b> protease <b>B.</b> amylase <b>C.</b> lipase activity of <i>H. armigera</i> second-instar larvae fed on <i>O. kilimandscharicum</i> plants at 12 h, 24 h, day 3 and day 6. One way ANOVA followed by Tukey's multiple comparisons test suggested significant difference between the data at. <i>p</i><0.001 (indicated as ‘***’), <i>p</i><0.01 (indicated as ‘**’), <i>p</i><0.05 (indicated as ‘*’). Results are an average of three independent experiments conducted in duplicate. Error bars represent Mean ± SD.</p

Two way analysis of variance for macromolecular content of <i>O. kilimandscharicum</i> leaves, stem and root on various days of <i>H. armigera</i> infestation.

<p>DF = Degrees of freedom, SS = Sum of squares, MS = Mean square, n = numerator, d = denominator, p = probability of significance, α = 0.05.</p

Metabolic changes in stems and roots of <i>O. kilimandscharicum</i> following <i>H. armigera</i> infestation.

<p>Heat map representing relative expression of a sub-set of volatiles elicited in <b>A.</b> stems and <b>B.</b> roots during <i>O. kilimandscharicum</i>- <i>H. armigera</i> interaction at 12 h, 24 h, and on days 3 (D3) and 6 (D6) as compared to control (C) plants.</p

BACE-1 inhibition by protriptyline.

<p><b>A</b>. Determination of IC50 of BACE-1 by using various concentrations of protriptyline. The sigmoidal curve indicates the best fit for the percentage inhibition data obtained <b>B</b>. Lineweaver-Burk analysis to estimate the kinetic constants. It showed competitive inhibition. <b>C</b>. Snapshot of drug binding with active site of BACE-1. Active site residues in BACE-1 are in line representation. <b>D</b>. Active site of BACE-1. The structures from unbound (green) and ligand bound (orange) simulations are shown after all - atom superimposition. Snapshots are generated using PyMol.</p

Virtual screening by docking.

<p><b>A</b>. Heat map analysis of binding constants of 140 FDA approved nervous system drugs screened against Aβ, AChE and β-secretase by Autodock tool 4.2. In the gradient ruler, red colour indicated strong binding (ΔG<−6 kcal/mol), while green colour indicate weak binding (ΔG>−3 kcal/mol) and the five drugs showing higher affinity to all the above mentioned targets were zoomed. <b>B</b>. Chemical structures of the five drugs. All are tricyclic anti-depressant drugs.</p