Methylenebissantin: a rare methylene-bridged bisflavonoid from Dodonaea viscosa which inhibits Plasmodium falciparum enoyl-ACP reductase

A new methylene-bridged bisflavonoid, methylenebissantin (1), and nine known compounds, including flavonoids (2-5), diterpenoids (6 and 7), and phenol derivatives (8-10) were isolated from the aerial parts of Dodonaea viscosa Jacq. The structure elucidation was based on spectroscopic data analyses. The isolated compounds were evaluated for the inhibition of Plasmodium falciparum enoyl-ACP reductase (PfENR). Methylenebissantin (1) exhibited a moderate inhibition (IC(50) 91.13 μM) against PfENR.     

On the reciprocal interaction between believing and feeling: an adaptive agent modelling perspective

An agent’s beliefs usually depend on informational or cognitive factors such as observation or received communication or reasoning, but also affective factors may play a role. In this paper, by adopting neurological theories on the role of emotions and feelings, an agent model is introduced incorporating the interaction between cognitive and affective factors in believing. The model describes how the strength of a belief may not only depend on information obtained, but also on the emotional responses on the belief. For feeling emotions a recursive body loop between preparations for emotional responses and feelings is assumed. The model introduces a second feedback loop for the interaction between feeling and belief. The strength of a belief and of the feeling both result from the converging dynamic pattern modelled by the combination of the two loops. For some specific cases it is described, for example, how for certain personal characteristics an optimistic world view is generated in the agent’s beliefs, or, for other characteristics, a pessimistic world view. Moreover, the paper shows how such affective effects on beliefs can emerge and become stronger over time due to experiences obtained. It is shown how based on Hebbian learning a connection from feeling to belief can develop. As these connections affect the strenghts of future beliefs, in this way an effect of judgment ‘by experience built up in the past’ or ‘by gut feeling’ can be obtained. Some example simulation results and a mathematical analysis of the equilibria are presented.     

Identification of Phosphate Binding Residues of <Emphasis Type="Italic">Escherichia coli</Emphasis> ATP Synthase

Four positively-charged residues, namely βLys-155, βArg-182, βArg-246, and αArg-376 have been identified as Pi binding residues in Escherichia coli ATP synthase. They form a triangular Pi binding site in catalytic site βE where substrate Pi initially binds for ATP synthesis in oxidative phosphorylation. Positive electrostatic charge in the vicinity of βArg-246 is shown to be one important component of Pi binding.     

Xanthones inhibitors of α-glucosidase and glycation from Garcinia nobilis

One new xanthone, caroxanthone (1) together with six known xanthones, 4-prenyl-2-(3,7-dimethyl-2,6-octadienyl)-1,3,5,8-tetrahydroxyxanthone (2), smeathxanthone A (3), gartanin (4), euxanthone (5), 8-hydroxycudraxanthone G (6) and morusignin I (7) were isolated from the stem bark of Garcinia nobilis. The structures were determined by 1D- and 2D-NMR techniques. All these compounds were tested for anti-glycation, α-glucosidase and α-chymotrypsin activities. Some of them exhibited strong to moderate α-glucosidase activities, while none of them inhibited α-chymotrypsin. Compounds 6 and 7 were found to be modest α-glucosidase inhibitors with IC₅₀ values of 76 μM and 84 μM, respectively.     

Bioregulators: unlocking their potential role in regulation of the plant oxidative defense system

Key message

Plant bioregulators play an important role in managing oxidative stress tolerance in plants. Utilizing their ability in stress sensitive crops through genetic engineering will be a meaningful approach to manage food production under the threat of climate change.

Abstract

Exploitation of the plant defense system against oxidative stress to engineer tolerant plants in the climate change scenario is a sustainable and meaningful strategy. Plant bioregulators (PBRs), which are important biotic factors, are known to play a vital role not only in the development of plants, but also in inducing tolerance in plants against various environmental extremes. These bioregulators include auxins, gibberellins, cytokinins, abscisic acid, brassinosteroids, polyamines, strigolactones, and ascorbic acid and provide protection against the oxidative stress-associated reactive oxygen species through modulation or activation of a plant’s antioxidant system. Therefore, exploitation of their functioning and accumulation is of considerable significance for the development of plants more tolerant of harsh environmental conditions in order to tackle the issue of food security under the threat of climate change. Therefore, this review summarizes a new line of evidence that how PBRs act as inducers of oxidative stress resistance in plants and how they could be modulated in transgenic crops via introgression of genes. Reactive oxygen species production during oxidative stress events and their neutralization through an efficient antioxidants system is comprehensively detailed. Further, the use of exogenously applied PBRs in the induction of oxidative stress resistance is discussed. Recent advances in engineering transgenic plants with modified PBR gene expression to exploit the plant defense system against oxidative stress are discussed from an agricultural perspective.

     

A Risk Prediction Model for the Assessment and Triage of Women with Hypertensive Disorders of Pregnancy in Low-Resourced Settings: The miniPIERS (Pre-eclampsia Integrated Estimate of RiSk) Multi-country Prospective Cohort Study

Background

Pre-eclampsia/eclampsia are leading causes of maternal mortality and morbidity, particularly in low- and middle- income countries (LMICs). We developed the miniPIERS risk prediction model to provide a simple, evidence-based tool to identify pregnant women in LMICs at increased risk of death or major hypertensive-related complications.

Methods and Findings

From 1 July 2008 to 31 March 2012, in five LMICs, data were collected prospectively on 2,081 women with any hypertensive disorder of pregnancy admitted to a participating centre. Candidate predictors collected within 24 hours of admission were entered into a step-wise backward elimination logistic regression model to predict a composite adverse maternal outcome within 48 hours of admission. Model internal validation was accomplished by bootstrapping and external validation was completed using data from 1,300 women in the Pre-eclampsia Integrated Estimate of RiSk (fullPIERS) dataset. Predictive performance was assessed for calibration, discrimination, and stratification capacity. The final miniPIERS model included: parity (nulliparous versus multiparous); gestational age on admission; headache/visual disturbances; chest pain/dyspnoea; vaginal bleeding with abdominal pain; systolic blood pressure; and dipstick proteinuria. The miniPIERS model was well-calibrated and had an area under the receiver operating characteristic curve (AUC ROC) of 0.768 (95% CI 0.735–0.801) with an average optimism of 0.037. External validation AUC ROC was 0.713 (95% CI 0.658–0.768). A predicted probability ≥25% to define a positive test classified women with 85.5% accuracy. Limitations of this study include the composite outcome and the broad inclusion criteria of any hypertensive disorder of pregnancy. This broad approach was used to optimize model generalizability.

Conclusions

The miniPIERS model shows reasonable ability to identify women at increased risk of adverse maternal outcomes associated with the hypertensive disorders of pregnancy. It could be used in LMICs to identify women who would benefit most from interventions such as magnesium sulphate, antihypertensives, or transportation to a higher level of care. Please see later in the article for the Editors'' Summary