Dodder (Cuscuta reflexa Roxb.), a severe parasitic weed on fennel (Foeniculum vulgare Mill.)

A survey on weed infestation in fennel (Foeniculum vulgare) undertaken in Tonk District of Rajasthan, India during rabi season of 1986-87, indicated that the parasitic weed Cuscuta reflexa was observed in 6 fields among the 11 fields surveyed. In infested fields, 70.70 to 23.04 per cent plants were parasitised. The seed yield was 25.27 to 11.32 g / plant in healthy plants and 10.18 to 4.47 g / plant in infested plants. The reduction in estimated seed yield due to infestation by C. reflexa ranged from 14.04 to 30.07 per cent. One hundred per cent infestation reduced the seed yield by 31.21 to 71.52 per cent. &nbsp

Dodder (Cuscuta reflexa Roxb.), a severe parasitic weed on fennel (Foeniculum vulgare Mill.)

A survey on weed infestation in fennel (Foeniculum vulgare) undertaken in Tonk District of Rajasthan, India during rabi season of 1986-87, indicated that the parasitic weed Cuscuta reflexa was observed in 6 fields among the 11 fields surveyed. In infested fields, 70.70 to 23.04 per cent plants were parasitised. The seed yield was 25.27 to 11.32 g / plant in healthy plants and 10.18 to 4.47 g / plant in infested plants. The reduction in estimated seed yield due to infestation by C. reflexa ranged from 14.04 to 30.07 per cent. One hundred per cent infestation reduced the seed yield by 31.21 to 71.52 per cent. &nbsp

Thermodynamic and structural insights into the repurposing of drugs that bind to SARS-CoV-2 main protease

Although researchers have been working tirelessly since the COVID-19 outbreak, so far only three drugs – remdesivir, ronapreve and molnupiravir – have been approved for use in some countries which directly target the SARS-CoV-2 virus. Given the slow pace and substantial costs of new drug discovery and development, together with the urgency of the matter, repurposing of existing drugs for the ongoing disease is an attractive proposition. In a recent study, a high-throughput X-ray crystallographic screen was performed for a selection of drugs which have been approved or are in clinical trials. Thirty-seven compounds have been identified from drug libraries all of which bind to the SARS-CoV-2 main protease (3CLpro). In the current study, we use molecular dynamics simulation and an ensemble-based free energy approach, namely, enhanced sampling of molecular dynamics with approximation of continuum solvent (ESMACS), to investigate a subset of the aforementioned compounds. The drugs studied here are highly diverse, interacting with different binding sites and/or subsites of 3CLpro. The predicted free energies are compared with experimental results wherever they are available and they are found to be in excellent agreement. Our study also provides detailed energetic insights into the nature of the associated drug–protein binding, in turn shedding light on the design and discovery of potential drugs

Alchemical Free Energy Estimators and Molecular Dynamics Engines: Accuracy, Precision, and Reproducibility

The binding free energy between a ligand and its target protein is an essential quantity to know at all stages of the drug discovery pipeline. Assessing this value computationally can offer insight into where efforts should be focused in the pursuit of effective therapeutics to treat a myriad of diseases. In this work, we examine the computation of alchemical relative binding free energies with an eye for assessing reproducibility across popular molecular dynamics packages and free energy estimators. The focus of this work is on 54 ligand transformations from a diverse set of protein targets: MCL1, PTP1B, TYK2, CDK2, and thrombin. These targets are studied with three popular molecular dynamics packages: OpenMM, NAMD2, and NAMD3 alpha. Trajectories collected with these packages are used to compare relative binding free energies calculated with thermodynamic integration and free energy perturbation methods. The resulting binding free energies show good agreement between molecular dynamics packages with an average mean unsigned error between them of 0.50 kcal/mol. The correlation between packages is very good, with the lowest Spearman's, Pearson's and Kendall's tau correlation coefficients being 0.92, 0.91, and 0.76, respectively. Agreement between thermodynamic integration and free energy perturbation is shown to be very good when using ensemble averaging

Quantifying Socioeconomic and Lifestyle Related Health Risks: Burden of Cardiovascular Disease Among Indian Males

Background: Non-communicable diseases account for a significant disease burden in the South East Asia region. India is facing an increased incidence of lifestyle-related diseases, such as cardiovascular disease. Socioeconomic and lifestyle risk factors for cardiovascular disease (CVD) have been under investigated in India. This study was designed to explore risk factors contributing to the development of cardiovascular disease among Indian males.Methods: A population-based cross-sectional study was conducted among 2,235 males in the age group of 18-60 years across three states of India. A household survey was used to collect demographic and socioeconomic status information in addition to lifestyle-related attributes such as smoking, alcohol consumption, diet, and physical activity. Descriptive statistics and logistic regression were performed to identify the role of various factors that may be associated with the development of cardiovascular disease in this population.Results: The prevalence of cardiovascular disease among the male respondents contacted through a household survey was reported to be 9.8%. Logistic regression revealed that males with higher education and higher income were more likely to report CVD. With age as a strong predictor of CVD, the risk of CVD was found to be five times higher in the older age group. Current smokers were 1.3 times more likely to have CVD compared to those who never smoked. Those who were engaged in physical activity were less likely to have CVD; however, the adverse effects of smoking and excessive consumption of red meat showed a stronger association with CVD than the protective effects of physical activity.Conclusion: In developing countries, where the increase in earning capacity and change in lifestyle has been found to be accompanied by substantial risk of heart disease for males, public health measures like health promotion programs need to be implemented to decrease CVD burden

Ensemble-Based Approaches Ensure Reliability and Reproducibility

It is increasingly widely recognized that ensemble-based approaches are required to achieve reliability, accuracy, and precision in molecular dynamics calculations. The purpose of the present article is to address a frequently raised question: what is the optimal way to perform ensemble simulation to calculate quantities of interest

Erratum to: Quantifying Socioeconomic and Lifestyle Related Health Risks: Burden of Cardiovascular Disease Among Indian Males

During the type-setting of the final version of the article,1 the title was misspelled on the website, page 2 of Word Document, and page 2 of PDF. The title was written as “Quantifying Socioeconomic and Lifestyle Related Health Risks: Burden of Cardiocascular Disease Among Indian Males” and the corrected title is “Quantifying Socioeconomic and Lifestyle Related Health Risks: Burden of Cardiovascular Disease Among Indian Males.

Recidivism and Time Served in Prison

A justification for lengthier stays in prison stems from the belief that spending more time in prison reduces recidivism. Extant studies, however, have provided limited evidence for that belief and, indeed, suggest the effect of time served may be minimal. Few studies have employed rigorous methodological approaches, examined time spans of more than one to two years, or investigated the potential for the relationship between recidivism and time served to be curvilinear. Drawing on prior scholarship, this paper identifies three sets of hypotheses about the functional form of the time served and recidivism relationship. Using generalized propensity score analysis to examine data on 90,423 inmates released from Florida prisons, we find three patterns: greater time served initially increases recidivism but then, after approximately one year, decreases it, and, after approximately two years, exerts no effect; estimation of the effects associated with durations of more than five years are uncertain. The results point to potential criminogenic and beneficial effects of time served and underscore the need to identify how varying durations of incarceration affect recidivism

Ensemble Simulations and Experimental Free Energy Distributions: Evaluation and Characterization of Isoxazole Amides as SMYD3 Inhibitors

Optimization of binding affinities for ligands to their target protein is a primary objective in rational drug discovery. Herein, we report on a collaborative study that evaluates various compounds designed to bind to the SET and MYND domain-containing protein 3 (SMYD3). SMYD3 is a histone methyltransferase and plays an important role in transcriptional regulation in cell proliferation, cell cycle, and human carcinogenesis. Experimental measurements using the scintillation proximity assay show that the distributions of binding free energies from a large number of independent measurements exhibit non-normal properties. We use ESMACS (enhanced sampling of molecular dynamics with approximation of continuum solvent) and TIES (thermodynamic integration with enhanced sampling) protocols to predict the binding free energies and to provide a detailed chemical insight into the nature of ligand-protein binding. Our results show that the 1-trajectory ESMACS protocol works well for the set of ligands studied here. Although one unexplained outlier exists, we obtain excellent statistical ranking across the set of compounds from the ESMACS protocol and good agreement between calculations and experiments for the relative binding free energies from the TIES protocol. ESMACS and TIES are again found to be powerful protocols for the accurate comparison of the binding free energies

The performance of ensemble-based free energy protocols in computing binding affinities to ROS1 kinase

Optimization of binding affinities for compounds to their target protein is a primary objective in drug discovery. Herein we report on a collaborative study that evaluates a set of compounds binding to ROS1 kinase. We use ESMACS (enhanced sampling of molecular dynamics with approximation of continuum solvent) and TIES (thermodynamic integration with enhanced sampling) protocols to rank the binding free energies. The predicted binding free energies from ESMACS simulations show good correlations with experimental data for subsets of the compounds. Consistent binding free energy differences are generated for TIES and ESMACS. Although an unexplained overestimation exists, we obtain excellent statistical rankings across the set of compounds from the TIES protocol, with a Pearson correlation coefficient of 0.90 between calculated and experimental activities