Evaluation of millets for physio-chemical and root morphological traits suitable for resilient farming and nutritional security in Eastern Himalayas.

Introduction: Millets are nutritionally superior and climate-resilient short-duration crops and hold a prominent place in cropping sequences around the world. They have immense potential to grow in a marginal environment due to diverse adaptive mechanisms. Methods: An experiment was conducted in an organic production system in the North Eastern Himalayan foothills of India for 3 consecutive years by evaluating high-yielding varieties (HYVs) of different millets, viz., finger millet, foxtail millet, little millet, barnyard millet, proso millet, and browntop millet, along with local landraces of finger millets (Sikkim-1 and Sikkim-2; Nagaland-1 and Nagaland-2) to identify stable, high-yielding, and nutritionally superior genotypes suited for the region. Results: Among the various millets, finger millet, followed by little millet and foxtail millet, proved their superiority in terms of productivity (ranging between 1.16 and 1.43 Mg ha-1) compared to other millets. Among different varieties of finger millets, cv. VL Mandua 352 recorded the highest average grain yield (1.43 Mg ha-1) followed by local landraces, Nagaland-2 (1.31 Mg ha-1) and Sikkim-1 (1.25 Mg ha-1). Root traits such as total root length, root volume, average diameter of roots, and root surface area were significantly higher in finger millet landraces Nagaland-1, Nagaland-2, and Sikkim-1 compared to the rest of the millet genotypes. The different millets were found to be rich sources of protein as recorded in foxtail millet cv. SiA 3088 (12.3%), proso millet cv. TNAU 145 (11.5%), and finger millet landraces, Sikkim-1 and Nagaland-2 (8.7% each). Finger millet landrace Sikkim-2 recorded the highest omega-6 content (1.16%), followed by barnyard millet cv. VL 207 (1.09%). Barnyard millet cv. VL 207 recorded the highest polyunsaturated fatty acid (PUFA) content (1.23%), followed by foxtail millet cv. SiA 3088 (1.09%). The local finger millet landraces Sikkim-1 and Sikkim-2 recorded the highest levels of histidine (0.41%) and tryptophan (0.12%), respectively. Sikkim-1 and Nagaland-2 recorded the highest level of thiamine (0.32%) compared to the HYVs. Conclusion: These findings indicate that finger millet has great potential in the organic production system of the North Eastern Himalayan Region (NEHR) of India, and apart from HYVs like VL Mandua 352, local landraces, viz., Nagaland-2 and Sikkim-1, should also be promoted for ensuring food and nutritional security in this fragile ecosystem.

Epigenetic Regulation of Antifungal Drug Resistance.

In medical mycology, epigenetic mechanisms are emerging as key regulators of multiple aspects of fungal biology ranging from development, phenotypic and morphological plasticity to antifungal drug resistance. Emerging resistance to the limited therapeutic options for the treatment of invasive fungal infections is a growing concern. Human fungal pathogens develop drug resistance via multiple mechanisms, with recent studies highlighting the role of epigenetic changes involving the acetylation and methylation of histones, remodeling of chromatin and heterochromatin-based gene silencing, in the acquisition of antifungal resistance. A comprehensive understanding of how pathogens acquire drug resistance will aid the development of new antifungal therapies as well as increase the efficacy of current antifungals by blocking common drug-resistance mechanisms. In this article, we describe the epigenetic mechanisms that affect resistance towards widely used systemic antifungal drugs: azoles, echinocandins and polyenes. Additionally, we review the literature on the possible links between DNA mismatch repair, gene silencing and drug-resistance mechanisms.

Persistence and Exposure Assessment of Insecticide Indoxacarb Residues in Vegetables.

Indoxacarb, a promising new generation insecticide, is gaining popularity among vegetable growers in West Bengal, India, for controlling a large number of insects. However, it may simultaneously also increase the risk of contamination in the edible portions of the vegetables. This study was planned to analyze the persistence behavior of indoxacarb in cabbages, tomatoes, and soil. Moreover, indoxacarb residue contents were estimated to assess both the dietary and soil ecological risks associated with the application of the same. The experimental location was important because West Bengal is the leading vegetables producing state in India. Indoxacarb was found to dissipate quickly with a half-life ranging between 1.55 and 2.76 days, irrespective of the vegetable, dose, and season, and the safe waiting period was very less. The findings indicate that both vegetables can be safely consumed 1 day after the final spray. However, the risk to soil algae is predicted to be unacceptably high, which needs to be studied extensively.

Design, synthesis of DNA-interactive 4-thiazolidinone-based indolo-/pyrroloazepinone conjugates as potential cytotoxic and topoisomerase I inhibitors.

With the rising cancer incidence and mortality globally, there is a prerequisite for effective design strategies towards the discovery of newer small molecular entities in chemotherapy. Hence, a series of new thiazolidinone-based indolo-/pyrroloazepinone conjugates was designed, synthesized via molecular hybridization, and evaluated for their in vitro cytotoxicity potential and DNA topoisomerase I and II inhibition. Among this series, conjugate 11g emerged as the most active compound with an IC50 value of 1.24 µM against A549 and 3.02-10.91 µM in the other tested cancer cell lines. Gratifyingly, 11g displayed 43-fold higher selectivity towards A549 cancer cells as compared to the non-cancer cells. Subsequently, conjugate 12g also demonstrated significant cytotoxicity against SK-MEL-28 cells. Basing the in vitro cytotoxicity results, SAR was established. Later, the conjugates 11g and 12g were further evaluated for their apoptosis-inducing ability, which was quantified by flow cytometric analysis, DNA-binding, Topo I inhibitory activity and IC50 value calculation. Molecular modeling studies provided profound insights about the binding nature of these compounds with DNA-Topo I complex. In silico ADME/T and prediction studies corroborated the drug-likeness of the two investigated compounds. TOPKAT toxicity profiling studies demonstrated the compounds' safety in many animal models with a minimal toxicological profile. Encouraging results obtained from in vitro and in silico studies could put this series of conjugates at the forefront of cancer drug discovery.

Syntheses and medicinal chemistry of azepinoindolones: a look back to leap forward.

Nitrogen-containing heterocyclic scaffolds constitute nearly 75% of small molecules which favorably act as drug candidates. For the past few decades, numerous natural and synthetic indole-based scaffolds have been reported for their diverse pharmacological profiles. In particular, indole-fused azepines, termed azepinoindolones, have come under the radar of medicinal chemists owing to their synthetic and pharmacological importance. A plethora of literature reports has been generated thereof, which calls for the need for the compilation of information to understand their current status in drug discovery. Accumulating reports of evidence suggest that compounds containing this privileged scaffold display their cytotoxic effects via inhibition of kinase, topoisomerase I, mitochondrial malate dehydrogenase (mMDH), and tubulin polymerization and as DNA minor groove binding agents. Herein, we endeavor to present a closer look at the advancements of various synthetic and derivatization methods of azepinoindolone-based compounds. We have further extended our efforts to discuss the pharmacological effects of azepinoindolones in the whole range of medicinal chemistry as anti-Alzheimer, anticancer, anti-inflammatory, antidiabetic, antileishmanial, and antipyranosomal agents and as drug delivery vectors. Our analysis of recent advances reveals that azepinoindolones will continue to serve as potential pharmaceutical modalities in the years to come and their substantial pool of synthetic methods will be ever expanding.

SUMOylation in Human Pathogenic Fungi: Role in Physiology and Virulence.

The small ubiquitin-related modifier (SUMO) protein is an important component of the post-translational protein modification systems in eukaryotic cells. It is known to modify hundreds of proteins involved in diverse cellular processes, ranging from nuclear pore dynamics to signal transduction pathways. Owing to its reversible nature, the SUMO-conjugation of proteins (SUMOylation) holds a prominent place among mechanisms that regulate the functions of a wide array of cellular proteins. The dysfunctional SUMOylation system has been associated with many human diseases, including neurodegenerative and autoimmune disorders. Furthermore, the non-pathogenic yeast Saccharomyces cerevisiae has served as an excellent model to advance our understanding of enzymes involved in SUMOylation and proteins modified by SUMOylation. Taking advantage of the tools and knowledge obtained from the S. cerevisiae SUMOylation system, research on fungal SUMOylation is beginning to gather pace, and new insights into the role of SUMOylation in the pathobiology of medically important fungi are emerging. Here, we summarize the known information on components of the SUMOylation machinery, and consequences of overexpression or deletion of these components in the human pathogenic fungi, with major focus on two prevalent Candida bloodstream pathogens, C. albicans and C. glabrata. Additionally, we have identified SUMOylation components, through in silico analysis, in four medically relevant fungi, and compared their sequence similarity with S. cerevisiae counterparts. SUMOylation modulates the virulence of C. albicans and C. glabrata, while it is required for conidia production in Aspergillus nidulans and A. flavus. In addition to highlighting these recent developments, we discuss how SUMOylation fine tunes the expression of virulence factors, and influences survival of fungal cells under diverse stresses in vitro and in the mammalian host.

Biological nutrient recovery from human urine by enriching mixed microalgal consortium for biodiesel production.

Utilization of waste resources is necessary to harness the long-term sustainability of algal technology. The study focused on the use of human urine as the basic nutrient source for culturing native microalgal consortium and further optimized the process parameters using response surface methodology. A full factorial, central composite rotatable design (CCRD) with three variables: urine concentration (1-10% vol of urine/vol of distil water [%v/v]), pH (6.5-9) and light intensity (50-350 µmolphotonsm-2sec-1) was used to evaluate the microalgal biomass and lipid content. Results indicated that at 95% confidence limits, the selected factors influence the biomass and lipid productivity. The maximum biomass productivity of 211.63 ± 1.40 mg l-1 d-1 was obtained under optimized conditions with 6.50% v/v of urine, pH of 7.69 and at light intensity of 205.40 µmolphotonsm-2sec-1. The lipid content was found to increase from 18.96 ± 1.30% in control media to 26.27 ± 1.94% under optimal conditions. The interactive effect of variables over the microalgal biomass and lipid content has also been elucidated. The data obtained were comparable to the BG11 media (control). Optimized diluted urine media in the presence of ammonium ions and under limited nitrate showed better lipid yields. Significant lipid biomolecules were detected in the algal oil extracts obtained from the diluted urine media characterized by Fourier transform infrared spectroscopy (FTIR) and Nuclear magnetic resonance (NMR). Gas chromatography-mass spectrometry (GCMS) revealed the presence of several monounsaturated and polyunsaturated fatty acids in the transesterified algal oil. Such studies would aid in technically realizing the field scale cultivation of microalgae for biofuels.

Persistence behaviour and safety risk evaluation of pyridalyl in tomato and cabbage.

A field experiment was set up to evaluate persistence behaviour of pyridalyl in tomato, cabbage and cultivated field soil over two consecutive seasons. An analytical method was developed to analyze pyridalyl residues in different matrices and duly validated, based on single laboratory method validation criteria. Pyridalyl residues were detected and quantified using a gas chromatograph equipped with an electron capture detector. The compound exhibited low persistence in tomato, cabbage and soil. A safe waiting period of 17-18 d after final insecticide application needs to be maintained before harvesting the crop. Both dietary and soil ecological risk were assessed and it was found that the harvested vegetables were toxicologically safe for consumption. However, there was concern about insecticidal toxicity against the algal population of soil which needs to be reconfirmed by further studies.

Persistence behavior of metamifop and its metabolite in rice ecosystem.

A field experiment was conducted to determine the persistence of metamifop in transplanted rice crop for two seasons. Metamifop 10% EC was applied at two doses: 100 g a.i. ha-1 and 200 g a.i. ha-1 at 2-3 leaf stage of Echinochloa crusgalli. The residues of metamifop along with its major metabolite, N-(2-fluorophenyl)-2-hydroxy-N-methylpropionamide (HFMPA), were estimated in rice plant, field water and soil using Liquid Chromatography Mass Spectrometry. Limit of detection and limit of quantification of the method for both the compounds were set at 0.003 µg g-1 and 0.010 µg g-1 respectively. Metamifop showed less persistence in field water and rice plant as compared to soil samples. Presence of HFMPA was recorded in rice plant and soil. Both the compounds were found below level of quantification in harvest samples of straw, grains, husk and soil. A safe waiting period of 52 d was suggested for harvesting of rice when metamifop was applied at 100 g a.i. ha-1 (recommended dose).

Dissipation kinetics and risk assessment of chlorfenapyr on tomato and cabbage.

A field experiment was conducted over two seasons to evaluate the dissipation kinetics and assess the risks of chlorfenapyr in tomato and cabbage following foliar application of chlorfenapyr 10% SC at 100 and 200 g a.i. ha-1. Samples of tomato, cabbage, and soil were analyzed and quantified by gas chromatography-electron capture detector (GC-ECD). The limit of detection (LOD) and limit of quantification (LOQ) of chlorfenapyr were found to be 0.01 and 0.03 mg kg-1, respectively, in tomato, cabbage, and soil. The dissipation of chlorfenapyr followed first-order kinetics. The compound showed less persistence in both the vegetables and soil as the calculated half-life values of chlorfenapyr ranged between 4.54 and 7.74 days considering two different doses and seasons. The residue was below detection limit in all the untreated plant and soil samples. The pre-harvest interval (PHI) of chlorfenapyr in both the vegetables was determined to be 9-14 days regardless of dose or season. The theoretical maximum residue contribution (TMRC) of chlorfenapyr was calculated for tomato and cabbage and was found to be lower than the maximum permissible intake (MPI) of the compound. Therefore, the application of chlorfenapyr at the recommended dose in tomato and cabbage for crop protection seems to be safe from both environmental contamination and consumer safety standpoints.

Persistence of chlorfluazuron in cabbage under different agro-climatic conditions of India and its risk assessment.

A multilocational field trial was conducted at 4 locations in India-Rajasthan, Gujarat, Madhya Pradesh, and West Bengal-to determine the persistence in cabbage of chlorfluazuron applied twice at 75 and 150 g active ingredient ha-1 . Cabbage head samples were collected from each replicated plot on 0 (2 h after spraying), 1, 3, 5, 7, 10, and 15 d after final insecticide application, including an untreated control. Chlorfluazuron residue in cabbage and field soil was estimated by high-performance liquid chromatography using a photo diode array detector. The limit of determination and limit of quantification of the method were recorded as 0.05 and 0.10 µg g-1 , respectively. Results revealed that chlorfluazuron dissipated linearly with progress of time, following first-order kinetics. The mean (± standard deviation) half-life value of chlorfluazuron in cabbage was found to be 7.18 ± 0.71 d, considering different locations and treatments. The residue was below the level of quantification in the harvested cabbage and soil samples. Harvesting cabbage in the experimental location, at least on day 7, after 2 applications of chlorfluazuron at the recommended dose, may not pose any ill effect for Indian adults. Environ Toxicol Chem 2017;36:3028-3033. © 2017 SETAC.