Protective role of Ashwagandha leaf extract and its component withanone on scopolamine-induced changes in the brain and brain-derived cells

Background

Scopolamine is a well-known cholinergic antagonist that causes amnesia in human and animal models. Scopolamine-induced amnesia in rodent models has been widely used to understand the molecular, biochemical, behavioral changes, and to delineate therapeutic targets of memory impairment. Although this has been linked to the decrease in central cholinergic neuronal activity following the blockade of muscarinic receptors, the underlying molecular and cellular mechanism(s) particularly the effect on neuroplasticity remains elusive. In the present study, we have investigated (i) the effects of scopolamine on the molecules involved in neuronal and glial plasticity both in vivo and in vitro and (ii) their recovery by alcoholic extract of Ashwagandha leaves (i-Extract).

Methodology/Principal Findings

As a drug model, scopolamine hydrobromide was administered intraperitoneally to mice and its effect on the brain function was determined by molecular analyses. The results showed that the scopolamine caused downregulation of the expression of BDNF and GFAP in dose and time dependent manner, and these effects were markedly attenuated in response to i-Extract treatment. Similar to our observations in animal model system, we found that the scopolamine induced cytotoxicity in IMR32 neuronal and C6 glioma cells. It was associated with downregulation of neuronal cell markers NF-H, MAP2, PSD-95, GAP-43 and glial cell marker GFAP and with upregulation of DNA damage- γH2AX and oxidative stress- ROS markers. Furthermore, these molecules showed recovery when cells were treated with i-Extract or its purified component, withanone.

Conclusion

Our study suggested that besides cholinergic blockade, scopolamine-induced memory loss may be associated with oxidative stress and Ashwagandha i-Extract, and withanone may serve as potential preventive and therapeutic agents for neurodegenerative disorders and hence warrant further molecular analyses.     

Dietary phytochemicals as rumen modifiers: a review of the effects on microbial populations

In the recent years, the exploration of bioactive phytochemicals as natural feed additives has been of great interest among nutritionists and rumen microbiologists to modify the rumen fermentation favorably such as defaunation, inhibition of methanogenesis, improvement in protein metabolism, and increasing conjugated linoleic acid content in ruminant derived foods. Many phytochemicals such as saponins, essential oils, tannins and flavonoids from a wide range of plants have been identified, which have potential values for rumen manipulation and enhancing animal productivity as alternatives to chemical feed additives. However, their effectiveness in ruminant production has not been proved to be consistent and conclusive. This review discusses the effects of phytochemicals such as saponins, tannins and essential oils on the rumen microbial populations, i.e., bacteria, protozoa, fungi and archaea with highlighting molecular diversity of microbial community in the rumen. There are contrasting reports of the effects of these phytoadditives on the rumen fermentation and rumen microbes probably depending upon the interactions among the chemical structures and levels of phytochemicals used, nutrient composition of diets and microbial components in the rumen. The study of chemical structure–activity relationships is required to exploit the phytochemicals for obtaining target responses without adversely affecting beneficial microbial populations. A greater understanding of the modulatory effects of phytochemicals on the rumen microbial populations together with fermentation will allow a better management of the rumen ecosystem and a practical application of this feed additive technology in livestock production.     

Proteasomal inhibition alters the trafficking of the neurotrophin receptor TrkA

Neurotrophin receptors of the Trk family promote neuronal survival. The signal transduction of Trk receptors is regulated by endosomal trafficking. Monoubiquitination of receptor tyrosine kinases is an established signal for sorting of internalized receptors to late endosomes. The NGF receptor TrkA is sorted to late endosomes and undergoes ubiquitination, indicating a so far undefined regulatory role of proteasomal activity in the trafficking of TrkA. Surprisingly, we found that proteasomal inhibition alters the trafficking of TrkA from the late endosomal sorting pathway to the recycling pathway. Many neurodegenerative diseases are associated with impaired proteasomal activity. Thus, our study suggests that missorting of neurotrophic receptors might contribute to neuronal death in those neurodegenerative diseases that are known to be associated with impaired proteasomal function.     

<Emphasis Type="Italic">Myrsidea agarwali</Emphasis> sp. n. (Phthiraptera: Menoponidae) from <Emphasis Type="Italic">Garrulax lineatus lineatus</Emphasis> (Passeriformes: Timaliidae)

A new species of chewing louse, Myrsidea agarwali, is described from Garrulax lineatus lineatus (Passeriformes: Timaliidae) from the Rampur district (India). A key is provided for the identification of males and females of Myrsidea from birds of the genus Garrulax.     

Characterization of cross-linked immobilized lipase from thermophilic mould Thermomyces lanuginosa using glutaraldehyde

Cross-linked enzyme aggregates (CLEAs) have emerged as an interesting biocatalyst design for immobilization. Using this approach, a 1,3 regiospecific, alkaline and thermostable lipase from Thermomyces lanuginosa was immobilized. Efficient cross-linking was observed when ammonium sulphate was used as precipitant along with a two fold increase in activity in presence of SDS. The TEM and SEM microphotographs of the CLEAs formed reveal that the enzyme aggregates are larger in size as compared to the free lipase due to the cross-linking of enzyme aggregates with glutaraldehyde. The stability and reusability of the CLEA with respect to olive oil hydrolysis was evaluated. The CLEA showed more than 90% residual activity even after 10 cycles of repeated use.     

Functional Inference of Complex Anatomical Tendinous Networks at a Macroscopic Scale via Sparse Experimentation

In systems and computational biology, much effort is devoted to functional identification of systems and networks at the molecular-or cellular scale. However, similarly important networks exist at anatomical scales such as the tendon network of human fingers: the complex array of collagen fibers that transmits and distributes muscle forces to finger joints. This network is critical to the versatility of the human hand, and its function has been debated since at least the 16^th century. Here, we experimentally infer the structure (both topology and parameter values) of this network through sparse interrogation with force inputs. A population of models representing this structure co-evolves in simulation with a population of informative future force inputs via the predator-prey estimation-exploration algorithm. Model fitness depends on their ability to explain experimental data, while the fitness of future force inputs depends on causing maximal functional discrepancy among current models. We validate our approach by inferring two known synthetic Latex networks, and one anatomical tendon network harvested from a cadaver''s middle finger. We find that functionally similar but structurally diverse models can exist within a narrow range of the training set and cross-validation errors. For the Latex networks, models with low training set error [<4%] and resembling the known network have the smallest cross-validation errors [∼5%]. The low training set [<4%] and cross validation [<7.2%] errors for models for the cadaveric specimen demonstrate what, to our knowledge, is the first experimental inference of the functional structure of complex anatomical networks. This work expands current bioinformatics inference approaches by demonstrating that sparse, yet informative interrogation of biological specimens holds significant computational advantages in accurate and efficient inference over random testing, or assuming model topology and only inferring parameters values. These findings also hold clues to both our evolutionary history and the development of versatile machines.     

Draft genome sequence of pigeonpea (Cajanus cajan), an orphan legume crop of resource-poor farmers

Pigeonpea is an important legume food crop grown primarily by smallholder farmers in many semi-arid tropical regions of the world. We used the Illumina next-generation sequencing platform to generate 237.2 Gb of sequence, which along with Sanger-based bacterial artificial chromosome end sequences and a genetic map, we assembled into scaffolds representing 72.7% (605.78 Mb) of the 833.07 Mb pigeonpea genome. Genome analysis predicted 48,680 genes for pigeonpea and also showed the potential role that certain gene families, for example, drought tolerance-related genes, have played throughout the domestication of pigeonpea and the evolution of its ancestors. Although we found a few segmental duplication events, we did not observe the recent genome-wide duplication events observed in soybean. This reference genome sequence will facilitate the identification of the genetic basis of agronomically important traits, and accelerate the development of improved pigeonpea varieties that could improve food security in many developing countries.     

Efficient 1–5 regioselective acylation of primary hydroxyl groups of fermentative derived xylitol catalyzed by an immobilized Pseudomonas aeruginosa lipase

The experiment described in this paper synthesizes xylitol acylated products from fermentative derived xylitol and acid anhydrides of various chain lengths in the presence of Tetrahydrofuran (THF) and acetonitrile using immobilized Pseudomonas aeruginosa (PL) lipase as a biocatalyst (97% residual activity up to five cycles) at 37°C, 200 rpm. This study examines a number of different acid anhydrides for their highly selective and efficient lipase-catalyzed acylation of primary hydroxyl groups in xylitol. Of those studied, the best results are obtained with butanoic anhydride, 80.12% after 4 h in acetonitrile followed by vinyl acetate, which results in 77.79% conversion after 8 h of incubation in THF as analyzed through high performance liquid chromatography (HPLC).     

Impact of PGPR inoculation on growth and antioxidant status of wheat under saline conditions

Two plant growth‐promoting rhizobacterial (PGPR) strains, Bacillus subtilis SU47 and Arthrobacter sp. SU18, were found to tolerate 8% NaCl. Wheat co‐inoculated with these two PGPR strains, and grown under different salinity regimes (2–6 dS m^?1), showed an increase in dry biomass, total soluble sugars and proline content. Wheat sodium content was reduced under co‐inoculated conditions but not after single inoculation with either strain or in the control. The activity of antioxidant enzymes in wheat leaves decreased under salinity stress after PGPR co‐inoculation, suggesting these PGPR species could be used for amelioration of stress in wheat plants. Activity of three antioxidant enzymes in wheat grown with both PGPR strains was reduced, most notably that of catalase activity at a salinity of 6 dS m^?1, when compared with the control. The results indicate that co‐inoculation with B. subtilis and Arthrobacter sp. could alleviate the adverse effects of soil salinity on wheat growth.