Picroside-II (P-II), an iridoid glycoside, has colossal therapeutic potential against numerous neurological and hepatic disorders. It is also used as an active ingredient of various commercial herbal formulations including, picroliv, available for treatment of liver ailments. Despite this, the knowledge of P-II biosynthesis remains scarce owing to its negligence in P. kurroa shoots which sets constant barrier for function validation experiments. In this study, we utilized natural variation for P-II content in stolon tissues of different P. kurroa accessions and deciphered its metabolic route by integrating metabolomics of intermediates with differential NGS transcriptomes. Upon navigating through high vs low P-II content accessions (1.3-2.6%), we have established that P-II is biosynthesized via degradation of ferulic acid to produce vanillic acid which acts as its immediate biosynthetic precursor. Moreover, the ferulic acid treatment in vitro at 150 µM concentration provided further confirmation with 2-fold rise in vanillic acid content. Interestingly, the cross-talk between different compartments of P. kurroa i.e. shoots and stolons, resolved spatial complexity of P-II biosynthesis and consequently speculated the burgeoning necessity to bridge gap between vanillic acid and P-II production in P. kurroa shoots. This work thus, offers a forward looking strategy to produce both P-I and P-II in shoot cultures, a step towards providing a sustainable production platform for these medicinal compounds via-a-vis relieving pressure from natural habitat of P. kurroa.

Solute carrier family 24 member 5 (SLC24A5) is a gene that is associated with oculocutaneous albinism type 6 (OCA6) disorder and is involved in skin and hair pigmentation. It is involved in the maturation of melanosomes and melanin synthesis. SLC24A5 gene is located in the chromosomal position of 15q21.1. The present study involves the use of computational techniques in order to obtain a detailed picture of the most probable mutations that are associated with SLC24A5. From the observed result it was found that the mutation S145F is most deleterious and disease associated is predicted using several bioinformatics tools. The 3-D structures of native and mutant (S145F) were modeled in order to understand protein functionality using ab initio Robetta server. The modeled structure validation was done with ERRAT, Verify-3D, Procheck and RAMPAGE Ramachandran plot analysis. The most validated structure undergoes molecular dynamics simulations (MDS) study to understand the structural and functional behaviour of the native and mutant proteins. The MDS result showed the more flexibility in the native SLC24A5 structure. Due to mutation in the SLC24A5 protein structure it became more rigid and might disturb the conformational changes and glycosylation function of protein structure and might play role in inducing the OCA6. This study provides a significant insight into the underlying molecular mechanism involved in albinism associated with OCA6. It further helps scientists to develop a drug therapy against OCA 6 disease. Communicated by Ramaswamy H. Sarma.

Alzheimer disease (AD) is characterized by amyloid-β (Aβ) plaques, neurofibrillary tangles, synaptic dysfunction, and progressive dementia. Midlife obesity increases the risk of developing AD. Adipocyte-derived small extracellular vesicles (ad-sEVs) have been implicated as a mechanism in several obesity-related diseases. We hypothesized that ad-sEVs from patients with AD would contain miRNAs predicted to downregulate pathways involved in synaptic plasticity and memory formation. We isolated ad-sEVs from the serum and cerebrospinal fluid (CSF) of patients with AD and controls and compared miRNA expression profiles. We performed weighted gene co-expression network analysis (WGCNA) on differentially expressed miRNAs to identify highly interconnected clusters correlating with clinical traits. The WGCNA identified a module of differentially expressed miRNAs, in both the serum and CSF, that was inversely correlated with the Mini-Mental State Examination scores. Within this module, miRNAs that downregulate CREB signaling in neurons were highly represented. These results demonstrate that miRNAs carried by ad-sEVs in patients with AD may downregulate CREB signaling and provide a potential mechanistic link between midlife obesity and increased risk of AD.

For understanding complex biological systems, a systems biology approach, involving both the top-down and bottom-up analyses, is often required. Numerous system components and their connections are best characterised as networks, which are primarily represented as graphs, with several nodes connected at multiple edges. Inefficient network visualisation is a common problem related to transcriptomic and genomic datasets. In this article, we demonstrate an miRNA analysis framework with the help of Jatropha curcas healthy and disease transcriptome datasets, functioning as a pipeline derived from the graph theory universe, and discuss how the network theory, along with gene ontology (GO) analysis, can be used to infer biological properties and other important features of a network. Network profiling, combined with GO, correlation, and co-expression analyses, can aid in efficiently understanding the biological significance of pathways, networks, as well as a studied system. The proposed framework may help experimental and computational biologists to analyse their own data and infer meaningful biological information.