The network map of Elabela signaling pathway in physiological and pathological conditions

Elabela (ELA; also called Apela and Toddler) is one of the recently discovered ligand among the two endogenous peptide ligands (Apelin and Elabela) of the apelin receptor (APLNR, also known as APJ). Elabela-induced signaling plays a crucial role in diverse biological processes, including formation of the embryonic cardiovascular system and early placental development by reducing the chances of occurrence of preeclampsia during pregnancy. It also plays the major role in the renoprotection by reducing kidney injury and the inflammatory response and regulation of gene expression associated with heart failure and fibrosis. Elabela may be processed into different active peptides, each of which binds to APLNR and predominantly activates the signals through PI3K/AKT pathway. Owing to its biomedical importance, we developed a consolidated signaling map of Elabela, in accordance with the NetPath criteria. The presented Elabela signaling map comprises 12 activation/inhibition events, 15 catalysis events, 1 molecular association, 34 gene regulation events and 32 protein expression events. The Elabela signaling pathway map is freely made available through the WikiPathways Database (https://www.wikipathways.org/index.php/Pathway:WP5100).Supplementary InformationThe online version contains supplementary material available at 10.1007/s12079-021-00640-4.     

Molecular modeling of 2-nitropropane dioxygenase domain of Mycobacterium tuberculosis H37Rv and docking of herbal ligands

The 3D structure of enoyl reductase (ER) domain generated by the SWISS MODEL server contains the 2-nitropropane dioxygenase (2NPD) structure displaying the TIM barrel fold. Though TIM barrel fold is made up of both main and inserted domains, in our study, we could only predict the structure of the main domain, which had central barrel of eight beta-strands surrounded by eight alpha-helices. Superimposition of the 2NPD region of ER domain of Mycobacterium tuberculosis H37Rv on to the corresponding region of 2UVA_G revealed a good structural alignment between the two, suggesting this template to be a good structural homologue. Among various herbal ligands that were screened as inhibitors, daucosterol was found to bind in closest proximity to the flavin mono nucleotide (FMN) binding site with the lowest docking energy.     

Bioinspired Gold Nanoparticle Synthesis Using Terminalia bellerica Fruit Parts and Exploring Their Anti‐bacterial Potency In Vitro

Gold nanoparticles with their excellent biocompatibility are extensively used in pharma and biological applications. Terminalia bellerica (TB) dry fruit parts mediated gold nanoparticles were synthesized using the aqueous extracts. The secondary metabolites screening of the aqueous extracts was done using phytochemical analysis. The green synthesized gold nanoparticles show vibrant colours. They were characterized using UV–Visible spectroscopy, FT-IR spectroscopy, XRD analysis and FE-SEM. The analytical characterization methods ensured the formation of nanoparticles and could predict the nanometric size of the nanoparticles. The study also lay to determine the antibacterial potential of the TB fruit parts and TB fruit parts mediated gold nanoparticles. The pathogens chosen for the study were pathogens from clinical species such as Acinetobacter pneumonia, Bacillus subtilis, and Enterococcus faecalis which cause common infections. The TB fruit part extracts, as well as TB fruit parts mediated gold nanoparticles were capable enough to destroy clinical pathogens.Supplementary InformationThe online version contains supplementary material available at 10.1007/s12088-021-00937-3.     

Developmental wave of Brn3b expression leading to RGC fate specification is synergistically maintained by miR‐23a and miR‐374

Differential regulation of Brn3b is essential for the Retinal Ganglion Cell (RGC) development in the two phases of retinal histogenesis. This biphasic Brn3b regulation is required first, during early retinal histogenesis for RGC fate specification and secondly, during late histogenesis, where Brn3b is needed for RGC axon guidance and survival. Here, we have looked into how the regulation of Brn3b at these two stages happens. We identified two miRNAs, miR‐23a and miR‐374, as regulators of Brn3b expression, during the early stage of RGC development. Temporal expression pattern of miR‐23a during E10–19, PN1–7, and adult retina revealed an inverse relation with Brn3b expression. Though miR‐374 did not show such a pattern, its co‐expression with miR‐23a evidently inhibited Brn3b. We further substantiated these findings by ex vivo overexpression of these miRNAs in E14 mice retina and found that miR‐23a and miR‐374 together brings about a change in Brn3b expression pattern in ganglion cell layer (GCL) of the developing retina. From our results, it appears that the combined expression of these miRNAs could be regulating the timing of the wave of Brn3b expression required for early ganglion cell fate specification and later for its survival and maturation into RGCs. Taken together, here we provide convincing evidences for the existence of a co‐ordinated mechanism by miRNAs to down regulate Brn3b that will ultimately regulate the development of RGCs from their precursors. © 2014 Wiley Periodicals, Inc. Develop Neurobiol 74: 1155–1171, 2014     

Evaluation of glycolamide esters of indomethacin as potential cyclooxygenase-2 (COX-2) inhibitors

A number of novel indomethacin glycolamide esters were synthesized and tested for their cyclooxygenase (COX-1 and COX-2) inhibition properties in vitro. Many of these compounds proved to be selective COX-2 inhibitors, and subtle structural changes in the substituents on the glycolamide ester moiety altered the inhibitory properties as well as potencies significantly. Their in vitro data were rationalized through molecular modeling studies. Few of them displayed anti-inflammatory activity in vivo. Compound 32, [1-(4-chlorobenzoyl)-5-methoxy-2-methyl-1H-indol-3-yl]acetic acid 2-morpholin-4-yl-2-oxo ethyl ester, was identified as a promising compound in this class and its good anti-inflammatory activity was demonstrated in the in vivo model.     

Determination of water quality,and trace metals in endemic Sarotherodon linellii,Pungu maclareni and Clarias maclareni,in crater Lake Barombi Mbo,Cameroon

Considering water pollution as a potential threat to some endemic cichlids of Lake Barombi Mbo, Cameroon, an investigation was done in 2011 to determine trace metals in its water, linking their uptake in gills and liver of fish to water chemistry. ICP-MS and ICP-OES analyses of trace metals based on total concentration of unfiltered lake water samples showed the presence of trace metals. All fish species accumulated Al, Mn and Sr in the highest concentrations in their gills, with Cu, Cd, Co, Cr, Pb and U highest in the liver. Pungu maclareni accumulated Al, Cr, Co, Sr and Pb in the highest concentrations. The highest mean gill Al concentration of 140 µg g^?1 dry weight was measured in P. maclareni gills, this being one of the critically endangered cichlids of the lake. Stable isotope analyses of carbon δ¹³C and nitrogen δ¹⁵N showed that P. maclareni had the highest mean δ¹³C (?30.2‰) and highest concentrations of Cr, Co, Pb and U in liver, probably linking the carbon source to the accumulation of metals. Though trace metal levels in the lake water were low, their presence in fish tissues suggest they are bioavailable, bioaccumulate and may pose a threat to the aquatic biota, and therefore should be monitored.     

Methanesulfonamide group at position-4 of the C-5-phenyl ring of 1,5-diarylpyrazole affords a potent class of cyclooxygenase-2 (COX-2) inhibitors

The effect of methanesulfonamide (MeSO(2)NH) group on COX-2 inhibitory activity of 1,5-diarylpyrazole is described. While this group being at position-4 of the N(1)-phenyl ring was found to be ineffective, its installation at position-4 of the C-5 phenyl ring offered several potent and selective inhibitors of COX-2 with IC(50) as low as 30 nM.     

Microbial Transport, Survival, and Succession in a Sequence of Buried Sediments

Abstract Two chronosequences of unsaturated, buried loess sediments, ranging in age from <10,000 years to >1 million years, were investigated to reconstruct patterns of microbial ecological succession that have occurred since sediment burial. The relative importance of microbial transport and survival to succession was inferred from sediment ages, porewater ages, patterns of abundance (measured by direct counts, counts of culturable cells, and total phospholipid fatty acids), activities (measured by radiotracer and enzyme assays), and community composition (measured by phospholipid fatty acid patterns and Biolog substrate usage). Core samples were collected at two sites 40 km apart in the Palouse region of eastern Washington State, near the towns of Washtucna and Winona. The Washtucna site was flooded multiple times during the Pleistocene by glacial outburst floods; the Winona site elevation is above flood stage. Sediments at the Washtucna site were collected from near surface to 14.9 m depth, where the sediment age was approximately 250 ka and the porewater age was 3700 years; sample intervals at the Winona site ranged from near surface to 38 m (sediment age: approximately 1 Ma; porewater age: 1200 years). Microbial abundance and activities declined with depth at both sites; however, even the deepest, oldest sediments showed evidence of viable microorganisms. Same-age sediments had equal quantities of microorganisms, but different community types. Differences in community makeup between the two sites can be attributed to differences in groundwater recharge and paleoflooding. Estimates of the microbial community age can be constrained by porewater and sediment ages. In the shallower sediments (<9 m at Washtucna, <12 m at Winona), the microbial communities are likely similar in age to the groundwater; thus, microbial succession has been influenced by recent transport of microorganisms from the surface. In the deeper sediments, the populations may be considerably older than the porewater ages, since microbial transport is severely restricted in unsaturated sediments. This is particularly true at the Winona site, which was never flooded.     

Comparative molecular docking and simulation analysis of molnupiravir and remdesivir with SARS-CoV-2 RNA dependent RNA polymerase (RdRp)

Treatment of SARS-CoV-2 targeting its RNA dependent RNA polymerase (RdRp) is of current interest. Remdesivir has been approved for the treatment of COVID-19 around the world. However, the drug has been linked with pharmacological limitations like adverse effects and reduced efficiency. Nevertheless, recent advancements have depicted molnupiravir as an effective therapeutic agent to target the SARS-CoV-2 RdRp. The drug has cleared both in vitro and in vivo screening. It is in phase-III clinical trial. Nonetheless, there are no data on themolecular binding interaction of molnupiravir with RdRp. Therefore, it is of interest to report the binding interaction of molnupiravir using molecular docking. It is also of interest to show its stability during interaction using molecular dynamics and binding free energy calculations along with drug likeliness and pharmacokinetic properties in comparison with remdesivir.     

First report of white stain of apple caused by Trichothecium kashmeriana in India

White stain symptoms were observed on the 05 apple varieties during the harvest season in India. The white stain appearance is due to the predominance of dense bunches of conidiophores and conidia. In samples collected from the 39 infected plants, a new pathogenic fungal species, Trichothecium kashmeriana sp.nov. has been isolated. The morphological and molecular mycotaxonomic characterisation revealed by double beam scanning electron microscopy followed by rDNA barcoding sequence analysis of Internal Transcribed Spacer region followed by the phylogenetic interpretations, marks the evolution of T. kashmeriana sp.nov. with genetic variance of 0.06 from the closely related species under the geographically distinct conditions. The pathogen is having a dramatic lethal effect on the natural populations of apple in India.