New 5-methylcoumarins from Ethulia conyzoides

The isolation of three new terpenoid 5-methylcoumarins in the form of diastereomeric mixtures from a north Indian collection of Ethulia conyzoides is reported. Stereochemistries were deduced by X-ray analysis of a pure acetate isomer obtained on acetylation of one of the diastereomeric mixtures.     

Design,synthesis, docking,Hirshfeld surface analysis and DFT calculations of 2-methylxanthen-9-with the FtsZ protein from Staphylococcus aureus

It is of interest to document the design, synthesis, docking, Hirshfeld surface analysis and DFT calculations of 2-methylxanthen-9-with the FtsZ protein (PDB ID: 3VOB) from Staphylococcus aureus for antimicrobial applications. We report the quantitative structure function data in this context.     

Systematic revision and sexual dimorphism in Choffatia (Ammonoidea: Perisphinctoidea) from the Callovian of Kutch,India

The genus Choffatia (Siemiradzki) is an important Callovian ammonite in Kutch biostratigraphy. Several species of the genus were described by the early workers who did not recognize intraspecific variability and sexual dimorphism in terms of the modern concepts. We have described here three dimorphic species based on material reposited in the Geological Survey of India, Kolkata as well as systematically collected additional specimens with precise stratigraphic information. These species are: Choffatia recuperoi (Gemmellaro, 1873), Choffatia cobra (Waagen, 1875), and Choffatia perdagata (Waagen, 1875). The microconchs of the three species, described here for the first time, are lappeted whereas the macroconchs have a simple aperture. However, these species have similar shell morphologies and they intergrade in shell shape and sculpture; thus it is difficult to distinguish them qualitatively. Statistical analyses (both bivariate and multivariate) support that they are distinct species and there is a good correlation among the degree of involution, the degree of inflation, and the strength of ornamentation. C. cobra is the most evolute, depressed, and strongly ribbed whereas C. perdagata is the most involute, compressed, and weakly ribbed. C. recuperoi occupies the intermediate position. This interspecific diversity of Choffatia thus supports Buckman's Law of Covariation.     

The effect of β2-α2 loop mutation on amyloidogenic properties of the prion protein

Recent studies revealed that elk-like S170N/N174T mutation in mouse prion protein (moPrP), which results in an increased rigidity of β2-α2 loop, leads to a prion disease in transgenic mice. Here we characterized the effect of this mutation on biophysical properties of moPrP. Despite similar thermodynamic stabilities of wild type and mutant proteins, the latter was found to have markedly higher propensity to form amyloid fibrils. Importantly, this effect was observed even under fully denaturing conditions, indicating that the increased conversion propensity of the mutant protein is not due to loop rigidity but rather results from greater amyloidogenic potential of the amino acid sequence within the loop region of S170N/N174T moPrP.     

Effect of toll-like receptor activation on thymosin beta-4 production by chicken macrophages

Thymosin beta-4 (Tβ4) is an actin-binding intracellular peptide that promotes wound healing, tissue remodeling, and angiogenesis. The mechanism of Tβ4 secretion to the extracellular environment is not understood. The macrophage is a rich source of Tβ4 which also participates in wound healing process. The objective of this study was to find how Tβ4 may be externalized. Using activation of macrophage through their toll-like receptors (TLR), the changes in cellular Tβ4 was studied. A naturally transformed chicken macrophage cell line HTC was treated with different TLR agonists and the cellular Tβ4 changes was determined at 6 and 24 h after stimulations using stable isotope labelling of amino acids in cell culture (SILAC) and mass spectrometry. Real time PCR was used to determine changes in gene expression. The results showed that TLR agonists such as peptidoglycan (PGN) or lipopolysacharide (LPS) caused depletions in cellular Tβ4 peptide along with its detection in the cell culture supernatant at 24 h. These TLR agonists also induced the expression of interleukins-1β, -6, and nitric oxide synthase genes at 6 h but failed to modulate Tβ4 gene at that time point indicating that the Tβ4 externalization was not associated with its production. To find whether Tβ4 externalization was associated with cell death, we measured the lactate dehydrogenase (LDH) activity of the conditioned media as an indicator of cell damage. The results showed that the TLR agonists which induced depletion of intracellular Tβ4 at 24 h also increased the LDH content of the conditioned media, suggesting that the Tβ4 in the extracellular media most likely originated from dying macrophages.     

Buchananine,a novel pyridine alkaloid from Cryptolepis buchanani

A new alkaloid, buchananine, was isolated from the stems of Cryptolepis buchanani. Its structure was determined as 6-O-nicotinoyl-α-d-glucopyranose by chemical and spectroscopic investigations.