Crystal structure of BMP-9 and functional interactions with pro-region and receptors

Bone morphogenetic proteins (BMPs), a subset of the transforming growth factor (TGF)-beta superfamily, regulate a diverse array of cellular functions during development and in the adult. BMP-9 (also known as growth and differentiation factor (GDF)-2) potently induces osteogenesis and chondrogenesis, has been implicated in the differentiation of cholinergic neurons, and may help regulate glucose metabolism. We have determined the structure of BMP-9 to 2.3 A and examined the differences between our model and existing crystal structures of other BMPs, both in isolation and in complex with their receptors. TGF-beta ligands are translated as precursors, with pro-regions that generally dissociate after cleavage from the ligand, but in some cases (including GDF-8 and TGF-beta1, -2, and -3), the pro-region remains associated after secretion from the cell and inhibits binding of the ligand to its receptor. Although the proregion of BMP-9 remains tightly associated after secretion, we find, in several cell-based assays, that the activities of BMP-9 and BMP-9.pro-region complex were equivalent. Activin receptor-like kinase 1 (ALK-1), an orphan receptor in the TGF-beta family, was also identified as a potential receptor for BMP-9 based on surface plasmon resonance studies (BIAcore) and the ability of soluble ALK-1 to block the activity of BMP-9.pro-region complex in cell-based assays.     

Cholera toxin gene-positive Vibrio cholerae O1 Ogawa and Inaba strains produce the new cholera toxin

Abstract Two strains of cholera toxin (CT) gene-positive Vibrio cholerae O1, Ogawa, isolated from patients with diarrhoea and the hypertoxigenic V. cholerae O1, Inaba (569B), were found to produce the new cholera toxin that has earlier been demonstrated to be elaborated by CT gene-negative human and environmental isolates of V. cholerae O1. The CT gene-positive strains produce the new cholera toxin simultaneously with CT, indicating that they contain the gene coding for the new cholera toxin in addition to that of CT.     

Effects of gossypol acetic acid on the absorptive and digestive functions of rat intestine

Oral administration of Gossypol acetic acid (10 mg/kg body wt./day, daily for 15 days), an experimental antifertility agent to male rats, caused significant reduction in the uptake of glucose, alanine, leucine and calcium in the small intestinal segments. Gossypol also caused significant decrease in the intestinal brush border membrane--associated enzymes, sucrase, lactase, maltase and alkaline phosphatase. Kinetic analysis indicated that Gossypol decreased the apparent velocity of the disaccharidases while the Km was not altered. It also caused a shift in the transition temperature in these enzymes and predictably changed the energy of activation both below and above the transition temperature, although the Arrhenius expressions of the temperature dependence still showed proximity and were parallel to the control group.     

A basic experimental approach in perspective of pineal and melatonin involvement in photoperiod-induced alteration of spermatogenesis in toad (Bufo melanostictus)

Blinding decreases spermatogenesis along with Leydig cell degeneration in toad. Pinealectomy decreases spermatogenesis with an increase in Leydig cell activity. Melatonin decreases spermatogenesis as well the Leyding cells. Possibly pineal and melatonin possess an inverse relationship with light and inhibit testis.     

Quantum mechanical studies on the activity of anticancerous drug — Ellipticine

Ellipticine compounds, derivatives of pyrido-(4-3b) carbazole are used in the human cancer therapy. Most of these drugs interact directly with DNA molecule. CNDO method, alongwith second order perturbation theory and multicentered-multipole approxiation have been used to compute intermolecular interaction energies of ellipticine with DNA ase pairs (GC and AT) in both normal and inverted cases. An attempt has been made to correlate the drug-nucleic acid interactions for ellipticine to locate site of drug action and binding pattern on the basis of intermolecular forces     

Carbon reservoir perturbations induced by Deccan volcanism: Stable isotope and biomolecular perspectives from shallow marine environment in Eastern India

The Deccan Traps in Western India is hypothesized to have caused significant fluctuations in climatic condition and organic matter (OM) productivity across the Cretaceous-Paleogene Boundary (K/PgB). The periodic release of large amounts of volatiles into the atmosphere is thought to drive these changes. Yet, direct impact of volcanism on the carbon cycle and ecosystem remains relatively unconstrained. For the first time, we attempt to trace changes in both marine and terrestrial carbon reservoirs from pre- and intervolcanic sedimentary units (infra- and inter-trappeans respectively) from Rajahmundry, ~1500 km SE of main eruption sites in Western India. Molecular level characterization of OM and stable isotope composition of carbonates (δ¹³C_carb), bulk OM (δ¹³C_org), and n-alkane (δ¹³C_alk and δD_alk) have been analysed to provide a chemo-stratigraphic framework. In Rajahmundry, high CO₂ concentration estimated from infra-trappean carbonate nodule is synchronous with the onset of the Deccan Traps and the Late Maastrichtian warming episode. Impact of the warming event is reflected in Rajahmundry from a major shift in the terrestrial ecosystem. Marine OM production also seems to have been low throughout the infra-trappean. A steady decrease in δ¹³C_carb values, increase in mortality rates and dwarfism in invertebrates immediately below the first volcanic units in Rajahmundry suggest stressed conditions from eruption in the western part of India ~40–60 kyrs prior to K/PgB. A significant increase in heterotrophic activity is observed after the volcanic deposits in Rajahmundry that seems to have controlled the marine carbon reservoir for a maximum of ~200 kyrs after the boundary. Advent of pteridophytes, increase in carbon content and positive shifts in δ¹³C_carb and δ¹³C_alk values in the upper inter-trappean units mark the onset of recovery in terrestrial and marine environments. Overall, our results suggest significant perturbations in the carbon reservoir as a consequence of the Deccan eruption.