Sub-optimal dose of Sodium Antimony Gluconate (SAG)-diperoxovanadate combination clears organ parasites from BALB/c mice infected with antimony resistant Leishmania donovani by expanding antileishmanial T-cell repertoire and increasing IFN-γ to IL-10 ratio

We demonstrate that the combination of sub-optimal doses of Sodium Antimony Gluconate (SAG) and the diperoxovanadate compound K[VO(O₂)₂(H₂O)], also designated as PV6, is highly effective in combating experimental infection of BALB/c mice with antimony resistant (Sb^R) Leishmania donovani (LD) as evident from the significant reduction in organ parasite burden where SAG is essentially ineffective. Interestingly, such treatment also allowed clonal expansion of antileishmanial T-cells coupled with robust surge of IFN-γ and concomitant decrease in IL-10 production. The splenocytes from the treated animals generated significantly higher amounts of IFN-γ inducible parasiticidal effector molecules like superoxide and nitric oxide as compared to the infected group. Our study indicates that the combination of sub-optimal doses of SAG and PV6 may be beneficial for the treatment of SAG resistant visceral leishmaniasis patients.     

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.     

Record of Naticid Predation on Scaphopods (Mollusca) from the Latest Maastrichtian of Rajahmundry,India

Drilling predation provides a rare opportunity to study and quantify prey-predator interactions in the fossil record. Records of drilling predation on scaphopod mollusc are rare. Here, we report naticid drilling predation on scaphopods from a “Turritelline-dominated assemblage” (TDA) stratigraphically just below the K-Pg boundary sections in Rajahmundry, India, which was situated in the Southern Hemisphere during that time. Low drilling frequency was found in the present assemblage based on 248 specimens, which was similar to most of the Cretaceous values previously reported. Majority of the specimens of previous studies were reported from higher latitudes in the Northern Hemisphere. Our report extended the palaeobiogeography of naticid predation on scaphopods into the Southern Hemisphere. Size and site stereotypy of drillholes on the scaphopod shell suggested that predatory behavior of naticids was already highly evolved, but evidence of escalation was less clear in scaphopod prey.     

Hyperoxic conditions inhibit airway smooth muscle myosin phosphatase in rat pups

Exposure of rat pups to 100% oxygen is a model for studying neonatal lung injury. Airway reactivity is increased in this model, in part due to impaired airway smooth muscle (ASM) relaxation. We compared biochemical determinants of ASM contractility in rat pups exposed to 100% oxygen for 7 days vs. littermates raised in room air. The baseline quantities of ASM contractile proteins, extent of phosphorylation of the 20-kDa myosin regulatory light chain (LC(20)), and amount of the myosin-binding subunit of smooth muscle myosin phosphatase (MYPT) were all comparable between the two groups. Bethanechol-induced contraction increased the extent of phosphorylation of both LC(20) and MYPT in the hyperoxic group (45% and 70% over control, respectively). Relaxation after electrical field stimulation demonstrated greater phosphorylation of both LC(20) and MYPT in the hyperoxic group compared with controls (67% and 84%, respectively). To determine if hyperoxia induced changes in the isoforms of MYPT, isoform expression was also compared but differences were not found. To determine potential mechanisms whereby MYPT phosphorylation was increased by hyperoxia, separate tracheas were treated with the Rho kinase inhibitor Y-27632. This treatment completely eliminated differences in MYPT phosphorylation between the groups. Because phosphorylation of MYPT impairs the phosphatase activity of myosin phosphatase, these data suggest that hyperoxic conditioning during early postnatal life impairs relaxation through prolonging LC(20) phosphorylation. This mechanism might contribute to increased ASM reactivity seen in bronchopulmonary dysplasia.     

Photophysical properties of Newkome-type dendrimers in aqueous medium.

Newkome-type first, second and third generation dendrimers, having t-butyl (GB), ethyl (GE) and carboxylic (GA) end groups, were synthesized. A pyrene group, which can act as fluorescent sensor, was attached to the core of the dendrimers and their photophysical properties in aqueous solution were studied. These dendrimers were found to aggregate in aqueous solution, which manifested as an excimer peak in the pyrene emission spectra for the first and second generation dendrimers with ethyl and t-butyl end groups. The excimer peak however was not seen in case of the third generation dendrimer. Dendrimers with carboxylic end groups, did not show the excimer peak in water, which implies the hydrophobic nature of the aggregation. It is observed that the intensity of the excimer peak decreases with the increase in the size of the dendrimer. Lifetime studies carried out on the first and second generation dendrimers showed the formation of excimer species as a risetime in the decay curve. The aggregation of the third generation dendrimer was proposed from the quenching studies using silver ions and CCl(4) as quenchers.     

Tocotrienols confer resistance to ischemia in hypercholesterolemic hearts: insight with genomics

Most clinical trials with vitamin E could not lower cholesterol and thus, have been deemed unsuccessful. Recently, tocotrienols, isomers of vitamin E have been found to lower LDL levels. To explore if tocotrienols could be the drug target for vitamin E, rabbits were kept on cholesterol diet for 60 days supplemented with tocotrienol-α, tocotrienol-δ, and tocotrienol-γ for the last 30 days. The serum cholesterol levels (in mmol/l) were 24.4 (tocotrienol-α), 34.9 (tocotrienol-δ), 19.8 (tocotrienol-γ) vs. 39.7 (control). Left ventricular function including aortic flow and developed pressure exhibited significantly improved recovery with tocotrienol-γ and -α, but not with tocotrienol-δ. The myocardial infarct size showed a similar pattern: 33% (tocotrienol-α), 23% (tocotrienol-γ), and 47% (tocotrienol-δ). To examine the molecular mechanisms of cardioprotective effects, gene expression profile was determined using Atlas 1.2/1.2II followed by determination of gene profiles using PedQuest 8.3 software. Based on genomic profiles, the following cholesterol-related proteins were examined: FABP, TGF-β (cholesterol suppresses TGF-β), ET-1 (increased by hypercholesterolemia), SPOT 14 (linked with hypercholesterolemia), and matrix metalloproteinase (MMP) 2 and MMP9 (cholesterol regulates MMP2 and MMP9 expression) in the heart. Consistent with the cardioprotective effects of tocotrienol-α and -γ, these two isomers reduced ET-1, decreased MMP2 and MM9, increased TGF-β and reduced SPOT 14, while tocotrienol-δ had no effects. The results of the present study demonstrate that the two isomers of tocotrienols, α and γ, render the hypercholesterolemic hearts resistant to ischemic reperfusion injury by lowering several hypercholesterolemic proteins including MMP2, MMP9, ET-1, and SPOT 14 and upregulating TGF-β.     

A mutation in the S6 segment of the KvAP channel changes the secondary structure and alters ion channel activity in a lipid bilayer membrane

Amino Acids - The peptide segment S6 is known to form the inner lining of the voltage-gated K+ channel KvAP (potassium channel of archaea-bacterium, Aeropyrum pernix). In our previous work, it has...