Peptidyl Carbamates: Efficient Synthesis Using N-Fmoc-β-aminoalkoxy Carbonyl Chlorides/Active Pentachlorophenyl Carbonates as Monomeric Building Blocks

A simple protocol for the synthesis of linear peptidylcarbamates employing Fmoc-β-aminoalkoxy carbonyl chlorides is described. The N-Fmoc-β-aminoalkoxy carbonyl chlorides were prepared by the reaction of phosgene or triphosgene with Fmoc-protected β-amino alcohol which were isolated as solids. These oxycarbonyl chlorides were also converted to the corresponding pentachlorophenyl carbonates by reacting with pentachlorophenol. Fmoc-β-aminoalkoxy carbonyl chlorides as well as pentachlorophenol carbonates were successfully used as monomeric building blocks for the synthesis of several peptidyl carbamates.     

Signaling different pathways of cell death: Abrin induced programmed necrosis in U266B1 cells

Abrin is a type II ribosome-inactivating protein comprising of two subunits, A and B. Of the two, the A-subunit harbours the RNA-N-glycosidase activity and the B subunit is a galactose specific lectin that enables the entry of the protein inside the cell. Abrin inhibits protein synthesis and has been reported to induce apoptosis in several cell types. Based on these observations abrin is considered to have potential for the construction of immunotoxin in cell targeted therapy. Preliminary data from our laboratory however showed that although abrin inhibited the protein synthesis in all cell types, the mode of cell death varied. The aim of the present study was therefore to understand different death pathways induced by abrin in different cells. We used the human B cell line, U266B1 and compared it with the earlier studied T cell line Jurkat, for abrin-mediated inhibition of protein translation as well as cell death. While abrin triggered programmed apoptosis in Jurkat cells in a caspase-dependent manner, it induced programmed necrosis in U266B1 cells in a caspase-independent manner, even when there was reactive oxygen species production and loss of mitochondrial membrane potential. The data revealed that abrin-mediated necrosis involves lysosomal membrane permeabilization and release of cathepsins from the lysosomes. Importantly, the choice of abrin-mediated death pathway in the cells appears to depend on which of the two events occurs first: lysosomal membrane permeabilization or loss of mitochondrial membrane potential that decides cell death by necrosis or apoptosis.     

Rhizobium-Mediated Induction of Phenolics and Plant Growth Promotion in Rice (Oryza sativa L.)

Qualitative and quantitative estimation of phenolic compounds was done through reverse phase–high performance liquid chromatography (RP-HPLC) from different parts (leaf, stem, and root) of rice plants after inoculation with two rhizobial strains, RRE6 (Rhizobium leguminosarum bv. phaseoli) and ANU 843 (R. leguminosarum bv. trifolii) and infection by Rhizoctonia solani. On the basis of their retention time, the major phenolic acids detected in HPLC analysis were gallic, tannic, ferulic, and cinnamic acids. Furthermore, in all Rhizobium-inoculated rice plants, synthesis of phenolic compounds was more consistently enhanced than in control (uninoculated plants), where the maximum accumulation of phenolic compounds was observed in plants inoculated with RRE6 and infection with R. solani. Under pathogenic stress, RRE6 performed better because a relatively higher amount of phenolics was induced as compared with plants treated with ANU 843. Phenolic acids mediate induced systemic resistance and provide bioprotection to plants during pathogenic stresses. In addition, both rhizobial strains promote growth and productivity of rice plants in greenhouse conditions. This report on Rhizobium-mediated defense responses and growth promotion of nonlegume (such as rice) provides a novel paradigm of symbiotic plant–microbe interaction.     

Analysis of Trace Elements During Different Developmental Stages of Somatic Embryogenesis in Plantago ovata Forssk Using Energy Dispersive X-ray Fluorescence

Energy dispersive X-ray fluorescence (ED-XRF) technique has been used for the determination of trace element profile during different developmental stages of somatic embryogenic callus of an economically important medicinal plant, Plantago ovata Forssk. Somatic embryogenesis is a plant tissue culture-based technique, which is used for plant regeneration and crop improvement. In the present investigation, elemental content was analysed using ED-XRF technique during different developmental stages and also determine the effect of additives—casein hydrolysate and coconut water on the trace elemental profile of embryogenic callus tissue of P. ovata. Subsequent experiments showed significant alteration in the concentration of K, Ca, Mn, Fe, Zn, Cu, Br, and Sr in both the embryogenic and non-embryogenic callus. Higher K, Ca, Fe, Cu, and Zn accumulation was in embryogenic tissue stage compared to other stages, suggesting these elements are crucial for successful embryogenesis. The results suggest that this information could be useful for formulating a media for in vitro embryo induction of P. ovata.     

Epoxyeicosatrienoic Acid inhibition alters renal hemodynamics during pregnancy

In this study we examined the expression of cytochrome P450 (CYP) 2C and CYP2J isoforms in renal proximal tubules and microvessels isolated from rats at different stages of pregnancy. We also selectively inhibited epoxyeicosatrienoic acid (EET) production by the administration of N-methanesulfonyl-6-(2-proparyloxyphenyl)hexanamide (MSPPOH 20 mg/kg/day iv) to rats during Days 14-17 of gestation and to age-matched virgin rats and determined the consequent effects on renal function. Western blot analysis showed that CYP2C11, CYP2C23, and CYP2J2 expression was significantly increased in the renal microvessels of pregnant rats on Day 12 of gestation. In the proximal tubules, CYP2C23 expression was significantly increased throughout pregnancy, while the expression of CYP2C11 was increased in early and late pregnancy and the expression of CYP2J2 was increased in middle and late pregnancy. MSPPOH treatment significantly increased pregnant rats' mean arterial pressure, renal vascular resistance, and sodium balance but significantly decreased renal blood flow, glomerular filtration rate, and urinary sodium excretion, as well as fetal pups' body weight and length. In contrast, MSPPOH treatment had no effect on renal hemodynamics or urinary sodium excretion in age-matched virgin rats. In pregnant rats, MSPPOH treatment also caused selective inhibition of renal cortical EET production and significantly decreased the expression of CYP2C11, CYP2C23, and CYP2J2 in the renal cortex, renal microvessels, and proximal tubules. These results suggest that upregulation of renal vascular and tubular EETs contributes to the control of blood pressure and renal function during pregnancy.     

Variability in nuclear DNA content within pigeonpea,Cajanus cajan (Fabaceae)

4C DNA values have been estimated in 16 cultivars ofCajanus cajan by cytophotometry. The values range between 6.19 pg to 7.97 pg, a 23.6% variation. The cultivars form four groups which differ significantly from each other but have insignificant difference within them. The implications of this variability with respect to the heterogeneity and origin of this legume crop are discussed.     

Janus kinases and their role in growth and disease.

Janus kinases (JAK) play a crucial role in the initial steps of cytokine signaling. Each of the four members (JAK1, JAK2, JAK3, TYK2) of this non-receptor tyrosine kinase family is indispensable for the effects of distinct cytokines. Moreover, recent reports have added to our knowledge on their highly specific functions: JAK3 knockout mice and JAK3 deficient patients cannot signal through the interleukin-2,4,7,9, or 15 receptors and suffer from severe combined immunodeficiency (SCID). JAK1 and JAK2 knockout mice do not survive, their cells again showing distinct patterns of cytokine signaling deficits. At the other end of the spectrum, JAK fusion proteins have been shown to play a role in leukemias. In addition, a new class of JAK-specific inhibitors was described by several groups, the CIS/SOCS/Jab family. This review on the rapidly growing field focuses on JAK function and regulation, and on their emerging role in development and human disease.