A small RNA that complements mutants in the RNA processing enzyme ribonuclease P

Four temperature-sensitive RNase P mutants were analyzed for the accumulation of 10 S RNA. In the 10 S region of the polyacrylamide gel two molecules appear, a and b. While the level of 10 Sa seems to be affected in some of the mutants, the 10 Sb molecule was not found in rnpB mutants. A plasmid (pL2), which contains Escherichia coli DNA sequences that complement, at least partially, rnp mutations, directs the synthesis of 10 Sb RNA. The presence of the pL2 plasmid complements the rnpA49, rnpB3187 and the rnpC241 mutations, as revealed by colony formation at “non-permissive” temperatures. However, the complementation of the rnpA49 mutation is much better than that of the other mutations. The complementation can also be measured by the increased level of RNase P activity in extracts. 10 Sa and b RNAs are unique among all RNAs tested thus far, since they are stable during exponential growth at 30 °C and 37 °C. However, at higher temperatures, such as 43 °C, the molecules are somewhat less stable, and they become rather labile when RNA synthesis is blocked by rifampicin. Structural analysis revealed that the 10 Sa and 10 Sb RNA molecules have dissimilar sequences.     

A process optimization for bio-catalytic production of substituted catechols (3-nitrocatechol and 3-methylcatechol

Background  

Substituted catechols are important precursors for large-scale synthesis of pharmaceuticals and other industrial products. Most of the reported chemical synthesis methods are expensive and insufficient at industrial level. However, biological processes for production of substituted catechols could be highly selective and suitable for industrial purposes.     

Influence of age,weaning, season and body weight on the levels of progesterone,oestradiol-17β and luteinizing hormone in growing buffalo heifers (Bubalus bubalis)

The influence of age, weaning, season of the year and body weight on the peripheral levels of progesterone, oestradiol-17β and luteinizing hormone (LH) were studied during neonatal, perinatal and peripubertal periods in buffalo heifers. The buffalo heifers exhibited oestrus only after 30 months of age and had higher levels of LH and oestradiol-17β and a lower level of progesterone on the day of oestrus. The progesterone concentration was affected significantly (P < 0.01) by different seasons, by weaning (P < 0.05) and varied between pubertal and neonatal periods (P < 0.01), whereas the oestradiol-17β level was affected significantly (P < 0.01) by weaning and varied at different seasons and with body weight. However, the LH concentration was greater during the neonatal period than the pre- and peripubertal periods and changed significantly (P < 0.01) between groups of ages and body weights. The results suggest that increases in the levels of oestradiol-17β and progesterone after 30 months of age are probably indicative of the onset of puberty in buffalo heifers. However, a further increase in oestradiol-17β, LH, and a decrease in progesterone are essential for oestrus and cyclicity to be exhibited in buffalo heifers.     

Phenothiazines: equal concentrations in lipid bilayers do not induce equal response

Perturbation of the order-disorder transition in dipalmitoyl-lecithin bilayer by a series of phenothiazines is measured by differential scanning calorimetry. The membrane concentrations of the various phenothiazines required to induce equal response (i.e., broadening of the phase transition profile) vary over a one hundred-fold concentration range, and correlate well (r = 0.97 for 38 compounds) with the total drug concentration that induces equal response.     

Visualization of drug-nucleic acid interactions at atomic resolution. III. Unifying structural concepts in understanding drug-DNA interactions and their broader implications in understanding protein-DNA interactions.

Structural information afforded by the X-ray crystallographic studies of ethidium-dinucleoside monophosphate crystalline complexes described in the preceding two papers has led to a detailed model for ethidium-DNA binding. Features of ethidium-DNA binding, in turn, have led to unifying structural concepts in understanding a wide range of drug-DNA interactions. It is possible that these concepts have still broader implications in understanding the nature of protein-DNA interactions.This paper begins by summarizing the stereochemical aspects of ethidium-DNA, actinomycin-DNA and irehdiamine-DNA binding, molecules that use intercalative and kinked-type geometries in binding to DNA. It then describes superhelical DNA structures formed by kinking DNA periodically varying numbers of base-pairs apart. κ-kinked B DNA, a structure formed by kinking DNA every ten base-pairs, is a left-handed superhelical structure that may be utilized in the organization of DNA within the nucleosome in chromatin. β-kinked B DNA is a right-handed superhelical structure formed by kinking DNA every two base-pairs. It is possible that premelting conformational changes occur in DNA which utilize elements of this structure. This would expose base-pairs to solvent denaturation, and could lower the activation energy necessary for strand separation during DNA denaturation. RNA polymerase and other DNA melting proteins could capitalize on this type of premelting conformational change when binding to DNA.The concept that conformational flexibility exists in DNA structure (and that drug intercalation is a phenomenon that reflects this flexibility) can, in addition, explain a wide variety of physicochemical data about DNA. In this paper we discuss the nature of these data in detail.     

Shannon's Measure and its Use in the Analysis of Cancer Data

In this paper, Shannon's measure of uncertainty is explored in the analysis of cancer data. The term ‘cancer diversity’ is defined and its potential application is illustrated.     

Complementarity between ferritin H mRNA and 28 S ribosomal RNA

We have found an interesting complementarity in sequences of human ferritin H mRNA and 28 S ribosomal RNA. Immediately upstream of the initiating AUG in the ferritin mRNA is a stretch of 67 nucleotides which contains sequences complementary to several regions in 28 S RNA. One such region can form 55 base pairings with the 5' noncoding region of the ferritin H mRNA. Most of the complementarity is due to repeats of CCG in the ferritin mRNA and GGC in the ribosomal RNA. The regions of complementarity in the 28 S RNA appear to be expansion sequences that have arisen in the evolution of eukaryotic ribosomal RNA. We suggest that interaction of ferritin mRNA and 28 S RNA may function to regulate the stability and/or translatability of ferritin mRNA.     

Effect of Asparagus racemosus Extract on Transdermal Delivery of Carvedilol: A Mechanistic Study

This study was designed for investigating the effect of Asparagus racemosus (AR) extract and chitosan (CTN) in facilitating the permeation of carvedilol (CDL) across rat epidermis. Transdermal flux of carvedilol through heat-separated rat epidermis was investigated in vitro using vertical Keshary–Chien diffusion cells. Biophysical and microscopic manifestations of epidermis treated with AR extract, CTN, and AR extract–CTN mixture were investigated by using differential scanning calorimetry, transepidermal water loss, scanning electron microscopy (SEM), and transmission electron microscopy (TEM). Biochemical estimations of cholesterol, sphingosine, and triglycerides were carried out for treated excised as well as viable rat epidermis. The antihypertensive activity of the patches in comparison with that of oral carvedilol was studied in deoxycorticosterone acetate-induced hypertensive rats. The permeation of carvedilol across excised rat epidermis was significantly higher (p < 0.05) when AR extract, CTN, or AR extract–CTN mixture was used as donor vehicle as compared to propylene glycol/ethanol (7:3) mixture. Epidermis obtained after 12 h treatment of viable rat skin with AR extract–CTN mixture showed significantly higher (p < 0.05) permeability to CDL as compared to that after treatment with AR extract or CTN alone. Further, the application of patches containing AR extract–CTN mixture resulted in sustained release of CDL which was able to control the hypertension in deoxycorticosterone acetate-induced hypertensive rats through 36 h. Estimation of micro constituents in rat epidermis revealed maximum extraction of cholesterol, sphingosine, and triglycerides after treatment with AR extract–CTN mixture. This was manifested in altered lipid and protein-specific thermotropic transitions. Further, increase in intercellular space, disordered lipid structure, and corneocyte detachment as observed in SEM and TEM suggested great potential of AR extract for use as percutaneous permeation enhancer. The developed transdermal patches of CDL containing AR extract–CTN mixture exhibited better performance as compared to oral administration in controlling hypertension in rats.