A natural compound, methyl angolensate, induces mitochondrial pathway of apoptosis in Daudi cells

Natural products discovered from medicinal plants have played an important role in the treatment of cancer. In an effort to identify novel small molecules which can affect the proliferation of lymphoma cells, we tested methyl angolensate (MA), a plant derived tetranortriterpenoid, purified from the crude extract of the root callus of Soymida febrifuga commonly known as Indian red wood tree. We have tested MA for its cytotoxic properties on Burkitt's lymphoma cell lines, using various cellular assays. We observed that MA induces cytotoxicity in Daudi cells in a dose-dependent manner using trypan blue, MTT and LDH assays. We find that the treatment with MA led to activation of DNA double-strand break repair proteins including KU70 and KU80, suggesting the activation of nonhomologous DNA end joining pathway in surviving cells. Further, we find that methyl angolensate could induce apoptosis by cell cycle analysis, annexin V-FITC staining, DNA fragmentation and PARP cleavage. Besides, MA treatment led to reactive oxygen species generation and loss of mitochondrial transmembrane potential. These results suggest the activation of mitochondrial pathway of apoptosis. Hence, we identify MA as a potential chemotherapeutic agent against Daudi cells.

Lopsidedness in WHISP galaxies I. Rotation curves and kinematic lopsidedness

The frequently observed lopsidedness of the distribution of stars and gas in disc galaxies is still considered as a major problem in galaxy dynamics. It is even discussed as an imprint of the formation history of discs and the evolution of baryons in dark matter haloes. Here, we analyse a selected sample of 70 galaxies from the Westerbork Hi Survey of Spiral and Irregular Galaxies. The Hi data allow us to follow the morphology and the kinematics out to very large radii. In the present paper, we present the rotation curves and study the kinematic asymmetry. We extract the rotation curves of the receding and approaching sides separately and show that the kinematic behaviour of disc galaxies can be classified into five different types: symmetric velocity fields where the rotation curves of the receding and approaching sides are almost identical; global distortions where the rotation velocities of the receding and approaching sides have an offset that is constant with radius; local distortions leading to large deviations in the inner and negligible deviations in the outer parts (and vice versa); and distortions that divide the galaxies into two kinematic systems that are visible in terms of the different behaviour of the rotation curves of the receding and approaching sides, which leads to a crossing and a change in side. The kinematic lopsidedness is measured from the maximum rotation velocities, averaged over the plateau of the rotation curves. This gives a good estimate of the global lopsidedness in the outer parts of the sample galaxies. We find that the mean value of the perturbation parameter denoting the lopsided potential as obtained from the kinematic data is 0.056. Altogether, 36% of the sample galaxies are globally lopsided, which can be interpreted as the disc responding to a halo that was distorted by a tidal encounter. In Paper II, we study the morphological lopsidedness of the same sample of galaxies.

Structural studies of protein unfolding

Methods for macromolecular structure determination (NMR and crystallography) are now being used to get structural information on partially folded and unfolded states of proteins. These techniques, in combination with proton hydrogen exchange studies are powerful tools to extract information on non-native states of proteins. This review discusses progress In this area of protein folding.

Hidden order in serrated flow of metallic glasses

We report results of statistical and dynamic analysis of the serrated stress-time curves obtained from compressive constant strain-rate tests on two metallic glass samples with different ductility levels in an effort to extract hidden information in the seemingly irregular serrations. Two distinct types of dynamics are detected in these two alloy samples. The stress-strain curve corresponding to the less ductile Zr65Cu15Ni10Al10 alloy is shown to exhibit a finite correlation dimension and a positive Lyapunov exponent, suggesting that the underlying dynamics is chaotic. In contrast, for the more ductile Cu47.5Zr47.5Al5 alloy, the distributions of stress drop magnitudes and their time durations obey a power-law scaling reminiscent of a self-organized critical state. The exponents also satisfy the scaling relation compatible with self-organized criticality. Possible physical mechanisms contributing to the two distinct dynamic regimes are discussed by drawing on the analogy with the serrated yielding of crystalline samples. The analysis, together with some physical reasoning, suggests that plasticity in the less ductile sample can be attributed to stick-slip of a single shear band, while that of the more ductile sample could be attributed to the simultaneous nucleation of a large number of shear bands and their mutual interactions. (C) 2011 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Progesterone receptor expression in the human placenta

The presence of progesterone receptors (PR) in the human placenta has been demonstrated using the reverse transcriptase-polymerase chain reaction technique. It was observed that the amount of PR in the human placenta is less during late gestation. Electrophoretic mobility shift assays with nuclear extract isolated from the first trimester and term placenta revealed three complexes when incubated with [P-32]dCTP-labelled progesterone response element, and, in competition with unlabelled progesterone response element, the formation of all three complexes was inhibited. When supershift analysis of these complexes was carried out using antibodies which cross-react with both the A and B types of the PR or only with the B type receptor, only the A-form of PR was detected in the human placenta.

Regulation of an 8-kDa peptide involved in testosterone production by luteinizing hormone in rat Leydig cells

Results of Western blot analysis carried out with an interstitial cell extract from male guinea pig and ovarian extract from immature female rats administered equine chorionic gonadotropin (eCG) provide supportive evidence to our earlier suggestion that an 8-kDa peptide is involved in acquisition of steroidogenic capacity by the rat Leydig cells. It was found that though the signal was observed in other tissues such as liver, kidney and lung which do not produce gonadal hormones, the peptide was modulated only by lutenizing hormone (LH) in the rat Leydig cells.

Transformations of morphine, codeine and their analogues by Bacillus sp

A bacterial strain belonging to the genus Bacillus isolated by enrichment culture technique using morphine as a sole source of carbon transforms morphine and codeine into 14-hydroxymorphinone and 14-hydroxycodeinone as major and 14-hydroxymorphine and 14-hydroxycodeine as minor metabolites, respectively. When the N-methyl group in morphine and codeine are replaced by higher alkyl groups, the organism still retains its ability to carry out 14-hydroxylation as well as oxidation of the C-6-hydroxyl group in these N-variants, although the level of metabolites formed are considerably low. The organism readily transforms dihydromorphine and dihydrocodeine into only dihydromorphinone and dihydrocodeinone, respectively; suggesting that the 7,8-double bond is a necessary structural feature to carry out 14-hydroxylation reaction. The cell free extract (20,000 x g supernatant), prepared from morphine grown cells, transforms morphine into 14-hydroxymorphinone in the presence of NAD(+), but fails to show activity against testosterone. However, the cell free extract prepared from testosterone grown cells contains significant levels of 17 beta- hydroxysteroid dehydrogenase but shows no activity against morphine.