On Core Collapse Supernovae in Normal and in Seyfert Galaxies

This paper estimates the relative frequency of different types of core-collapse supernovae, in terms of the ratio f between the number of type Ib--Ic and of type II supernovae. We estimate f independently for all normal and Seyfert galaxies whose radial velocity is <=14000 km/s, and which had at least one supernova event recorded in the Asiago catalogue from January 1986 to August 2000. We find that the ratio f is approx. 0.23+/-0.05 in normal galaxies. This value is consistent with constant star formation rate and with a Salpeter Initial Mass Function and average binary rate approx. 50 %. On the contrary, Seyfert galaxies exceed the ratio f in normal galaxies by a factor approx. 4 at a confidence level >= 2 sigma. A caveat is that the numbers for Seyferts are still small (6 type Ib-Ic and 6 type II supernovae discovered as yet). Assumed real, this excess of type Ib and Ic with respect to type II supernovae, may indicate a burst of star formation of young age (<= 20 Myr), a high incidence of binary systems in the inner regions (r <= 0.4 R25) of Seyfert galaxies, or a top-loaded mass function.Comment: Accepted for Publication in MNRA

Synthesis and Structure-Activity Relationships of Pyridoxal-6-arylazo-5'-phosphate and Phosphonate Derivatives as P2 Receptor Antagonists.

Novel analogs of the P2 receptor antagonist pyridoxal-5'-phosphate-6-phenylazo-2',4'-disulfonate (PPADS) were synthesized. Modifications were made through functional group substitution on the sulfophenyl ring and at the phosphate moiety through the inclusion of phosphonates, demonstrating that a phosphate linkage is not required for P2 receptor antagonism. Substituted 6-phenylazo and 6-naphthylazo derivatives were also evaluated. Among the 6-phenylazo derivatives, 5'-methyl, ethyl, propyl, vinyl, and allyl phosphonates were included. The compounds were tested as antagonists at turkey erythrocyte and guinea-pig taenia coli P2Y(1) receptors, in guinea-pig vas deferens and bladder P2X(1) receptors, and in ion flux experiments by using recombinant rat P2X(2) receptors expressed in Xenopus oocytes. Competitive binding assay at human P2X(1) receptors in differentiated HL-60 cell membranes was carried out by using [(35)S]ATP-?-S. A 2'-chloro-5'-sulfo analog of PPADS (C(14)H(12)O(9)N(3)ClPSNa), a vinyl phosphonate derivative (C(15)H(12)O(11)N(3)PS(2)Na(3)), and a naphthylazo derivative (C(18)H(14)O(12)N(3)PS(2)Na(2)), were particularly potent in binding to human P2X(1) receptors. The potencies of phosphate derivatives at P2Y(1) receptors were generally similar to PPADS itself, except for the p-carboxyphenylazo phosphate derivative C(15)H(13)O(8)N(3)PNa and its m-chloro analog C(15)H(12)O(8)N(3)ClPNa, which were selective for P2X vs. P2Y(1) receptors. C(15)H(12)O(8)N(3)ClPNa was very potent at rat P2X(2) receptors with an IC(50) value of 0.82 ?M. Among the phosphonate derivatives, [4-formyl-3-hydroxy-2-methyl-6-(2-chloro-5-sulfonylphenylazo)-pyrid-5-yl]methylphosphonic acid (C(14)H(12)-O(8)N(3)ClPSNa) showed high potency at P2Y(1) receptors with an IC(50) of 7.23 ?M. The corresponding 2,5-disulfonylphenyl derivative was nearly inactive at turkey erythrocyte P2Y(1) receptors, whereas at recombinant P2X(2) receptors had an IC(50) value of 1.1 ?M. An ethyl phosphonate derivative (C(15)H(15)O(11)N(3)PS(2)Na(3)), whereas inactive at turkey erythrocyte P2Y(1) receptors, was particularly potent at recombinant P2X(2) receptors

NMR evidence for a strong modulation of the Bose-Einstein Condensate in BaCuSi2_2O6_6

We present a $^{63,65}$Cu and $^{29}$Si NMR study of the quasi-2D coupled spin 1/2 dimer compound BaCuSi$_2$O$_6$ in the magnetic field range 13-26 T and at temperatures as low as 50 mK. NMR data in the gapped phase reveal that below 90 K different intra-dimer exchange couplings and different gaps ($\Delta_{\rm{B}}/\Delta_{\rm{A}}$ = 1.16) exist in every second plane along the c-axis, in addition to a planar incommensurate (IC) modulation. $^{29}$Si spectra in the field induced magnetic ordered phase reveal that close to the quantum critical point at $H_{\rm{c1}}$ = 23.35 T the average boson density $\bar{n}$ of the Bose-Einstein condensate is strongly modulated along the c-axis with a density ratio for every second plane $\bar{n}_{\rm{A}}/\bar{n}_{\rm{B}} \simeq 5$. An IC modulation of the local density is also present in each plane. This adds new constraints for the understanding of the 2D value $\phi$ = 1 of the critical exponent describing the phase boundary

Cytotoxicity of Mahanimbine, Murryafoline A and S-Benzyldithiocarbazate on Human Leukemic Cell Line, CEM-SS

Mahanimbine, a carbazole alkaloid was isolated from an ether extract of the stem bark of Murraya koenigii whilst Murrayafoline A was isolated from petroleum ether extract of the roots of Murraya koenigii. S-Benzyldithiocarbazate is a dithiocarbazic acid Schiff base derived from S-alkyl esters. They were found to exhibit cytotoxic activity against CEM-SS human T-lymphoblastic leukemic cells. The cytotoxic activity of Mahanimbine, Murrayafoline A and S-Benzyldithiocarbazate that inhibit 50 % growth (IC₅₀) of CEM-SS were 6 µg/ml, S µg/ml and 7.S µg/ml respectively. For comparative purposes, the IC₅₀ of several commercial cytotoxic drugs against CEM-SS were determined. The inhibition effect of Mahanimbine, Murrayafoline A and SBenzyldithiocarbazate were better than Methotrexate (IC₅₀ > 30 µg/ml), Doxorubicine (IC₅₀ = 21 µg/ml), Cytarabine (IC₅₀ > 30 µg/ml) and Colchecine (IC₅₀ = 8 µg/ml).These compounds were found to be less active than cis-diamine dichloroplatinwn and Vinorelbine tartrate with a IC₅₀ value of 3 µg/ml. In contrast, these three compounds were found to be less active against normal mouse fibroblasts cell, 3T3 with the IC₅₀ value of 11 µg/ml (Mahanimbine), 17 µg/ml (Murrayafoline A) and 10 µg/ml (SBenzyldithiocarbazate) respectively. The study showed that the proliferation of cells was inhibited before the cells were being killed. In addition, Mahanimbine, MurrayafolineA and S-Benzyldithiocarbazate caused programmed cell death by showing apoptotic features such as nucleus fragmentation, cell shrinkage, membrane blebbing and formation of apoptotic bodies. These were further confirmed with DNA laddering in agarose gel electrophoresis assay due to DNA fragmentation. DNA laddering was obtained after 24 hours of treatment by these three compounds in a doseindependent but time-dependent way. Mahanimbine and Murrayafoline A were shown to arrest CEM-SS cells at G1 phase of cell cycle using flowcytometry method. As a result, Mahanimbine, Murrayafoline A and S-Benzyldithiocarbazate were found as potent antitumor agents

Models for the Type Ic Hypernova SN 2003lw associated with GRB 031203

The Gamma-Ray Burst 031203 at a redshift z=0.1055 revealed a highly reddened Type Ic Supernova, SN 2003lw, in its afterglow light. This is the third well established case of a link between a long-duration GRB and a type Ic SN. The SN light curve is obtained subtracting the galaxy contribution and is modelled together with two spectra at near-maximum epochs. A red VLT grism 150I spectrum of the SN near peak is used to extend the spectral coverage, and in particular to constrain the uncertain reddening, the most likely value for which is E_{G+H}(B-V) about 1.07 +/- 0.05. Accounting for reddening, SN 2003lw is about 0.3 mag brighter than the prototypical GRB-SN 1998bw. Light curve models yield a 56Ni mass of about 0.55 solar mass. The optimal explosion model is somewhat more massive (ejecta mass about 13 solar mass) and energetic (kinetic energy about 6 times 10^52 erg) than the model for SN 1998bw, implying a massive progenitor (40 - 50 solar mass). The mass at high velocity is not very large (1.4 solar mass above 30000 km/s, but only 0.1 solar mass above 60000 km/s), but is sufficient to cause the observed broad lines. The similarity of SNe 2003lw and 1998bw and the weakness of their related GRBs, GRB031203 and GRB980425, suggest that both GRBs may be normal events viewed slightly off-axis or a weaker but possibly more frequent type of GRB.Comment: 19 pages, 8 figures, accepted for publication in Ap

Cytotoxicity of Elaoephorbia drupifera and other Cameroonian medicinal plants against drug sensitive and multidrug resistant cancer cells

BACKGROUND: Multidrug resistance (MDR) is a major hurdle for cancer treatment worldwide and accounts for chemotherapy failure in over 90% of patients with metastatic cancer. Evidence of the cytotoxicity of Cameroonian plants against cancer cell lines including MDR phenotypes is been intensively and progressively provided. The present work was therefore designed to evaluate the cytotoxicity of the methanol extracts of twenty-two Cameroonian medicinal plants against sensitive and MDR cancer cell lines. METHODS: The methanol maceration was used to obtain the crude plant extracts whilst the cytotoxicity of the studied extracts was determined using a resazurin reduction assay. RESULTS: A preliminary assay on leukemia CCRF-CEM cells at 40 μg/mL shows that six of the twenty plant extract were able to enhance less than 50% of the growth proliferation of CCRF-CEM cells. These include Crinum zeylanicum (32.22%), Entada abyssinica (34.67%), Elaoephorbia drupifera (35.05%), Dioscorea bulbifera (45.88%), Eremomastax speciosa (46.07%) and Polistigma thonningii (45.11%). Among these six plants, E. drupifera showed the best activity with IC(50) values below or around 30 μg/mL against the nine tested cancer cell lines. The lowest IC(50) value of 8.40 μg/mL was recorded with the extract of E. drupifera against MDA-MB231 breast cancer cell line. The IC(50) values below 10 μg/mL were recorded with the extracts of E. drupifera against MDA-MB231 breast cancer cells, C. zeylanicum against HCT116 p53(+)/(+) and HCT116p53(-)/(-) colon cancer cells and E. abyssinica against HCT116 p53(+)/(+) cells. CONCLUSION: The results of the present study provide evidence of the cytotoxic potential of some Cameroonian medicinal plants and a baseline information for the potential use of Elaoephorbia drupifera in the treatment of sensitive and drug-resistant cancer cell lines

The Chemical Constituents of Ficus benjamina Linn. and Their Biological Activities

The leaves, bark and fruits of Ficus benjamina Linn. were subjected to extraction and isolation using chromatographic techniques to yield six compounds (cinnamic acid, lactose, naringenin, quercetin, caffeic acid and stigmasterol). The structures of the compounds were determined by spectroscopic techniques and by comparison with published data. The compounds were screened for antimicrobial activity against two species of bacteria (Bacillus cereus and Pseudomonas aeruginosa) and cytotoxic activity against T-lyrnphoblastic leukemic (CEM-SS) cell line. Caffeic acid exhibited strong cytotoxic activity with IC 50 value of 25 mg/mL

M2 pyruvate kinase provides a mechanism for nutrient sensing and regulation of cell proliferation

We show that the M2 isoform of pyruvate kinase (M2PYK) exists in equilibrium between monomers and tetramers regulated by allosteric binding of naturally occurring small-molecule metabolites. Phenylalanine stabilizes an inactive T-state tetrameric conformer and inhibits M2PYK with an IC(50) value of 0.24 mM, whereas thyroid hormone (triiodo-l-thyronine, T3) stabilizes an inactive monomeric form of M2PYK with an IC(50) of 78 nM. The allosteric activator fructose-1,6-bisphosphate [F16BP, AC(50) (concentration that gives 50% activation) of 7 μM] shifts the equilibrium to the tetrameric active R-state, which has a similar activity to that of the constitutively fully active isoform M1PYK. Proliferation assays using HCT-116 cells showed that addition of inhibitors phenylalanine and T3 both increased cell proliferation, whereas addition of the activator F16BP reduced proliferation. F16BP abrogates the inhibitory effect of both phenylalanine and T3, highlighting a dominant role of M2PYK allosteric activation in the regulation of cancer proliferation. X-ray structures show constitutively fully active M1PYK and F16BP-bound M2PYK in an R-state conformation with a lysine at the dimer-interface acting as a peg in a hole, locking the active tetramer conformation. Binding of phenylalanine in an allosteric pocket induces a 13° rotation of the protomers, destroying the peg-in-hole R-state interface. This distinct T-state tetramer is stabilized by flipped out Trp/Arg side chains that stack across the dimer interface. X-ray structures and biophysical binding data of M2PYK complexes explain how, at a molecular level, fluctuations in concentrations of amino acids, thyroid hormone, and glucose metabolites switch M2PYK on and off to provide the cell with a nutrient sensing and growth signaling mechanism

Direct comparison of the histidine-rich protein-2 enzyme-linked immunosorbent assay (HRP-2 ELISA) and malaria SYBR green I fluorescence (MSF) drug sensitivity tests in Plasmodium falciparum reference clones and fresh ex vivo field isolates from Cambodia

BACKGROUND: Performance of the histidine-rich protein-2 enzyme-linked immunosorbent assay (HRP-2 ELISA) and malaria SYBR Green I fluorescence (MSF) drug sensitivity tests were directly compared using Plasmodium falciparum reference strains and fresh ex vivo isolates from Cambodia against a panel of standard anti-malarials. The objective was to determine which of these two common assays is more appropriate for studying drug susceptibility of “immediate ex vivo” (IEV) isolates, analysed without culture adaption, in a region of relatively low malaria transmission. METHODS: Using the HRP-2 and MSF methods, the 50% inhibitory concentration (IC(50)) values against a panel of malaria drugs were determined for P. falciparum reference clones (W2, D6, 3D7 and K1) and 41 IEV clinical isolates from an area of multidrug resistance in Cambodia. Comparison of the IC(50) values from the two methods was made using Wilcoxon matched pair tests and Pearson’s correlation. The lower limit of parasitaemia detection for both methods was determined for reference clones and IEV isolates. Since human white blood cell (WBC) DNA in clinical samples is known to reduce MSF assay sensitivity, SYBR Green I fluorescence linearity of P. falciparum samples spiked with WBCs was evaluated to assess the relative degree to which MSF sensitivity is reduced in clinical samples. RESULTS: IC(50) values correlated well between the HRP-2 and MSF methods when testing either P. falciparum reference clones or IEV isolates against 4-aminoquinolines (chloroquine, piperaquine and quinine) and the quinoline methanol mefloquine (Pearson r = 0.85-0.99 for reference clones and 0.56-0.84 for IEV isolates), whereas a weaker IC(50) value correlation between methods was noted when testing artemisinins against reference clones and lack of correlation when testing IEV isolates. The HRP-2 ELISA produced a higher overall success rate (90% for producing IC(50) best-fit sigmoidal curves), relative to only a 40% success rate for the MSF assay, when evaluating ex vivo Cambodian isolates. Reduced sensitivity of the MSF assay is likely due to an interference of WBCs in clinical samples. CONCLUSIONS: For clinical samples not depleted of WBCs, HRP-2 ELISA is superior to the MSF assay at evaluating fresh P. falciparum field isolates with low parasitaemia (<0.2%) generally observed in Southeast Asia