Butyrate suppresses expression of neuropilin I in colorectal cell lines through inhibition of Sp1 transactivation

Background: Neuropilin is a transmembrane receptor for vascular endothelial growth factor (VEGF) and is expressed in normal endothelial cells and upregulated in cancer cells. Neuropilin-1 (NRP-1) has been shown to promote tumour cell migration and survival in colon cancer in response to VEGF binding. The expression profiles of neuropilins, associated co-receptors and known ligands have been mapped in three colorectal cell lines: Caco-2, HCT116 & HT29. We have previously shown that butyrate, a naturally occurring histone deacetylase inhibitor (HDACi) produced by fermentation of fibre in the colon, causes apoptosis of colon cancer cell lines. Results: Here we demonstrate that butyrate down-regulates NRP-1 and VEGF at the mRNA and protein level in colorectal cancer cell lines. NRP-1 is a known transcriptional target of Sp1, whose activity is regulated by acetylation. NRP-1 down-regulation by butyrate was associated with decreased binding affinity of Sp1 for canonical Sp-binding sites in the NRP-1 promoter. siRNA-mediated knock-down of Sp1 implied that Sp1 may have strong DNA binding activity but weak transactivation potential. Conclusion: The downregulation of the key apoptotic and angiogenesis regulator NRP-1 by butyrate suggests a novel contributory mechanism to the chemopreventive effect of dietary fibre

A further result on the oscillation of delay difference equations

AbstractIn this paper, we are concerned with the delay difference equations of the form∗yn+1 − yn + pnyn−k = 0, n = 0, 1, 2, …, (∗)where pn ≥ 0 and k is a positive integer. We prove by using a new technique that∑n=0∞ ∑i=nn+kpi ln ∑i=nn+k pi + 1 − sign ∑i=nn+k pi − ∑i=n+1n+k pi ln ∑i=n+1n+k pi + 1 − sign ∑i=n+1n+k pi = ∞guarantees that all solutions of equation (∗) oscillate, which improves many previous well-known results. In particular, our theorems also fit the case where Σn−1i=n−kpi ≤ kk+1(k + 1)k+1. In addition, we present a nonoscillation sufficient condition for equation (∗)

Sp1 acetylation is associated with loss of DNA binding at promoters associated with cell cycle arrest and cell death in a colon cell line

Butyrate, a known histone deacetylase inhibitor (HDACi) and product of fibre fermentation, is postulated to mediate the protective effect of dietary fibre against colon cancer. The transcription factor Sp1 is a target of acetylation and is known to be associated with class I HDACs, including HDAC1. Sp1 is a ubiquitous transcription factor and Sp1-regulated genes include those involved in cell cycle regulation, apoptosis and lipogenesis: all major pathways in cancer development. The only known acetylated residue of Sp1 is lysine703 which resides in the DNA binding domain. Here we show that acetylated Sp1 loses p21- and bak-promoter -binding function in vitro. Furthermore treatment with a panel of HDAC inhibitors showed clustering of activities for a subset of inhibitors, causing G2 cell cycle arrest, Sp1 acetylation, p21 and Bak over-expression, all with very similar EC50 concentrations. These HDACi activities were not distributed according to the molecular class of compound. In order to mimic loss of binding, an siRNA strategy was used to reduce Sp1 expression. This resulted in altered expression of multiple elements of the p53/p21 pathway. Taken together our data suggest a mechanistic model for the chemopreventive actions of butyrate in colon epithelial cells, and provide new insight into the differential activities some classes of HDAC inhibitors

Hairpin DNA functionalized gold nanorods for mRNA detection in homogenous solution

We report a novel fluorescent probe for mRNA detection. It consists of a gold nanorod (GNR) functionalized with fluorophore labeled hairpin oligonucleotides (hpDNA) that are complementary to the mRNA of a target gene. This nanoprobe was found to be sensitive to a complementary oligonucleotide, as indicated by significant changes in both fluorescence intensity and lifetime. The influence of the surface density of hpDNA on the performance of this nanoprobe was investigated, suggesting that high hybridization efficiency could be achieved at a relatively low surface loading density of hpDNA. However, steady-state fluorescence spectroscopy revealed better overall performance, in terms of sensitivity and detection range, for nanoprobes with higher hairpin coverage. Time-resolved fluorescence lifetime spectroscopy revealed significant lifetime changes of the fluorophore upon hybridization of hpDNA with targets, providing further insight on the hybridization kinetics of the probe as well as the quenching efficiency of GNRs

Nonmonotonic inelastic tunneling spectra due to surface spin excitations in ferromagnetic junctions

The paper addresses inelastic spin-flip tunneling accompanied by surface spin excitations (magnons) in ferromagnetic junctions. The inelastic tunneling current is proportional to the magnon density of states which is energy-independent for the surface waves and, for this reason, cannot account for the bias-voltage dependence of the observed inelastic tunneling spectra. This paper shows that the bias-voltage dependence of the tunneling spectra can arise from the tunneling matrix elements of the electron-magnon interaction. These matrix elements are derived from the Coulomb exchange interaction using the itinerant-electron model of magnon-assisted tunneling. The results for the inelastic tunneling spectra, based on the nonequilibrium Green's function calculations, are presented for both parallel and antiparallel magnetizations in the ferromagnetic leads.Comment: 9 pages, 4 figures, version as publishe

Do maternal health problems influence child's worrying status? Evidence from the British Cohort Study

Conventional methods apply symmetric prior distributions such as a normal distribution or a Laplace distribution for regression coefficients, which may be suitable for median regression and exhibit no robustness to outliers. This work develops a quantile regression on linear panel data model without heterogeneity from a Bayesian point of view, i.e. upon a location-scale mixture representation of the asymmetric Laplace error distribution, and provides how the posterior distribution is summarized using Markov chain Monte Carlo methods. Applying this approach to the 1970 British Cohort Study (BCS) data, it finds that a different maternal health problem has different influence on child's worrying status at different quantiles. In addition, applying stochastic search variable selection for maternal health problems to the 1970 BCS data, it finds that maternal nervous breakdown, among the 25 maternal health problems, contributes most to influence the child's worrying status

Plasmon attenuation and optical conductivity of a two-dimensional electron gas

In a ballistic two-dimensional electron gas, the Landau damping does not lead to plasmon attenuation in a broad interval of wave vectors q << k_F. Similarly, it does not contribute to the optical conductivity \sigma (\omega, q) in a wide domain of its arguments, E_F > \omega > qv_F, where E_F, k_F and v_F are, respectively, the Fermi energy, wavevector and velocity of the electrons. We identify processes that result in the plasmon attenuation in the absence of Landau damping. These processes are: the excitation of two electron-hole pairs, phonon-assisted excitation of one pair, and a direct plasmon-phonon conversion. We evaluate the corresponding contributions to the plasmon linewidth and to the optical conductivity.Comment: 8 pages, 4 figures; final form, misprints correcte

Revealing the photophysics of gold-nanobeacons via time-resolved fluorescence spectroscopy

We demonstrate that time-resolved fluorescence spectroscopy is a powerful tool to investigate the conformation states of hairpin DNA on the surface of gold nanoparticles (AuNPs) and energy transfer processes in Au-nanobeacons. Long-range fluorescence quenching of Cy5 by AuNPs has been found to be in good agreement with electrodynamics modelling. Moreover, time-correlated single-photon counting (TCSPC) is shown to be promising for real-time monitoring of the hybridization kinetics of Au-nanobeacons, with up to 60% increase in decay time component and 300% increase in component fluorescence fraction observed. Our results also indicate the importance of the stem and spacer designs for the performance of Au-nanobeacons

Interplay among critical temperature, hole content, and pressure in the cuprate superconductors

Within a BCS-type mean-field approach to the extended Hubbard model, a nontrivial dependence of T_c on the hole content per unit CuO_2 is recovered, in good agreement with the celebrated non-monotonic universal behaviour at normal pressure. Evaluation of T_c at higher pressures is then made possible by the introduction of an explicit dependence of the tight-binding band and of the carrier concentration on pressure P. Comparison with the known experimental data for underdoped Bi2212 allows to single out an `intrinsic' contribution to d T_c / d P from that due to the carrier concentration, and provides a remarkable estimate of the dependence of the inter-site coupling strength on the lattice scale.Comment: REVTeX 8 pages, including 5 embedded PostScript figures; other required macros included; to be published in Phys. Rev. B (vol. 54

Comparison of the effects of kanamycin and geneticin on regeneration of papaya from root tissue

Kanamycin and geneticin are commonly used for the selection of neomycin phosphotransferase II (npt II) transformed plants. Since papaya tissue is sensitive to both antibiotics, it is difficult to explore their effects on the regeneration process solely based on using non-transformed tissues. Adventitious roots derived from npt II-transgenic and non-transgenic papaya shoots in vitro were used as explants in this investigation. The effects of kanamycin and geneticin on callus formation, embryogenesis, and conversion of somatic embryos to shoots were compared. Callus growth derived from npt II-transformed root explants was apparently enhanced on kanmycin within 50-200 mg l(-1) or on geneticin within 12.5-50 mg l(-1) as compared to those on antibiotic-free controls. The percentages of npt II-transformed somatic embryo-forming callus were not significantly different (16.3-18.3%) on geneticin less than 6.25 mg l(-1) and only slightly reduced (11.2-15.7%) on geneticin within 12.5-50 mg l(-1), whereas, formation of somatic embryos was strongly suppressed on kanamycin media. Conversion rates of npt II-transformed somatic embryos to shoots were not significantly different among all kanamycin or geneticin treatments. Percentages of the callus derived from non-transformed root explants were greatly reduced on the medium containing more than 25 mg l(-1) kanamycin or geneticin, and no somatic embryos formed from untransformed callus on any kanamycin or geneticin media. Our results indicated that somatic embryogenesis of callus derived from npt II-transformed root explants of papaya was strongly inhibited by kanamycin. Thus, to regenerate npt II-transformed cells from papaya root tissue, we recommend using the lower concentration geneticin (12.5-25 mg l(-1)) to avoid the adverse effects of kanamycin on embryogenesis