Nisin, an apoptogenic bacteriocin and food preservative, attenuates HNSCC tumorigenesis via CHAC 1

Nisin, a bacteriocin and commonly used food preservative, may serve as a novel potential therapeutic for treating head and neck squamous cell carcinoma ( HNSCC ), as it induces preferential apoptosis, cell cycle arrest, and reduces cell proliferation in HNSCC cells, compared with primary keratinocytes. Nisin also reduces HNSCC tumorigenesis in vivo. Mechanistically, nisin exerts these effects on HNSCC , in part, through CHAC 1, a proapoptotic cation transport regulator, and through a concomitant CHAC 1‐independent influx of extracellular calcium. In addition, although CHAC 1 is known as an apoptotic mediator, its effects on cancer cell apoptosis have not been examined. Our studies are the first to report CHAC 1's new role in promoting cancer cell apoptosis under nisin treatment. These data support the concept that nisin decreases HNSCC tumorigenesis in vitro and in vivo by inducing increased cell apoptosis and decreased cell proliferation; effects that are mediated by activation of CHAC 1, increased calcium influxes, and induction of cell cycle arrest. These findings support the use of nisin as a potentially novel therapeutic for HNSCC , and as nisin is safe for human consumption and currently used in food preservation, its translation into a clinical setting may be facilitated. Nisin decreases HNSCC tumorigenesis in vitro and in vivo by inducing increased cell apoptosis and decreased cell proliferation; effects that are mediated by activation of CHAC1, increased calcium influxes, and induction of cell cycle arrest. These findings support the use of nisin as a potentially novel therapeutic for HNSCC , and as nisin is safe for human consumption and currently used in food preservation, its translation into a clinical setting may be facilitated.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/94527/1/cam435.pd

Shedding of NG2 by MMP-13 Attenuates Anoikis

Disruption of cell?matrix interactions can lead to anoikis?apoptosis due to loss of matrix contacts. We previously showed that Nerve/glial antigen 2 (NG2) is a novel anoikis receptor. Specifically, overexpression of NG2 leads to anoikis propagation, whereas its suppression leads to anoikis attenuation. Interestingly, NG2 expression decreases in late anoikis, suggesting that NG2 reduction is also critical to this process. Thus, we hypothesized that NG2 undergoes cleavage to curtail anoikis propagation. Further, since matrix metalloproteinases (MMPs) cleave cell surface receptors, play a major role in modulating apoptosis, and are associated with death receptor cleavage during apoptosis, we further hypothesized that cleavage of NG2 could be mediated by MMPs to regulate anoikis. Indeed, anoikis conditions triggered release of the NG2 extracellular domain into condition media during late apoptosis, and this coincided with increased MMP-13 expression. Treatment with an MMP-13 inhibitor and MMP-13 siRNA increased anoikis, since these treatments blocked NG2 release. Further, NG2-positive cells exhibited increased anoikis upon MMP-13 inhibition, whereas MMP-13 inhibition did not increase anoikis in NG2-null cells, corroborating that retention of NG2 on the cell membrane is critical for sustaining anoikis, and its cleavage for mediating anoikis attenuation. Similarly, NG2 suppression with siRNA inhibited NG2 release and anoikis. In contrast, MMP-13 overexpression or exogenous MMP-13 reduced anoikis by more effectively shedding NG2. In conclusion, maintenance of NG2 on the cell surface promotes anoikis propagation, whereas its shedding by MMP-13 actions attenuates anoikis. Given that these findings are derived in the context of periodontal ligament fibroblasts, these data have implications for periodontal inflammation and periodontal disease pathogenesis.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/140362/1/dna.2014.2399.pd

Inhomogeneous superconductivity in organic conductors: role of disorder and magnetic field

Several experimental studies have shown the presence of spatially inhomogeneous phase coexistence of superconducting and non superconducting domains in low dimensional organic superconductors. The superconducting properties of these systems are found to be strongly dependent on the amount of disorder introduced in the sample regardless of its origin. The suppression of the superconducting transition temperature $T_c$ shows clear discrepancy with the result expected from the Abrikosov-Gor'kov law giving the behavior of $T_c$ with impurities. Based on the time dependent Ginzburg-Landau theory, we derive a model to account for the striking feature of $T_c$ in organic superconductors for different types of disorder by considering the segregated texture of the system. We show that the calculated $T_c$ quantitatively agrees with experiments. We also focus on the role of superconducting fluctuations on the upper critical fields $H_{c2}$ of layered superconductors showing slab structure where superconducting domains are sandwiched by non-superconducting regions. We found that $H_{c2}$ may be strongly enhanced by such fluctuations.Comment: to appear in Journal of Physics: Condensed Matte

Mechanosensitive activation of K+ channel via phospholipase C-induced depletion of phosphatidylinositol 4,5-bisphosphate in B lymphocytes

In various types of cells mechanical stimulation of the plasma membrane activates phospholipase C (PLC). However, the regulation of ion channels via mechanosensitive degradation of phosphatidylinositol 4,5-bisphosphate (PIP(2)) is not known yet. The mouse B cells express large conductance background K(+) channels (LK(bg)) that are inhibited by PIP(2). In inside-out patch clamp studies, the application of MgATP (1 mm) also inhibited LK(bg) due to the generation of PIP(2) by phosphoinositide (PI)-kinases. In the presence of MgATP, membrane stretch induced by negative pipette pressure activated LK(bg), which was antagonized by PIP(2) (> 1 microm) or higher concentration of MgATP (5 mm). The inhibition by PIP(2) was partially reversible. However, the application of methyl-beta-cyclodextrin, a cholesterol scavenger disrupting lipid rafts, induced the full recovery of LK(bg) activity and facilitated the activation by stretch. In cell-attached patches, LK(bg) were activated by hypotonic swelling of B cells as well as by negative pressure. The mechano-activation of LK(bg) was blocked by U73122, a PLC inhibitor. Neither actin depolymerization nor the inhibition of lipid phosphatase blocked the mechanical effects. Direct stimulation of PLC by m-3M3FBS or by cross-linking IgM-type B cell receptors activated LK(bg). Western blot analysis and confocal microscopy showed that the hypotonic swelling of WEHI-231 induces tyrosine phosphorylation of PLCgamma2 and PIP(2) hydrolysis of plasma membrane. The time dependence of PIP(2) hydrolysis and LK(bg) activation were similar. The presence of LK(bg) and their stretch sensitivity were also proven in fresh isolated mice splenic B cells. From the above results, we propose a novel mechanism of stretch-dependent ion channel activation, namely, that the degradation of PIP(2) caused by stretch-activated PLC releases LK(bg) from the tonic inhibition by PIP(2)

The effects of food safety education on adolescents' hand hygiene behavior: an analysis of stages of change

The hand hygiene behavior of 400 middle school students (grades 1-3) in Seoul and Gyeonggi-Do was studied to determine how stages of change were affected by food safety education, focusing on hand hygiene and general food safety. Subjects were 51.3% male and 44.3% of study subjects were first graders of middle school. Approximately 40% of subjects were at the stage of action, 42.7% were at the stage of contemplation, and 16.4% were at pre-contemplation. The most important factor that influenced proper hand washing was self efficacy (P < 0.001). Proper hand washing was also correlated significantly with positive belief (P < 0.01) and stages of change (P < 0.01). After food safety education by high-school mentors, middle-school students who were in the stages of pre-contemplation (11.1%) and contemplation (88.9%) showed significant progression toward the action stage (P < 0.001). Proper hand washing (P < 0.01) and food safety knowledge (P < 0.05) were also significantly increased after educational intervention

Quadrupole Anisotropy in Dihadron Azimuthal Correlations in Central dd++Au Collisions at sNN\sqrt{s_{_{NN}}}=200 GeV

The PHENIX collaboration at the Relativistic Heavy Ion Collider (RHIC) reports measurements of azimuthal dihadron correlations near midrapidity in $d$$+$Au collisions at $\sqrt{s_{_{NN}}}$=200 GeV. These measurements complement recent analyses by experiments at the Large Hadron Collider (LHC) involving central $p$$+$Pb collisions at $\sqrt{s_{_{NN}}}$=5.02 TeV, which have indicated strong anisotropic long-range correlations in angular distributions of hadron pairs. The origin of these anisotropies is currently unknown. Various competing explanations include parton saturation and hydrodynamic flow. We observe qualitatively similar, but larger, anisotropies in $d$$+$Au collisions compared to those seen in $p$$+$Pb collisions at the LHC. The larger extracted $v_2$ values in $d$$+$Au collisions at RHIC are consistent with expectations from hydrodynamic calculations owing to the larger expected initial-state eccentricity compared with that from $p$$+$Pb collisions. When both are divided by an estimate of the initial-state eccentricity the scaled anisotropies follow a common trend with multiplicity that may extend to heavy ion data at RHIC and the LHC, where the anisotropies are widely thought to arise from hydrodynamic flow.Comment: 375 authors, 7 pages, 5 figures. Published in Phys. Rev. Lett. v2 has minor changes to text and figures in response to PRL referee suggestions. Plain text data tables for the points plotted in figures for this and previous PHENIX publications are (or will be) publicly available at http://www.phenix.bnl.gov/papers.htm

Cross section for bbˉb\bar{b} production via dielectrons in d++Au collisions at sNN=200\sqrt{s_{_{NN}}}=200 GeV

We report a measurement of $e^+e^-$ pairs from semileptonic heavy-flavor decays in $d$$+$Au collisions at $\sqrt{s_{_{NN}}}=200$ GeV. Exploring the mass and transverse-momentum dependence of the yield, the bottom decay contribution can be isolated from charm, and quantified by comparison to {\sc pythia} and {\sc mc@nlo} simulations. The resulting $b\bar{b}$-production cross section is $\sigma^{d{\rm Au}}_{b\bar{b}}=1.37{\pm}0.28({\rm stat}){\pm}0.46({\rm syst})$~mb, which is equivalent to a nucleon-nucleon cross section of $\sigma^{NN}_{bb}=3.4\pm0.8({\rm stat}){\pm}1.1({\rm syst})\ \mu$b.Comment: 375 authors, 16 pages, 8 figures, 7 tables, 2008 data. Submitted to Phys. Rev. C Plain text data tables for the points plotted in figures for this and previous PHENIX publications are (or will be) publicly available at http://www.phenix.bnl.gov/papers.htm

Centrality categorization for R_{p(d)+A} in high-energy collisions

High-energy proton- and deuteron-nucleus collisions provide an excellent tool for studying a wide array of physics effects, including modifications of parton distribution functions in nuclei, gluon saturation, and color neutralization and hadronization in a nuclear environment, among others. All of these effects are expected to have a significant dependence on the size of the nuclear target and the impact parameter of the collision, also known as the collision centrality. In this article, we detail a method for determining centrality classes in p(d)+A collisions via cuts on the multiplicity at backward rapidity (i.e., the nucleus-going direction) and for determining systematic uncertainties in this procedure. For d+Au collisions at sqrt(s_NN) = 200 GeV we find that the connection to geometry is confirmed by measuring the fraction of events in which a neutron from the deuteron does not interact with the nucleus. As an application, we consider the nuclear modification factors R_{p(d)+A}, for which there is a potential bias in the measured centrality dependent yields due to auto-correlations between the process of interest and the backward rapidity multiplicity. We determine the bias correction factor within this framework. This method is further tested using the HIJING Monte Carlo generator. We find that for d+Au collisions at sqrt(s_NN)=200 GeV, these bias corrections are small and vary by less than 5% (10%) up to p_T = 10 (20) GeV. In contrast, for p+Pb collisions at sqrt(s_NN) = 5.02 TeV we find these bias factors are an order of magnitude larger and strongly p_T dependent, likely due to the larger effect of multi-parton interactions.Comment: 375 authors, 18 pages, 16 figures, 4 tables. Submitted to Phys. Rev. C. Plain text data tables for the points plotted in figures for this and previous PHENIX publications are (or will be) publicly available at http://www.phenix.bnl.gov/papers.htm

Cross Section and Transverse Single-Spin Asymmetry of η\eta Mesons in p↑+pp^{\uparrow}+p Collisions at s=200\sqrt{s}=200 GeV at Forward Rapidity

We present a measurement of the cross section and transverse single-spin asymmetry ($A_N$) for $\eta$ mesons at large pseudorapidity from $\sqrt{s}=200$~GeV $p^{\uparrow}+p$ collisions. The measured cross section for $0.5<p_T<5.0$~GeV/$c$ and $3.0<|\eta|<3.8$ is well described by a next-to-leading-order perturbative-quantum-chromodynamics calculation. The asymmetries $A_N$ have been measured as a function of Feynman-$x$ ($x_F$) from $0.2<|x_{F}|<0.7$, as well as transverse momentum ($p_T$) from $1.0<p_T<4.5$~GeV/$c$. The asymmetry averaged over positive $x_F$ is $\langle{A_{N}}\rangle=0.061{\pm}0.014$. The results are consistent with prior transverse single-spin measurements of forward $\eta$ and $\pi^{0}$ mesons at various energies in overlapping $x_F$ ranges. Comparison of different particle species can help to determine the origin of the large observed asymmetries in $p^{\uparrow}+p$ collisions.Comment: 484 authors, 13 pages, 11 figures, 4 tables, 2008 data. v2 is version accepted by Phys. Rev. D. Plain text data tables for the points plotted in figures for this and previous PHENIX publications are (or will be)publicly available at http://www.phenix.bnl.gov/papers.htm