10,294 research outputs found
Induction of Apoptosis by Methyl Alcohol Extract of Enteromorpha linza (Linnaeus) J Agardh in U937 Human Leukemia Cells
Purpose: To investigate the anti-cancer effect of methyl alcohol extract of Enteromorpha linza (Linnaeus) J. Agardh (MEEL) in U937 human leukemia cells.Methods: Cytotoxicity was evaluated by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay. Apoptosis was detected using 4',6-diamidino-2-phenylindole (DAPI) staining, agarose gel electrophoresis, and flow cytometry. Protein levels were determined by Western blot analysis. Caspase activity was measured spectrophotometrically at 405 nm.Results: MEEL inhibited U937 cell proliferation and induced apoptosis through up-regulation of death receptor-related gene expression, caspase-8 activation and truncation of Bid, which was associated with the loss of mitochondrial membrane potential. Subsequently, the levels of anti-apoptotic proteins such as Bcl-2 and Bcl-xL, and IAP family proteins decreased but those of pro-apoptotic proteins including Bax and Bad increased in MEEL-treated U937 cells. MEEL treatment also resulted in activation of caspase-9 and -3 as well as concomitant cleavage of poly(ADP-ribose) polymerase and phopholipase Cγ-1. However, pretreatment of U937 cells with z-VAD-fmk, a pan caspase inhibitor, abrogated chromatin condensation and DNA fragmentation and prevented cell death induced by the MEEL.Conclusion: The findings suggest that MEEL induced apoptosis in U937 cells through a signaling cascade of death-receptor-mediated extrinsic as well as mitochondria-mediated intrinsic pathways, thus raising the possibility that MEEL may be of value in the development of novel therapeutic approaches for treating leukemia.Keywords: Enteromorpha linza, Apoptosis, Caspase, U937 cell
Sparticle Spectrum of Large Volume Compactification
We examine the large volume compactification of Type IIB string theory or its
F theory limit and the associated supersymmetry breakdown and soft terms. It is
crucial to incorporate the loop-induced moduli mixing, originating from
radiative corrections to the Kahler potential. We show that in the presence of
moduli mixing, soft scalar masses generically receive a D-term contribution of
the order of the gravitino mass m_{3/2} when the visible sector cycle is
stabilized by the D-term potential of an anomalous U(1) gauge symmetry, while
the moduli-mediated gaugino masses and A-parameters tend to be of the order of
m_{3/2}/8pi^2. It is noticed also that a too large moduli mixing can
destabilize the large volume solution by making it a saddle point.Comment: 29 page
Mixed Mediation of Supersymmetry Breaking with Anomalous U(1) Gauge Symmetry
Models with anomalous U(1) gauge symmetry contain various superfields which
can have nonzero supersymmetry breaking auxiliary components providing the
origin of soft terms in the visible sector, e.g. the U(1) vector superfield,
the modulus or dilaton superfield implementing the Green-Schwarz anomaly
cancellation mechanism, U(1)-charged but standard model singlet matter
superfield required to cancel the Fayet-Iliopoulos term, and finally the
supergravity multiplet. We examine the relative strength between these
supersymmetry breaking components in a simple class of models, and find that
various different mixed mediations of supersymmetry breaking, involving the
modulus, gauge, anomaly and D-term mediations, can be realized depending upon
the characteristics of D-flat directions and how those D-flat directions are
stabilized with a vanishing cosmological constant. We identify two parameters
which represent such properties and thus characterize how the various
mediations are mixed. We also discuss the moduli stabilization and soft terms
in a variant of KKLT scenario, in which the visible sector K\"ahler modulus is
stabilized by the D-term potential of anomalous U(1) gauge symmetry.Comment: 30 pages, 5 figure
QCD axion and quintessential axion
The axion solution of the strong CP problem is reviewed together with the
other strong CP solutions. We also point out the quintessential
axion(quintaxion) whose potential can be extremely flat due to the tiny ratio
of the hidden sector quark mass and the intermediate hidden sector scale. The
quintaxion candidates are supposed to be the string theory axions, the model
independent or the model dependent axions.Comment: 15 pages. Talk presented at Castle Ringberg, June 9-14, 200
Wnt5a induces ROR1 to complex with HS1 to enhance migration of chronic lymphocytic leukemia cells.
ROR1 (receptor tyrosine kinase-like orphan receptor 1) is a conserved, oncoembryonic surface antigen expressed in chronic lymphocytic leukemia (CLL). We found that ROR1 associates with hematopoietic-lineage-cell-specific protein 1 (HS1) in freshly isolated CLL cells or in CLL cells cultured with exogenous Wnt5a. Wnt5a also induced HS1 tyrosine phosphorylation, recruitment of ARHGEF1, activation of RhoA and enhanced chemokine-directed migration; such effects could be inhibited by cirmtuzumab, a humanized anti-ROR1 mAb. We generated truncated forms of ROR1 and found its extracellular cysteine-rich domain or kringle domain was necessary for Wnt5a-induced HS1 phosphorylation. Moreover, the cytoplamic, and more specifically the proline-rich domain (PRD), of ROR1 was required for it to associate with HS1 and allow for F-actin polymerization in response to Wnt5a. Accordingly, we introduced single amino acid substitutions of proline (P) to alanine (A) in the ROR1 PRD at positions 784, 808, 826, 841 or 850 in potential SH3-binding motifs. In contrast to wild-type ROR1, or other ROR1P→︀A mutants, ROR1P(841)A had impaired capacity to recruit HS1 and ARHGEF1 to ROR1 in response to Wnt5a. Moreover, Wnt5a could not induce cells expressing ROR1P(841)A to phosphorylate HS1 or activate ARHGEF1, and was unable to enhance CLL-cell motility. Collectively, these studies indicate HS1 plays an important role in ROR1-dependent Wnt5a-enhanced chemokine-directed leukemia-cell migration
Electric-field controlled spin reversal in a quantum dot with ferromagnetic contacts
Manipulation of the spin-states of a quantum dot by purely electrical means
is a highly desirable property of fundamental importance for the development of
spintronic devices such as spin-filters, spin-transistors and single-spin
memory as well as for solid-state qubits. An electrically gated quantum dot in
the Coulomb blockade regime can be tuned to hold a single unpaired spin-1/2,
which is routinely spin-polarized by an applied magnetic field. Using
ferromagnetic electrodes, however, the properties of the quantum dot become
directly spin-dependent and it has been demonstrated that the ferromagnetic
electrodes induce a local exchange-field which polarizes the localized spin in
the absence of any external fields. Here we report on the experimental
realization of this tunneling-induced spin-splitting in a carbon nanotube
quantum dot coupled to ferromagnetic nickel-electrodes. We study the
intermediate coupling regime in which single-electron states remain well
defined, but with sufficiently good tunnel-contacts to give rise to a sizable
exchange-field. Since charge transport in this regime is dominated by the
Kondo-effect, we can utilize this sharp many-body resonance to read off the
local spin-polarization from the measured bias-spectroscopy. We show that the
exchange-field can be compensated by an external magnetic field, thus restoring
a zero-bias Kondo-resonance, and we demonstrate that the exchange-field itself,
and hence the local spin-polarization, can be tuned and reversed merely by
tuning the gate-voltage. This demonstrates a very direct electrical control
over the spin-state of a quantum dot which, in contrast to an applied magnetic
field, allows for rapid spin-reversal with a very localized addressing.Comment: 19 pages, 11 figure
On SUSY GUTs with a degenerate Higgs mass matrix
Certain supersymmetric grand unified models predict that the coefficients of
the quadratic terms in the MSSM Higgs potential should be degenerate at the GUT
scale. We discuss some examples for such models, and we analyse the
implications of this peculiar condition of a GUT-scale degenerate Higgs mass
matrix for low-scale MSSM phenomenology. To this end we explore the parameter
space which is consistent with existing experimental constraints by means of a
Markov Chain Monte Carlo analysis.Comment: 31 pages, 27 figures; v2: typos correcte
Universal contributions to scalar masses from five dimensional supergravity
We compute the effective Kahler potential for matter fields in warped
compactifications, starting from five dimensional gauged supergravity, as a
function of the matter fields localization. We show that truncation to zero
modes is inconsistent and the tree-level exchange of the massive gravitational
multiplet is needed for consistency of the four-dimensional theory. In addition
to the standard Kahler coming from dimensional reduction, we find the quartic
correction coming from integrating out the gravity multiplet. We apply our
result to the computation of scalar masses, by assuming that the SUSY breaking
field is a bulk hypermultiplet. In the limit of extreme opposite localization
of the matter and the spurion fields, we find zero scalar masses, consistent
with sequestering arguments. Surprisingly enough, for all the other cases the
scalar masses are tachyonic. This suggests the holographic interpretation that
a CFT sector always generates operators contributing in a tachyonic way to
scalar masses. Viability of warped su- persymmetric compactifications
necessarily asks then for additional contributions. We discuss the case of
additional bulk vector multiplets with mixed boundary conditions, which is a
partic- ularly simple and attractive way to generate large positive scalar
masses. We show that in this case successful fermion mass matrices implies
highly degenerate scalar masses for the first two generations of squarks and
sleptons.Comment: 23 pages. v2: References added, new section on effect of additional
bulk vector multiplets and phenomenolog
Spontaneous Parity Violation in SUSY Strong Gauge Theory
We suggest simple models of spontaneous parity violation in supersymmetric
strong gauge theory. We focus on left-right symmetric model and investigate
vacuum with spontaneous parity violation. Non-perturbative effects are
calculable in supersymmetric gauge theory, and we suggest two new models. The
first model shows confinement, and the second model has a dual description of
the theory. The left-right symmetry breaking and electroweak symmetry breaking
are simultaneously occurred with the suitable energy scale hierarchy. The
second model also induces spontaneous supersymmetry breaking.Comment: 14 page
Intragenic DNA methylation: implications of this epigenetic mechanism for cancer research
Epigenetics is the study of all mechanisms that regulate gene transcription and genome stability that are maintained throughout the cell division, but do not include the DNA sequence itself. The best-studied epigenetic mechanism to date is DNA methylation, where methyl groups are added to the cytosine base within cytosine–guanine dinucleotides (CpG sites). CpGs are frequently clustered in high density (CpG islands (CGIs)) at the promoter of over half of all genes. Current knowledge of transcriptional regulation by DNA methylation centres on its role at the promoter where unmethylated CGIs are present at most actively transcribed genes, whereas hypermethylation of the promoter results in gene repression. Over the last 5 years, research has gradually incorporated a broader understanding that methylation patterns across the gene (so-called intragenic or gene body methylation) may have a role in transcriptional regulation and efficiency. Numerous genome-wide DNA methylation profiling studies now support this notion, although whether DNA methylation patterns are a cause or consequence of other regulatory mechanisms is not yet clear. This review will examine the evidence for the function of intragenic methylation in gene transcription, and discuss the significance of this in carcinogenesis and for the future use of therapies targeted against DNA methylation
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