795 research outputs found
SDF-1 and PDGF enhance [alpha]v[beta]5-mediated ERK activation and adhesion-independent growth of human pre-B cell lines
CD23 acts through the [alpha]v[beta]5 integrin to promote growth of human pre-B cell lines in an adhesion-independent manner. [alpha]v[beta]5 is expressed on normal B-cell precursors in the bone marrow. Soluble CD23 (sCD23), short CD23-derived peptides containing the arg-lys-cys (RKC) motif recognized by [alpha]v[beta]5 and anti-[alpha]v[beta]5 monoclonal antibodies (MAbs) all sustain growth of pre-B cell lines. The chemokine stromal cell-derived factor-1 (SDF-1) regulates key processes during B-cell development. SDF-1 enhanced the growth-sustaining effect driven by ligation of [alpha]v[beta]5 with anti-[alpha]v[beta]5 MAb 15F-11, sCD23 or CD23-derived RKC-containing peptides. This effect was restricted to B-cell precursors and was specific to SDF-1. The enhancement in growth was associated with the activation of extracellular signal-regulated kinase (ERK) and both these responses were attenuated by the MEK inhibitor U0126. Finally, platelet-derived growth factor also enhanced both [alpha]v[beta]5-mediated cell growth and ERK activation. The data suggest that adhesion-independent growth-promoting signals delivered to B-cell precursors through the [alpha]v[beta]5 integrin can be modulated by cross-talk with receptors linked to both G-protein and tyrosine kinase-coupled signalling pathways
Molecular Structural Dynamics in Water-Ethanol Mixtures: Spectroscopy with Polarized Neutrons Simultaneously Accessing Collective and Self-Diffusion
Binary mixtures of water with lower alcohols display non-linear phase
behaviour upon mixing which are attributed to potential cluster formation at
molecular level. Unravelling such elusive structures requires the investigation
of hydrogen-bonding sub-nanosecond dynamics. We employ high-resolution neutron
time-of-flight spectroscopy with polarization analysis in combination with
selective deuteration to study the concentration-dependent structural dynamics,
in the water rich part of the phase diagram of water-ethanol mixtures. This
method enables the simultaneous access to atomic correlations in space and
time, and allows us to separate spatially incoherent scattering probing
self-diffusion of the ethanol fraction from the coherent scattering probing
collective diffusion of the water network as a whole. Our observations indicate
an enhanced rigidity of the hydrogen bond network at mesoscopic lengthscale
compared to the intra-molecular scale as the ethanol fraction increases, which
is consistent with the hypothesis of clusters
Piezoelectric-based apparatus for strain tuning
We report the design and construction of piezoelectric-based apparatus for
applying continuously tuneable compressive and tensile strains to test samples.
It can be used across a wide temperature range, including cryogenic
temperatures. The achievable strain is large, so far up to 0.23% at cryogenic
temperatures. The apparatus is compact and compatible with a wide variety of
experimental probes. In addition, we present a method for mounting
high-aspect-ratio samples in order to achieve high strain homogeneity.Comment: 8 pages, 8 figure
Recommended from our members
Self-assembly of minimal peptoid sequences
Peptoids are biofunctional N-substituted glycine peptidomimics. Their self-assembly is of fundamental interest because they demonstrate alternatives to conventional peptide structures based on backbone chirality and beta-sheet hydrogen bonding. The search for self-assembling, water-soluble “minimal” sequences, be they peptide or peptidomimic, is a further challenge. Such sequences are highly desired for their compatibility with biomacromolecules and convenient synthesis for broader application. We report the self-assembly of a set of trimeric, water-soluble α-peptoids that exhibit a relatively low critical aggregation concentration (CAC ∼ 0.3 wt %). Cryo-EM and angle-resolved DLS show different sequence-dependent morphologies, namely uniform ca. 6 nm wide nanofibers, sheets, and clusters of globular assemblies. Absorbance and fluorescence spectroscopies indicate unique phenyl environments for π-interactions in the highly ordered nanofibers. Assembly of our peptoids takes place when the sequences are fully ionized, representing a departure from superficially similar amyloid-type hydrogen-bonded peptide nanostructures and expanding the horizons of assembly for sequence-specific bio- and biomimetic macromolecules
The modifying effect of supramolecular gel fibres on the diffusion of paracetamol and ibuprofen sodium on the picosecond timescale
Employing neutron spectroscopy, we follow the tracer diffusion of two non-steroidal anti-inflammatory drug molecules, paracetamol (PCM) and ibuprofen sodium (IBU), in a supramolecular gel and the corresponding bulk solution. Both solutes show altered diffusion behaviour in the gel phase, deviating from each other and their bulk solution. Whilst picosecond diffusion of IBU is slightly quicker in the gel, this effect is significantly increased for PCM, which is up to 70% quicker in the gel than in solution.This effect is independent of changes in the solvent diffusion reported previously. An increased residence time of PCM in solution at lower temperatures points towards the onset of nucleation and crystallisation. This work reports one of the first experiments on the novel Backscattering and Time-of-Flight option (BATS) on the IN16B spectrometer at the Institut Laue-Langevin, France, which with its range and resolution in neutron energy and momentum transfer is ideally suited to observe this type of diffusion
Commensurate period Charge Density Modulations throughout the Pseudogap Regime
Theories based upon strong real space (r-space) electron electron
interactions have long predicted that unidirectional charge density modulations
(CDM) with four unit cell (4) periodicity should occur in the hole doped
cuprate Mott insulator (MI). Experimentally, however, increasing the hole
density p is reported to cause the conventionally defined wavevector of
the CDM to evolve continuously as if driven primarily by momentum space
(k-space) effects. Here we introduce phase resolved electronic structure
visualization for determination of the cuprate CDM wavevector. Remarkably, this
new technique reveals a virtually doping independent locking of the local CDM
wavevector at throughout the underdoped phase diagram of the
canonical cuprate . These observations have significant
fundamental consequences because they are orthogonal to a k-space (Fermi
surface) based picture of the cuprate CDM but are consistent with strong
coupling r-space based theories. Our findings imply that it is the latter that
provide the intrinsic organizational principle for the cuprate CDM state
Conserved hydrogen bonding in tetrahydrocarbazolone derivatives: influence of solution-state assembly on crystal form nucleation
Two tetrahydocarbazolone derivatives were found to show multiple unsolvated crystal forms. A persistent dimer motif was detected in solution by FTIR spectroscopy that is maintained in the kinetic crystal forms. Rationally introduced steric bulk induces the formation of a more stable catemeric form
Assessment of potential anti-cancer stem cell activity of marine algal compounds using an in vitro mammosphere assay
Background: The cancer stem cell (CSC) theory proposes that tumours arise from and are sustained by a subpopulation of cells with both cancer and stem cell properties. One of the key hallmarks of CSCs is the ability to grow anchorage-independently under serum-free culture conditions resulting in the formation of tumourspheres. It has further been reported that these cells are resistant to traditional chemotherapeutic agents.
Methods: In this study, the tumoursphere assay was validated in MCF-7 cells and used to screen novel marine algal compounds for potential anti-cancer stem cell (CSC) activity in vitro.
Results: MCF-7 breast cancer cells were observed to generate tumourspheres or mammospheres after 3-5 days growth in anchorage-independent conditions and an apparent enrichment in potential CSCs was observed by an increase in the proportion of CD44high/CD24low marker-bearing cells and Oct4 expression compared to those in the bulk population grown in regular adherent conditions. Using this assay, a set of algal metabolites was screened for the ability to inhibit mammosphere development as a measure of potential anti-CSC activity. We report that the polyhalogenated monoterpene stereoisomers RU017 and RU018 isolated from the red alga Plocamium cornutum, both of which displayed no cytotoxicity against either adherent MCF-7 breast cancer or MCF-12A non-transformed breast epithelial cells, were able to prevent MCF-7 mammosphere formation in vitro. On the other hand, neither the brown algal carotenoid fucoxanthin nor the chemotherapeutic paclitaxel, both of which were toxic to adherent MCF-7 and MCF-12A cells, were able to inhibit mammosphere formation. In fact, pre-treatment with paclitaxel appeared to enhance mammosphere formation and development, a finding which is consistent with the reported resistance of CSCs to traditional chemotherapeutic agents.
Conclusion: Due to the proposed clinical significance of CSC in terms of tumour initiation and metastasis, the identification of agents able to inhibit this subpopulation has clinical significance
- …