872 research outputs found
Regulation of sonic hedgehog-GLI1 downstream target genes PTCH1, Cyclin D2, Plakoglobin, PAX6 and NKX2.2 and their epigenetic status in medulloblastoma and astrocytoma
Abstract Background The Sonic hedgehog (Shh) signaling pathway is critical for cell growth and differentiation. Impairment of this pathway can result in both birth defects and cancer. Despite its importance in cancer development, the Shh pathway has not been thoroughly investigated in tumorigenesis of brain tumors. In this study, we sought to understand the regulatory roles of GLI1, the immediate downstream activator of the Shh signaling pathway on its downstream target genes PTCH1, Cyclin D2, Plakoglobin, NKX2.2 and PAX6 in medulloblastoma and astrocytic tumors. Methods We silenced GLI1 expression in medulloblastoma and astrocytic cell lines by transfection of siRNA against GLI1. Subsequently, we performed RT-PCR and quantitative real time RT-PCR (qRT-PCR) to assay the expression of downstream target genes PTCH1, Cyclin D2, Plakoglobin, NKX2.2 and PAX6. We also attempted to correlate the pattern of expression of GLI1 and its regulated genes in 14 cell lines and 41 primary medulloblastoma and astrocytoma tumor samples. We also assessed the methylation status of the Cyclin D2 and PTCH1 promoters in these 14 cell lines and 58 primary tumor samples. Results Silencing expression of GLI1 resulted up-regulation of all target genes in the medulloblastoma cell line, while only PTCH1 was up-regulated in astrocytoma. We also observed methylation of the cyclin D2 promoter in a significant number of astrocytoma cell lines (63%) and primary astrocytoma tumor samples (32%), but not at all in any medulloblastoma samples. PTCH1 promoter methylation was less frequently observed than Cyclin D2 promoter methylation in astrocytomas, and not at all in medulloblastomas. Conclusions Our results demonstrate different regulatory mechanisms of Shh-GLI1 signaling. These differences vary according to the downstream target gene affected, the origin of the tissue, as well as epigenetic regulation of some of these genes.http://deepblue.lib.umich.edu/bitstream/2027.42/78313/1/1471-2407-10-614.xmlhttp://deepblue.lib.umich.edu/bitstream/2027.42/78313/2/1471-2407-10-614.pdfPeer Reviewe
Neutron interferometric measurement of the scattering length difference between the triplet and singlet states of n-He
We report a determination of the n-He scattering length difference
(
(statistical) (systematic)) fm between the triplet and singlet
states using a neutron interferometer. This revises our previous result (-5.610 (statistical) (systematic)
fm obtained using the same technique in 2008. This revision is due to a
re-analysis of the 2008 experiment that includes a more robust treatment of the
phase shift caused by magnetic field gradients near the He cell.
Furthermore, we more than doubled our original data set from 2008 by acquiring
six months of additional data in 2013. Both the new data set and a re-analysis
of the older data are in good agreement. Scattering lengths of low Z isotopes
are valued for use in few-body nuclear effective field theories, provide
important tests of modern nuclear potential models and in the case of He
aid in the interpretation of neutron scattering from quantum liquids. The
difference was determined by measuring the relative phase
shift between two incident neutron polarizations caused by the spin-dependent
interaction with a polarized He target. The target He gas was sealed
inside a small, flat windowed glass cell that was placed in one beam path of
the interferometer. The relaxation of He polarization was monitored
continuously with neutron transmission measurements. The neutron polarization
and spin flipper efficiency were determined separately using He analyzers
and two different polarimetry analysis methods. A summary of the measured
scattering lengths for n-He with a comparison to nucleon interaction models
is given
Decoupling of a Neutron Interferometer from Temperature Gradients
Neutron interferometry enables precision measurements that are typically
operated within elaborate, multi-layered facilities which provide substantial
shielding from environmental noise. These facilities are necessary to maintain
the coherence requirements in a perfect crystal neutron interferometer which is
extremely sensitive to local environmental conditions such as temperature
gradients across the interferometer, external vibrations, and acoustic waves.
The ease of operation and breadth of applications of perfect crystal neutron
interferometry would greatly benefit from a mode of operation which relaxes
these stringent isolation requirements. Here, the INDEX Collaboration and
National Institute of Standards and Technology demonstrates the functionality
of a neutron interferometer in vacuum and characterize the use of a compact
vacuum chamber enclosure as a means to isolate the interferometer from spatial
temperature gradients and time-dependent temperature fluctuations. The vacuum
chamber is found to have no depreciable effect on the performance of the
interferometer (contrast) while improving system stability, thereby showing
that it is feasible to replace large temperature isolation and control systems
with a compact vacuum enclosure for perfect crystal neutron interferometry
Novel bioactive tetracycline-containing electrospun polymer fibers as a potential antibacterial dental implant coating
The purpose of this investigation was to determine the ability of tetracycline-containing fibers to inhibit biofilm formation of peri-implantitis-associated pathogens [i.e., Porphyromonas gingivalis (Pg), Fusobacterium nucleatum (Fn), Prevotella intermedia (Pi), and Aggregatibacter actinomycetemcomitans (Aa)]. Tetracycline hydrochloride (TCH) was added to a poly(DL-lactide) [PLA], poly(ε-caprolactone) [PCL], and gelatin [GEL] polymer blend solution at distinct concentrations to obtain the following fibers: PLA:PCL/GEL (TCH-free, control), PLA:PCL/GEL + 5 % TCH, PLA:PCL/GEL + 10 % TCH, and PLA:PCL/GEL + 25 % TCH. The inhibitory effect of TCH-containing fibers on biofilm formation was assessed by colony-forming units (CFU/mL). Qualitative analysis of biofilm inhibition was done via scanning electron microscopy (SEM). Statistical significance was reported at p < 0.05. Complete inhibition of biofilm formation on the fibers was observed in groups containing TCH at 10 and 25 wt%. Fibers containing TCH at 5 wt% demonstrated complete inhibition of Aa biofilm. Even though a marked reduction in CFU/mL was observed with an increase in TCH concentration, Pi proved to be the most resilient microorganism. SEM images revealed the absence of or a notable decrease in bacterial biofilm on the TCH-containing nanofibers. Collectively, our data suggest that tetracycline-containing fibers hold great potential as an antibacterial dental implant coating
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Effects of antiplatelet therapy after stroke due to intracerebral haemorrhage (RESTART): a randomised, open-label trial
Antiplatelet therapy reduces the risk of major vascular events for people with occlusive vascular disease, although it might increase the risk of intracranial haemorrhage. Patients surviving the commonest subtype of intracranial haemorrhage, intracerebral haemorrhage, are at risk of both haemorrhagic and occlusive vascular events, but whether antiplatelet therapy can be used safely is unclear. We aimed to estimate the relative and absolute effects of antiplatelet therapy on recurrent intracerebral haemorrhage and whether this risk might exceed any reduction of occlusive vascular events
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