1,667 research outputs found
Uncoupling JAK3 activation induces apoptosis in human lymphoid cancer cells via regulating critical survival pathways
AbstractIn the current work, we report that specific inhibition of Janus tyrosine kinase (JAK3) via NC1153 induces apoptosis of certain leukemia/lymphoma cell lines. Affymetrix microarray profiling following NC1153 treatment unveiled JAK3 dependent survival modulating pathways (p53, TGF-β, TNFR and ER stress) in Kit225 cells. IL-2 responsive NC1153 target genes were regulated in human JAK3 positive, but not in JAK3 negative lymphoid tumor cells. Moreover, primary lymphoma samples revealed that a number of these genes were reciprocally regulated during disease progression and JAK3 inhibition suggesting that downstream targets of JAK3 could be exploited in the development of novel cancer treatment regimes
STAT5 regulation of BCL10 parallels constitutive NFkappaB activation in lymphoid tumor cells.
BACKGROUND: Signal Transducer and Activator of Transcription 5 A and B (STAT5) are key survival factors in cells of the lymphoid lineage. Identification of novel, tissue-specific STAT5 regulated genes would advance the ability to combat diseases due to aberrant STAT5 signaling. In the present work a library of human STAT5 bound genomic elements was created and validated. RESULTS: Of several STAT5 responsive genomic regulatory elements identified, one was located within the first intron of the human BCL10 gene. Chromatin immuno-precipitation reactions confirmed constitutive in vivo STAT5 binding to this intronic fragment in various human lymphoid tumor cell lines. Interestingly, non-phosphorylated STAT5 was found in the nuclei of Kit225 and YT cells in the absence of cytokine stimulation that paralleled constitutive NFkappaB activation. Inhibition of the hyperactive JAK3/STAT5 pathway in MT-2 cells via the Mannich-base, NC1153, diminished the constitutive in vivo occupancy of BCL10-SBR by STAT5, reduced NFkappaB activity and BCL10 protein expression in a dose dependent manner. Moreover, depletion of STAT5 via selective antisense oligonucleotide treatment similarly resulted in decreased BCL10 mRNA and protein expression, cellular viability and impaired NFkappaB activity independent of IL-2. CONCLUSION: These results suggest that the NFkappaB regulator BCL10 is an IL-2-independent STAT5 target gene. These findings proffer a model in which un-activated STAT5 can regulate pathways critical for lymphoid cell survival and inhibitors that disrupt STAT5 function independent of tyrosine phosphorylation may be therapeutically effective in treating certain leukemias/lymphomas
STAT5 regulation of BCL10 parallels constitutive NFκB activation in lymphoid tumor cells
<p>Abstract</p> <p>Background</p> <p>Signal Transducer and Activator of Transcription 5 A and B (STAT5) are key survival factors in cells of the lymphoid lineage. Identification of novel, tissue-specific STAT5 regulated genes would advance the ability to combat diseases due to aberrant STAT5 signaling. In the present work a library of human STAT5 bound genomic elements was created and validated.</p> <p>Results</p> <p>Of several STAT5 responsive genomic regulatory elements identified, one was located within the first intron of the human <it>BCL10 </it>gene. Chromatin immuno-precipitation reactions confirmed constitutive <it>in vivo </it>STAT5 binding to this intronic fragment in various human lymphoid tumor cell lines. Interestingly, non-phosphorylated STAT5 was found in the nuclei of Kit225 and YT cells in the absence of cytokine stimulation that paralleled constitutive NFκB activation. Inhibition of the hyperactive JAK3/STAT5 pathway in MT-2 cells via the Mannich-base, NC1153, diminished the constitutive <it>in vivo </it>occupancy of BCL10-SBR by STAT5, reduced NFκB activity and BCL10 protein expression in a dose dependent manner. Moreover, depletion of STAT5 via selective antisense oligonucleotide treatment similarly resulted in decreased BCL10 mRNA and protein expression, cellular viability and impaired NFκB activity independent of IL-2.</p> <p>Conclusion</p> <p>These results suggest that the NFκB regulator BCL10 is an IL-2-independent STAT5 target gene. These findings proffer a model in which un-activated STAT5 can regulate pathways critical for lymphoid cell survival and inhibitors that disrupt STAT5 function independent of tyrosine phosphorylation may be therapeutically effective in treating certain leukemias/lymphomas.</p
X-ray enabled MOCASSIN: a 3D code for photoionized media
We present a new version of the fully 3D photoionization and dust radiative
transfer code, MOCASSIN, that uses a Monte Carlo approach for the transfer of
radiation. The X-ray enabled MOCASSIN allows a fully geometry independent
description of low-density gaseous environments strongly photoionized by a
radiation field extending from radio to gamma rays. The code has been
thoroughly benchmarked against other established codes routinely used in the
literature, using simple plane parallel models designed to test performance
under standard conditions. We show the results of our benchmarking exercise and
discuss applicability and limitations of the new code, which should be of
guidance for future astrophysical studies with MOCASSIN.Comment: Accepted for publication in ApJS 9 pages, 5 figure
using provenance data and DNA
Re-examination of the historical range of the greater prairie chicke
Divergent evolutionary processes associated with colonization of offshore islands
Peer reviewedPublisher PD
The clustering of galaxies in the SDSS-III Baryon Oscillation Spectroscopic Survey: measuring structure growth using passive galaxies
We explore the benefits of using a passively evolving population of galaxies
to measure the evolution of the rate of structure growth between z=0.25 and
z=0.65 by combining data from the SDSS-I/II and SDSS-III surveys. The
large-scale linear bias of a population of dynamically passive galaxies, which
we select from both surveys, is easily modeled. Knowing the bias evolution
breaks degeneracies inherent to other methodologies, and decreases the
uncertainty in measurements of the rate of structure growth and the
normalization of the galaxy power-spectrum by up to a factor of two. If we
translate our measurements into a constraint on sigma_8(z=0) assuming a
concordance cosmological model and General Relativity (GR), we find that using
a bias model improves our uncertainty by a factor of nearly 1.5. Our results
are consistent with a flat Lambda Cold Dark Matter model and with GR.Comment: Accepted for publication in MNRAS (clarifications added, results and
conclusions unchanged
Arthritis of the sternoclavicular joint masquerading as rupture of the cervical oesophagus: a case report
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