Background: Clinical trial and epidemiological data support that the cardiovascular effects of estrogen are complex, including a mixture of both potentially beneficial and harmful effects. In animal models, estrogen protects females from vascular injury and inhibits atherosclerosis. These effects are mediated by estrogen receptors (ERs), which when bound to estrogen can bind to DNA to directly regulate transcription. ERs can also activate several cellular kinases by inducing a rapid non-nuclear signaling cascade. However, the biologic significance of this rapid signaling pathway has been unclear.
Rapid estrogen receptor signaling is essential for the protective effects of estrogen against vascular injury.
No sample metadata fields
View SamplesIdentification of all genes expressed by mouse olfactory sensory neurons; genes expressed in mature neurons, immature neurons, or both were distinguished. Independent validation of enrichment ratio values supported by statistical assessment of error rates was used to build a database of statistical probabilities of the expression of all mRNAs detected in mature neurons, immature neurons, both types of neurons (shared), and the residual population of all other cell types.
Genomics of mature and immature olfactory sensory neurons.
Sex, Specimen part
View SamplesExpression profiling of mRNA abundance in the adult mouse olfactory epithelium during replacement of OSNs forced by the bilateral ablation of the olfactory bulbs. The experiment was done on 6 week old male C57Bl/6 mice. Olfactory epithelium tissue samples were collected on days 1, 5, and 7 after bulbectomy. The cellular processes activated by bulbectomy include apoptosis of mature olfactory sensory neurons, infiltration of macrophages and dendritic cells, stimulation of proliferation of basal cell progenitors, and differentation of new sensory neurons.
Transcriptional changes during neuronal death and replacement in the olfactory epithelium.
No sample metadata fields
View SamplesReduction in the cellular levels of the cyclin kinase inhibitor p27kip1 are frequently found in many human cancers and correlate directly with patient prognosis. Specifically ubiquitin dependent proteasomal turnover has been shown to cause reduced p27 expression in many human cancers. We recently demonstated that expression of a stabilized version of p27kip1 (p27kip1T187A) in a genetically modified mouse significantly reduced the number of intestinal adenomatous polyps which progressed to invasive carcinomas. Based on this work we set out to identify compounds which lead to a re-expression of p27 in cancer tissues. In this work we identify Argyrin A a compound derived from myxobacterium archangium gephyra as a potent inducer of p27kip1 expression. Argyrin A induces apoptosis in human colon cancer xenografts and tumor vasculature in vivo leading to a profound reduction in tumor size at well tolerated levels. Argyrin A functions are strictly dependent on the expression of p27kip1 as neither tumor cells nor endothelial cells which do not express p27kip1 respond to this compound. Surprisingly the molecular mechanism by which Argyrin A exerts its p27 dependent biological function is through a potent inhibition of the 20S proteasome.
Argyrin a reveals a critical role for the tumor suppressor protein p27(kip1) in mediating antitumor activities in response to proteasome inhibition.
Specimen part
View SamplesAnticipating the risk for infectious disease during space exploration and habitation is a critical factor to ensure safety, health and performance of the crewmembers. As a ubiquitous environmental organism that is occasionally part of the human flora, Pseudomonas aeruginosa could pose a health hazard for the immuno-compromised astronauts. In order to gain insights in the behavior of P. aeruginosa in spaceflight conditions, two spaceflight-analogue culture systems, i.e. the rotating wall vessel (RWV) and the random position machine (RPM), were used. Microarray analysis of P. aeruginosa PAO1 grown in the low shear modeled microgravity (LSMMG) environment of the RWV compared to the normal gravity control (NG), revealed a regulatory role for AlgU (RpoE). Specifically, P. aeruginosa cultured in LSMMG exhibited increased alginate production and up-regulation of AlgU-controlled transcripts, including those encoding stress-related proteins. This study also shows the involvement of Hfq in the LSMMG response, consistent with its previously identified role in the Salmonella LSMMG- and spaceflight response. Furthermore, cultivation in LSMMG increased heat- and oxidative stress resistance and caused a decrease in the culture oxygen transfer rate. Interestingly, the global transcriptional response of P. aeruginosa grown in the RPM was similar to that in NG. The possible role of differences in fluid mixing between the RWV and RPM is discussed, with the overall collective data favoring the RWV as the optimal model to study the LSMMG-response of suspended cells. This study represents a first step towards the identification of specific virulence mechanisms of P. aeruginosa activated in response to spaceflight-analogue conditions, and could direct future research regarding the risk assessment and prevention of Pseudomonas infections for the crew in flight and the general public.
Response of Pseudomonas aeruginosa PAO1 to low shear modelled microgravity involves AlgU regulation.
No sample metadata fields
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Identification of an interleukin 13-induced epigenetic signature in allergic airway inflammation.
Specimen part
View SamplesAsthma is a common chronic inflammatory airway condition with a strong genetic and inheritability component, as siblings and first-degree relatives of those with the disease are often affected.
Identification of an interleukin 13-induced epigenetic signature in allergic airway inflammation.
Specimen part
View SamplesIn development, timing is of the utmost importance, and the timing of various developmental processes are often changed during evolution. During human evolution sexual maturation has been delayed relative to other primates and this may have played a critical role for both the increase of human brain size and the rise of human-specific cognitive traits .
Transcriptional neoteny in the human brain.
Sex, Age, Specimen part
View SamplesIn development, timing is of the utmost importance, and the timing of various developmental processes are often changed during evolution. During human evolution sexual maturation has been delayed relative to other primates and this may have played a critical role for both the increase of human brain size and the rise of human-specific cognitive traits .
Transcriptional neoteny in the human brain.
Sex, Age, Specimen part
View SamplesIn development, timing is of the utmost importance, and the timing of various developmental processes are often changed during evolution.
Transcriptional neoteny in the human brain.
Sex, Age, Specimen part
View Samples