MPK6 shows transient increase in activity under hypoxia with maximal activity at 2 hrs. To study the role of MPK6 in hypoxia in Arabidopsis, 10 do seedlings of WT, mpk6 and MPK6 plants were exposed to 2 hrs hypoxia and 2hr air (mock).
Transient MPK6 activation in response to oxygen deprivation and reoxygenation is mediated by mitochondria and aids seedling survival in Arabidopsis.
Specimen part
View SamplesAlthough anemia is common in Shwachman-Diamond syndrome (SDS), the underlying mechanism remains unclear. We asked whether SBDS, which is mutated in most SDS patients, is critical for erythroid development. We found that SBDS expression is high early during erythroid differentiation. Inhibition of SBDS in CD34+ hematopoietic stem cells and early progenitors (HSC/Ps) and K562 cells led to slow cell expansion during erythroid differentiation. Induction of erythroid differentiation resulted in markedly accelerated apoptosis in the knockdown cells; however, proliferation was only mildly reduced. The percentage of cells entering differentiation was not reduced.
The ribosome-related protein, SBDS, is critical for normal erythropoiesis.
Specimen part, Disease, Disease stage
View SamplesGlioblastoma is the most common primary malignant brain tumor in adults and associated with poor survival. Standard-of-care chemotherapy and radiation confer a median overall survival of under two years. The Ivy Foundation Early Phase Clinical Trials Consortium conducted a randomized, multi institution clinical trial to evaluate immune responses and survival following neoadjuvant and/or adjuvant therapy with pembrolizumab, a programmed cell death protein 1 (PD-1) monoclonal antibody, in 35 patients with recurrent, surgically resectable glioblastoma. Patients who were randomized to receive neoadjuvant pembrolizumab, with continued adjuvant therapy following surgery, had significantly extended overall survival compared to patients that were randomized to receive adjuvant, post-surgical PD-1 blockade alone (hazard ratio = 0.39; P = 0.04, log-rank test). Neoadjuvant PD-1 blockade was associated with upregulation of T cell and interferon-?-related genes, but downregulation of cell cycle related genes within the tumor, which was not seen in patients that received adjuvant therapy alone. Focal induction of programmed death-ligand 1 (PD-L1) in the tumor microenvironment was observed more frequently in the neoadjuvant group than in tumors obtained from patients treated only in the adjuvant setting. Similarly, neoadjuvant pembrolizumab was associated with clonal T cell expansion and the overlap of T cell receptors between tumor and blood, decreased PD-1 expression in T cells and a decreasing peripheral monocytic population. These findings suggest that the neoadjuvant administration of PD-1 blockade enhances the local and systemic anti-tumor immune response and may represent a more efficacious approach to the treatment of this uniformly lethal brain tumor. This trial was registered with ClinicalTrials.gov under the identifier NCT02852655 (https://clinicaltrials.gov/ct2/show/NCT02852655). Overall design: This dataset contains the transcriptomes of recurrent glioblastoma with either neoadjuvant (1 dose) or adjuvant pembrolizumab treatment
Neoadjuvant anti-PD-1 immunotherapy promotes a survival benefit with intratumoral and systemic immune responses in recurrent glioblastoma.
Subject
View SamplesThe endogenous peptide Apelin is crucial for maintaining heart function in pressure overload and aging
Impaired heart contractility in Apelin gene-deficient mice associated with aging and pressure overload.
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