| 1. |
- Vu, Ly P., et al.
(författare)
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Functional screen of MSI2 interactors identifies an essential role for SYNCRIP in myeloid leukemia stem cells
- 2017
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 49:6, s. 866-875
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Tidskriftsartikel (refereegranskat)abstract
- The identity of the RNA-binding proteins (RBPs) that govern cancer stem cells remains poorly characterized. The MSI2 RBP is a central regulator of translation of cancer stem cell programs. Through proteomic analysis of the MSI2-interacting RBP network and functional shRNA screening, we identified 24 genes required for in vivo leukemia. Syncrip was the most differentially required gene between normal and myeloid leukemia cells. SYNCRIP depletion increased apoptosis and differentiation while delaying leukemogenesis. Gene expression profiling of SYNCRIP-depleted cells demonstrated a loss of the MLL and HOXA9 leukemia stem cell program. SYNCRIP and MSI2 interact indirectly though shared mRNA targets. SYNCRIP maintains HOXA9 translation, and MSI2 or HOXA9 overexpression rescued the effects of SYNCRIP depletion. Altogether, our data identify SYNCRIP as a new RBP that controls the myeloid leukemia stem cell program. We propose that targeting these RBP complexes might provide a novel therapeutic strategy in leukemia.
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| 2. |
- Lee, S. W., et al.
(författare)
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Sol-gel integrated protein microarray for high-resolution signal readout of psa (prostate specific antigen) in clinical samples
- 2010
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Ingår i: 14th International Conference on Miniaturized Systems for Chemistry and Life Sciences 2010, MicroTAS 2010. - 9781618390622 ; 2, s. 800-802
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Konferensbidrag (refereegranskat)abstract
- In this study, we demonstrate a new protein microarray technology for highly sensitive detection of PSA (prostate caser specific antigen) in scrum samples. Using the optically active sol-gel nanocomposites, which can hold capturing probes in native and surface morphology tailored porous silicon, purified PSA (Prostate Specific Antigen) in human female serum was assessed by FlTC-antiPSA in broad dynamic range of the sandwich (1 pg/mL to Ing/mL). Additionally, we tested reverse phase assay using our developed system, which purified PSA imbedded in sol-gel and FITC labeled its counter antibody was accessed. Dynamic range was 60 fg/mL to 6ng/mL. Our concept can allow the measurement oflow amount of PSA at pg/ml range and thus, it is possible to do relative quantification for marker protein as well.
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| 3. |
- Puram, Rishi V, et al.
(författare)
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Core Circadian Clock Genes Regulate Leukemia Stem Cells in AML
- 2016
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Ingår i: Cell. - : Elsevier BV. - 1097-4172 .- 0092-8674. ; 165:2, s. 16-303
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Tidskriftsartikel (refereegranskat)abstract
- Leukemia stem cells (LSCs) have the capacity to self-renew and propagate disease upon serial transplantation in animal models, and elimination of this cell population is required for curative therapies. Here, we describe a series of pooled, in vivo RNAi screens to identify essential transcription factors (TFs) in a murine model of acute myeloid leukemia (AML) with genetically and phenotypically defined LSCs. These screens reveal the heterodimeric, circadian rhythm TFs Clock and Bmal1 as genes required for the growth of AML cells in vitro and in vivo. Disruption of canonical circadian pathway components produces anti-leukemic effects, including impaired proliferation, enhanced myeloid differentiation, and depletion of LSCs. We find that both normal and malignant hematopoietic cells harbor an intact clock with robust circadian oscillations, and genetic knockout models reveal a leukemia-specific dependence on the pathway. Our findings establish a role for the core circadian clock genes in AML.
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| 10. |
- Järås, Marcus, et al.
(författare)
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Csnk1a1 inhibition has p53-dependent therapeutic efficacy in acute myeloid leukemia
- 2014
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Ingår i: Journal of Experimental Medicine. - : Rockefeller University Press. - 1540-9538 .- 0022-1007. ; 211:4, s. 605-612
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Tidskriftsartikel (refereegranskat)abstract
- Despite extensive insights into the underlying genetics and biology of acute myeloid leukemia (AML), overall survival remains poor and new therapies are needed. We found that casein kinase 1 alpha (Csnk1a1), a serine-threonine kinase, is essential for AML cell survival in vivo. Normal hematopoietic stem and progenitor cells (HSPCs) were relatively less affected by shRNA-mediated knockdown of Csnk1a1. To identify downstream mediators of Csnk1a1 critical for leukemia cells, we performed an in vivo pooled shRNA screen and gene expression profiling. We found that Csnk1a1 knockdown results in decreased Rps6 phosphorylation, increased p53 activity, and myeloid differentiation. Consistent with these observations, p53-null leukemias were insensitive to Csnk1a1 knockdown. We further evaluated whether D4476, a casein kinase 1 inhibitor, would exhibit selective antileukemic effects. Treatment of leukemia stem cells (LSCs) with D4476 showed highly selective killing of LSCs over normal HSPCs. In summary, these findings demonstrate that Csnk1a1 inhibition causes reduced Rps6 phosphorylation and activation of p53, resulting in selective elimination of leukemia cells, revealing Csnk1a1 as a potential therapeutic target for the treatment of AML.
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| 11. |
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| 12. |
- Lopez, Luis, et al.
(författare)
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Syngas conversion to ethanol over a mesoporous Cu/MCM-41 catalyst : Effect of K and Fe promoters
- 2016
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Ingår i: Applied Catalysis A. - : Elsevier. - 0926-860X .- 1873-3875. ; 526, s. 77-83
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Tidskriftsartikel (refereegranskat)abstract
- Transportation fuels such as ethanol can be obtained through thermochemical processing of biomass. Interest in the development of more selective catalysts for the conversion of biomass-derived syngas (H2 + CO) to ethanol is increasing in both academia and industry. In this work, we have evaluated the performances of K and Fe as metal promoters of a mesoporous Cu/MCM-41 catalyst and their effects on the product selectivity and especially on ethanol formation. The metal loading was 29 wt.% Cu, 2 wt.% Fe and 1.6 wt.% K. The catalysts were tested at 300 °C, 20 bar and gas-hourly-space-velocities in the range of 1500–30000 mlsyngas/gcat h; under these conditions the syngas conversion level was between 2 and 11%. The non-promoted Cu/MCM-41 catalyst showed interesting selectivity toward oxygenated compounds, mostly methanol. The addition of K as promoter increases the selectivity toward methanol even more, while the addition of Fe as promoter favors the formation of hydrocarbon compounds. When both K and Fe as promoters are incorporated into the Cu/MCM-41 catalyst, the reaction rate to oxygenated compounds is notably increased, especially for ethanol. The space time yield for ethanol for the Cu/MCM-41 catalyst is 0.3 × 10−5 carbon-mol/gcath which increases to 165.5 × 10−5 carbon-mol/gcath for the Cu-Fe-K/MCM-41 catalyst. From XPS analysis, the Cu-Fe-K/MCM-41 catalyst was found to have the following atomic composition: Cu0.34Fe0.08K0.08Si1.00. The promoting effect of both K and Fe, may be related to an increased reaction rate toward CO non-dissociation and CO-dissociation paths, respectively, which is beneficial for the ethanol formation. Further catalytic results, catalyst characterization and discussion of results are presented in this work.
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| 13. |
- Nassos, S., et al.
(författare)
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The influence of Ni load and support material on catalysts for the selective catalytic oxidation of ammonia in gasified biomass
- 2007
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Ingår i: Applied Catalysis B. - : Elsevier BV. - 0926-3373 .- 1873-3883. ; 74:1-2, s. 92-102
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Tidskriftsartikel (refereegranskat)abstract
- The effect of nickel (Ni) load (0, 5 and 10 wt.%) and support material (Ce0.9La0.1O2, Ce0.9Zr0.1O2 and gamma-Al2O3), together the amount of oxygen (lambda = 0.25 and lambda = 0.5) and gas hourly space velocity (50 000, 100 000 and 150 000 h(-1)) were investigated for the selective catalytic oxidation of ammonia in gasified biomass. The mixed metal oxide support materials were prepared by microemulsion, whereas the alumina was a commercial product. Ni was added to the different supports by incipient wetness. All the obtained catalysts were characterised by BET and XRD analysis. Cordierite monoliths coated with 20 wt.% catalytic material were tested in a tubular quartz reactor. For simulating the gasified biomass fuel, 500 ppm of NH3 was added to the fuel. Water was also present during the activity tests, which were carried out between 500 and 750 degrees C. The results from the activity tests at lambda = 0.25 and gas hourly space velocity of 100 000 h(-1) indicated that the 10 wt.% Ni on Ce0.9La0.1O2 was the best catalyst obtaining 65 and 97% N-2 yield at 500 and 750 degrees C, respectively. By increasing lambda to 0.5 and decreasing the gas hourly space velocity, the N-2 yield improved considerably at low temperature level (500 degrees C). Moreover, NOx emissions maintained at low levels depending on the experimental conditions. Constant conversion and negligible carbon deposition were also two other important observations from the mixed metal oxide supported catalysts. On the contrary, all the alumina-based catalysts displayed the lowest performance.
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| 14. |
- Persson, Katarina, et al.
(författare)
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Catalytic combustion of methane over bimetallic Pd-Pt catalysts: The influence of support materials
- 2006
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Ingår i: Applied Catalysis B: Environmental. - : Elsevier BV. - 0926-3373. ; 66, s. 175-185
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Tidskriftsartikel (refereegranskat)abstract
- The effect of support material on the catalytic performance for methane combustion has been studied for bimetallic palladium-platinum catalysts and compared with a monometallic palladium catalyst on alumina. The catalytic activities of the various catalysts were measured in a tubular reactor, in which both the activity and stability of methane conversion were monitored. In addition, all catalysts were analysed by temperature-programmed oxidation and in situ XRD operating at high temperatures in order to study the oxidation/reduction properties.The activity of the monometallic palladium catalyst decreases under steady-state conditions, even at a temperature as low as 470 degrees C. In situ XRD results showed that no decomposition of bulk PdO into metallic palladium occurred at temperatures below 800 degrees C. Hence, the reason for the drop in activity is probably not connected to the bulk PdO decomposition.All Pd-Pt catalysts, independently of the support, have considerably more stable methane conversion than the monometallic palladium catalyst. However. dissimilanties in activity and ability to reoxidise PdO were observed for the various support materials. Pd-Pt supported on Al2O3 was the most active catalyst in the low-temperature region, Pd-Pt supported on ceria-stabilised ZrO2 was the most active between 620 and 800 degrees C, whereas Pd-Pt supported on LaMnAl11O19 was superior for temperatures above 800 degrees C. The ability to reoxidise metallic Pd into PdO was observed to vary between the supports. The alumina sample showed a very slow reoxidation, whereas ceria-stabilised ZrO2 was clearly faster
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| 15. |
- Rojas, S., et al.
(författare)
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Preparation of carbon supported Pt and PtRu nanoparticles from microemulsion - Electrocatalysts for fuel cell applications
- 2005
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Ingår i: Applied Catalysis A. - : Elsevier BV. - 0926-860X .- 1873-3875. ; 285:02-jan, s. 24-35
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Tidskriftsartikel (refereegranskat)abstract
- A series of platinum and platinum ruthenium carbon supported electrocatalyst have been prepared by the microemulsion technique. The influence of parameters such as the preparation route, the metal loading and the PtRu stoichiometry on the morphology of the final nanoparticles has been studied. Irrespective the total metal loading, nanosized particles, displaying a narrow size distribution were obtained. In addition, particle size was found to be independent of the metal loading. Structural characteristics of these systems have been studied by XPS, X-ray diffraction, TEM, and TPR-TPO and their textural parameters by N-2 adsorption. The catalytic performance of the samples was evaluated in the electrochemical oxidation of methanol. The influence of the morphology on the catalytic performance of the catalysts is discussed in terms of their synthesis route. © 2005 Elsevier B.V. All rights reserved.
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| 16. |
- Shrestha, Sarita, 1991-, et al.
(författare)
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Association between inflammatory bowel disease and spondyloarthritis : findings from a nationwide study in Sweden
- 2022
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Ingår i: Journal of Crohn's & Colitis. - : Oxford University Press. - 1873-9946 .- 1876-4479 .- 1197-4982. ; 16:1, s. 1540-1550
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND AIMS: Inflammatory bowel disease (IBD) has been associated with spondyloarthritis (SpA), but population-based estimates are scarce. Here we compare the occurrence of SpA before and after a diagnosis of IBD to the general population, overall and by IBD subtype and age.METHODS: We used a nationwide register-based cohort study of 39,203 patients diagnosed with IBD during 2006-2016, identified from Swedish registers and gastrointestinal biopsy data, and 390,490 matched reference individuals from the general population. Conditional logistic regression models were used to estimate odds ratios (ORs) for a prior (prevalent) SpA diagnosis and conditional Cox regression to calculate hazard ratios (HRs) for a subsequent (incident) SpA diagnosis in IBD patients.RESULTS: IBD patients were more likely to have prevalent SpA at IBD diagnosis (2.5%) compared to reference individuals (0.7%) with an OR of 3.48 (95%CI:3.23-3.75). They also more often received an incident diagnosis of SpA; during 23,341,934 person-years of follow-up in IBD patients, there were 1,030 SpA events (5.0/1,000 person-years) compared to 1,524 SpA events in the reference group (0.72/1,000 person-years), corresponding to an HR of 7.15 (95%CI:6.60-7.75). In subgroup analyses, associations were most pronounced among patients with Crohn's disease [(OR=5.20; 95%CI:4.59-5.89), and (HR=10.55; 95%CI:9.16-12.15)] and paediatric onset IBD [(OR=3.63; 95%CI:2.35-5.59) and (HR=15.03; 95%CI:11.01-20.53)].CONCLUSION: IBD patients more frequently experience SpA both before and after the diagnosis of IBD compared to the general population, supporting evidence of a shared pathophysiology. The variation in SpA comorbidity across IBD subtypes and age-groups, calls for targeted approaches to facilitate timely diagnosis and intervention.
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