| 831. |
|
|
| 832. |
- Hart, GT, et al.
(författare)
-
Adaptive NK cells in people exposed to Plasmodium falciparum correlate with protection from malaria
- 2019
-
Ingår i: The Journal of experimental medicine. - : Rockefeller University Press. - 1540-9538 .- 0022-1007. ; 216:6, s. 1280-1290
-
Tidskriftsartikel (refereegranskat)abstract
- How antibodies naturally acquired during Plasmodium falciparum infection provide clinical immunity to blood-stage malaria is unclear. We studied the function of natural killer (NK) cells in people living in a malaria-endemic region of Mali. Multi-parameter flow cytometry revealed a high proportion of adaptive NK cells, which are defined by the loss of transcription factor PLZF and Fc receptor γ-chain. Adaptive NK cells dominated antibody-dependent cellular cytotoxicity responses, and their frequency within total NK cells correlated with lower parasitemia and resistance to malaria. P. falciparum–infected RBCs induced NK cell degranulation after addition of plasma from malaria-resistant individuals. Malaria-susceptible subjects with the largest increase in PLZF-negative NK cells during the transmission season had improved odds of resistance during the subsequent season. Thus, antibody-dependent lysis of P. falciparum–infected RBCs by NK cells may be a mechanism of acquired immunity to malaria. Consideration of antibody-dependent NK cell responses to P. falciparum antigens is therefore warranted in the design of malaria vaccines.
|
|
| 833. |
|
|
| 834. |
- Hernandez, Svea, et al.
(författare)
-
First Cospatial Comparison of Stellar, Neutral-gas, and Ionized-gas Metallicities in a Metal-rich Galaxy : M83
- 2021
-
Ingår i: Astrophysical Journal. - : American Astronomical Society. - 0004-637X .- 1538-4357. ; 908:2
-
Tidskriftsartikel (refereegranskat)abstract
- We carry out a comparative analysis of the metallicities from the stellar, neutral-gas, and ionized-gas components in the metal-rich spiral galaxy M83. We analyze spectroscopic observations taken with the Hubble Space Telescope, the Large Binocular Telescope, and the Very Large Telescope. We detect a clear depletion of the H i gas, as observed from the H i column densities in the nuclear region of this spiral galaxy. We find column densities of log[N(H i) cm−2] < 20.0 at galactocentric distances of <0.18 kpc, in contrast to column densities of log[N(H i) cm−2] ~ 21.0 in the galactic disk, a trend observed in other nearby spiral galaxies. We measure a metallicity gradient of −0.03 ± 0.01 dex kpc−1 for the ionized gas, comparable to the metallicity gradient of a local benchmark of 49 nearby star-forming galaxies of −0.026 ± 0.002 dex kpc−1. Our cospatial metallicity comparison of the multiphase gas and stellar populations shows excellent agreement outside of the nucleus of the galaxy, hinting at a scenario where the mixing of newly synthesized metals from the most massive stars in the star clusters takes longer than their lifetimes (~10 Myr). Finally, our work shows that caution must be taken when studying the metallicity gradient of the neutral-gas component in star-forming galaxies, since this can be strongly biased, as these environments can be dominated by molecular gas. In these regions the typical metallicity tracers can provide inaccurate abundances, as they may trace both the neutral- and molecular-gas components.
|
|
| 835. |
|
|
| 836. |
- Hornborg, Alf, et al.
(författare)
-
Money, value, and entropy
- 2023
-
Ingår i: Handbook of inequality and the environment. - 9781800881129
-
Bokkapitel (refereegranskat)
|
|
| 837. |
- Ingelshed, Katrine, et al.
(författare)
-
The MDM2 Inhibitor Navtemadlin Arrests Mouse Melanoma Growth In Vivo and Potentiates Radiotherapy
- 2022
-
Ingår i: Cancer Research Communications. - : American Association For Cancer Research (AACR). - 2767-9764. ; 2:9, s. 1075-1088
-
Tidskriftsartikel (refereegranskat)abstract
- The tumor suppressor protein p53 is mutated in close to 50% of human tumors and is dysregulated in many others, for instance by silencing or loss of p14ARF. Under steady-state conditions, the two E3 ligases MDM2/MDM4 interact with and inhibit the transcriptional activity of p53. Inhibition of p53–MDM2/4 interaction to reactivate p53 in tumors with wild-type (WT) p53 has therefore been considered a therapeutic strategy. Moreover, studies indicate that p53 reactivation may synergize with radiation and increase tumor immunogenicity. In vivo studies of most MDM2 inhibitors have utilized immunodeficient xenograft mouse models, preventing detailed studies of action of these molecules on the immune response. The mouse melanoma cell line B16-F10 carries functional, WT p53 but does not express the MDM2 regulator p19ARF. In this study, we tested a p53-MDM2 protein–protein interaction inhibitor, the small molecule Navtemadlin, which is currently being tested in phase II clinical trials. Using mass spectrometry–based proteomics and imaging flow cytometry, we identified specific protein expression patterns following Navtemadlin treatment of B16-F10 melanoma cells compared with their p53 CRISPR-inactivated control cells. In vitro, Navtemadlin induced a significant, p53-dependent, growth arrest but little apoptosis in B16-F10 cells. When combined with radiotherapy, Navtemadlin showed synergistic effects and increased apoptosis. In vivo, Navtemadlin treatment significantly reduced the growth of B16-F10 melanoma cells implanted in C57Bl/6 mice. Our data highlight the utility of a syngeneic B16-F10 p53+/+ mouse melanoma model for assessing existing and novel p53-MDM2/MDM4 inhibitors and in identifying new combination therapies that can efficiently eliminate tumors in vivo.Significance:The MDM2 inhibitor Navtemadlin arrests mouse tumor growth and potentiates radiotherapy. Our results support a threshold model for apoptosis induction that requires a high, prolonged p53 signaling for cancer cells to become apoptotic.
|
|
| 838. |
- Ivanov, Alexander, et al.
(författare)
-
Boronate-containing polymer brushes: Characterization, interaction with saccharides and mammalian cancer cells.
- 2009
-
Ingår i: Journal of Biomedical Materials Research. Part A. - : Wiley. - 1552-4965 .- 1549-3296. ; 88:1, s. 213-225
-
Tidskriftsartikel (refereegranskat)abstract
- Boronate-containing polymer brushes were synthesized by free radical copolymerization of N,N-dimethylacrylamide (DMAA) and N-acryloyl-m-phenylboronic acid (NAAPBA) (9:1) on the surface of 3-mercaptopropyl-silylated glass plates and capillaries. The brushes were characterized with time-of-flight secondary ion mass-spectrometry (ToF SIMS), atomic force microscopy and contact angle measurements. Fructose caused a well-expressed drop spreading on the surface of copolymer-grafted glass, due to the strong interaction with the boronate groups. Sedimentation of murine hybridoma cells M2139 or human myeloid leukemia cells KG1 onto the DMAA-NAAPBA copolymer-grafted glass plates from 10 mM phosphate buffer solution (pH 8.0) resulted in the cell adhesion. The adhered M2139 and KG1 cells could be quantitatively detached from the grafted plates with 0.1M fructose, which competed with cell surface carbohydrates for binding to the boronates. Evaluation of the binding strength between M2139 cells and the copolymer brush was performed by exposure of the adhered cells to a shear stress. Detachment of a fraction of 18% of the adhered M2139 cells was obtained at a shear force of 1400-2800 pN/cell generated by the running phosphate buffer (pH 8.0), whereas the remaining adhered cells (70%) could be detached with 0.1M fructose dissolved in the same buffer. Possible applications of the boronate-containing polymer brushes to affinity cell separation can be based upon the facile recovery of the attached cells. (c) 2008 Wiley Periodicals, Inc. J Biomed Mater Res 2008.
|
|
| 839. |
- Jain, Neeraj, et al.
(författare)
-
Targetable genetic alterations of TCF4 (E2-2) drive immunoglobulin expression in diffuse large B cell lymphoma
- 2019
-
Ingår i: Science Translational Medicine. - : American Association for the Advancement of Science (AAAS). - 1946-6234 .- 1946-6242. ; 11:497
-
Tidskriftsartikel (refereegranskat)abstract
- The activated B cell (ABC-like) subtype of diffuse large B cell lymphoma (DLBCL) is characterized by chronic activation of signaling initiated by immunoglobulin m (IgM). By analyzing the DNA copy number profiles of 1000 DLBCL tumors, we identified gains of 18q21.2 as the most frequent genetic alteration in ABC-like DLBCL. Using integrative analysis of matched gene expression profiling data, we found that the TCF4 (E2-2) transcription factor gene was the target of these alterations. Overexpression of TCF4 in ABC-like DLBCL cell lines led to its occupancy on immunoglobulin (IGHM) and MYC gene enhancers and increased expression of these genes at the transcript and protein levels. Inhibition of TCF4 activity with dominant-negative constructs was synthetically lethal to ABC-like DLBCL cell lines harboring TCF4 DNA copy gains, highlighting these gains as an attractive potential therapeutic target. Furthermore, the TCF4 gene was one of the top BRD4-regulated genes in DLBCL cell lines. BET proteolysistargeting chimera (PROTAC) ARV771 extinguished TCF4, MYC, and IgM expression and killed ABC-like DLBCL cells in vitro. In DLBCL xenograft models, ARV771 treatment reduced tumor growth and prolonged survival. This work highlights a genetic mechanism for promoting immunoglobulin signaling in ABC-like DLBCL and provides a functional rationale for the use of BET inhibitors in this disease.
|
|
| 840. |
- Jarvis, Erich D., et al.
(författare)
-
Whole-genome analyses resolve early branches in the tree of life of modern birds
- 2014
-
Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 346:6215, s. 1320-1331
-
Tidskriftsartikel (refereegranskat)abstract
- To better determine the history of modern birds, we performed a genome-scale phylogenetic analysis of 48 species representing all orders of Neoaves using phylogenomic methods created to handle genome-scale data. We recovered a highly resolved tree that confirms previously controversial sister or close relationships. We identified the first divergence in Neoaves, two groups we named Passerea and Columbea, representing independent lineages of diverse and convergently evolved land and water bird species. Among Passerea, we infer the common ancestor of core landbirds to have been an apex predator and confirm independent gains of vocal learning. Among Columbea, we identify pigeons and flamingoes as belonging to sister clades. Even with whole genomes, some of the earliest branches in Neoaves proved challenging to resolve, which was best explained by massive protein-coding sequence convergence and high levels of incomplete lineage sorting that occurred during a rapid radiation after the Cretaceous-Paleogene mass extinction event about 66 million years ago.
|
|
