ORCID Profile
0000-0001-6584-3795
Current Organisations
China University of Geosciences (Beijing)
,
University of Pittsburgh School of Medicine
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Publisher: Copernicus GmbH
Date: 26-06-2023
Publisher: Springer Science and Business Media LLC
Date: 10-04-2017
DOI: 10.1038/NG.3838
Publisher: Springer Science and Business Media LLC
Date: 06-04-2014
DOI: 10.1038/NG.2936
Publisher: Elsevier BV
Date: 06-2020
DOI: 10.1016/J.CELL.2020.04.047
Abstract: Posterior fossa A (PFA) ependymomas are lethal malignancies of the hindbrain in infants and toddlers. Lacking highly recurrent somatic mutations, PFA ependymomas are proposed to be epigenetically driven tumors for which model systems are lacking. Here we demonstrate that PFA ependymomas are maintained under hypoxia, associated with restricted availability of specific metabolites to diminish histone methylation, and increase histone demethylation and acetylation at histone 3 lysine 27 (H3K27). PFA ependymomas initiate from a cell lineage in the first trimester of human development that resides in restricted oxygen. Unlike other ependymomas, transient exposure of PFA cells to ambient oxygen induces irreversible cellular toxicity. PFA tumors exhibit a low basal level of H3K27me3, and, paradoxically, inhibition of H3K27 methylation specifically disrupts PFA tumor growth. Targeting metabolism and/or the epigenome presents a unique opportunity for rational therapy for infants with PFA ependymoma.
Publisher: Copernicus GmbH
Date: 12-07-2023
Abstract: Abstract. The ocean mixed layer is the interface between the ocean interior and the atmosphere or sea ice and plays a key role in climate variability. It is thus critical that numerical models used in climate studies are capable of a good representation of the mixed layer, especially its depth. Here we evaluate the mixed-layer depth (MLD) in six pairs of non-eddying (1∘ grid spacing) and eddy-rich (up to 1/16∘) models from the Ocean Model Intercomparison Project (OMIP), forced by a common atmospheric state. For model evaluation, we use an updated MLD dataset computed from observations using the OMIP protocol (a constant density threshold). In winter, low-resolution models exhibit large biases in the deep-water formation regions. These biases are reduced in eddy-rich models but not uniformly across models and regions. The improvement is most noticeable in the mode-water formation regions of the Northern Hemisphere. Results in the Southern Ocean are more contrasted, with biases of either sign remaining at high resolution. In eddy-rich models, mesoscale eddies control the spatial variability in MLD in winter. Contrary to a hypothesis that the deepening of the mixed layer in anticyclones would make the MLD larger globally, eddy-rich models tend to have a shallower mixed layer at most latitudes than coarser models do. In addition, our study highlights the sensitivity of the MLD computation to the choice of a reference level and the spatio-temporal s ling, which motivates new recommendations for MLD computation in future model intercomparison projects.
Publisher: Elsevier BV
Date: 05-2013
Publisher: Copernicus GmbH
Date: 28-02-2023
DOI: 10.5194/EGUSPHERE-2023-310
Abstract: Abstract. The ocean mixed layer is the interface between the ocean interior and the atmosphere or sea ice, and plays a key role in climate variability. It is thus critical that numerical models used in climate studies are capable of a good representation of the mixed layer, especially its depth. Here we evaluate the mixed layer depth (MLD) in six pairs of non-eddying (1° resolution) and eddy-rich (up to 1/16°) models from the Ocean Model Intercomparison Project (OMIP), forced by a common atmospheric state. For model validation, we use an updated MLD dataset computed from observations using the OMIP protocol (a constant density threshold). In winter, low resolution models exhibit large biases in the deep water formation regions. These biases are reduced in eddy-rich models but not uniformly across models and regions. The improvement is most noticeable in the mode water formation regions of the northern hemisphere. Results in the Southern Ocean are more contrasted, with biases of either sign remaining at high resolution. In eddy-rich models, mesoscale eddies control the spatial variability of MLD in winter. Contrary to a hypothesis that the deepening of the mixed layer in anticyclones would make the MLD larger globally, eddy-rich models tend to have a shallower mixed layer at most latitudes than coarser models do. In addition, our study highlights the sensitivity of the MLD computation to the choice of a reference level and the spatio-temporal s ling, which motivates new recommendations for MLD computation in future model intercomparison projects.
Publisher: Elsevier BV
Date: 06-2017
Publisher: Proceedings of the National Academy of Sciences
Date: 13-08-2013
Abstract: Gliomas represent the most common type of brain tumor, but show considerable variability in histologic appearance and clinical outcome. The phenotypic differences between types and grades of gliomas have not been explained solely on the grounds of differing oncogenic stimuli. Several studies have demonstrated that some phenotypic differences may be attributed to regional differences in the neural stem cells from which tumors arise. We hypothesized that temporal differences may also play a role, with tumor phenotypic variability reflecting intrinsic differences in neural stem cells at distinct developmental stages. To determine how the tumorigenic potential of lineally related stem cells changes over time, we used a conditional transgenic system that integrates Cre-Lox–mediated and Tet-regulated expression to drive K-ras G12D expression in neuro-glial progenitor populations at different developmental time points. Using this model, we demonstrate that K-ras G12D –induced transformation is dependent on the developmental stage at which it is introduced. Diffuse malignant brain tumors develop during early embryogenesis but not when K-ras G12D expression is induced during late embryogenesis or early postnatal life. We show that differential expression of cell-cycle regulators during development may be responsible for this differing susceptibility to malignant transformation and that loss of p53 can overcome the transformation resistance seen at later developmental stages. These results highlight the interplay between genetic alterations and the molecular changes that accompany specific developmental stages early progenitors may lack the regulatory mechanisms present at later, more lineage-restrictive, developmental time points, making them more susceptible to transformation.
Publisher: Copernicus GmbH
Date: 26-06-2023
DOI: 10.5194/GMD-2023-123
Abstract: Abstract. This study evaluates the impact of increasing resolution on Arctic Ocean simulations using five pairs of matched low- and high-resolution models within the OMIP-2 framework. The primary objective is to assess whether higher resolution can mitigate typical biases observed in low-resolution models and improve the representation of key climate-relevant variables. We reveal that increasing horizontal resolution contributes to a reduction in biases in mean temperature and salinity, and improves the simulation of the Atlantic Water layer and its decadal warming events. Higher resolution also leads to improved agreement with observed surface mixed layer depth, cold halocline base depth and Arctic gateway transports. However, the simulation of the mean state and temporal changes in Arctic freshwater content does not show improvement with increased resolution. While the use of higher resolution demonstrates positive outcomes for certain variables, it is crucial to recognize that model numerics and parameterizations also play a significant role in achieving faithful simulations. Overall, higher resolution shows promise in improving the simulation of key Arctic Ocean features and processes, but comprehensive model development is required to achieve more accurate representations across all climate-relevant variables.
Location: China
Location: United States of America
No related grants have been discovered for SAMEER AGNIHOTRI.