Proteomics, post-translational modifications, and integrative analyses reveal molecular heterogeneity within medulloblastoma subgroups

There is a pressing need to identify therapeutic targets in tumors with low mutation rates such as the malignant pediatric brain tumor medulloblastoma. To address this challenge, we quantitatively profiled global proteomes and phospho-proteomes of 45 medulloblastoma samples. Integrated analyses revealed that tumors with similar RNA expression vary extensively at the post-transcriptional and post-translational levels. We identified distinct pathways associated with two subsets of SHH tumors, and found post-translational modifications of MYC that are associated with poor outcomes in group 3 tumors. We found kinases associated with subtypes and showed that inhibiting PRKDC sensitizes MYC-driven cells to radiation. Our study shows that proteomics enables a more comprehensive, functional readout, providing a foundation for future therapeutic strategies

Approaches to modelling land erodibility by wind

Land susceptibility to wind erosion is governed by complex multiscale interactions between soil erodibility and non-erodible roughness elements populating the land surface. Numerous wind erosion modelling systems have been developed to quantify soil loss and dust emissions at the field, regional and global scales. All of these models require some component that defines the susceptibility of the land surface to erosion, ie, land erodibility. The approaches taken to characterizing land erodibility have advanced through time, following developments in empirical and process-based research into erosion mechanics, and the growing availability of moderate to high-resolution spatial data that can be used as model inputs. Most importantly, the performance of individual models is highly dependent on the means by which soil erodibility and surface roughness effects are represented in their land erodibility characterizations. This paper presents a systematic review of a selection of wind erosion models developed over the last 50 years. The review evaluates how land erodibility has been modelled at different spatial and temporal scales, and in doing this the paper identifies concepts behind parameterizations of land erodibility, trends in model development, and recent progress in the representation of soil, vegetation and land management effects on the susceptibility of landscapes to wind erosion. The paper provides a synthesis of the capabilities of the models in assessing dynamic patterns of land erodibility change, and concludes by identifying key areas that require research attention to enhance our capacity to achieve this task