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A new paradigm in benchmark absorption-scattering radiative transfer is presented that enables both the globally averaged and spatially resolved testing of climate model radiation parameterizations in order to uncover persistent sources of biases in the aerosol instantaneous radiative effect (IRE). A proof of concept is demonstrated with the Geophysical Fluid Dynamics Laboratory AM4 and Community Earth System Model 1.2.2 climate models. Instead of prescribing atmospheric conditions and aerosols, as in prior intercomparisons, native snapshots of the atmospheric state and aerosol optical properties from the participating models are used as inputs to an accurate radiation solver to uncover model-relevant biases. These diagnostic results show that the models' aerosol IRE bias is of the same magnitude as the persistent range cited (~1 W/m2) and also varies spatially and with intrinsic aerosol optical properties. The findings underscore the significance of native model error analysis and its dispositive ability to diagnose global biases, confirming its fundamental value for the Radiative Forcing Model Intercomparison Project.

Mesoscale convective systems (MCSs) are pivotal in global energy/water cycles and typically produce extreme weather events. Despite their importance, our understanding of their future change remains limited, largely due to inadequate representation in current climate models. Here, using a global storm‐resolving model that accurately simulates MCSs, we conclude contrasting responses to increased SST in their occurrence, that is, notable decreases over land but increases over ocean. This land‐ocean contrast is attributed to the changes in convective available potential energy (CAPE) and convective inhibition (CIN). Over land, notable rises in CIN alongside moderate increases in CAPE effectively suppress (favor) weak to moderate (intense) MCSs, resulting in an overall reduction in MCS occurrences. In contrast, substantial increases in CAPE with minimal changes in CIN over ocean contribute to a significant rise in MCS occurrences. The divergent response in MCS occurrence has profound impacts on both mean and extreme precipitation. Plain Language Summary: Mesoscale convective systems (MCSs) account for more than half of tropical total rainfall and are the primary drivers of extreme rainfall and flooding events. However, understanding how the frequency of these systems will change in a warming climate remains a challenge. This is due to both the incomplete representation of these disturbances in global climate models and a lack of fundamental theory to explain their dynamics. In this study, we employ a global storm resolving model to shed light on the response of tropical MCS occurrences to climate warming. What emerges is a striking contrast: MCSs over tropical land are projected to decrease in frequency, while their occurrence over tropical oceans is anticipated to rise. This difference is linked to the relative changes in convective available potential energy and convective inhibition. The divergent response in MCS occurrences has significant implications for both average and extreme precipitation patterns. As a result, it presents challenges for developing regional climate adaptation and mitigation strategies in the face of a warming climate. Key Points: A global storm resolving model is employed to study the response of global mesoscale convective systems (MCSs) to a warming climateTropical MCS occurrence exhibits divergent responses to increased SST, declining over land while increasing over the oceanThis land‐ocean contrast is attributed to the changes in convective available potential energy and convective inhibition, on MCSs [ABSTRACT FROM AUTHOR]

Over 20% of the drugs for treating human diseases target ion channels, but no cancer drug approved by the US Food and Drug Administration (FDA) is intended to target an ion channel. We found that the EAG2 (Ether-a-go-go 2) potassium channel has an evolutionarily conserved function for promoting brain tumor growth and metastasis, delineate downstream pathways, and uncover a mechanism for different potassium channels to functionally cooperate and regulate mitotic cell volume and tumor progression. EAG2 potassium channel was enriched at the trailing edge of migrating medulloblastoma (MB) cells to regulate local cell volume dynamics, thereby facilitating cell motility. We identified the FDA-approved antipsychotic drug thioridazine as an EAG2 channel blocker that reduces xenografted MB growth and metastasis, and present a case report of repurposing thioridazine for treating a human patient. Our findings illustrate the potential of targeting ion channels in cancer treatment.

TP53 mutations confer subgroup specific poor survival for children with medulloblastoma. We hypothesized that WNT activation which is associated with improved survival for such children abrogates TP53 related radioresistance and can be used to sensitize TP

Ependymomas are common childhood brain tumours that occur throughout the nervous system, but are most common in the paediatric hindbrain. Current standard therapy comprises surgery and radiation, but not cytotoxic chemotherapy as it does not further increase survival. Whole-genome and whole-exome sequencing of 47 hindbrain ependymomas reveals an extremely low mutation rate, and zero significant recurrent somatic single nucleotide variants. Although devoid of recurrent single nucleotide variants and focal copy number aberrations, poor-prognosis hindbrain ependymomas exhibit a CpG island methylator phenotype. Transcriptional silencing driven by CpG methylation converges exclusively on targets of the Polycomb repressive complex 2 which represses expression of differentiation genes through trimethylation of H3K27. CpG island methylator phenotype-positive hindbrain ependymomas are responsive to clinical drugs that target either DNA or H3K27 methylation both in vitro and in vivo. We conclude that epigenetic modifiers are the first rational therapeutic candidates for this deadly malignancy, which is epigenetically deregulated but genetically bland.

Telomerase reverse transcriptase (TERT) promoter mutations were recently shown to drive telomerase activity in various cancer types, including medulloblastoma. However, the clinical and biological implications of TERT mutations in medulloblastoma have not