RESUMO
Ferritin from the marine pennate diatom Pseudo-nitzschia multiseries (PmFTN) plays a key role in sustaining growth in iron-limited ocean environments. The di-iron catalytic ferroxidase center of PmFTN (sites A and B) has a nearby third iron site (site C) in an arrangement typically observed in prokaryotic ferritins. Here we demonstrate that Glu-44, a site C ligand, and Glu-130, a residue that bridges iron bound at sites B and C, limit the rate of post-oxidation reorganization of iron coordination and the rate at which Fe(3+) exits the ferroxidase center for storage within the mineral core. The latter, in particular, severely limits the overall rate of iron mineralization. Thus, the diatom ferritin is optimized for initial Fe(2+) oxidation but not for mineralization, pointing to a role for this protein in buffering iron availability and facilitating iron-sparing rather than only long-term iron storage.
Assuntos
Diatomáceas/metabolismo , Ferritinas/metabolismo , Ferro/metabolismo , Catálise , Clonagem Molecular , OxirreduçãoRESUMO
Pediatric brain tumors are a leading cause of cancer-related death in children. In recent years, the application of next-generation sequencing and other high-throughput technologies to analysis of pediatric brain tumors has generated an abundance of molecular information. This has provided an unprecedented understanding of their biology and is refining tumor classification into clinically relevant subgroups. In this review, we provide an overview of our evolving molecular knowledge of the commonest pediatric brain tumors, pilocytic astrocytomas, ependymomas, medulloblastomas, and pediatric glioblastomas, as well as the biological and potential clinical implications of this new knowledge. Studies aimed at investigating intratumoral heterogeneity are also discussed.
Assuntos
Neoplasias Encefálicas/genética , Biologia Molecular/métodos , Biologia Molecular/tendências , Pediatria , Astrocitoma/genética , Neoplasias Encefálicas/classificação , Ependimoma/genética , Glioblastoma/genética , HumanosRESUMO
Follicular lymphoma (FL) and diffuse large B-cell lymphoma (DLBCL) are the two most common non-Hodgkin lymphomas (NHLs). Here we sequenced tumour and matched normal DNA from 13 DLBCL cases and one FL case to identify genes with mutations in B-cell NHL. We analysed RNA-seq data from these and another 113 NHLs to identify genes with candidate mutations, and then re-sequenced tumour and matched normal DNA from these cases to confirm 109 genes with multiple somatic mutations. Genes with roles in histone modification were frequent targets of somatic mutation. For example, 32% of DLBCL and 89% of FL cases had somatic mutations in MLL2, which encodes a histone methyltransferase, and 11.4% and 13.4% of DLBCL and FL cases, respectively, had mutations in MEF2B, a calcium-regulated gene that cooperates with CREBBP and EP300 in acetylating histones. Our analysis suggests a previously unappreciated disruption of chromatin biology in lymphomagenesis.
