Histone H3.3 beyond cancer: Germline mutations in Histone 3 Family 3A and 3B cause a previously unidentified neurodegenerative disorder in 46 patients

Although somatic mutations in Histone 3.3 (H3.3) are well-studied drivers of oncogenesis, the role of germline mutations remains unreported. We analyze 46 patients bearing de novo germline mutations in histone 3 family 3A (H3F3A) or H3F3B with progressive neurologic dysfunction and congenital anomalies without malignancies. Molecular modeling of all 37 variants demonstrated clear disruptions in interactions with DNA, other histones, and histone chaperone proteins. Patient histone posttranslational modifications (PTMs) analysis revealed notably aberrant local PTM patterns distinct from the somatic lysine mutations that cause global PTM dysregulation. RNA sequencing on patient cells demonstrated up-regulated gene expression related to mitosis and cell division, and cellular assays confirmed an increased proliferative capacity. A zebrafish model showed craniofacial anomalies and a defect in Foxd3-derived glia. These data suggest that the mechanism of germline mutations are distinct from cancer-associated somatic histone mutations but may converge on control of cell proliferation

Advances in Zeolite Imidazolate Frameworks (ZIFs) Derived Bifunctional Oxygen Electrocatalysts and Their Application in Zinc–Air Batteries

Secondary Zn-air batteries (ZABs) are recognized as one of the most promising power sources for the future with lucrative features of low cost, high energy density, eco-friendliness, and high safety. However, the widespread implementation of ZABs is still hampered by the sluggish oxygen redox reactions. Thus the deployment of cost-effective and highly efficient air electrodes to substitute precious metals (Pt/Ir), is highly challenging, however, highly desired. Zeolitic imidazolate frameworks (ZIFs) are emerging functional materials, which demonstrate several outstanding characteristics, such as high specific surface area, high conductivity, self-doped N, open pore structure, versatile compositions and favourable chemical stability. Through varying the metal/organic moiety or by employing different synthesis protocols, ZIFs with different properties could be obtained. Being adaptable, desired functionalities may be further incorporated into ZIFs through pre-treatment, in situ treatment, and post treatment. Thus, ZIFs are the ideal precursors for the preparation of variety of bi-functional air electrodes for ZABs by materials tuning, morphological control, or by materials hybridization. Here, the recent advances of ZIFs-based materials are critically surveyed from the perspective of synthesis, morphology, structure and properties, and correlated with performance indicators of ZABs. Finally, the major challenges and future prospects of ZIFs associated with ZABs are discussed