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This unusual in situ bypass is possible when redundancy of the AICA and PICA allow their approximation in the CPA. The anastomosis is performed lateral to the lower cranial nerves in a relatively open and superficial plane. The extended retrosigmoid approach provides adequate exposure for both the bypass and aneurysm trapping. In situ AICA-PICA bypass enables anterograde and retrograde AICA revascularization with side-to-side anastomosis. The occipital artery-to-AICA bypass and the V3 vertebral artery-to-AICA interpositional bypass are alternatives when intracranial anatomy is unfavorable for this in situ bypass.1-6 Used with permission from Barrow Neurological Institute, Phoenix, Arizona. Copyright © 2020 by the Congress of Neurological Surgeons.Aberrant Notch signaling plays a pivotal role in T-cell acute lymphoblastic leukemia (T-ALL) and chronic lymphocytic leukemia (CLL). Amplitude and duration of the Notch response is controlled by ubiquitin-dependent proteasomal degradation of the Notch1 intracellular domain (NICD1), a hallmark of the leukemogenic process. Here, we show that HDAC3 controls NICD1 acetylation levels directly affecting NICD1 protein stability. Either genetic loss-of-function of HDAC3 or nanomolar concentrations of HDAC inhibitor apicidin lead to downregulation of Notch target genes accompanied by a local reduction of histone acetylation. Importantly, an HDAC3-insensitive NICD1 mutant is more stable but biologically less active. Collectively, these data show a new HDAC3- and acetylation-dependent mechanism that may be exploited to treat Notch1-dependent leukemias. © The Author(s) 2020. Published by Oxford University Press on behalf of Nucleic Acids Research.BACKGROUND Biopsies in patients with a suspected glioma are occasionally nondiagnostic. OBJECTIVE To explore the utility of molecular testing in this setting by determining whether IDH1 and TERT promoter (pTERT) mutations could be detected in nondiagnostic biopsies from glioma patients. METHODS Using SNaPshot polymerase chain reaction, we retrospectively assessed IDH1 and pTERT mutation status in nondiagnostic biopsies from 28 glioma patients. RESULTS The nondiagnostic biopsy (needle biopsy n&nbsp;=&nbsp;25, open or endoscopic biopsy n&nbsp;=&nbsp;3) consisted of slight glial cell hypercellularity, hemorrhage, and/or necrosis. After another biopsy (n&nbsp;=&nbsp;23) or a subsequent surgical resection (n&nbsp;=&nbsp;5) the diagnosis was an IDH1-wildtype (WT) pTERT-mutant glioma (glioblastoma n&nbsp;=&nbsp;16, astrocytoma n&nbsp;=&nbsp;4), an IDH1-mutant pTERT-mutant oligodendroglioma (n&nbsp;=&nbsp;1), an IDH1-mutant pTERT-WT astrocytoma (n&nbsp;=&nbsp;1), and an IDH1-WT pTERT-WT glioblastoma (n&nbsp;=&nbsp;6). An IDH1 mutation was identified in the nondiagnostic biopsies of the 2 IDH-mutant gliomas, and a pTERT mutation in the nondiagnostic biopsies of 16 out of the 21 of pTERT mutant-gliomas (76%). Overall, an IDH1 and/or a pTERT mutation were detected in 17 out of 28 (61%) of nondiagnostic biopsies. Retrospective analysis of the nondiagnostic biopsies based on these results and on imaging characteristics suggested that a new biopsy could have been avoided in 6 patients in whom a diagnosis of "molecular glioblastoma" could have been done with a high level of confidence. CONCLUSION In the present series, IDH1 and pTERT mutations could be detected in a high proportion of nondiagnostic biopsies from glioma patients. Molecular testing may facilitate the interpretation of nondiagnostic biopsies in patients with a suspected glioma. Copyright © 2020 by the Congress of Neurological Surgeons.Nutrient stresses induce foliar chlorosis and growth defects. Here we propose heterotrimeric G protein as signaling mediators of various nutrient stresses, through meta-analyses of more than 20 transcriptomic data associated with nutrient stresses or G-protein mutations. Systematic comparison of transcriptomic data yielded 104 genes regulated by G protein subunits under common nutrient stresses; 69 genes under Gβ subunit (AGB1) and 35 genes under Gα subunit (GPA1) control. Quantitative RT-PCR experiments validate that several transcription factors and metal transporters changed in expression level under suboptimal iron, zinc and/or copper concentrations, while being mis-regulated in Arabidopsis Gβ-null (agb1) mutant. The agb1 mutant altered metal ion profiles and exhibited severe growth arrest under zinc stress and aberrant root waving under iron and zinc stresses, while Gα-null mutation attenuated leaf chlorosis under iron deficiency both in Arabidopsis and rice. Our transcriptional network analysis inferred computationally that WRKY-family transcription factors mediate the AGB1-dependent nutrient responses. As corroborating evidence of our inference, ectopic expression of WRKY25 or WRKY33 rescued the zinc-stress phenotypes and the expressions of zinc transporters in the agb1-2 background. These results, together with gene ontology analyses, suggest two contrasting roles of G protein-coupled signaling pathways in micronutrient stress responses; one enhancing general stress tolerance, while the other modulating ion homeostasis through WRKY transcriptional regulatory networks. In addition, tolerance to iron stress in rice Gα mutant provides an inroad to improve nutrient stress tolerance of agricultural crops by manipulating G-protein signaling. © The Author(s) 2020. [https://www.selleckchem.com/ see more] Published by Oxford University Press on behalf of the Society for Experimental Biology.Under natural conditions, plants are exposed to various abiotic and biotic stresses that trigger rapid changes in the production and removal of reactive oxygen species (ROS) such as hydrogen peroxide (H2O2). The ascorbate-glutathione pathway has been recognized to be a key player in H2O2 metabolism, in which reduced glutathione (GSH) regenerates ascorbate by reducing dehydroascorbate (DHA), either chemically or via DHA reductase (DHAR), an enzyme belonging to the glutathione S-transferase (GST) superfamily. Thus, DHAR has been considered to be important in maintaining the ascorbate pool and its redox state. Although some GSTs and peroxiredoxins may contribute to GSH oxidation, analyzing Arabidopsis dhar mutants has identified the key role of DHAR in coupling H2O2 to GSH oxidation. The reaction of DHAR was proposed to be proceeded by a ping-pong mechanism, in which binding of DHA to the free, reduced form of the enzyme is followed by binding of GSH. Recently, crystal structure information shed light on the formation of sulfenic acid at the catalytic cysteine of DHAR with the reduction of DHA.