Determination of a phosphorylation site in Nipah virus nucleoprotein and its involvement in virus transcription

Many viruses use their host’s cellular machinery to regulate the functions of viral proteins. The phosphorylation of viral proteins is known to play a role in genome transcription and replication in paramyxoviruses. The paramyxovirus nucleoprotein (N), the most abundant protein in infected cells, is a component of the N–RNA complex and supports the transcription and replication of virus mRNA and genomic RNA. Recently, we reported that the phosphorylation of measles virus N is involved in the regulation of viral RNA synthesis. In this study, we report a rapid turnover of phosphorylation in the Nipah virus N (NiV-N). The phosphorylated NiV-N was hardly detectable in steady-state cells, but was detected after inhibition of cellular protein phosphatases. We identified a phosphorylated serine residue at Ser451 of NiV-N by peptide mass fingerprinting by electrospray ionization–quadrupole time-of-flight mass spectrometry. In the NiV minigenome assay, using luciferase as a reporter gene, the substitution of Ser451 for alanine in NiV-N resulted in a reduction in luciferase activity of approximately 45 % compared with the wild-type protein. Furthermore, the substitution of Ser451 for glutamic acid, which mimics a phosphoserine, led to a more significant decrease in luciferase activity – approximately 81 %. Northern blot analysis showed that both virus transcription and replication were reduced by these mutations. These results suggest that a rapid turnover of the phosphorylation of NiV-N plays an important role in virus transcription and replication

Usefulness of Combined Screening with Conventional Procedure and Screening Mammography in the Detection of Breast Cancer : Results from the Mass Survey for Breast Cancer in Kumamoto Prefecture

The aim of this study was to evaluate the usefulness of combined screening with conventional procedure and screening mammography by comparing a number and detection rate of breast cancers between conventional procedure without (CP group) and with screening mammography (MMG group) performed in Kumamoto prefecture from 1999 to 2005

HIGH STEROL ESTER 1 is a key factor in plant sterol homeostasis

ステロールの過剰集積を防ぐ植物の技を解明 --二段階フェイルセーフ・システム--. 京都大学プレスリリース. 2019-11-15.Plants strictly regulate the levels of sterol in their cells, as high sterol levels are toxic. However, how plants achieve sterol homeostasis is not fully understood. We isolated an Arabidopsis thaliana mutant that abundantly accumulated sterol esters in structures of about 1 µm in diameter in leaf cells. We designated the mutant high sterol ester 1 (hise1) and called the structures sterol ester bodies. Here, we show that HISE1, the gene product that is altered in this mutant, functions as a key factor in plant sterol homeostasis on the endoplasmic reticulum (ER) and participates in a fail-safe regulatory system comprising two processes. First, HISE1 downregulates the protein levels of the β-hydroxy β-methylglutaryl-CoA reductases HMGR1 and HMGR2, which are rate-limiting enzymes in the sterol synthesis pathway, resulting in suppression of sterol overproduction. Second, if the first process is not successful, excess sterols are converted to sterol esters by phospholipid sterol acyltransferase1 (PSAT1) on ER microdomains and then segregated in SE bodies

Two cases of acute‐onset cystoid macular edema and serous retinal detachment associated with combined use of encorafenib and binimetinib for advanced melanoma: A possible confounding risk for drug intolerance

Abstract While combined use of BRAF/MEK inhibitors has elicited dramatic clinical efficacy in incurable melanoma, drug‐associated retinopathy has become an emerging adverse event. We present two Japanese men with advanced melanoma who developed visual impairment due to serous retinal detachments (SRDs) with cystoid macular edema (CME) immediately after initial administration of encorafenib/binimetinib, a BRAF and MEK inhibitor. One case had drug‐intolerable retinopathy on repeat dosing. Both cases were switched to another BRAF/MEK inhibitors, dabrafenib/trametinib, with no recurrence of SRDs. Co‐existing CME may be a confounding risk for the early development of SRDs with encorafenib/binimetinib therapy, providing attention during drug administration

Genome evolution of a nonparasitic secondary heterotroph, the diatom Nitzschia putrida

International audienceSecondary loss of photosynthesis is observed across almost all plastid-bearing branches of the eukaryotic tree of life. However, genome-based insights into the transition from a phototroph into a secondary heterotroph have so far only been revealed for parasitic species. Free-living organisms can yield unique insights into the evolutionary consequence of the loss of photosynthesis, as the parasitic lifestyle requires specific adaptations to host environments. Here, we report on the diploid genome of the free-living diatom Nitzschia putrida (35 Mbp), a nonphotosynthetic osmotroph whose photosynthetic relatives contribute ca. 40% of net oceanic primary production. Comparative analyses with photosynthetic diatoms and heterotrophic algae with parasitic lifestyle revealed that a combination of gene loss, the accumulation of genes involved in organic carbon degradation, a unique secretome, and the rapid divergence of conserved gene families involved in cell wall and extracellular metabolism appear to have facilitated the lifestyle of a free-living secondary heterotroph