Edited by Zhijie Chang R-spondin3 (Rspo3) is a secreted protein, which acts as an agonist of canonical Wnt/b-catenin signaling that plays an important role in embryonic development and homeostasis. In this study, we focused on C-mannosylation, a unique type of glycosylation, of human Rspo3. Rspo3 has two putative Cmannosylation sites at Trp 153 and Trp 156 ; however, it had been unclear whether these sites are C-mannosylated or not. We demonstrated that Rspo3 was C-mannosylated at both Trp 153 and Trp 156 by mass spectrometry. Using C-mannosylation-defective Rspo3 mutant-overexpressing cell lines, we found that C-mannosylation of Rspo3 promotes its secretion and activates Wnt/bcatenin signaling.

This study addresses one of the functions of output proposed by Swain (1993, 1995, 1998). In particular, the activity of producing the target language may, under certain circumstances, prompt L2 learners to recognize some of their linguistic problems and bring to their attention something they need to discover about their L2. Two research questions were posed: (a) Does output promote noticing of linguistic form? and (b) Does output result in improved performance on the target form? In treatment phase 1, participants reconstructed a short passage after being exposed to it, followed by a second exposure to the same input material and a second reconstruction opportunity. In phase 2, participants wrote on given topics, followed by the presentation of a model written by a native speaker. Participants wrote a second time on the same topic. To test the noticing function of output, participants underlined parts of the sentences they thought were “particularly necessary” for subsequent (re)production. The control group was exposed to the same input materials but was not required to produce any output. Although phase 1 tasks resulted in noticing and immediate incorporation of the target form, the posttest performance failed to reveal their effects. In contrast, phase 2 tasks resulted in improvement on posttest 2. The results are discussed in terms of the efficacy of output in promoting noticing and learning and the conditions that may be required for output to be useful for SLA.

Previously we reported that a direct-acting mutagen can be formed from N-nitrosomorpholine (NMOR) on exposure to near-ultraviolet light (UVA, 320-400 nm). We have now studied the spectrum of mutations caused by NMOR plus UVA. M13mp2 phages suspended in a sodium phosphate buffer were treated with NMOR under UVA irradiation and Escherichia coli NR9099 was then infected with the phage. Mutations induced in the phage DNA lacZ alpha region were analyzed. The majority (approximately 50%) of the induced sequence changes were G to T transversions. This suggested that modifications in guanine residues were responsible for these transversions. We explored the formation of 7,8-dihydro-8-oxodeoxyguanosine (8-oxodG) in the DNA. When the phage were treated with NMOR plus UVA, 8-oxodG/dG in DNA increased up to 12-fold over the value in untreated control. When a mutM-deficient mutant of E. coli CSH50 was used as the host, the mutation level was higher than that observed with CSH50. We conclude that 8-oxodG may be involved in mutations induced by NMOR plus UVA.

A 73-year-old woman in complete remission from localized small-cell lung cancer associated with Lambert-Eaton myasthenic syndrome (LEMS) 22 years earlier was referred to our hospital and diagnosed with non-small-cell lung cancer. After three courses of pembrolizumab, an immune checkpoint inhibitor, the patient complained of muscle weakness, fatigue, ptosis, and dysarthria. The anti-voltage-gated calcium channel antibody level was elevated, and waxing was observed on a high-frequency repetitive stimulation test using an electromyogram. We diagnosed her with recurrence of LEMS as an immune-related adverse event (irAE) induced by pembrolizumab. After intravenous immunoglobulin therapy, the patient's symptoms improved, and she was discharged.