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The authors investigated the distribution and local valence states of transition metal ions in a positive electrode material for lithium-ion batteries, Li1.2Mn0.4Fe0.4O2 nanoparticles, by electron energy-loss spectroscopy combined with scanning transmission electron microscopy. The experiments clarified the coexistence of Mn-rich and Fe-rich nanodomains in each single particle, and it is found that Fe-rich nanodomains contain Mn3+ ions which should be active in a redox reaction in spite of previous views of inactive Mn4+ ions in this material. The authors discuss a redox mechanism associated with the nanodomains. [ABSTRACT FROM AUTHOR]

Abstract: 40%-titanium substituted Li2MnO3 (Li1+x (Ti0.4Mn0.6)1−x O2, 0 < x < 1/3) before and after carbothermal reduction was characterized by annular dark field scanning transmission electron microscopy (ADF-STEM) and electron energy-loss spectroscopy (EELS) to investigate the effects of the pre-reduction treatment. EELS spectra with high energy resolution using monochromator clearly reveal the appearance of reduced Mn ions after the reduction process. The spatial distribution of the reduced phase was visualized by multi-linear least-squares (MLLS) fitting method using Mn L-edge energy-loss near-edge structure (ELNES). The morphology change of a primary particle was observed around the Mn reduction phase. [Copyright &y& Elsevier]

Abstract: The growth mode and electronic structure of Au nano-clusters grown on NiO and TiO2 were analyzed by reflection high-energy electron diffraction, a field-emission type scanning electron microscope, medium energy ion scattering and photoelectron spectroscopy. Au was deposited on clean NiO(001)-1×1 and TiO2(110)-1×1 surfaces at room temperature with a Knudsen cell at a rate of 0.25–0.35ML/min (1ML=1.39×1015 atoms/cm2:Au(111)). Initially two-dimensional (2D) islands with thickness of one Au-atom layer grow epitaxially on NiO(001) and then neighboring 2D-islands link each other to form three-dimensional (3D)-islands with the c-axis oriented to the [111] direction. The critical size to form 3D-islands is estimated to be about 5nm2. The shape of the 3D-islands is well approximated by a partial sphere with a diameter d and height h ranging from 2.0 to 11.8nm and from 0.95 to 4.2nm, respectively for Au coverage from 0.13 to 4.6ML. The valence band spectra show that the Au/NiO and Au/TiO2 surfaces have metallic characters for Au coverage above 0.9ML. We observed Au 4f spectra and found no binding energy shift for Au/NiO but significant higher binding energy shifts for Au/TiO2 due to an electron charge transfer from Au to TiO2. The work function of Au/NiO(001) gradually increases with increase in Au coverage from 4.4eV (NiO(001)) to 5.36eV (Au(111)). In contrast, a small Au deposition(0.15 to 1.5ML) on TiO2(110) leads to reduction of the work function, which is correlated with an electron charge transfer from Au to TiO2 substrate. [Copyright &y& Elsevier]

Abstract: Interfacial atomic structures of Cu/Al2O3(0001) and Cu/Al2O3() prepared by the pulsed-laser deposition technique were characterized by high-resolution transmission electron microscopy (HRTEM). It was found that (111) and (001) planes of Cu were epitaxially oriented to Al2O3(0001) and Al2O3() planes, respectively. Chemical bonding states at the interfaces were analysed by electron energy-loss spectroscopy (EELS). In oxygen–K edge energy-loss near-edge structure (O–K ELNES) of the Cu/Al2O3(0001) and Cu/Al2O3() interfaces, a shoulder peak appeared at the lower energy side of the main peak. This indicates that Cu–O interactions were formed across these Cu/Al2O3 interfaces. In fact, the simulated HRTEM images based on the O-terminated interface models agreed well with the experimental ones. It can be concluded that the O-terminated interfaces were formed in the present Cu/Al2O3 interfaces. [Copyright &y& Elsevier]

The local barrier height (LBH) was measured on TiO2(1 1 0) single crystal surfaces with and without Au deposition using scanning tunneling microscopy (STM). On the clean TiO2(1 1 0) surface, the LBH values measured at (1×1) and (1×2) rows were almost the same, while the value at defect sites was much smaller. This indicates that the LBH of TiO2 surfaces is dependent on the presence of topmost oxygen atoms. On the Au deposited surfaces, the LBH was dependent on the height of Au particles: the LBH of large particles (>0.4 nm in height) was about 0.3 eV larger than that of the substrate, whereas the LBH of small particles (<0.4 nm in height) was comparable to that of the substrate. The critical height of 0.4 nm for the LBH could be correlated with the metal–nonmetal transition of Au particles. [Copyright &y& Elsevier]

Major histocompatibility complex class II (MHC-II) is the most significant genetic risk factor for systemic lupus erythematosus (SLE), but the nature of the self-antigens that trigger autoimmunity remains unclear. Unusual self-antigens, termed neoself-antigens, are presented on MHC-II in the absence of the invariant chain essential for peptide presentation. Here, we demonstrate that neoself-antigens are the primary target for autoreactive T cells clonally expanded in SLE. When neoself-antigen presentation was induced by deleting the invariant chain in adult mice, neoself-reactive T cells were clonally expanded, leading to the development of lupus-like disease. Furthermore, we found that neoself-reactive CD4 + T cells were significantly expanded in SLE patients. A high frequency of Epstein-Barr virus reactivation is a risk factor for SLE. Neoself-reactive lupus T cells were activated by Epstein-Barr-virus-reactivated cells through downregulation of the invariant chain. Together, our findings imply that neoself-antigen presentation by MHC-II plays a crucial role in the pathogenesis of SLE., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Introduction: The "weekday effect" on elective surgery remains controversial. We aimed to examine the association between the day of surgery and short-term outcomes after elective surgery for stage I-III colorectal cancer (CRC)., Methods: We performed a multicenter retrospective analysis of 2574 patients who underwent primary colorectal resection for CRC between January 2017 and December 2019 at 15 institutions belonging to the Hiroshima Surgical Study Group of Clinical Oncology. Patients were divided into two groups according to the day of surgery: Friday and non-Friday (Monday to Thursday). After propensity score matching (PSM), we compared 30-day mortality and postoperative outcomes., Results: Out of the total, 368 patients underwent surgery on Fridays, and the remaining 2206 underwent surgery on non-Fridays. The overall mortality rate was 0.04% (n = 1). In 1685 patients with colon cancer, the proportion of American Society of Anesthesiologists scores was significantly lower in the Friday group than in the non-Friday group before PSM. After PSM of patient, tumor, and operative characteristics, operative time was slightly more prolonged and blood loss was slightly greater in the Friday group; however, these differences were not clinically meaningful. In the 889 patients with rectal cancer, the proportion of patients with abnormal respiratory patterns was significantly lower in the Friday group than in the non-Friday group before PSM. After PSM, the Friday group had a higher incidence of morbidity (≥ Clavien-Dindo 3a), higher incidence of digestive complications, and prolonged postoperative hospital stay., Conclusions: The results may be useful in determining the day of the week for CRC surgery, which requires more advanced techniques and higher skills., (Copyright © 2024. Published by Elsevier Inc.)

Animal-mediated pollination is an essential ecosystem service for the production of many fruit trees. To reveal the community composition of flower-visiting wild insects which potentially contribute to fruit production and to examine the effects of geographic location, local meteorological conditions and locally introduced domesticated pollinators on them, we investigated the community composition of insects visiting the flowers (hereafter, "visitors") of apple, Japanese pear and Oriental persimmon for 1‒3 years at 20 sites around Japan. While most of the variation (82%) of the community composition was explained by tree species with a slight contribution by geographic distance (2%), maximum temperature and tree species contributed 62% and 41% of the variation in total abundance of the visitors, respectively. Though the dominant families of the visitors varied spatiotemporally, the community composition of the visitors of apple and Japanese pear clearly differed from that of Oriental persimmon. While Andrenidae and Syrphidae together accounted for 46%‒64% of the visitors of apple and Japanese pear, Apidae represented 57% of the visitors of Oriental persimmon. The taxonomic richness, diversity and evenness of the visitors were best predicted by locally introduced domesticated pollinators and local meteorological conditions of wind speed and maximum temperature. Amongst these selected factors, locally introduced domesticated pollinators could have the largest impact. It seemed to be strongly related to the reduction of taxonomic richness, diversity and evenness of the visitors, accounting for 41‒89% of the variation. Results suggested that the community composition and total abundance of potential pollinators were predominantly determined by tree species and temperature, but locally introduced domesticated pollinators could have a determinantal pressure on the taxonomic diversity of the community., Competing Interests: No conflict of interest to declare Disclaimer: This article is (co-)authored by any of the Editors-in-Chief, Managing Editors or their deputies in this journal., (Shoko Nakamura, Hisatomo Taki, Tomonori Arai, Ken Funayama, Shunsuke Furihata, Yuki Furui, Takamasa Ikeda, Hiromitsu Inoue, Kiyohiko Kagawa, Hidenari Kishimoto, Mitsuko Kohyama, Michiyo Komatsu, Akihiro Konuma, Ken Nakada, Suguru Nakamura, Nobuo Sawamura, Shoji Sonoda, Masahiro Sueyoshi, Seishi Toda, Katsuhiko Yaginuma, Shunsuke Yamamoto, Koki Yoshida, Tomoyuki Yokoi, Masatoshi Toyama.)

The U1RNP complex, Ro/SSA, and La/SSB are major RNA-containing autoantigens. Immune complexes (ICs) composed of RNA-containing autoantigens and autoantibodies are suspected to be involved in the pathogenesis of some systemic autoimmune diseases. Therefore, RNase treatment, which degrades RNA in ICs, has been tested in clinical trials as a potential therapeutic agent. However, no studies to our knowledge have specifically evaluated the effect of RNase treatment on the Fcγ receptor-stimulating (FcγR-stimulating) activity of RNA-containing ICs. In this study, using a reporter system that specifically detects FcγR-stimulating capacity, we investigated the effect of RNase treatment on the FcγR-stimulating activity of RNA-containing ICs composed of autoantigens and autoantibodies from patients with systemic autoimmune diseases such as systemic lupus erythematosus. We found that RNase enhanced the FcγR-stimulating activity of Ro/SSA- and La/SSB-containing ICs, but attenuated that of the U1RNP complex-containing ICs. RNase decreased autoantibody binding to the U1RNP complex, but increased autoantibody binding to Ro/SSA and La/SSB. Our results suggest that RNase enhances FcγR activation by promoting the formation of ICs containing Ro/SSA or La/SSB. Our study provides insights into the pathophysiology of autoimmune diseases involving anti-Ro/SSA and anti-La/SSB autoantibodies, and into the therapeutic application of RNase treatment for systemic autoimmune diseases.

Purpose: Several factors have been reported as risk factors for anastomotic leakage after resection of rectal cancer. This study aimed to evaluate the risk factors for anastomotic leakage, including nutritional and immunological indices, following rectal cancer resection., Methods: This study used a multicenter database of 803 patients from the Hiroshima Surgical study group of Clinical Oncology who underwent rectal resection with stapled anastomosis for rectal cancer between October 2016 and April 2020., Results: In total, 64 patients (8.0%) developed postoperative anastomotic leakage. Five factors were significantly associated with the development of anastomotic leakage after rectal cancer resection with stapled anastomosis: male sex, diabetes mellitus, C-reactive protein/albumin ratio ≥ 0.07, prognostic nutritional index < 40, and low anastomosis under peritoneal reflection. The incidence of anastomotic leakage was correlated with the number of risk factors. The novel predictive formula based on odds ratios in the multivariate analysis was useful for identifying patients at high risk for anastomotic leakage. Diverting ileostomy reduced the ratio of anastomotic leakage ≥ grade III after rectal cancer resection., Conclusions: Male sex, diabetes mellitus, C-reactive protein/albumin ratio ≥ 0.07, prognostic nutritional index < 40, and low anastomosis under peritoneal reflection are possible risk factors for developing anastomotic leakage after rectal cancer resection with the stapled anastomosis. Patients at high risk of anastomotic leakage should be assessed for the potential benefits of diverting stoma., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Localized colorectal amyloidosis has a good prognosis, but cases involving bleeding or perforation may require surgery. However, there are few case reports discussing the differences in the surgical strategy between the segmental and pan-colon types., Case Presentation: A 69-year-old woman with a history of abdominal pain and melena was diagnosed with amyloidosis localized in the sigmoid colon by colonoscopy. Since preoperative imaging and intraoperative findings could not rule out malignancy, we performed laparoscopic sigmoid colectomy with lymph-node dissection. Histopathological examination and immunohistochemical staining revealed a diagnosis of AL amyloidosis (λ type). We diagnosed localized segmental gastrointestinal amyloidosis, because there was no amyloid protein in the margins, and the tumor was localized. There were no malignant findings., Conclusions: Unlike systemic amyloidosis, localized amyloidosis has a favorable prognosis. Localized colorectal amyloidosis can be classified into the segmental type, in which amyloid protein is deposited locally, and the pan-colon type, in which amyloid protein is deposited extensively in the colon. Amyloid protein causes ischemia due to vascular deposition, weakening of the intestinal wall due to muscle layer deposition, and decreased peristalsis due to nerve plexus deposition. No amyloid protein should remain outside the resection area. The pan-colon type is often reported to cause complications such as anastomotic leakage, and primary anastomosis should be avoided. On the other hand, if there is no contamination or tumor remnants in the margin, the segmental type may be considered for primary anastomosis., (© 2023. The Author(s).)

Many patients with severe COVID-19 suffer from pneumonia and the elucidation of the mechanisms underlying the development of this severe condition is important. The in vivo function of the ORF8 protein secreted by SARS-CoV-2 is not well understood. Here, we analyzed the function of ORF8 protein by generating ORF8-knockout SARS-CoV-2 and found that the lung inflammation observed in wild-type SARS-CoV-2-infected hamsters was decreased in ORF8-knockout SARS-CoV-2-infected hamsters. Administration of recombinant ORF8 protein to hamsters also induced lymphocyte infiltration into the lungs. Similar pro-inflammatory cytokine production was observed in primary human monocytes treated with recombinant ORF8 protein. Furthermore, we demonstrated that the serum ORF8 protein levels are well-correlated with clinical markers of inflammation. These results demonstrated that the ORF8 protein is a SARS-CoV-2 viral cytokine involved in the immune dysregulation observed in COVID-19 patients, and that the ORF8 protein could be a novel therapeutic target in severe COVID-19 patients., (© The Author(s) 2022. Published by Oxford University Press on behalf of The Japanese Society for Immunology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: During neoadjuvant chemotherapy for giant gastrointestinal stromal tumors, changes in gastrointestinal stromal tumor size are rarely associated with events such as perforation and bleeding that require emergency surgery. Moreover, it is very rare for gastrointestinal stromal tumors to shrink and become mobile, resulting in gastric volvulus. Herein, we report a case of gastrointestinal stromal tumor shrinkage during neoadjuvant imatinib treatment, resulting in gastric volvulus that required surgery. To the best of our knowledge, this is the first reported occurrence of gastric volvulus during neoadjuvant imatinib treatment for a giant gastrointestinal stromal tumor., Case Presentation: A 58-year-old Japanese woman who was diagnosed with a giant gastric gastrointestinal stromal tumor and administered neoadjuvant imatinib presented to our hospital with complaints of abdominal pain and retching. Enhanced computed tomography revealed that the gastrointestinal stromal tumor had shrunk and shifted in position, and the stomach had organoaxially twisted. Accordingly, the patient was diagnosed with gastric volvulus caused by a gastric gastrointestinal stromal tumor. Conservative treatment did not improve the volvulus; hence, laparotomy was performed. The tumor developed from the lesser curvature of the stomach and caused rotation of the gastric body. The local gastric wall was resected. Histopathological examination confirmed the diagnosis of gastrointestinal stromal tumor. The patient received adjuvant imatinib for 3 years and has been alive for 5 years without recurrence., Conclusions: Gastric volvulus can be caused by the laxity of the ligaments that hold the stomach and gastric ptosis or esophageal hernia and diaphragmatic hernia; therefore, gastric gastrointestinal stromal tumors rarely cause gastric volvulus. However, a risk of torsion exists if the gastrointestinal stromal tumor develops extramural to lesser curvature and attains a certain size., (© 2023. The Author(s).)

Specific MHC class II alleles are strongly associated with susceptibility to various autoimmune diseases. Although the primary function of MHC class II molecules is to present peptides to helper T cells, MHC class II molecules also function like a chaperone to transport misfolded intracellular proteins to the cell surface. In this study, we found that autoantibodies in patients with Graves' disease preferentially recognize thyroid-stimulating hormone receptor (TSHR) complexed with MHC class II molecules of Graves' disease risk alleles, suggesting that the aberrant TSHR transported by MHC class II molecules is the target of autoantibodies produced in Graves' disease. Mice injected with cells expressing mouse TSHR complexed with MHC class II molecules, but not TSHR alone, produced anti-TSHR autoantibodies. These findings suggested that aberrant self-antigens transported by MHC class II molecules exhibit antigenic properties that differ from normal self-antigens and abrogate self-tolerance, providing a novel mechanism for autoimmunity.

Objective: Specific HLA class II alleles are associated with susceptibility to systemic lupus erythematosus (SLE). The role of HLA class II molecules in SLE pathogenesis remains unclear, although anti-DNA antibodies are specific to SLE and correlate with disease activity. We previously demonstrated that misfolded proteins bound to HLA class II molecules are specific targets for the autoantibodies produced in autoimmune diseases. This study was undertaken to validate our hypothesis that DNA binds to HLA class II molecules in a manner similar to that of misfolded proteins and that DNA bound to HLA class II molecules is involved in SLE pathogenesis., Methods: We analyzed the binding of DNA to HLA class II molecules, as well as the response of cells expressing anti-DNA B cell receptors (BCRs) to cells expressing the DNA/HLA class II complex., Results: Efficient binding of DNA to HLA class II molecules was observed in risk alleles of SLE, such as HLA-DRB1*15:01. The efficiency of DNA binding to each HLA-DR allele was positively associated with the risk of SLE conferred by the HLA-DR allele. In addition, reporter cells carrying anti-DNA BCRs were activated by cells expressing DNA/HLA class II complexes., Conclusion: These results provide evidence that DNA bound to HLA class II molecules is involved in SLE pathogenesis., (© 2021, American College of Rheumatology.)

Canavan disease is an autosomal recessive leukodystrophy caused by mutations in the gene encoding aspartoacylase (ASPA), which hydrolyses N-acetylaspartate (NAA) to acetate and aspartate. A similar feline neurodegenerative disease associated with a mutation in the ASPA gene is reported herein. Comprehensive clinical, genetic, and pathological analyses were performed on 4 affected cats. Gait disturbance and head tremors initially appeared at 1 to 19 months of age. These cats eventually exhibited dysstasia and seizures and died at 7 to 53 months of age. Magnetic resonance imaging of the brain revealed diffuse symmetrical intensity change of the cerebral cortex, brainstem, and cerebellum. Gas chromatography-mass spectrometry analysis of urine showed significant excretion of NAA. Genetic analysis of the 4 affected cats identified a missense mutation (c.859G>C) in exon 6 of the ASPA gene, which was not detected in 4 neurologically intact cats examined as controls. Postmortem analysis revealed vacuolar changes predominantly distributed in the gray matter of the cerebrum and brain stem as well as in the cerebellar Purkinje cell layer. Immunohistochemically, these vacuoles were surrounded by neurofilaments and sometimes contained MBP- and Olig2-positive cells. Ultrastructurally, a large number of intracytoplasmic vacuoles containing mitochondria and electron-dense granules were detected in the cerebral cortex. All 4 cats were diagnosed as spongy encephalopathy with a mutation in the ASPA gene, a syndrome analogous to human Canavan disease. The histopathological findings suggest that feline ASPA deficiency induces intracytoplasmic edema in neurons and oligodendrocytes, resulting in spongy degeneration of the central nervous system.

Introduction: The International Guidelines for Groin Hernia Management recommends an anterior repair after a failed posterior repair, and laparoscopic repair after a failed anterior tissue repair or Lichtenstein repair. However, there are not enough studies to guide decision-making for patients with recurrent hernia patients after combined anterior-posterior repair. We investigate the safety and usefulness of transabdominal preperitoneal repair (TAPP) for recurrent hernia patients after failed anterior-posterior repair., Methods: We conducted a retrospective analysis of 13 consecutive patients with recurrent groin hernia who underwent TAPP after prior anterior preperitoneal mesh repair (that created anterior and posterior scarring) between September 2013 and October 2018. The control group comprised 45 patients who underwent TAPP for recurrent hernia after anterior repair (43 nonmesh repairs and two Lichtenstein repairs)., Results: There were no intraoperative complications, and chronic pain was not reported by the patients with prior anterior preperitoneal mesh repair. The mean operative time was 113 ± 31.3 minutes, and the mean postoperative stay was 1.62 ± 0.87 days. The Wong-Baker FACES rating scale score for pain on postoperative day 1 was 1.91 ± 1.5; on postoperative day 7, the score was 1.0 ± 0.89. None of these findings was significantly different from the findings in patients who had a prior anterior repair. A single patient experienced a further recurrence and underwent repeat TAPP., Conclusions: The use of TAPP after failed combined anterior-posterior mesh repair may be feasible and safe for recurrent groin hernia. Further study is needed to determine long-term outcomes., (© 2020 Asia Endosurgery Task Force and Japan Society of Endoscopic Surgery and John Wiley & Sons Australia, Ltd.)

Antibodies against the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein prevent SARS-CoV-2 infection. However, the effects of antibodies against other spike protein domains are largely unknown. Here, we screened a series of anti-spike monoclonal antibodies from coronavirus disease 2019 (COVID-19) patients and found that some of antibodies against the N-terminal domain (NTD) induced the open conformation of RBD and thus enhanced the binding capacity of the spike protein to ACE2 and infectivity of SARS-CoV-2. Mutational analysis revealed that all of the infectivity-enhancing antibodies recognized a specific site on the NTD. Structural analysis demonstrated that all infectivity-enhancing antibodies bound to NTD in a similar manner. The antibodies against this infectivity-enhancing site were detected at high levels in severe patients. Moreover, we identified antibodies against the infectivity-enhancing site in uninfected donors, albeit at a lower frequency. These findings demonstrate that not only neutralizing antibodies but also enhancing antibodies are produced during SARS-CoV-2 infection., Competing Interests: Declaration of interests Osaka University and HuLA immune have filed a patent application on the method to detect the enhancing antibodies and the design of spike protein that does not induce the enhancing antibodies. Y.L., H.A., and Y.S. are listed as inventors. M.Matsumoto, Y.N., and Y.S. are employees of HuLA immune. H.A. and Y.S. are stockholders of HuLA immune., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Plasmodium falciparum causes the most severe form of malaria. Acquired immunity against P. falciparum provides insufficient protection even after repeated infections. Therefore, P. falciparum parasites might exploit inhibitory receptors for immune evasion. P. falciparum RIFINs are products of a multigene family consisting of 150-200 genes. Previously, we demonstrated that some RIFINs downregulate the immune response through the leukocyte immunoglobulin-like receptor (LILR) family inhibitory receptor, LILRB1, and leukocyte-associated immunoglobulin-like receptor 1, LAIR1. In this study, we further analyzed the expression of inhibitory receptor ligands on P. falciparum-infected erythrocytes and found that P. falciparum-infected erythrocytes expressed ligands for another LILR family inhibitory receptor, LILRB2, that recognizes HLA class I molecules as a host ligand. Furthermore, we identified that a specific RIFIN was a ligand for LILRB2 by using a newly developed RIFIN expression library. In addition, the domain 3 of LILRB2 was involved in RIFIN binding, whereas the domains 1 and 2 of LILRB2 were involved in the binding to HLA class I molecules. These results suggest that inhibitory receptor LILRB2 is also targeted by RIFIN for immune evasion of P. falciparum similar to LILRB1 and LAIR1., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Type 1 diabetes (T1D) is an autoimmune disease caused by destruction of insulin-producing β cells. The response of autoreactive T cells to β cell antigens plays a central role in the development of T1D. Recently, fusion peptides composed by insulin C-peptide fragments and other proteins were reported as β cell target antigens for diabetogenic CD4 + T cells in non-obese diabetic (NOD) mice. In this study, we generated a T cell-receptor (TCR)-like monoclonal antibody (mAb) against a fusion peptide bound to major histocompatibility complex (MHC) class II component to elucidate the function of the fusion peptides in T1D. In addition, we developed a novel NFAT-GFP TCR reporter system to evaluate the TCR-like mAb. The NFAT-GFP reporter T cells expressing the diabetogenic TCR were specifically activated by the fusion peptide presented on the MHC class II molecules. By using the NFAT-GFP reporter T cells, we showed that the TCR-like mAb blocks the diabetogenic T cell response against the fusion peptide presented on the MHC class II molecules. Furthermore, the development of T1D was ameliorated when pre-diabetic NOD mice were treated with this mAb. These findings suggest that NFAT-GFP reporter T cells are useful to assess the function of specific TCR and the recognition of fusion peptides by T cells is crucial for the pathogenesis of T1D., Competing Interests: Declaration of competing interest The authors declare that they have no conflicts of interest., (Copyright © 2020 Elsevier Inc. All rights reserved.)

In May 2018, three leaf samples were collected from Japanese pear trees cv. "Hosui" that exhibited typical chlorotic spot symptoms (Supplementary Figure S1) in a germplasm nursery in Tsukuba, Ibaraki. Total RNA was prepared using the rapid CTAB method (Gambino et al. 2008) for high-throughput sequencing, as described by Kubota et al. (2020). In brief, after removing ribosomal RNAs, a library was constructed by fragmenting RNA, synthesizing cDNA, and polymerase chain reaction (PCR) amplification. Sequencing was performed using NovaSeq 6000 sequencer (Illumina, San Diego, CA, U.S.A.) with paired-end 150 nt reads. De novo assembly was performed using CLC Genomics Workbench 11.0 Software (Qiagen, Hilden, Germany), with a minimum length of 500 bp. A total of 36,017 contigs derived from 33,565,182 reads were obtained and subjected to BLASTX search against the GenBank sequence database as of January 2019. Viruses commonly found in stone fruits, i.e., apple stem pitting virus, apple green crinkle-associated virus, apricot latent virus (foveaviruses), and apple stem grooving virus (a capillovirus), were detected. In addition, five contigs with amino acid sequence homologies to P1-P4 of known emaraviruses and the P7 of High Plains wheat mosaic virus (Tatineni et al. 2014) were detected and designated as PEV-Jp. The complete nucleotide (nt) sequences of the five segments of PEV-Jp were determined by Sanger sequencing of cloned reverse transcription (RT)-PCR amplification products using the primers shown in Supplementary Table S1; the 5'- and 3'-terminal sequences were RACE verified (Takara Bio, Shiga, Japan). In pairwise comparisons, the complete RNA1 to RNA5 of PEV-Jp (LC554756-760) shared 90.7% to 98.7% nt identities with those of PCLSaV-CG1 (MK602177-181), indicating that PEV-Jp is an isolate of PCLSaV. Using newly designed segment-specific primers (Supplementary Table S1), 12 symptomatic Japanese pear trees cv. "Kosui" sampled in 2020 from the same nursery tested positive for PCLSaV by RT-PCR while 12 symptomless trees were negative for the virus. Similar chlorotic spots, sometimes accompany necrotic spots, were observed on European pear ( Pyrus communis ) cv. "Le Lectier." (Fig. S1F) in Niigata in 2019; PCLSaV was detected by RT-PCR in leaf tissue samples from symptomatic trees (n = 3/3) but not in symptomless trees (n = 0/2). No vector for PCLSaV has been identified (Liu et al. 2020) but acaricide sprays in the early spring are effective for preventing occurrence of chlorotic spots in pear orchards (Nakai et al. 2018). Since the infestations of Eriophyes chibaensis Kadono, an eriophyid mite often observed on the Japanese pear (Fig. S1G to S1I) (Kadono, 1981), has been associated with occurrences of the chlorotic spots (Shimizu et al. 2019), samples of E. chibaensis individuals were collected from PCLSaV-positive Japanese pear cvs. "Akizuki" and "Kosui"and P. communis cv. "Le Lectier." for total nucleic acid isolations via phenol-chloroform extraction, followed by quantitative RT-PCR (Supplementary Table S1). The expected RNA1 and RNA5 specific 150 bp products were detected from mite samples collected from Akizuki (n = 6/12), Kosui (n = 13/18), and Le Lectier (n = 6/8). The results indicate that E. chibaensis can ingest PCLSaV and may be a potential vector for the virus, although additional experiments are needed to demonstrate its vector competency. To our knowledge, this is the first report of PCLSaV in Japan and the first report of its detection in E. chibaensis .

Early B cell development is regulated by stage-specific transcription factors. PU.1, an ETS-family transcription factor, is essential for coordination of early B cell maturation and immunoglobulin gene (Ig) rearrangement. Here we show that RAG DNA double-strand breaks (DSBs) generated during Ig light chain gene (Igl) rearrangement in pre-B cells induce global changes in PU.1 chromatin binding. RAG DSBs activate a SPIC/BCLAF1 transcription factor complex that displaces PU.1 throughout the genome and regulates broad transcriptional changes. SPIC recruits BCLAF1 to gene-regulatory elements that control expression of key B cell developmental genes. The SPIC/BCLAF1 complex suppresses expression of the SYK tyrosine kinase and enforces the transition from large to small pre-B cells. These studies reveal that RAG DSBs direct genome-wide changes in ETS transcription factor activity to promote early B cell development., (Copyright © 2019 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: The pathogenesis of delayed gastric emptying (DGE), a common complication of pancreaticoduodenectomy, is unclear. Loss of skeletal muscle mass (sarcopenia) is associated with post-pancreaticoduodenectomy complications; however, few studies have investigated the relationship between sarcopenia and DGE. The aim of this study was to investigate whether post-pancreaticoduodenectomy DGE is affected by pre-operative skeletal muscle mass., Methods: We retrospectively analysed the data of 112 consecutive patients who had undergone pancreaticoduodenectomy and divided them into the following two groups: no DGE (n = 100) and with DGE (n = 12). Patients were stratified by quartiles according to each element of body composition. The lowest quartile for skeletal muscle mass was defined as having sarcopenia., Results: Ten and two patients had grades B and C DGE, respectively. According to univariate analysis, body mass index (P = 0.031), clinically relevant post-operative pancreatic fistula (P < 0.001) and skeletal muscle mass (P = 0.002) were significantly associated with DGE. According to multivariate analysis, high body mass index (≥25 kg/cm 2 ) (P = 0.005), post-operative pancreatic fistula (P = 0.027) and low skeletal muscle mass (P = 0.004) were independently associated with DGE., Conclusion: Sarcopenia is an independent predictor of DGE after pancreaticoduodenectomy., (© 2019 Royal Australasian College of Surgeons.)

Natural killer (NK) cells are a major FcγRIIIA-expressing lymphocyte population that mediate antibody-dependent cellular cytotoxicity. Although NK cells are critical for immunity against viruses and tumors, they are also activated in the joints of patients with rheumatoid arthritis (RA) and may be involved in disease progression. We previously found that human leukocyte antigen (HLA) class II molecules transport misfolded cellular proteins, such as IgG heavy chain (IgGH), to the cell surface via association with their peptide-binding grooves. Furthermore, we found that IgGHs bound to HLA class II molecules encoded by RA susceptibility alleles are specific targets for rheumatoid factor, an auto-antibody involved in RA. Here, we report that IgGHs bound to HLA class II molecules preferentially stimulate FcγRIIIA-expressing but not FcγRI-expressing cells. A significant correlation was observed between the reactivity of FcγRIIIA-expressing cells to IgGH complexed with a specific HLA-DR allele and the odds ratio for HLA-DR allele's association with RA. Moreover, primary human NK cells expressing FcγRIIIA demonstrated IFN-γ production and cytotoxicity against cells expressing IgGH complexed with HLA class II molecules. Our findings suggest that IgGH complexed with HLA class II molecules are involved in the activation of FcγRIIIA-expressing NK cells observed within arthritic joints., (© The Japanese Society for Immunology. 2019. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

HLA class I molecules play a central role in the immune system by presenting peptide antigens to cytotoxic T cells. Although most HLA class I molecules are associated with β2-microglobulin, HLA class I heavy chain that is not associated with β2-microglobulin is also expressed on certain cells. We recently found that cellular misfolded proteins are transported to the cell surface by HLA class II molecules via association with their peptide-binding grooves. Furthermore, misfolded self-antigens bound to autoimmune disease-susceptible HLA class II molecules are the targets for autoantibodies produced in certain autoimmune diseases. In the present study, we found that misfolded proteins were also transported to the cell surface by specific HLA class I molecules including HLA-B27, which is strongly associated with ankylosing spondylitis. In addition, the efficiency with which HLA class I molecules encoded by each allele transport misfolded proteins to the cell surface was significantly correlated with HLA class I free heavy chain expression on that surface. Moreover, misfolded proteins were coprecipitated with HLA class I free heavy chain but not with correctly folded HLA class I molecules. These findings reveal a novel function of HLA class I molecules to transport misfolded proteins to the cell surface, which might help us to understand the pathogenesis of HLA class I-associated diseases., (Copyright © 2019 Elsevier Inc. All rights reserved.)