The Co-Transplantation of Bone Marrow Derived Mesenchymal Stem Cells Reduced Inflammation in Intramuscular Islet Transplantation

Aims/HypothesisAlthough the muscle is one of the preferable transplant sites in islet transplantation, its transplant efficacy is poor. Here we attempted to determine whether an intramuscular co-transplantation of mesenchymal stem cells (MSCs) could improve the outcome.MethodsWe co-cultured murine islets with MSCs and then analyzed the morphological changes, viability, insulin-releasing function (represented by the stimulation index), and gene expression of the islets. We also transplanted 500 islets intramuscularly with or without 5 × 10⁵ MSCs to diabetic mice and measured their blood glucose level, the glucose changes in an intraperitoneal glucose tolerance test, and the plasma IL-6 level. Inflammation, apoptosis, and neovascularization in the transplantation site were evaluated histologically.ResultsThe destruction of islets tended to be prevented by co-culture with MSCs. The stimulation index was significantly higher in islets co-cultured with MSCs (1.78 ± 0.59 vs. 7.08 ± 2.53; p = 0.0025). In terms of gene expression, Sult1c2, Gstm1, and Rab37 were significantly upregulated in islets co-cultured with MSCs. Although MSCs were effective in the in vitro assays, they were only partially effective in facilitating intramuscular islet transplantation. Co-transplanted MSCs prevented an early inflammatory reaction from the islets (plasma IL-6; p = 0.0002, neutrophil infiltration; p = 0.016 inflammatory area; p = 0.021), but could not promote neovascularization in the muscle, resulting in the failure of many intramuscular transplanted islets to engraft.ConclusionsIn conclusion, co-culturing and co-transplanting MSCs is potentially useful in islet transplantation, especially in terms of anti-inflammation, but further augmentation for an anti-apoptosis effect and neovascularization is necessary.     

Interactome analysis of herpes simplex virus 1 envelope glycoprotein H

Herpes simplex virus 1 (HSV‐1) envelope glycoprotein H (gH) is important for viral entry into cells and nuclear egress of nucleocapsids. To clarify additional novel roles of gH during HSV‐1 replication, host cell proteins that interact with gH were screened for by tandem affinity purification coupled with mass spectrometry‐based proteomics in 293T cells transiently expressing gH. This screen identified 123 host cell proteins as potential gH interactors. Of these proteins, general control nonderepressive‐1 (GCN1), a trans‐acting positive effector of GCN2 kinase that regulates phosphorylation of the α subunit of translation initiation factor 2 (eIF2α), was subsequently confirmed to interact with gH in HSV‐1‐infected cells. eIF2α phosphorylation is known to downregulate protein synthesis, and various viruses have evolved mechanisms to prevent the accumulation of phosphorylated eIF2α in infected cells. Here, it was shown that GCN1 knockdown reduces phosphorylation of eIF2α in HSV‐1‐infected cells and that the gH‐null mutation increases eIF2α in HSV‐1‐infected cells, whereas gH overexpression in the absence of other HSV‐1 proteins reduces eIF2α phosphorylation. These findings suggest that GCN1 can regulate eIF2α phosphorylation in HSV‐1‐infected cells and that the GCN1‐binding viral partner gH is necessary and sufficient to prevent the accumulation of phosphorylated eIF2α. Our database of 123 host cell proteins potentially interacting with gH will be useful for future studies aimed at unveiling further novel functions of gH and the roles of cellular proteins in HSV‐1‐infected cells.     

Compound heterozygote for lipoprotein lipase deficiency: Ser----Thr244 and transition in 3'' splice site of intron 2 (AG----AA) in the lipoprotein lipase gene.

Cloning and sequencing of translated exons and intron-exon boundaries of the lipoprotein lipase gene in a patient of French descent who has the chylomicronemia syndrome revealed that he was a compound heterozygote for two nucleotide substitutions. One (TCC----ACC) leads to an amino acid substitution (Ser----Thr244), while the other alters the 3' splice site of intron 2 (AG----AA). The functional significance of the Thr244 amino acid substitution was established by in vitro expression in cultured mammalian cells.     

Digging and eating of underground plant-parts by wild Japanese monkeys (Macaca fuscata)

It has been reported that Japanese monkeys pull out and eat underground parts of plants, but they do so only a little and occasionally. The authors observed that wild Japanese monkeys in the mountains area near Hinohara Village ate underground plant-parts as one of the main components of their diet and they spent a lot of time digging for them. From information obtained from local old people, it appears that they have exhibited this behavior for many years as part of their feeding repertoire.     

Synthesis and evaluation of novel antifungal agents-quinoline and pyridine amide derivatives

Quinoline amide, azaindole amide and pyridine amides were synthesized and tested for in vitro antifungal activity against fungi. These synthesized amides have potent antifungal activity against Candida albicans and Aspergillus fumigatus. Our results suggest that hetero ring amides may be potent antifungal agents that operate by inhibiting the function of Gwt1 protein in the GPI biosynthetic pathway.     

Occurrence patterns of crop‐foraging sika deer distribution in an agriculture–forest landscape revealed by nitrogen stable isotopes

Conflicts arising from the consumption of anthropogenic foods by wildlife are increasing worldwide. Conventional tools for evaluating the spatial distribution pattern of large terrestrial mammals that consume anthropogenic foods have various limitations, despite their importance in management to mitigate conflicts. In this study, we examined the spatial distribution pattern of crop‐foraging sika deer by performing nitrogen stable isotope analyses of bone collagen. We evaluated whether crop‐foraging deer lived closer to agricultural crop fields during the winter and spring, when crop production decreases. We found that female deer in proximity to agricultural crop fields during the winter and spring were more likely to be crop‐foraging individuals. Furthermore, the likelihood of crop consumption by females decreased by half as the distance to agricultural crop fields increased to 5–10 km. We did not detect a significant trend in the spatial distribution of crop‐foraging male deer. The findings of spatial distribution patterns of crop‐foraging female deer will be useful for the establishment of management areas, such as zonation, for efficient removal of them.     

Dose to contralateral breast from whole breast irradiation by automated tangential IMRT planning: comparison of flattening-filter and flattening-filter-free modes

BackgroundThe most common secondary cancer is contralateral breast (CLB) cancer after whole breast irradiation (WBI). The aim of this study was to quantify the reduction of CLB dose in tangential intensity modulated radiotherapy (t-IMRT) for WBI using flattening-filter-free (FFF) beams.Materials and methodsWe generated automated planning of 20 young breast cancer patients with limited user interaction. Dose-volume histograms of the planning target volume (PTV), ipsilateral lung, heart, and CLB were calculated. The dose of PTV, the most medial CLB point, and the CLB point below the nipple was measured using an ionization chamber inserted in a slab phantom. We compared the two t-IMRT plans generated by FFF beams and flattening-filter (FF) beams.ResultsAll plans were clinically acceptable. There was no difference in the conformal index, the homogeneity for FFF was significantly worse. For the ipsilateral lung, the maximum dose (D_max) was significantly higher; however, V₂₀ showed a tendency to be lower in the FFF plan. No differences were found in the D_max and V₃₀ to the heart of the left breast cancer. FF planning showed significantly lower D_max and mean dose to the CLB. In contrast to the calculation results, the measured dose of the most medial CLB point and the CLB point below the nipple were significantly lower in FFF mode than in FF mode, with mean reductions of 21.1% and 20%, respectively.ConclusionsT-IMRT planning using FFF reduced the measured out-of-field dose of the most medial CLB point and the CLB point below the nipple.     

nArgBP2, a novel neural member of ponsin/ArgBP2/vinexin family that interacts with synapse-associated protein 90/postsynaptic density-95-associated protein (SAPAP).

Postsynaptic density (PSD)-95/synapse-associated protein (SAP) 90 and synaptic scaffolding molecule (S-SCAM) are synaptic membrane-associated guanylate kinases. Both the proteins interact with SAP90/PSD-95-associated protein (SAPAP) (also called guanylate kinase-associated protein/Dlg-associated protein). SAPAP is a protein highly enriched in the PSD fraction and may link PSD-95/SAP90 and S-SCAM to Triton X-100-insoluble structures. We found here a novel SAPAP-interacting protein, which was specifically expressed in neural tissue and was present in the postsynaptic density fraction in brain. This protein had a sorbin homology domain in the N terminus, a zinc finger motif in the middle region, and three src homology (SH) 3 domains in the C terminus and was homologous to the ponsin/ArgBP2/vinexin family proteins. We named this protein nArgBP2 because it was the most homologous to ArgBP2. nArgBP2 is a neural member of a growing family of SH3-containing proteins. nArgBP2 bound to the proline-rich region of SAPAP via its third SH3 domain and was coimmunoprecipitated with SAPAP from the extract of rat brain. Furthermore, nArgBP2 was colocalized with SAPAP at synapses in cerebellum. nArgBP2 bound to not only SAPAP but also vinculin and l-afadin, known to bind to ponsin and vinexin. nArgBP2 may be implicated in the protein network around SAPAP in the PSD.     

Characterization of a Facultatively Psychrophilic Bacterium, Vibrio rumoiensis sp. nov., That Exhibits High Catalase Activity

A novel facultatively psychrophilic bacterium, strain S-1, which exhibits extraordinarily high catalase activity was isolated from the drain pool of a fish product processing plant that uses H₂O₂ as a bleaching and microbicidal agent. The catalase activity of the isolate was 1 or 2 orders of magnitude higher than those of Corynebacterium glutamicum, Staphylococcus aureus, Pseudomonas fluorescens, and five other species tested in this study. The strain seemed to possess only one kind of catalase, according to the results of polyacrylamide gel electrophoresis of the cell extract. The optimum temperature for catalase activity was about 30°C, which was about 20°C lower than that for bovine catalase activity. Electron microscopic observation revealed that the surface of the microorganism was covered by blebs. Although the isolate was nonflagellated, its taxonomic position on the basis of physiological and biochemical characteristics and analysis of 16S rRNA sequence and DNA-DNA relatedness data indicated that strain S-1 is a new species belonging to the genus Vibrio. Accordingly, we propose the name Vibrio rumoiensis. The type strain is S-1 (FERM P-14531).