Interferon-free Anti-hepatitis C Virus Treatment for Long-term Liver Transplantation Recipients with Failed Interferon Therapy

Article信州医学雑誌 67(6): 417-423(2019)journal articl

Apoptosis in the repair process of experimental proliferative glomerulonephritis

Apoptosis in the repair process of experimental proliferative glomerulonephritis. The recovery from the proliferative glomerulonephritis (GN) with reduction of hypercellularity is known in various experimental and human GN. To elucidate the participation of apoptosis in GN, we studied the experimental Thy-1.1 GN for six weeks. Apoptosis was recognized by both light and electron microscopy, and the biochemical expression of apoptosis was morphologically confirmed by in situ end-labeling method of fragmented DNA, using terminal deoxy-transferase. Mesangioproliferative GN was induced by a single administration of anti-Thy-1.1 monoclonal antibody in a rat. Mesangial cell proliferation started early in the process and the number of glomerular cells peaked from day 7 to day 10. Subsequently, the degree of proliferative lesion diminished with obvious reconstruction of the capillary structure, as well as decrease in the number of glomerular cells. During this period, proliferated mesangial cells returned to their original level of cellularity and apoptosis apparently increased in number among the glomeruli. Apoptosis was significantly noted from day 7 to week 4 and was in its maximum at day 10 to week 2. Following this period, by week 6 most of the glomeruli reverted to their original structure. The number of infiltrated neutrophils and macrophages in the glomeruli slowly decreased during the course of the disease, and a few apoptosis were also observed. It is concluded that proliferated glomerular cells regress by apoptosis in the repairing process of GN. Apoptosis plays an essential role in the recovery to the original glomerular structure in GN

A virtual myoelectric prosthesis training system capable of providing instructions on hand operations

This article proposes a virtual hand and a virtual training system for controlling the MyoBock—the most commonly used myoelectric prosthetic hand worldwide. As the virtual hand is controlled using the method also adopted for the MyoBock hand, the proposed system provides upper-limb amputees with operation sensibilities similar to those experienced in MyoBock control. It can also display an additional virtual hand for the provision of instructions on hand operation, such as the recommended posture for object grasping and the trajectory desirable to reach a target. In virtual hand control experiments conducted with an amputee to evaluate the proposed virtual hand’s operability, the subject successfully performed stable opening and closing with high discrimination rates (89.3±6.65%), thanks to the virtual hand’s incorporation of the MyoBock’s operational characteristics. A training experiment using the proposed system was also conducted with eight healthy participants over a period of 5 days. The participants were asked to perform the box and block test using the MyoBock hand in a real environment on the first and final days. The results showed that the number of blocks transported in 1 min significantly increased and that the participants using the instruction virtual hand changed the orientation of the hand approaching blocks from vertical to lateral. The outcomes of the experiment indicate that the proposed system can be used to improve MyoBock hand control operation both quantitatively and qualitatively.This work was partially supported by a Grant-in-Aid for Young Scientists B Number 26730111 and a Grant-in-Aid for Scientific Research C Number 26462242

Long-tail Behavior in Locomotion of Caenorhabditis elegans

The locomotion of Caenorhabditis elegans exhibits complex patterns. In particular, the worm combines mildly curved runs and sharp turns to steer its course. Both runs and sharp turns of various types are important components of taxis behavior. The statistics of sharp turns have been intensively studied. However, there have been few studies on runs, except for those on klinotaxis (also called weathervane mechanism), in which the worm gradually curves toward the direction with a high concentration of chemicals; this phenomenon was discovered recently. We analyzed the data of runs by excluding sharp turns. We show that the curving rate obeys long-tail distributions, which implies that large curving rates are relatively frequent. This result holds true for locomotion in environments both with and without a gradient of NaCl concentration; it is independent of klinotaxis. We propose a phenomenological computational model on the basis of a random walk with multiplicative noise. The assumption of multiplicative noise posits that the fluctuation of the force is proportional to the force exerted. The model reproduces the long-tail property present in the experimental data.Comment: 30 pages, 11 figures, some errors were correcte

Epithelial EP4 plays an essential role in maintaining homeostasis in colon

Colonic epithelial cells comprise the mucosal barrier, and their dysfunction promotes microbial invasion from the gut lumen and induces the development of intestinal inflammation. The EP4 receptor is known to mediate the protective effect of prostaglandin (PG) E2 in the gastrointestinal tract; however, the exact role of epithelial EP4 in intestinal pathophysiology remains unknown. In the present study, we aimed to investigate the role of epithelial EP4 in maintaining colonic homeostasis by characterizing the intestinal epithelial cell-specific EP4 knockout (EP4 cKO) mice. Mice harboring the epithelial EP4 deletion showed significantly lower colonic crypt depth and lower numbers of secretory cell lineages, as well as impaired epithelial cells in the colon. Interestingly, EP4-deficient colon epithelia showed a higher number of apoptotic cells. Consistent with the defect in mucosal barrier function of colonic epithelia and secretory cell lineages, EP4 cKO colon stroma showed enhanced immune cell infiltration, which was accompanied by increased production of inflammatory cytokines. Furthermore, EP4-deficient colons were susceptible to dextran sulfate sodium (DSS)-induced colitis. Our study is the first to demonstrate that epithelial EP4 loss resulted in potential "inflammatory" status under physiological conditions. These findings provided insights into the crucial role of epithelial PGE2/EP4 axis in maintaining intestinal homeostasis

Total Synthesis and Structural Revision of Cyclotetrapeptide Asperterrestide A

The structural revision of cyclotetrapeptide asperterrestide A has been achieved based on total synthesis and molecular modeling. For these studies, (2R,3S)-MePhe­(3-OH) and (2S,3S)-MePhe­(3-OH) suitably protected for peptide synthesis were prepared via a stereoselective reduction of a ketone precursor derived from L- or d-serine, using L-selectride or DIBAL-H. The synthesis of the proposed structure of asperterrestide A (1a) was accomplished by solution-phase synthesis of a linear precursor followed by macrolactamization. The NMR spectra of our synthetic 1a were not identical to those reported for the natural compound. Molecular modeling studies suggested that the correct structure 1b was the one in which the stereochemistry at the α-positions of the Ala and MePhe­(3-OH) residues is the opposite to that of the proposed structure. This was confirmed by the total synthesis of 1b and its subsequent structural characterization

Tomato root-associated Sphingobium harbors genes for catabolizing toxic steroidal glycoalkaloids

トマト根に定着する細菌からトマトの毒を分解する酵素を発見 --土壌微生物が植物の分泌する有害成分を解毒するメカニズムの理解に貢献--. 京都大学プレスリリース. 2023-10-02.Roots of Bloody Mary. Tomato root-associated Sphingobium harbors genes for neutralizing toxic compound. 京都大学プレスリリース. 2023-10-06.Plant roots exude various organic compounds, including plant specialized metabolites (PSMs), into the rhizosphere. The secreted PSMs enrich specific microbial taxa to shape the rhizosphere microbiome, which is crucial for the healthy growth of the host plants. PSMs often exhibit biological activities; in turn, some microorganisms possess the capability to either resist or detoxify them. Saponins are structurally diverse triterpene-type PSMs that are mainly produced by angiosperms. They are generally considered as plant defense compounds. We have revealed that α-tomatine, a steroid-type saponin secreted from tomato (Solanum lycopersicum) roots, increases the abundance of Sphingobium bacteria. To elucidate the mechanisms underlying the α-tomatine-mediated enrichment of Sphingobium, we isolated Sphingobium spp. from tomato roots and characterized their saponin-catabolizing abilities. We obtained the whole-genome sequence of Sphingobium sp. RC1, which degrades steroid-type saponins but not oleanane-type ones, and performed a gene cluster analysis together with a transcriptome analysis of α-tomatine degradation. The in vitro characterization of candidate genes identified six enzymes that hydrolyzed the different sugar moieties of steroid-type saponins at different positions. In addition, the enzymes involved in the early steps of the degradation of sapogenins (i.e., aglycones of saponins) were identified, suggesting that orthologs of the known bacterial steroid catabolic enzymes can metabolize sapogenins. Furthermore, a comparative genomic analysis revealed that the saponin-degrading enzymes were present exclusively in certain strains of Sphingobium spp., most of which were isolated from tomato roots or α-tomatine-treated soil. Taken together, these results suggest a catabolic pathway for highly bioactive steroid-type saponins in the rhizosphere

Tobacco Root Endophytic Arthrobacter Harbors Genomic Features Enabling the Catabolism of Host-Specific Plant Specialized Metabolites

Plant roots constitute the primary interface between plants and soilborne microorganisms and harbor microbial communities called the root microbiota. Recent studies have demonstrated a significant contribution of plant specialized metabolites (PSMs) to the assembly of root microbiota. However, the mechanistic and evolutionary details underlying the PSM-mediated microbiota assembly and its contribution to host specificity remain elusive. Here, we show that the bacterial genus Arthrobacter is predominant specifically in the tobacco endosphere and that its enrichment in the tobacco endosphere is partially mediated by a combination of two unrelated classes of tobacco-specific PSMs, santhopine and nicotine. We isolated and sequenced Arthrobacter strains from tobacco roots as well as soils treated with these PSMs and identified genomic features, including but not limited to genes for santhopine and nicotine catabolism, that are associated with the ability to colonize tobacco roots. Phylogenomic and comparative analyses suggest that these genes were gained in multiple independent acquisition events, each of which was possibly triggered by adaptation to particular soil environments. Taken together, our findings illustrate a cooperative role of a combination of PSMs in mediating plant species-specific root bacterial microbiota assembly and suggest that the observed interaction between tobacco and Arthrobacter may be a consequence of an ecological fitting process

ホウレンソウ雌性間性株における突然変異誘発ならびに低シュウ酸個体の選抜

This study was conducted to evalute mutagenesis in gynomonoecious spinach (Spinacia oleracea L.) plants for inducing low oxalate variants.Gamma-ray and ion beams of 220 MeV12C5+ and 50MeV 4He2+ ware used as mutagen in seed irradiation. Optimum dosages for irradiation were determined to be about 100Gy, 15-20Gy and 150-200Gy in gamma-ray, 12C5+ and 4He2+, respectively. In M2 generation, there was one line segregating albino seedlings, one line segregating xantha seedlings and two lines segregating dioesious spinach. To save on labor and time for analysis, selection of low oxalate variants in M2generation was conducted by a two-step selebtion which consisted of the first snalysis of bulked leaves from 2 plants as one specimen followed by the second analysis of selected individual plants. In the first analysis of 813 specimens, we selected 13 specimens as low and 9 specimens as high in oxalate content. In the second analysus, there was consistency in the distribution of low and high oxalate content corresponding to the first screening, indicating that selebtion of low oxalate variants could be achived by this two-step selebtion with half the labor and time for analysis as compares to non-bulked method. There were no clear differences in distribution of oxalate content between M3progenies of plants selected as low or high oxalate content, suggesting that the low oxalate content in plants isolated in M2generation was not of a genetic origin. From these results, it seems to be necessary to explore a variant with obvious deviation from the bontinuous variation of oxalate content in the M 2 generation.本実験では，ホウレンソウ雌性間性株における突然変異誘発ならびに低シュウ酸個体の選抜を試みた．種子照射の変異原としては，γ線と220MeV 12