Extracellular cyclophilin A possesses chemotaxic activity in cattle

International audienceCyclophilin A (CyPA) was originally discovered in bovine thymocytes as a cytosolic binding protein of the immunosuppressive drug cyclosporine A. Recent studies have revealed that in mice and humans, CyPA is secreted from cells in injured or infected tissues and plays a role in recruiting inflammatory cells in those tissues. Here we found that in cattle abundant level of extracellular CyPA was observed in tissues with inflammation. To aid in investigating the role of extracellular CyPA in cattle, we generated recombinant bovine CyPA (rbCyPA) and tested its biological activity as an inflammatory mediator. When bovine peripheral blood cells were treated with rbCyPA in vitro, we observed that rbCyPA reacts with the membranous surface of granulocytes, monocytes and lymphocytes. Chemotaxis analysis showed that the granulocytes migrate toward rbCyPA and the migration is inhibited by pre-treatment with an anti-bovine CyPA antibody. These results indicate that, as for mice and humans, extracellular CyPA possesses chemotactic activity to recruit inflammatory cells (e.g., granulocytes) in cattle, and could thus be a potential therapeutic target for the treatment of inflammation

ZAK Inhibitor PLX4720 Promotes Extrusion of Transformed Cells via Cell Competition

Previous studies have revealed that, at the initial step of carcinogenesis, transformed cells are often eliminated from epithelia via cell competition with the surrounding normal cells. In this study, we performed cell competition-based high-throughput screening for chemical compounds using cultured epithelial cells and confocal microscopy. PLX4720 was identified as a hit compound that promoted apical extrusion of RasV12-transformed cells surrounded by normal epithelial cells. Knockdown/knockout of ZAK, a target of PLX4720, substantially enhanced the apical elimination of RasV12 cells in vitro and in vivo. ZAK negatively modulated the accumulation or activation of multiple cell competition regulators. Moreover, PLX4720 treatment promoted apical elimination of RasV12-transformed cells in vivo and suppressed the formation of potentially precancerous tumors. This is the first report demonstrating that a cell competition-promoting chemical drug facilitates apical elimination of transformed cells in vivo, providing a new dimension in cancer preventive medicine

ADAM-like Decysin-1 (ADAMDEC1) is a positive regulator of Epithelial Defense Against Cancer (EDAC) that promotes apical extrusion of RasV12-transformed cells

Recent studies have revealed that newly emerging transformed cells are often eliminated from epithelia via cell competition with the surrounding normal epithelial cells. However, it remains unknown whether and how soluble factors are involved in this cancer preventive phenomenon. By performing stable isotope labeling with amino acids in cell culture (SILAC)-based quantitative mass spectrometric analyses, we have identified ADAM-like Decysin-1(ADAMDEC1) as a soluble protein whose expression is upregulated in the mix culture of normal and RasV12-transformed epithelial cells. Expression of ADAMDEC1 is elevated in normal epithelial cells co-cultured with RasV12 cells. Knockdown of ADAMDEC1 in the surrounding normal cells substantially suppresses apical extrusion of RasV12 cells, suggesting that ADAMDEC1 secreted by normal cells positively regulate the elimination of the neighboring transformed cells. In addition, we show that the metalloproteinase activity of ADAMDEC1 is dispensable for the regulation of apical extrusion. Furthermore, ADAMDEC1 facilitates the accumulation of filamin, a crucial regulator of Epithelial Defense Against Cancer (EDAC), in normal cells at the interface with RasV12 cells. This is the first report demonstrating that an epithelial intrinsic soluble factor is involved in cell competition in mammals

A statistical modeling approach based on the small-scale field trial and meteorological data for preliminary prediction of the impact of low temperature on Eucalyptus globulus trees

Abstract Eucalyptus trees are important for industrial forestry plantations because of their high potential for biomass production, but their susceptibility to damage at low temperatures restricts their plantation areas. In this study, a 6-year field trial of Eucalyptus globulus was conducted in Tsukuba, Japan, which is the northernmost reach of Eucalyptus plantations, and leaf damage was quantitatively monitored over four of six winters. Leaf photosynthetic quantum yield (QY) levels, an indicator of cold stress-induced damage, fluctuated synchronously with temperature in the winters. We performed a maximum likelihood estimation of the regression model explaining leaf QY using training data subsets for the first 3 years. The resulting model explained QY by the number of days when the daily maximum temperature was below 9.5 °C over approximately the last 7 weeks as an explanatory variable. The correlation coefficient and coefficient of determination of prediction by the model between the predicted and observed values were 0.84 and 0.70, respectively. The model was then used to perform two kinds of simulations. Geographical simulations of potential Eucalyptus plantation areas using global meteorological data from more than 5,000 locations around the world successfully predicted an area that generally agreed with the global Eucalyptus plantation distribution reported previously. Another simulation based on meteorological data of the past 70 years suggested that global warming will increase the potential E. globulus plantation area in Japan approximately 1.5-fold over the next 70 years. These results suggest that the model developed herein would be applicable to preliminary predictions of E. globulus cold damage in the field

Granulomatous Mastitis Occurring during Pregnancy: A Case Report

Background and Objectives: Granulomatous mastitis is a benign disease with a clinical presentation similar to that of breast cancer, and is most commonly observed in women of childbearing age. Although it has been suggested that autoimmune diseases are involved in its pathogenesis, no specific treatments have been established. The occurrence of this disease during pregnancy has rarely been reported. We presented the case of a 37-year-old woman who complained of left breast induration at 24 weeks’ gestation. Materials and Methods: She was pregnant and manifested a dichorionic, diamniotic placenta. At 24 weeks of gestation, the patient experienced a sensation of hardness in her left breast. Mastitis was suspected, and she was treated with cephem antibiotics. Simultaneously, she was diagnosed with erythema nodosum in the extremities. As her symptoms did not improve, an incisional drainage was performed. Bacterial cultures were obtained at 31 weeks of gestation, and Corynebacterium kroppenstedtii was detected. Results: An elective cesarean section was performed at 37 weeks of gestation, and the baby was delivered safely. After delivery, a needle biopsy was performed, and the patient was diagnosed with granulomatous mastitis. She was completely cured with prednisolone after weaning. In this case, the patient’s condition was maintained through incision and drainage, as well as antibiotic, anti-inflammatory, and analgesic drugs during pregnancy. This approach was chosen, taking into consideration the potential side effects of steroids. Conclusions: This case suggests that incisional drainage and antibiotic therapy, as well as steroids and surgery, may be considered in the treatment of granulomatous mastitis occurring during pregnancy. This may also be true for management during delivery. After delivery, breastfeeding and steroidal therapy proved to be effective in treating the condition