Cathepsin G, a Neutrophil Protease, Induces Compact Cell-Cell Adhesion in MCF-7 Human Breast Cancer Cells

Cathepsin G is a serine protease secreted by activated neutrophils that play a role in the inflammatory response. Because neutrophils are known to be invading leukocytes in various tumors, their products may influence the characteristics of tumor cells such as the growth state, motility, and the adhesiveness between cells or the extracellular matrix. Here, we demonstrate that cathepsin G induces cell-cell adhesion of MCF-7 human breast cancer cells resulting from the contact inhibition of cell movement on fibronectin but not on type IV collagen. Cathepsin G subsequently induced cell condensation, a very compact cell colony, resulting due to the increased strength of E-cadherin-mediated cell-cell adhesion. Cathepsin G action is protease activity-dependent and was inhibited by the presence of serine protease inhibitors. Cathepsin G promotes E-cadherin/catenin complex formation and Rap1 activation in MCF-7 cells, which reportedly regulates E-cadherin-based cell-cell junctions. Cathepsin G also promotes E-cadherin/protein kinase D1 (PKD1) complex formation, and Go6976, the selective PKD1 inhibitor, suppressed the cathepsin G-induced cell condensation. Our findings provide the first evidence that cathepsin G regulates E-cadherin function, suggesting that cathepsin G has a novel modulatory role against tumor cell-cell adhesion

Product gas analysis of laminar premixed ammonia-methane flames in stagnation flows

Ammonia is a promising hydrogen energy vector and a carbon-free fuel; hence the use of ammonia-hydrocarbon fuel blends can be viewed as an intermediate step towards a hydrogen economy. The characterization of methane-ammonia emissions is essential for designing combustors for a broader range of fuels while fulfilling strict NOx emission requirements and global warming targets. The product gas trends of laminar premixed ammonia-methane flames at atmospheric pressure were studied for 0.1 to 0.6 ammonia heat ratios at the operable range of equivalence ratios. Gases including NO, N2O, NO2, HCN, CO and NH3 were measured using the dual dilution gas method and compared against numerical predictions. Experimental results showed the highest NO emissions at approximately 8,000 ppm for the 0.3 and 0.4 ammonia heat ratios, reducing twofold at the extreme heat ratio conditions. The optimal condition for reducing NOx emissions while maintaining low unburnt NH3 was found to occur at a 1.20 equivalence ratio for higher ammonia ratios, moving incrementally closer towards 1.35 as the methane ratio was increased. These results can aid a further reaction model analysis due to the availability of stain stabilised stagnation flame models in numerical software

HSP60 possesses a GTPase activity and mediates protein folding with HSP10

The mammalian molecular chaperone, HSP60, plays an essential role in protein homeostasis through mediating protein folding and assembly. The structure and ATP-dependent function of HSP60 has been well established in recent studies. After ATP, GTP is the major cellular nucleotide. In this paper, we have investigated the role of GTP in the activity of HSP60. It was found that HSP60 has different properties with respect to allostery, complex formation and protein folding activity depending on the nucleoside triphosphate present. The presence of GTP slightly affected the ATPase activity of HSP60 during protein folding. These results provide clues as to the functional mechanism of the HSP60-HSP10 complex

Functional Fv fragment of an antibody specific for CD28: Fv-mediated co-stimulation of T cells

AbstractThe most predominant co-stimulation pathway, which is critical for T cell activation and proliferation, is the CD28-B7 pathway. The anti-CD28 monoclonal antibody (mAb) also provides a co-stimulatory signal to T cells. In order to construct a functional Fv fragment (complex of VH and VL domains) of anti-CD28 antibody using a bacterial expression system, cDNA encoding the variable regions of immunoglobulin from 15E8 hybridoma cells was cloned and expressed in Escherichia coli. The Fv fragment was obtained as a soluble protein from the periplasmic fraction and showed a binding pattern similar to parental IgG. The Fv fragment induced proliferation of peripheral blood mononuclear cells in the presence of anti-CD3 or anti-CD2 mAb and enhanced anti-tumor activity of anti-MUC1×anti-CD3 bispecific antibody when tested with lymphokine-activated killer cells with T cell phenotype. Thus, the anti-CD28 Fv fragment will be promising not only for the study of co-stimulation, but also for cancer immunotherapy

Numerical and experimental study of product gas characteristics in premixed ammonia/methane/air laminar flames stabilised in a stagnation flow

The adoption of ammonia/hydrocarbon fuel blends can be viewed as an intermediate step towards a hydrogen economy, hence the characterization of methane/ammonia flame product gas trends is essential for designing combustors for a broader range of low-carbon fuel blends while fulfilling strict NOx requirements. This paper describes the product gas content of laminar premixed ammonia/methane flames for a range of equivalence ratios and ammonia heat ratios ranging from 10% to 60%, using a strain stabilized burner at atmospheric pressure and room temperature. The optimal condition to reduce NOx emissions while maintaining below 100 ppm of unburnt NH3 emissions was found to be at equivalence ratio of 1.20 for higher ammonia ratios, moving incrementally closer over 1.35 as the methane fuel content was increased. Meanwhile, the highest measured NO values were ∼6,950 ppm at an equivalence ratio of 0.9, peaking at heat ratios of 30% to 40% at this equivalence ratio. Detailed reaction mechanisms were evaluated against the experimental data and rate constants of NO production/consumption steps featuring both NH and HNO intermediates and thermal NOx reactions were updated for Okafor's mechanism. Changes in reaction rate constants improved the mechanism accuracy for NO emissions in lean to stoichiometric flames. Meanwhile, in the rich region, modelled NO values were less responsive to changes in reaction constants, suggesting the need for an alternative approach to improve NO predictions for rich, high methane content flames. However, N2O performance in the rich region could be improved, highlighting the significance of the HNO+CONH+CO2 reaction

Restraint-Induced Expression of Endoplasmic Reticulum Stress-Related Genes in the Mouse Brain

ABSTRACT Depression is a significant public health concern but its pathology remains unclear. Previously, increases in an end

Salivary Biomarkers May Be Useful to Assess Stress State in Patients with Lung Cancer Undergoing Chemotherapy

ABSTRAC

Study on N2O production mechanisms of lean ammonia/hydrogen/air premixed laminar flames

Application of ammonia as fuel is a potential candidate to achieve carbon neutrality. As laminar burning velocity of ammonia is slow, hydrogen addition is also considered to improve combustion characteristics with no carbon emission. In this study, we experimentally investigated product gas characteristics of strain stabilized ammonia/hydrogen/air premixed laminar flames under atmospheric pressure for various equivalence ratios. In a lean condition, large amount of N2O production was observed. To clarify N2O production mechanisms, numerical simulations were conducted using a reaction mechanism developed by Gotama et al. In the Gotama reaction mechanism, major N2O production path was NH+NO=N2O+H and major N2O consumption paths were N2O+H=N2+OH and N2O(+M)=N2+O(+M). It was clarified that a decrease in N2O consumption via N2O(+M)=N2+O(+M) increases N2O emission for lean and strained conditions

Hypergastrinemia and a duodenal ulcer caused by gastric duplication

BackgroundHypergastrinemia and the resultant peptic ulcer related to an enteric duplication has been quite rarely reported in the literature.Case presentationWe herein report the case of a 4-year-old girl who presented with hypergastrinemia and a duodenal ulcer at 2 years of age. She had been followed up with a proton pump inhibitor, which resulted in resolution of the ulcer; however, unexplained hypergastrinemia had continued. A cystic lesion at the antrum was discovered at 4 years of age, which we suspected to be a gastric duplication. After we resected the lesion, the hypergastrinemia resolved without recurrence of the duodenal ulcer. The histology was compatible with a gastric duplication, and the lumen was lined with antral mucosa that strongly stained positive for gastrin. We presumed that the antral mucosa inside the duplication in our case had no hydrogen ion feedback inhibition of gastrin release from gastrin cells and increased release of gastrin from the mucosa inside the duplication led to the duodenal ulcer. Only two cases have been reported in the literature that had hypergastrinemia related to enteric duplication.ConclusionGastric duplication should be included in the differential diagnosis of sustained hypergastrinemia in children