Salicylaldehyde Suppresses IgE-Mediated Activation of Mast Cells and Ameliorates Anaphylaxis in Mice

Mast cells (MCs) play key roles in IgE-mediated immunoresponses, including in the protection against parasitic infections and the onset and/or symptoms of allergic diseases. IgE-mediated activation induces MCs to release mediators, including histamine and leukotriene, as an early response, and to produce cytokines as a late phase response. Attempts have been made to identify novel antiallergic compounds from natural materials such as Chinese medicines and food ingredients. We herein screened approximately 60 compounds and identified salicylaldehyde, an aromatic aldehyde isolated from plant essential oils, as an inhibitor of the IgE-mediated activation of MCs. A degranulation assay, flow cytometric analyses, and enzyme-linked immunosorbent assays revealed that salicylaldehyde inhibited the IgE-mediated degranulation and cytokine expression of bone-marrow-derived MCs (BMMCs). The salicylaldehyde treatment reduced the surface expression level of FcεRI, the high affinity receptor for IgE, on BMMCs, and suppressed the IgE-induced phosphorylation of tyrosine residues in intercellular proteins, possibly Lyn, Syk, and Fyn, in BMMCs. We also examined the effects of salicylaldehyde in vivo using passive anaphylaxis mouse models and found that salicylaldehyde administration significantly enhanced the recovery of a reduced body temperature due to systemic anaphylaxis and markedly suppressed ear swelling, footpad swelling, and vascular permeability in cutaneous anaphylaxis.     

SIG-1451, a Novel,Non-Steroidal Anti-Inflammatory Compound,Attenuates Light-Induced Photoreceptor Degeneration by Affecting the Inflammatory Process

Age-related macular degeneration is a progressive retinal disease that is associated with factors such as oxidative stress and inflammation. In this study, we evaluated the protective effects of SIG-1451, a non-steroidal anti-inflammatory compound developed for treating atopic dermatitis and known to inhibit Toll-like receptor 4, in light-induced photoreceptor degeneration. SIG-1451 was intraperitoneally injected into rats once per day before exposure to 1000 lx light for 24 h; one day later, optical coherence tomography showed a decrease in retinal thickness, and electroretinogram (ERG) amplitude was also found to have decreased 3 d after light exposure. Moreover, SIG-1451 partially protected against this decrease in retinal thickness and increase in ERG amplitude. One day after light exposure, upregulation of inflammatory response-related genes was observed, and SIG-1451 was found to inhibit this upregulation. Iba-1, a microglial marker, was suppressed in SIG-1451-injected rats. To investigate the molecular mechanism underlying these effects, we used lipopolysaccharide (LPS)-stimulated rat immortalised Müller cells. The upregulation of C-C motif chemokine 2 by LPS stimulation was significantly inhibited by SIG-1451 treatment, and Western blot analysis revealed a decrease in phosphorylated I-κB levels. These results indicate that SIG-1451 indirectly protects photoreceptor cells by attenuating light damage progression, by affecting the inflammatory responses.     

Characterization of economic requirements for a "carbon-debt-free country"

In recent years, greenhouse gas emission controls that incorporate the supply chains of products and services, thereby emphasizing the role of consumers rather than producers, have been drawing increasing attention. A country's consumption-based emissions, including those due to global supply chains, reflect the total emissions on which the national economy relies. To design effective emissions control strategies there is therefore an urgent need for countries to elucidate the structural relationship between their domestic economy and emissions occurring through global supply chains. Here we consider the structural characteristics of consumption-based emissions in Japan, which in 2005 totaled 1675 Mt CO(2)eq. Outside the country the Japanese economy generated global emissions of 541 Mt CO(2)eq, 35.7% of which were UNFCCC Annex I emissions and 64.3% were non-Annex I and other emissions. This figure of 64.3% reveals that Japan is actually relying to a considerable degree on emissions that are subject to no international obligations. We identify key economic contributors to consumption-based emissions at the commodity level and specify items of household expenditure that are effective options for both financial savings and emissions reduction. We then discuss the importance of emissions control for evolving toward a "carbon-debt-free country".     

Prophylactic effect of Lactobacillus oral vaccine expressing a Japanese cedar pollen allergen

Lactic acid bacteria (LAB) represent an attractive delivery vehicle for oral allergy vaccine because of their safety as a food microorganism as well as their potent adjuvant activity triggering anti-allergic immune response. Here, we report the generation of recombinant LAB expressing a major Japanese cedar pollen allergen Cry j 1 (Cry j 1-LAB), and their prophylactic effect in vivo. To facilitate heterologous expression, the codon usage in the Cry j 1 gene was optimized for the host LAB strain Lactobacillus plantarum by the recursive PCR-based exhaustive site-directed mutagenesis. Use of the codon-optimized Cry j 1 cDNA and a lactate dehydrogenase gene fusion system led to a successful production of recombinant Cry j 1 in L. plantarum NCL21. We also found that oral vaccination with the Cry j 1-LAB suppressed allergen-specific IgE response and nasal symptoms in a murine model of cedar pollinosis.     

A Modified Methodology to Evaluate Viscosity of Non-Newtonian Liquid Foods with a Flow Channel Instrument

Through experimental analysis of the liquid flows in a flow channel instrument, prompt evaluation of the physically defined viscosity of non-Newtonian liquid foods was investigated for development into a structurally simple and easy-to-use viscometer. For Newtonian and non-Newtonian test liquids, a relation between the friction coefficient and Reynolds number, which was dimensionless as derived from an expression of analysis as a gravity current, indicated a condition under which the flow in the instrument was laminar and under which an average shear rate was on the order of less than 1 s~. Prediction organized based on this empirical relation reproduced practically the flow curve determined for the liquid foods using a rotor type viscometer. Utilization of the channel instrument as a viscometer was formulated in terms of physical meanings of measurements such as the flow length and elapsed time.     

Scalar gradient behaviour in MILD combustion

The results of three-dimensional Direct Numerical Simulation (DNS) of Moderate, Intense Low-oxygen Dilution (MILD) and conventional premixed turbulent combustion conducted using a skeletal mechanism including the effects of non-unity Lewis numbers and temperature dependent transport properties are analysed to investigate combustion characteristics using scalar gradient information. The DNS data is also used to synthesise laser induced fluorescence (LIF) signals of OH, CH₂O, and CHO. These signals are analysed to verify if they can be used to study turbulent MILD combustion and it has been observed that at least two (OH and CH₂O) LIF signals are required since the OH increase across the reaction zone is smaller in MILD combustion compared to premixed combustion. The scalar gradient PDFs conditioned on the reaction rate obtained from the DNS data and synthesised LIF signals suggests a strong gradient in the direction normal to the MILD reaction zone with moderate reaction rate implying flamelet combustion. However, the PDF of the normal gradient is as broad as for the tangential gradient when the reaction rate is high. This suggests a non-flamelet behaviour, which is due to interaction of reaction zones. The analysis of the conditional PDFs for the premixed case confirms the expected behaviour of scalar gradient in flamelet combustion. It has been shown that the LIF signals synthesised using 2D slices of DNS data also provide very similar insights. These results demonstrate that the so-called flameless combustion is not an idealised homogeneous reactive mixture but has common features of conventional combustion while containing distinctive characteristics.     

Morphological and statistical features of reaction zones in MILD and premixed combustion

Direct numerical simulation (DNS) results of turbulent MILD premixed and conventional (undiluted) premixed combustion have been investigated to shed light on the physical aspects of reaction zones and their morphology in MILD combustion. Results of a premixed case are used for comparative analyses. The analyses show that the regions with strong chemical activity in MILD combustion are distributed over a substantial portion of the computational domain unlike in the premixed case where these regions are confined to a small portion of the domain. Also, interactions of reaction zones are observed in MILD combustion with their spatial extent increasing with dilution level. These interactions give an appearance of distributed combustion for MILD conditions. The morphology of these reaction zones is investigated using the Minkowski functionals and shapefinders commonly employed in cosmology. Predominant sheet-like structures are observed for the premixed combustion case whereas a pancake-like structure is observed as the most probable shape for the MILD cases. Spatial and statistical analyses of various fluxes involved in a progress variable transport equation are conducted to study autoignitive or propagative characteristics of MILD reaction zones. The results suggest that there are local regions with autoignition, propagating-flames, and their coexistence for the conditions considered in this study. Typically, reaction dominated or ignition front and propagating-flame dominated regions are entangled for high dilution cases. Scalar gradient plays a strong role on whether reaction or propagating-flame dominated activities are favoured locally.     

Construction of FLAG tagging vectors for Candida albicans

We have constructed three new vectors for Candida albicans (pFLAG-Act1, pFLAG-Mal2, and pFLAG-Met3). The proteins can be expressed as C-terminal FLAG-tagged proteins under the control of different promoters (ACT1, MAL2, and MET3). To confirm the protein expression, we used the Renilla reniformis luciferase and the drug efflux pump Cdr1p of Candida albicans as reporters. The luciferase protein expressed by the MET3 promoter was found to have the strongest activity of the three promoters when cultured in a methionine-depleted synthetic medium. Cdr1p was expressed as a C-terminal FLAG-tagged protein using either these vectors or PCR-mediated integration. The fluconazole resistance was increased by the Cdr1p expression in a CDR1 homozygous disruptant. The expressed proteins were detected by Western blotting using the anti-FLAG antibody. We also constructed a Cdr1p-FLAG expressing strain, in which we directly tagged Cdr1p with FLAG on the genome loci, using a PCR-based integrative marker cassette that was amplified using the pFLAG vector. We then confirmed the protein expression by Western blotting. Thus, these new vectors are useful as C. albicans genetic tools.