Antifungal activities of vineyard-habitat wild yeast for grape gray-mold disease and its effects on spontaneous winemaking.

Microorganisms, including native yeasts, are abundant in vineyard fields. Herein, we studied the possibility of using vineyard-derived wild yeast as a microbial pesticide against Botrytis cinerea, a pathogen that causes grape gray mold disease, to boost the initial alcohol production of spontaneously fermented wine. We identified the Saccharomyces cerevisiae strain KONDO170908, which showed the most effective antifungal activity in an ex vivo yeast dripping experiment on grape berries. This strain was utilized in an in vivo spray test on grape bunches in vineyard fields and was proven to significantly suppress gray mold disease on the grape berries in test plot #16 when the yeast was sprayed during both the flowering and ripening periods (morbidity 11.2% against 15.3% of the control plot, χ2 test, p < 0.0001). However, in test plot #17, spraying the yeast during only the ripening period had no effect (morbidity 16.3%). The grapes from each test plot were also submitted for spontaneous wine fermentation. Alcoholic fermentation of the grapes from test plot #16 provided the most active bubbling of CO2 gas and the highest ethanol production and colony counts over seven days of fermentation. Unique changes in the different strains of S. cerevisiae among the plots were observed throughout the early fermentation stage. Thus, yeast spraying during the flowering period might trigger modification of the entire microbiota and could ultimately contribute to promoting alcohol production in the spontaneously fermented wine, although it decreased the grape yield by 20%.

Synaesthetic colour associations for Japanese Kanji characters: from the perspective of grapheme learning.

One of the fundamental questions about grapheme-colour synaesthesia is how specific associations between the graphemes and colours are formed. We addressed this question by focusing on the determinants of synaesthetic colours for Japanese Kanji characters (logographic characters) using a psycholinguistic approach. Study 1 explored the influence meaning has on synaesthetic colours for Kanji characters representing abstract meanings by examining synaesthetic colours for antonym pairs (i.e. characters with meanings opposed to each other) in Japanese synaesthetes. Results showed that semantic relations influenced the grapheme-colour associations for characters representing abstract meanings in the early stages of learning abstract Kanji, while the influence was reduced in the grapheme-colour associations for those learned later. Study 2 examined the effect that learning new sounds or meanings of graphemes has on synaesthetic colours for those graphemes. Japanese synaesthetes were taught new sounds or new meanings for familiar Kanji characters. Results indicated that acquiring new information for graphemes slightly but significantly reduced the test-retest grapheme-colour association consistency, suggesting that synaesthetic colours can be modulated to reflect the synaesthete's latest knowledge about graphemes. Implications of these findings are discussed from the perspective of the relationship between synaesthesia and grapheme learning. This article is part of a discussion meeting issue 'Bridging senses: novel insights from synaesthesia'.

Association between plasma α-aminobutyric acid and depressive symptoms in older community-dwelling adults in Japan.

AIM: To examine the association between depressive symptoms and plasma amino acid related metaboli in older adults. METHODS: A total of 152 older adults aged ≥65 years, residing in Niigata, Japan, were used for analysis. We evaluated depressive symptoms using the Geriatric Depression Scale-15, which has been validated in older community-dwelling individuals, and used a cut off score of ≥5 to classify participants as having depressive symptoms. We used high-performance liquid chromatography-electrospray ionization mass spectrometry to measure the concentrations of plasma amino acid-related metabolites, and carried out logistic regression analysis to assess the association between depressive symptoms and plasma amino acid-related metabolites. RESULTS: Of the 119 older adults (mean age 76.3 years) included in the analysis, 22 were classified as having depressive symptoms (depressive group). There were no significant differences in physical and cognitive impairments between participants in the depressive and non-depressive groups. The plasma α-aminobutyric acid (AABA) level was significantly lower in the depressive group than in the non-depressive group (P < 0.001). Logistic regression analysis showed the best-fit model, which included AABA, leucine, threonine, hydroxyl proline and histidine levels (area under the receiver operating characteristic curve 0.8346; 95% confidence interval 0.7365-0.9326). In particular, the plasma AABA level was strongly associated with depressive symptoms. CONCLUSIONS: Plasma AABA level is significantly associated with depression symptoms in older community-dwelling adults in Japan. Thus, plasma AABA might serve as a potential marker of depression in older adults aged ≥65 years. Geriatr Gerontol Int 2019; 19: 254-258.

C-type lectin-like domain and fibronectin-like type II domain of phospholipase A(2) receptor 1 modulate binding and migratory responses to collagen.

Phospholipase A2 receptor 1 (PLA2R) mediates collagen-dependent migration. The mechanisms by which PLA2R interacts with collagen remain unclear. We produced HEK293 cells expressing full-length wild-type PLA2R or a truncated PLA2R that lacks fibronectin-like type II (FNII) domains or several regions of C-type lectin-like domain (CTLD). We show that the CTLD1-2 as well as the FNII domain of PLA2R are responsible for binding to collagen and for collagen-dependent migration. Thus, multiple regions and domains of the extracellular portion of PLA2R participate in the responses to collagen. These data suggest a potentially new mechanism for PLA2R-mediated biological response beyond that of a receptor for secretory PLA2.

The expression of groups IIE and V phospholipase A2 is associated with an increased expression of osteogenic molecules in human calcified aortic valves.

AIM: Eicosanoids play various pathogenic roles in aortic valve calcification. Eicosanoids are derived from the arachidonic acid generated by phospholipase A2 (PLA2). We therefore sought to determine whether PLA2s are expressed in human aortic valves and, if so, whether the expression of PLA2s is related to the expression of osteogenic molecules in these tissues. METHODS: Histological and gene expression analyses of 38 non-rheumatic aortic valves obtained at the time of cardiac valve replacement surgery were conducted. Moreover, gene expression analyses were performed using valve interstitial cells (VICs) obtained from human aortic valves. RESULTS: Among the PLA2s examined, the degree of immunoreactivity for PLA2s-IIE and -V was found to significantly correlate with the grade of calcification in the aortic valves. The degree of immunoreactivity and gene expression levels of PLA2s-IIE and -V significantly correlated with those of bone morphogenetic protein (BMP)-2, osteopontin and alkaline phosphatase (ALP). In addition, immunoreactivity for cyclooxygenase (COX)-1, COX-2 and 5-lipoxygenase, downstream enzymes of PLA2 in the arachidonic acid cascade, was co-localized with that for PLA2s-IIE and -V in cells expressing α-smooth muscle actin and macrophages expressing CD68. Furthermore, in the in vitro experiments using cultured VICs, the mRNA expression levels of BMP-2, osteopontin and ALP were suppressed by the inhibition of the expression of PLA2s-IIE or -V with specific siRNAs. CONCLUSIONS: The expression of PLA2s-IIE and -V correlates with the development of calcification as well as the expression of pro-osteogenic molecules in human aortic valves, and inhibiting the expression of PLA2s-IIE and -V suppresses the induction of osteogenic molecules in cultured cells. Therefore, PLA2s-IIE and -V may play a role in the pathogenesis of valve calcification.

Lack of phospholipase A2 receptor increases susceptibility to cardiac rupture after myocardial infarction.

RATIONALE: Recent evidence indicates that the biological effects of secretory phospholipase A2 (sPLA2) cannot be fully explained by its catalytic activity. A cell surface receptor for sPLA2 (PLA2 receptor 1 [PLA2R]) and its high-affinity ligands (including sPLA2-IB, sPLA2-IIE, and sPLA2-X) are expressed in the infarcted myocardium. OBJECTIVE: This study asked whether PLA2R might play a pathogenic role in myocardial infarction (MI) using mice lacking PLA2R (PLA2R(-/-)). METHODS AND RESULTS: MI was induced by permanent ligation of the left coronary artery. PLA2R(-/-) mice exhibited higher rates of cardiac rupture after MI compared with PLA2R wild-type (PLA2R(+/+)) mice (46% versus 21%, respectively; P=0.015). PLA2R(-/-) mice had a 31% decrease in collagen content and a 45% decrease in the number of α-smooth muscle actin-positive fibroblasts in the infarcted region compared with PLA2R(+/+) mice. PLA2R was primarily found in myofibroblasts in the infarcted region. PLA2R(-/-) myofibroblasts were impaired in collagen-dependent migration, proliferation, and activation of focal adhesion kinase in response to sPLA2-IB. Binding of sPLA2-IB to PLA2R promoted migration and proliferation of myofibroblasts through functional interaction with integrin ß1, independent of the catalytic activity of sPLA2-IB. In rescue experiments, the injection of PLA2R(+/+) myofibroblasts into the infarcted myocardium prevented post-MI cardiac rupture and reversed the decrease in collagen content in the infarcted region in PLA2R(-/-) mice. CONCLUSIONS: PLA2R deficiency increased the susceptibility to post-MI cardiac rupture through impaired healing of the infarcted region. This might be partly explained by a reduction in integrin ß1-mediated migratory and proliferative responses of PLA2R(-/-) myofibroblasts.

Phospholipase A2 expression in coronary thrombus is increased in patients with recurrent cardiac events after acute myocardial infarction.

OBJECTIVES: Intracoronary thrombus is a source of active lipid mediators including eicosanoids that play a critical role in the pathogenesis of acute myocardial infarction (AMI). Eicosanoids are derived from arachidonic acid generated by phospholipase A(2) (PLA(2)). This study examined whether PLA(2) is expressed in the aspirated coronary thrombus and whether PLA(2) expression in the thrombus may be related to recurrence of cardiac events and development of atherosclerosis in the culprit coronary artery after AMI. METHODS: Intracoronary thrombus was obtained using an aspiration catheter from 48 patients with AMI, who had successful emergent treatment with percutaneous coronary intervention (PCI). Repeated intravascular ultrasound in the culprit coronary artery was performed at emergent PCI and 6 months later in a subgroup of 20 patients. RESULTS: There was a higher prevalence of cells in the thrombus that were immunopositive to group IIA, IVA, V and X PLA2s in patients with (n = 11) than without (n = 37) cardiac events during 6 months of follow-up (P < 0.05 for all). The prevalence of the cells that were immunopositive to group IIA, IVA and V PLA2s in the thrombus was significantly associated with the percent increase in atheroma volume (r = 0.60, 0.55 and 0.45, respectively, P < 0.05 for all) after 6 months in the native coronary segment distal to the culprit coronary lesion. CONCLUSION: PLA(2) expression in coronary thrombus is associated with recurrence of cardiac events and development of atherosclerosis in the culprit coronary artery in AMI survivors.

Deficiency of phospholipase A2 receptor exacerbates ovalbumin-induced lung inflammation.

Secretory phospholipase A2 (sPLA2) plays a critical role in the genesis of lung inflammation through proinflammatory eicosanoids. A previous in vitro experiment showed a possible role of cell surface receptor for sPLA2 (PLA2R) in the clearance of extracellular sPLA2. PLA2R and groups IB and X sPLA2 are expressed in the lung. This study examined a pathogenic role of PLA2R in airway inflammation using PLA2R-deficient (PLA2R(-/-)) mice. Airway inflammation was induced by immunosensitization with OVA. Compared with wild-type (PLA2R(+/+)) mice, PLA2R(-/-) mice had a significantly greater infiltration of inflammatory cells around the airways, higher levels of groups IB and X sPLA2, eicosanoids, and Th2 cytokines, and higher numbers of eosinophils and neutrophils in bronchoalveolar lavage fluid after OVA treatment. In PLA2R(-/-) mice, intratracheally instilled [(125)I]-labeled sPLA2-IB was cleared much more slowly from bronchoalveolar lavage fluid compared with PLA2R(+/+) mice. The degradation of the instilled [(125)I]-labeled sPLA2-IB, as assessed by trichloroacetic acid-soluble radioactivity in bronchoalveolar lavage fluid after instillation, was lower in PLA2R(-/-) mice than in PLA2R(+/+) mice. In conclusion, PLA2R deficiency increased sPLA2-IB and -X levels in the lung through their impaired clearance from the lung, leading to exaggeration of lung inflammation induced by OVA treatment in a murine model.

Usefulness of LDL-C-related parameters to predict cardiovascular risk and effect of pravastatin in mild-to-moderate hypercholesterolemia.

AIM: Low-density lipoprotein cholesterol (LDL-C), the ratio of LDL-C to high-density lipoprotein cholesterol (HDL-C; LDL-C/HDL-C), and non-HDL-C were evaluated to determine their ability to predict cardiovascular disease (CVD) risk with pravastatin treatment. METHODS: We conducted a large-scale randomized primary prevention trial in Japan (MEGA Study), in which we randomly allocated 7832 mild hypercholesterolemic patients to diet alone (n= 3966) and diet plus pravastatin groups (n= 3866) and followed them for an average of 5 years. We compared baseline levels and the CVD incidence in the diet alone group, and time-dependent receiver operating characteristic curves in the overall population. To determine the best parameter for predicting the efficacy of pravastatin, the diet plus pravastatin group was divided into tertiles to compare lipid parameters and CVD incidence versus the diet alone group. RESULTS: Significantly graded correlations were found between CVD and LDL-C/HDL-C and non-HDL-C. Significantly more CVD events were associated with non-HDL-C [corrected] > 186 mg/dL and LDL-C/HDL-C > 2.9. Furthermore, LDL-C/HDL-C or non-HDL-C was more predictive than LDL-C. By measuring LDL-C/HDL-C or non-HDL-C, we allocated 32% of the diet plus pravastatin group into a different risk category. The lowest significant incidence of CVD was found in patients with LDL-C 119.8-133.4 mg/dL, LDL-C/HDL-C < 1.9, and non-HDL-C 145.2-160.8 mg/dL. CONCLUSION: Non-HDL-C and LDL-C/HDL-C have a greater ability to predict CVD risk in mild-to-moderate hypercholesterolemic Japanese individuals than LDL-C, and are more useful to evaluate the effect of pravastatin; however, these parameters should be interpreted independently when assessing CVD risk.