Evidence for the Existence of Secretory Granule (Dense-Core Vesicle)-Based Inositol 1,4,5-Trisphosphate-Dependent Ca2+ Signaling System in Astrocytes

BACKGROUND: The gliotransmitters released from astrocytes are deemed to play key roles in the glial cell-neuron communication for normal function of the brain. The gliotransmitters, such as glutamate, ATP, D-serine, neuropeptide Y, are stored in vesicles of astrocytes and secreted following the inositol 1,4,5-trisphosphate (IP3)-induced intracellular Ca2+ releases. Yet studies on the identity of the IP3-dependent intracellular Ca2+ stores remain virtually unexplored. PRINCIPAL FINDINGS: We have therefore studied the potential existence of the IP3-sensitive intracellular Ca2+ stores in the cytoplasm of astrocytes using human brain tissue samples in contrast to cultured astrocytes that had primarily been used in the past. It was thus found that secretory granule marker proteins chromogranins and secretogranin II localize in the large dense core vesicles of astrocytes, thereby confirming the large dense core vesicles as bona fide secretory granules. Moreover, consistent with the major IP3-dependent intracellular Ca2+ store role of secretory granules in secretory cells, secretory granules of astrocytes also contained all three (types 1, 2, and 3) IP3R isoforms. SIGNIFICANCE: Given that the secretory granule marker proteins chromogranins and secretogranin II are high-capacity, low-affinity Ca2+ storage proteins and chromogranins interact with the IP3Rs to activate the IP3R/Ca2+ channels, i.e., increase both the mean open time and the open probability of the channels, these results imply that secretory granules of astrocytes function as the IP3-sensitive intracellular Ca2+ store

Effect of Interleukin-18 Gene Polymorphisms on Sensitization to Wheat Flour in Bakery Workers

Lower respiratory symptoms in bakery workers may be induced by wheat flour and endotoxins. We hypothesized that endotoxins from wheat flour may stimulate innate immunity and that interleukin-18 (IL-18) gene polymorphisms may affect their regulatory role in innate immune responses to endotoxins. To investigate the genetic contribution of IL-18 to sensitization to wheat flour, we performed a genetic association study of IL-18 in Korean bakery workers. A total of 373 bakery workers undertook a questionnaire regarding work-related symptoms. Skin prick tests with common and occupational allergens were performed and specific antibodies to wheat flour were measured by ELISA. Three polymorphisms of the IL-18 gene (-607A/C, -137G/C, 8674C/G) were genotyped, and the functional effects of the polymorphisms were analyzed using the luciferase reporter assay. Genotypes of -137G/C (GC or CC) and haplotype ht3 [ACC] showed a significant association with the rate of sensitization to wheat flour. Luciferase activity assay indicated ht3 [AC] as a low transcript haplotype. In conclusion, the regulatory role of IL-18 in lipopolysaccharide-induced responses in bakery workers may be affected by this polymorphism, thus contributing to the development of sensitization to wheat flour and work-related respiratory symptoms

Pepper EST database: comprehensive in silico tool for analyzing the chili pepper (Capsicum annuum) transcriptome

<p>Abstract</p> <p>Background</p> <p>There is no dedicated database available for Expressed Sequence Tags (EST) of the chili pepper (<it>Capsicum annuum</it>), although the interest in a chili pepper EST database is increasing internationally due to the nutritional, economic, and pharmaceutical value of the plant. Recent advances in high-throughput sequencing of the ESTs of chili pepper cv. Bukang have produced hundreds of thousands of complementary DNA (cDNA) sequences. Therefore, a chili pepper EST database was designed and constructed to enable comprehensive analysis of chili pepper gene expression in response to biotic and abiotic stresses.</p> <p>Results</p> <p>We built the Pepper EST database to mine the complexity of chili pepper ESTs. The database was built on 122,582 sequenced ESTs and 116,412 refined ESTs from 21 pepper EST libraries. The ESTs were clustered and assembled into virtual consensus cDNAs and the cDNAs were assigned to metabolic pathway, Gene Ontology (GO), and MIPS Functional Catalogue (FunCat). The Pepper EST database is designed to provide a workbench for (i) identifying unigenes in pepper plants, (ii) analyzing expression patterns in different developmental tissues and under conditions of stress, and (iii) comparing the ESTs with those of other members of the <it>Solanaceae </it>family. The Pepper EST database is freely available at <url>http://genepool.kribb.re.kr/pepper/</url>.</p> <p>Conclusion</p> <p>The Pepper EST database is expected to provide a high-quality resource, which will contribute to gaining a systemic understanding of plant diseases and facilitate genetics-based population studies. The database is also expected to contribute to analysis of gene synteny as part of the chili pepper sequencing project by mapping ESTs to the genome.</p

Junctional membrane inositol 1,4,5-trisphosphate receptor complex coordinates sensitization of the silent EGF-induced Ca2+ signaling

Ca2+ is a highly versatile intracellular signal that regulates many different cellular processes, and cells have developed mechanisms to have exquisite control over Ca2+ signaling. Epidermal growth factor (EGF), which fails to mobilize intracellular Ca2+ when administrated alone, becomes capable of evoking [Ca2+]i increase and exocytosis after bradykinin (BK) stimulation in chromaffin cells. Here, we provide evidence that this sensitization process is coordinated by a macromolecular signaling complex comprised of inositol 1,4,5-trisphosphate receptor type I (IP3R1), cAMP-dependent protein kinase (PKA), EGF receptor (EGFR), and an A-kinase anchoring protein, yotiao. The IP3R complex functions as a focal point to promote Ca2+ release in two ways: (1) it facilitates PKA-dependent phosphorylation of IP3R1 in response to BK-induced elevation of cAMP, and (2) it couples the plasmalemmal EGFR with IP3R1 at the Ca2+ store located juxtaposed to the plasma membrane. Our study illustrates how the junctional membrane IP3R complex connects different signaling pathways to define the fidelity and specificity of Ca2+ signaling

Long-term impact of coronavirus disease 2019 pandemic on emergency department utilization in a metropolitan emergency department in Korea

Purpose As coronavirus disease 2019 pandemic has been prolonged, it became crucial to analyze the long-term impact of the pandemic on emergency department (ED) utilization for efficient use of emergency medicine resources. Methods We reviewed the data of children (≤ 18 years) who visited the ED in Daejeon, Korea, from February 2019 through January 2021. This period was dichotomized by February 2020 into the reference and pandemic periods. The latter period was further divided into the early (February-August 2020) and late pandemic periods. Between the reference and pandemic periods, and between the early and late pandemic periods, we respectively compared proportions of children in all patients (including adults), age groups, high acuity (the Korean Triage and Acuity Scale 1-2), diagnostic codes, visits via ambulances, ED length of stay, and ED disposition. Results Compared to the reference and early pandemic periods, the pandemic and late pandemic periods respectively showed changes as follows: proportion of children in all patients (from 29.8% to 19.0% and from 19.8% to 18.1%; all Ps < 0.001), children younger than 5 years (from 56.7% to 49.9% and from 52.1% to 47.4%; all Ps < 0.001), high acuity (from 12.0% to 7.8% [P < 0.001] and from 8.8% to 6.7% [P = 0.004]), “Injury, poisoning and certain other consequences of external causes (S00-T98; from 30.0% to 49.0% and from 48.3% to 49.8%),” and “Diseases of the respiratory system (J00-J99; from 29.6% to 10.3% and from 12.8% to 7.5%).” Increases in the visits via ambulances, ED length of stay, children undergoing intensive care unit hospitalization or death were noted only in comparison between the reference and pandemic periods. Conclusion A long-term impact of the pandemic on ED use may be a decrease in the proportion of young or ill children

Chemical Stability of Conductive Ceramic Anodes in LiCl–Li2O Molten Salt for Electrolytic Reduction in Pyroprocessing

AbstractConductive ceramics are being developed to replace current Pt anodes in the electrolytic reduction of spent oxide fuels in pyroprocessing. While several conductive ceramics have shown promising electrochemical properties in small-scale experiments, their long-term stabilities have not yet been investigated. In this study, the chemical stability of conductive La0.33Sr0.67MnO3 in LiCl–Li2O molten salt at 650°C was investigated to examine its feasibility as an anode material. Dissolution of Sr at the anode surface led to structural collapse, thereby indicating that the lifetime of the La0.33Sr0.67MnO3 anode is limited. The dissolution rate of Sr is likely to be influenced by the local environment around Sr in the perovskite framework