New era of research on cancer-associated glycosphingolipids

Cancer-associated glycosphingolipids have been used as markers for diagnosis and targets for immunotherapy of malignant tumors. Recent progress in the analysis of their implications in the malignant properties of cancer cells revealed that cancer-associated glycosphingolipids are not only tumor markers, but also functional molecules regulating various signals introduced by membrane microdomains, lipid rafts. In particular, a novel approach, enzyme-mediated activation of radical sources combined with mass spectrometry, has enabled us to clarify the mechanisms by which cancer-associated glycosphingolipids regulate cell signals based on the interaction with membrane molecules and formation of molecular complexes on the cell surface. Novel findings obtained from these approaches are now providing us with insights into the development of new anticancer therapies targeting membrane molecular complexes consisting of cancer-associated glycolipids and their associated membrane molecules. Thus, a new era of cancer-associated glycosphingolipids has now begun

Ceramide structures involved in the recognition of Siglec-7

To analyze the binding specificity of a sialic acid–recognizing lectin, sialic acid-binding Ig-like lectin 7 (SIGLEC7), to disialyl gangliosides (GD3s), here we established GD3-expressing cells by introducing GD3 synthase (GD3S or ST8SIA1) cDNA into a colon cancer cell line, DLD-1, that expresses no ligands for the recombinant protein SIGLEC7-Fc. SIGLEC7-Fc did not recognize newly-expressed GD3 on DLD-1 cells, even though GD3 was highly expressed, as detected by an anti-GD3 antibody. Because milk-derived GD3 could be recognized by this fusion protein when incorporated onto the surface of DLD-1 cells, we compared the ceramides in DLD-1–generated and milk-derived GD3s to identify the SIGLEC7-specific GD3 structures on the cell membrane, revealing that SIGLEC7 recognizes only GD3-containing regular ceramides but not phytoceramides. This was confirmed by knockdown/knockout of the sphingolipid delta(4)-desaturase/C4-monooxygenase (DES2) gene, involved in phytoceramide synthesis, disclosing that DES2 inhibition confers SIGLEC7 binding. Furthermore, knocking out fatty acid 2-hydroxylase also resulted in the emergence of SIGLEC7 binding to the cell surface. To analyze the effects of binding between SIGLEC7 and various GD3 species on natural killer function, we investigated cytotoxicity of peripheral blood mononuclear cells from healthy donors toward GD3S-transfected DLD-1 (DLD-1–GD3S) cells and DLD-1–GD3S cells with modified ceramides. We found that cytotoxicity is suppressed in DLD-1–GD3S cells with dehydroxylated GD3s. These results indicate that the ceramide structures in glycosphingolipids affect SIGLEC7 binding and distribution on the cell surface and influence cell sensitivity to killing by SIGLEC7-expressing effector cells

Development of image analysis for detection of defects of BGA by using X-ray images

In the surface mount technology, Ball Grid Array (BGA) has been used in a production of PC boards, because of their excellent characters such as high density of the lead pin pitch, better lead rigidity and self-alignment during re-flow processing. This paper deals with the development of image analysis for the detection of defects at BGA solder joints in PC boards by using X-ray images. In the conventional IC boards, it is possible to detect defects of solder joints by visual inspection, because the lead of IC package is set on its outside. However, we can't detect visually defects at BGA solder joints, because they are hidden under the IC package. In a production line, the inspection of BGA in PC boards depends on the function test of electric circuits in the final process. To improve a cost performance and the reliability of PC boards, an inspection of BGA is required in the surface mount process. Types of defects at BGA solder joints are solder bridge, missing connection, solder voids, open connection and miss-registration of parts. As we can find mostly solder bridge in these defects, we pick up this to detect solder bridge in a production line. The problems of image analysis for the detection of defects at BGA solder joints are the detection accuracy and image processing time according to a line speed of production. To get design data for the development of the inspection system, which can be used easily in the surface mount process, it is important to develop image analysis techniques based on X-ray image data. At the first step of our study, we attempt to detect the characteristic of the solder bridges based on an image analysis. </p

Detection of defects at BGA solder joints by using X-ray imaging

In the surface mount technology, a ball grid array (BGA) has been used in the production of PC boards. This paper deals with the detection of defects at BGA solder joints in PC boards by using X-ray imaging. Types of defects at BGA solder joints are solder bridge, missing connection, solder voids, open connection and misregistration of parts. The problems of image analysis for the detection of defects at BGA solder joints are the detection accuracy and image processing time according to the speed of the production line. To get the design data for the development of the inspection system used in the surface mount process, it is important to develop image analysis techniques based on X-ray image data. At the first step of our study, we attempt to detect the characteristics of the solder bridges based on the image analysis technique. </p

Novel Molecular Mechanisms of Gangliosides in the Nervous System Elucidated by Genetic Engineering

Acidic glycosphingolipids, i.e., gangliosides, are predominantly and consistently expressed in nervous tissues of vertebrates at high levels. Therefore, they are considered to be involved in the development and function of nervous systems. Recent studies involving genetic engineering of glycosyltransferase genes have revealed novel aspects of the roles of gangliosides in the regulation of nervous tissues. In this review, novel findings regarding ganglioside functions and their modes of action elucidated mainly by studies of gene knockout mice are summarized. In particular, the roles of gangliosides in the regulation of lipid rafts to maintain the integrity of nervous systems are reported with a focus on the roles in the regulation of neuro-inflammation and neurodegeneration via complement systems. In addition, recent advances in studies of congenital neurological disorders due to genetic mutations of ganglioside synthase genes and also in the techniques for the analysis of ganglioside functions are introduced

ASC amino acid transporter 2, defined by enzyme-mediated activation of radical sources, enhances malignancy of GD2-positive small-cell lung cancer

Ganglioside GD2 is specifically expressed in small-cell lung cancer (SCLC) cells, leading to enhancement of malignant phenotypes, such as cell proliferation and migration. However, how GD2 promotes malignant phenotypes in SCLC cells is not well known. In this study, to reveal the mechanisms by which GD2 increases malignant phenotypes in SCLC cells, we used enzyme-mediated activation of radical sources combined with mass spectrometry in GD2+ SCLC cells. Consequently, we identified ASC amino acid transporter 2 (ASCT2), a major glutamine transporter, which coordinately works with GD2. We showed that ASCT2 was highly expressed in glycolipid-enriched microdomain/rafts in GD2+ SCLC cells, and colocalized with GD2 in both proximity ligation assay and immunocytostaining, and bound with GD2 in immunoprecipitation/TLC immunostaining. Malignant phenotypes of GD2+ SCLC cells were enhanced by glutamine uptake, and were suppressed by L-γ-glutamyl-p-nitroanilide, a specific inhibitor of ASCT2, through reduced phosphorylation of p70 S6K1 and S6. These results suggested that ASCT2 enhances glutamine uptake in glycolipid-enriched microdomain/rafts in GD2+ SCLC cells, leading to the enhancement of cell proliferation and migration through increased phosphorylation of the mTOR complex 1 signaling axis

Mobilization and Drainage of the Pancreatic Bed as a Treatment for Severe Acute Pancreatitis

A new surgical procedure, mobilization and drainage of the pancreatic bed, was performed on two cases of severe acute pancreatitis in shock state, one edematous type and another necrotic type, and prompt improvement of shock state and excellent healing of pancreatitis were observed clinically. The authors have experimentally proved that shock in acute pancreatitis developed as the retroperitoneal tissues directly absorbed the pancreatic exudate. The advantage of this surgical procedure was also proved on experimental dogs whose severe hypotension was successfully treated. The authors believe that this procedure is a simple and reasonable surgical method for acute pancreatitis

Observations of dendritic quartz crystallization growth from supercooled granitic melts

第3回極域科学シンポジウム/第32回極域地学シンポジウム 11月30日（金） 国立極地研究所 ３階ラウン

Imiquimod for Cervical and Vaginal Intraepithelial Neoplasia: A Systematic Review and Meta-analysis.

OBJECTIVE To evaluate the treatment efficacy and the risk of adverse events of imiquimod for cervical intraepithelial neoplasia (CIN) and vaginal intraepithelial neoplasia (VAIN), compared with placebo or no intervention. DATA SOURCES We searched Cochrane, PubMed, ISRCTN registry, ClinicalTrials.gov, and the World Health Organization International Clinical Trials Registry Platform up to November 23, 2022. METHODS OF STUDY SELECTION We included randomized controlled trials and prospective nonrandomized studies with control arms that investigated the efficacy of imiquimod for histologically confirmed CIN or VAIN. The primary outcomes were histologic regression of the disease (primary efficacy outcome) and treatment discontinuation due to side effects (primary safety outcome). We estimated pooled odds ratios (ORs) of imiquimod, compared with placebo or no intervention. We also conducted a meta-analysis of the proportions of patients with adverse events in the imiquimod arms. TABULATION, INTEGRATION, AND RESULTS Four studies contributed to the pooled OR for the primary efficacy outcome. An additional four studies were available for meta-analyses of proportions in the imiquimod arm. Imiquimod was associated with increased probability of regression (pooled OR 4.05, 95% CI 2.08-7.89). Pooled OR for CIN in the three studies was 4.27 (95% CI 2.11-8.66); results of one study were available for VAIN (OR, 2.67, 95% CI 0.36-19.71). Pooled probability for primary safety outcome in the imiquimod arm was 0.07 (95% CI 0.03-0.14). The pooled probabilities (95% CI) of secondary outcomes were 0.51 (0.20-0.81) for fever, 0.53 (0.31-0.73) for arthralgia or myalgia, 0.31 (0.18-0.47) for abdominal pain, 0.28 (0.09-0.61) for abnormal vaginal discharge or genital bleeding, 0.48 (0.16-0.82) for vulvovaginal pain, and 0.02 (0.01-0.06) for vaginal ulceration. CONCLUSION Imiquimod was found to be effective for CIN, whereas data on VAIN were limited. Although local and systemic complications are common, treatment discontinuation is infrequent. Thus, imiquimod is potentially an alternative therapy to surgery for CIN. SYSTEMATIC REVIEW REGISTRATION PROSPERO, CRD42022377982