Epidemiological study using IgM and IgG antibody titers against SARS-CoV-2 in The University of Tokyo, Japan (UT-CATS).

INTRODUCTION: The worldwide pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has continued to date. Given that some of the patients with coronavirus disease 2019 (COVID-19) are asymptomatic, antibody tests are useful to determine whether there is a previous infection with SARS-CoV-2. In this study, we measured IgM and IgG antibody titers against SARS-CoV-2 in the serum of asymptomatic healthy subjects in The University of Tokyo, Japan. METHODS: From June 2020, we recruited participants, who were students, staff, and faculty members of The University of Tokyo in the project named The University of Tokyo COVID-19 Antibody Titer Survey (UT-CATS). Following blood sample collection, participants were required to answer an online questionnaire about their social and health information. We measured IgG and IgM titers against SARS-CoV-2 using iFlash-SARS-CoV-2 IgM and IgG detection kit which applies a chemiluminescent immunoassay (CLIA) for the qualitative detection. RESULTS: There were 6609 volunteers in this study. After setting the cutoff value at 10 AU/mL, 32 (0.48%) were positive for IgG and 16 (0.24%) for IgM. Of six participants with a history of COVID-19, five were positive for IgG, whereas all were negative for IgM. The median titer of IgG was 0.40 AU/mL and 0.39 AU/mL for IgM. Both IgG and IgM titers were affected by gender, age, smoking status, and comorbidities. CONCLUSIONS: Positive rates of IgG and IgM titers were relatively low in our university. Serum levels of these antibodies were affected by several factors, which might affect the clinical course of COVID-19.

The raspberry bushy dwarf virus 1b gene enables pollen grains to function efficiently in horizontal pollen transmission.

Horizontal pollen transmission by the raspberry bushy dwarf virus 1b deletion mutant (RBΔ1bstop), which is defective in virus virulence, was significantly decreased compared to wild-type raspberry bushy dwarf virus (wtRBDV). We assessed accumulation of viral genomic (g) RNAs in pollen grains from RBΔ1bstop-infected plants and found that the pollen grains had less viral gRNA than those from wtRBDV-infected plants. In addition, pollen grains from 1b-expressing transgenic plants (1b-plants) infected with RBΔ1bstop were more efficient in horizontal virus transmission to healthy plants after pollination than pollen from RBΔ1bstop-infected wild type plants. Moreover, viral gRNA accumulation in pollen grains from RBΔ1bstop-infected 1b-plants was higher than in pollen from RBΔ1bstop-infected wild type plants. We suggest that 1b increases the amount of viral gRNAs released from elongating pollen grains.

Hepatocyte ELOVL Fatty Acid Elongase 6 Determines Ceramide Acyl-Chain Length and Hepatic Insulin Sensitivity in Mice.

BACKGROUND AND AIMS: Dysfunctional hepatic lipid metabolism is a cause of nonalcoholic fatty liver disease (NAFLD), the most common chronic liver disorder worldwide, and is closely associated with insulin resistance and type 2 diabetes. ELOVL fatty acid elongase 6 (Elovl6) is responsible for converting C16 saturated and monounsaturated fatty acids (FAs) into C18 species. We have previously shown that Elovl6 contributes to obesity-induced insulin resistance by modifying hepatic C16/C18-related FA composition. APPROACH AND RESULTS: To define the precise molecular mechanism by which hepatic Elovl6 affects energy homeostasis and metabolic disease, we generated liver-specific Elovl6 knockout (LKO) mice. Unexpectedly, LKO mice were not protected from high-fat diet-induced insulin resistance. Instead, LKO mice exhibited higher insulin sensitivity than controls when consuming a high-sucrose diet (HSD), which induces lipogenesis. Hepatic patatin-like phospholipase domain-containing protein 3 (Pnpla3) expression was down-regulated in LKO mice, and adenoviral Pnpla3 restoration reversed the enhancement in insulin sensitivity in HSD-fed LKO mice. Lipidomic analyses showed that the hepatic ceramide(d18:1/18:0) content was lower in LKO mice, which may explain the effect on insulin sensitivity. Ceramide(d18:1/18:0) enhances protein phosphatase 2A (PP2A) activity by interfering with the binding of PP2A to inhibitor 2 of PP2A, leading to Akt dephosphorylation. Its production involves the formation of an Elovl6-ceramide synthase 4 (CerS4) complex in the endoplasmic reticulum and a Pnpla3-CerS4 complex on lipid droplets. Consistent with this, liver-specific Elovl6 deletion in ob/ob mice reduced both hepatic ceramide(d18:1/18:0) and PP2A activity and ameliorated insulin resistance. CONCLUSIONS: Our study demonstrates the key role of hepatic Elovl6 in the regulation of the acyl-chain composition of ceramide and that C18:0-ceramide is a potent regulator of hepatic insulin signaling linked to Pnpla3-mediated NAFLD.

Autotaxin and soluble IL-2 receptor concentrations in cerebrospinal fluids are useful for the diagnosis of central nervous system invasion caused by haematological malignancies.

BACKGROUND: Invasion of the central nervous system by haematological malignancies is diagnosed by cytological analyses of cerebrospinal fluid or diagnostic imaging, while quantitative biomarkers for central nervous system invasion are not available and needed to be developed. METHODS: In this study, we measured the concentrations of autotaxin and soluble IL-2 receptor in cerebrospinal fluid and evaluated their usefulness as biomarkers for central nervous system invasion. RESULTS: We observed that both the autotaxin and soluble IL-2 receptor concentrations in cerebrospinal fluid were higher in subjects with central nervous system invasion than in those without, and the cerebrospinal fluid concentrations were independent from the serum concentrations of these biomarkers. ROC analyses revealed that the soluble IL-2 receptor concentration in cerebrospinal fluid was a strong discriminator of central nervous system invasion in subjects with haematological malignancies, while the autotaxin concentration in cerebrospinal fluid also had a strong ability to discriminate central nervous system invasion when the subjects were limited to those with lymphoma. The combined measurement of autotaxin and soluble IL-2 receptor in cerebrospinal fluid improved the sensitivity without notably reducing the specificity for central nervous system invasion in subjects with lymphoma when central nervous system invasion was diagnosed in cases where either value was beyond the respective cut-off value. CONCLUSION: These results suggest the possible usefulness of soluble IL-2 receptor and autotaxin concentrations in cerebrospinal fluid for the diagnosis of central nervous system invasion.

Transgenic Mice Overexpressing SREBP-1a in Male ob/ob Mice Exhibit Lipodystrophy and Exacerbate Insulin Resistance.

Sterol regulatory element-binding protein (SREBP)-1a is a key transcription factor that activates the expression of genes involved in the synthesis of fatty acids, triglycerides (TGs), and cholesterol. Transgenic mice that overexpress the nuclear form of SREBP-1a under the control of the phosphoenolpyruvate carboxykinase promoter (Tg-1a) were previously shown to display a lipodystrophic phenotype characterized by enlarged and fatty livers, diminished peripheral white adipose tissue (WAT), and insulin resistance. In the current study, we crossed these Tg-1a mice with genetically obese (ob/ob) mice (Tg-1a;ob/ob) and examined change in fat distribution between liver and adipose tissues in severe obesity and mechanism underlying the lipodystrophic phenotype in mice with Tg-1a. Tg-1a;ob/ob mice developed more severe steatohepatitis but had reduced WAT mass and body weight compared with ob/ob mice. The reduction of WAT mass in Tg-1a and Tg-1a;ob/ob mice was accompanied by enhanced lipogenesis and lipid uptake in the liver, reduced plasma lipid levels, impaired adipocyte differentiation, reduced food intake, enhanced energy expenditure, and extended macrophage infiltration and fibrosis in WAT. Despite the improved glucose tolerance, Tg-1a;ob/ob mice showed severe peripheral insulin resistance. Adenoviral hepatic expression of SREBP-1a mimicked these phenotypes. The "fat steal"-like lipodystrophy phenotype of the Tg-1a;ob/ob model demonstrates that hepatic SREBP-1a activation has a strong impact on the partition of TG accumulation, resulting in adipose-tissue remodeling by inflammation and fibrosis and insulin resistance.