Biology subjects

Sano, T.

Publications and source records attributed to Sano, T..

22 records · Page 2Linked to original sources

bioRxiv2020

Redundant cytokine requirement for intestinal microbiota-induced Th17 cell differentiation in draining lymph nodes

Differentiation of intestinal T helper 17 (Th17) cells, which contribute to mucosal barrier protection from invasive pathogens, is dependent on colonization with distinct commensal bacteria. Segmented filamentous bacteria (SFB) are sufficient to support Th17 cell differentiation in mouse, but the molecular and cellular requirements for this process remain incompletely characterized. Here we show that intestine-draining mesenteric lymph nodes (MLN) are the dominant site of SFB-induced intestinal Th17 cell differentiation. Subsequent migration of these cells to the intestinal lamina propria is dependent on their up-regulation of integrin {beta}7. Stat3-dependent induction of ROR{gamma}t, the Th17 cell-specifying transcription factor, largely depends on IL-6, but signaling through the receptors for IL-21 and IL-23 can compensate for absence of IL-6 to promote SFB-directed Th17 cell differentiation. These results indicate that redundant cytokine signals guide commensal microbe-dependent Th17 cell differentiation in the MLN and accumulation of the cells in the lamina propria.

immunology↗

bioRxiv2019

Cardiovascular effects of intravenous colforsin in normal and acute respiratory acidosis canine models: a dose-response study

AbstractIn acidosis, catecholamines are attenuated and higher doses are often required to improve cardiovascular function. Colforsin activates adenylate cyclase in cardiomyocytes without mediating the beta adrenoceptor. In this study, six beagles were administered either colforsin or dobutamine four times during eucapnia (partial pressure of arterial carbon dioxide 35-40 mm Hg; normal) and hypercapnia (ibid 90-110 mm Hg; acidosis) conditions. The latter was induced by carbon dioxide inhalation. Anesthesia was induced with propofol and maintained with isoflurane. Cardiovascular function was measured by thermodilution and a Swan-Ganz catheter. Cardiac output, heart rate, and systemic vascular resistance were determined at baseline and 60 min after 0.3 g/kg/min (low), 0.6 g/kg/min (middle), and 1.2 g/kg/min (high) colforsin administration. The median pH was 7.38 [range 7.34-7.42] and 7.04 [range 7.01-7.08] at baseline in the Normal and Acidosis conditions, respectively. Endogenous adrenaline and noradrenaline levels at baseline were significantly (P < 0.05) higher in the Acidosis than in the Normal condition. Colforsin induced cardiovascular effects similar to those caused by dobutamine. Colforsin increased cardiac output in the Normal condition (baseline: 198.8 mL/kg/min [range 119.6-240.9], low: 210.8 mL/kg/min [range 171.9-362.6], middle: 313.8 mL/kg/min [range 231.2-473.2], high: 441.4 mL/kg/min [range 373.9-509.3]; P < 0.001) and the Acidosis condition (baseline: 285.0 mL/kg/min [range 195.9-355.0], low: 297.4 mL/kg/min [213.3-340.6], middle: 336.3 mL/kg/min [291.3-414.5], high: 366.7 mL/kg/min [339.7-455.7] ml/kg/min; P < 0.001). Colforsin significantly increased heart rate (P < 0.05 in both conditions) and decreased systemic vascular resistance (P < 0.05 in both conditions) compared to values at baseline. Systemic vascular resistance was lower in the Acidosis than in the Normal condition (P < 0.001). Dobutamine increased pulmonary artery pressure, whereas colforsin did not. Colforsin offsets the effects of endogenous catecholamines and may not increase cardiac output during hypercapnia.

pharmacology and toxicology↗

bioRxiv2018

Comparative evaluation of the GeeniusTM HIV 1/2 Confirmatory Assay and the HIV-1 and HIV-2 Western blots in the Japanese population

Accurate diagnosis of earlier HIV infection is essential for treatment and prevention. Currently, confirmation tests of HIV infection in Japan are performed using Western blot (WB), but WB has several limitations including low sensitivity and cross-reactivity between HIV-1 and HIV-2 antibodies. To address these problems, a new HIV testing algorithm and a more reliable confirmation and HIV-1/2 differentiation assay are required. The Bio-Rad Geenius HIV-1/2 Confirmatory Assay (Geenius) has recently been approved and recommended for use in the revised guidelines for diagnosis of HIV infection by the Center for Disease Control and Prevention (USA). We made comprehensive comparison of the performance of Geenius and the Bio-Rad NEW LAV BLOT 1 and 2 (NLB 1 and 2) which are WB kits for HIV-1 and HIV-2, respectively, to examine if Geenius is a suitable alternative to these WB assays which are now being used in HIV testing in Japan. A total of 166 HIV-1 positive samples (146 from patients with established HIV-1 infection and 20 from patients with acute infection), five HIV-1 seroconversion panels containing 21 samples and 30 HIV-2 positive samples were used. In addition, a total of 140 HIV negative samples containing 10 false-positives on screening tests were examined. The sensitivity of Geenius and NLB 1 for HIV-1 positive samples was 99.3% and 98.6%, respectively. Geenius provided more positive results in the samples from acute infections and detected positivity 0 to 32 days earlier in seroconversion panels than NLB 1. NLB 2 gave positive results in 12.3% of HIV-1 positive samples. The sensitivity of both Geenius and NLB 2 for HIV-2 positive samples was 100%. The specificity of Geenius, NLB 1 and NLB 2 was 98.5%, 81.5% and 90.0%, respectively. Geenius is an attractive alternative to WB for confirmation and differentiation of HIV-1 and HIV-2 infections. The adaptation of Geenius to the HIV testing algorithm may be advantageous for rapid diagnosis and the reduction of testing costs.

molecular biology↗

bioRxiv2017

Trans-omic analysis reveals fed and fasting insulin signal across phosphoproteome, transcriptome, and metabolome

The concentration and temporal pattern of insulin selectively regulate multiple cellular functions. To understand how insulin dynamics are interpreted by cells, we constructed a trans-omic network of insulin action in FAO hepatoma cells from three networks--a phosphorylation-dependent cellular functions regulatory network using phosphoproteomic data, a transcriptional regulatory network using phosphoproteomic and transcriptomic data, and a metabolism regulatory network using phosphoproteomic and metabolomic data. With the trans-omic regulatory network, we identified selective regulatory networks that mediate differential responses to insulin. Akt and Erk, hub molecules of insulin signaling, encode information of a wide dynamic range of dose and time of insulin. Down-regulated genes and metabolites in glycolysis had high sensitivity to insulin (fasting insulin signal); up-regulated genes and dicarboxylic acids in the TCA cycle had low sensitivity (fed insulin signal). This integrated analysis enables molecular insight into how cells interpret physiologically fed and fasting insulin signals.\n\nHighlightsO_LIWe constructed a trans-omic network of insulin action using multi-omic data.\nC_LIO_LIThe trans-omic network integrates phosphorylation, transcription, and metabolism.\nC_LIO_LIWe classified signaling, transcriptome, and metabolome by sensitivity to insulin.\nC_LIO_LIWe identified fed and fasting insulin signal flow across the trans-omic network.\nC_LI

systems biology↗