ZFAT is an antiapoptotic molecule and critical for cell survival in MOLT-4 cells

AbstractZFAT (also known as ZNF406), originally identified as a candidate gene for autoimmune thyroid disease, encodes a zinc-finger protein, however, its function has not been elucidated. Here, we report that human ZFAT protein is expressed in peripheral B and T lymphocytes and a human acute T lymphoblastic leukaemia cell line, MOLT-4 cells. Intriguing is that mouse ZFAT expression in CD4+ lymphocytes is increased during blast formation. Furthermore, ZFAT-knockdown in MOLT-4 induces apoptosis via activation of caspases. These results suggested that ZFAT protein is a critical regulator involved in apoptosis and cell survival for immune-related cells

Plasma level of oxidized low-density lipoprotein is an independent determinant of coronary macrovasomotor and microvasomotor responses induced by bradykinin

AbstractObjectivesWe examined the relationship between coronary endothelium-dependent vasodilation in response to bradykinin (BK) and plasma levels of oxidized low-density lipoprotein (oxLDL) in subjects with normal coronary arteries.BackgroundIt is unclear whether the plasma oxLDL level is a determinant of coronary endothelial function. Bradykinin plays an important role in regulating resting coronary tone and flow-mediated coronary vasomotion.MethodsCoronary blood flow (CBF) in the left anterior descending (LAD) coronary artery was assessed by quantitative angiography and a Doppler flow wire in 94 consecutive subjects with normal coronary arteries. The plasma oxLDL level was measured by enzyme-linked immunosorbent assay using DLH3R, a specific antibody against oxLDL.ResultsPlasma levels of oxLDL in diabetic subjects (n = 13) were higher than those in non-diabetic subjects (n = 81). Plasma levels of oxLDL correlated with body mass index (BMI). Bradykinin at doses of 0.2, 0.6, and 2.0 μg/min caused dose-dependent increases in diameter and CBF in the LAD coronary artery. By a univariate analysis, oxLDL levels significantly correlated with epicardial (r = −0.30, p < 0.0001) and resistant (r = −0.36, p = 0.003) coronary vasodilator responses to BK at 2.0 μg/min, whereas total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and triglycerides were not associated with these coronary responses. In a stepwise multivariate analysis, oxLDL levels were significantly correlated with epicardial and resistant coronary vasomotor responses to BK, independent of age, gender, smoking status, other lipid levels, BMI, hypertension, and diabetes.ConclusionsThe plasma level of oxLDL is an appropriate surrogate for assessing coronary endothelial-dependent vasomotor function as estimated by responses to BK compared with conventional risk factors for atherosclerosis

Japanese VLBI Network observations of radio-loud narrow-line Seyfert 1 galaxies

We performed phase-reference very long baseline interferometry (VLBI) observations on five radio-loud narrow-line Seyfert 1 galaxies (NLS1s) at 8.4 GHz with the Japanese VLBI Network (JVN). Each of the five targets (RXS J08066+7248, RXS J16290+4007, RXS J16333+4718, RXS J16446+2619, and B3 1702+457) in milli-Jansky levels were detected and unresolved in milli-arcsecond resolutions, i.e., with brightness temperatures higher than 10^7 K. The nonthermal processes of active galactic nuclei (AGN) activity, rather than starbursts, are predominantly responsible for the radio emissions from these NLS1s. Out of the nine known radio-loud NLS1s, including the ones chosen for this study, we found that the four most radio-loud objects exclusively have inverted spectra. This suggests a possibility that these NLS1s are radio-loud due to Doppler beaming, which can apparently enhance both the radio power and the spectral frequency.Comment: 8 pages, 2 figures, accepted for publication in PAS

The novel latex agglutination turbidimetric immunoassay system for simultaneous measurements of calprotectin and hemoglobin in feces

Background/Aims Fecal calprotectin (Fcal) as well as the fecal immunochemical test (FIT) are useful biomarkers for detecting activity and mucosal healing in inflammatory bowel diseases. Here, we report the performance of simultaneous measurements of Fcal and FIT for ulcerative colitis (UC) patients using the newly-developed latex agglutination turbidimetric immunoassay (LATIA) system. Methods Fcal and hemoglobin were measured by the LATIA system in 152 UC patients who underwent colonoscopy. Fcal was also quantified with a conventional enzyme-linked immunosorbent assay (ELISA). Fecal markers were evaluated in conjunction with the mucosal status of UC, which was assessed via the Mayo endoscopic subscore (MES) classification. Results The LATIA system could quantify calprotectin and hemoglobin simultaneously with the same fecal samples within 10 minutes. The values of the Fcal-LATIA closely correlated with those of the Fcal-ELISA (Spearman rank correlation coefficient, r=0.84; P Conclusions The performance of the novel Fcal-LATIA was equivalent to that of the conventional Fcal assay. Simultaneous measurements with FITs would promote the clinical relevance of fecal biomarkers in UC

Resetting transcription factor control circuitry toward ground-state pluripotency in human.

Current human pluripotent stem cells lack the transcription factor circuitry that governs the ground state of mouse embryonic stem cells (ESC). Here, we report that short-term expression of two components, NANOG and KLF2, is sufficient to ignite other elements of the network and reset the human pluripotent state. Inhibition of ERK and protein kinase C sustains a transgene-independent rewired state. Reset cells self-renew continuously without ERK signaling, are phenotypically stable, and are karyotypically intact. They differentiate in vitro and form teratomas in vivo. Metabolism is reprogrammed with activation of mitochondrial respiration as in ESC. DNA methylation is dramatically reduced and transcriptome state is globally realigned across multiple cell lines. Depletion of ground-state transcription factors, TFCP2L1 or KLF4, has marginal impact on conventional human pluripotent stem cells but collapses the reset state. These findings demonstrate feasibility of installing and propagating functional control circuitry for ground-state pluripotency in human cells.This research was supported by the UK Medical Research Council, the Japan Science and Technology agency (JST, PRESTO), the Genome Biology Unit of the European Molecular Biology Laboratory, European Commission projects PluriMes, BetaCellTherapy, EpiGeneSys, and Blueprint, and the Wellcome Trust. Y.T. was a University of Cambridge Herchel Smith Fellow. A.S. is a Medical Research Council Professor

Improved Sendai viral system for reprogramming to naive pluripotency

優れた多分化能を持つヒトのナイーブ型iPS細胞を迅速に作製する方法を発明. 京都大学プレスリリース. 2022-10-18.A novel method for generating naive human iPS cells with significantly higher differentiation potency. 京都大学プレスリリース. 2022-11-15.Naive human induced pluripotent stem cells (iPSCs) can be generated by reprogramming somatic cells with Sendai virus (SeV) vectors. However, only dermal fibroblasts have been successfully reprogrammed this way, and the process requires culture on feeder cells. Moreover, SeV vectors are highly persistent and inhibit subsequent differentiation of iPSCs. Here, we report a modified SeV vector system to generate transgene-free naive human iPSCs with superior differentiation potential. The modified method can be applied not only to fibroblasts but also to other somatic cell types. SeV vectors disappear quickly at early passages, and this approach enables the generation of naive iPSCs in a feeder-free culture. The naive iPSCs generated by this method show better differentiation to trilineage and extra-embryonic trophectoderm than those derived by conventional methods. This method can expand the application of iPSCs to research on early human development and regenerative medicine

Synthesis of [11C]uric acid, using [11C]phosgene, as a possible biomarker in PET imaging for diagnosis of gout

The synthesis and in vivo evaluation of 11C -labeled uric acid ([11C]1), a potential imaging agent for the diagnosis of urate-related life-style diseases, was performed using positron emission tomography (PET) image analysis. First, the synthesis of [11C]1 was achieved by reacting 5,6-diaminouracil (2) with 11C-labeled phosgene ([11C]COCl2). The radiochemical yield of [11C]1 was 37 ± 7% (decay-corrected based on [11C]COCl2) with specific radioactivities of 96-152 GBq/μmol at the end of synthesis (n = 6). The average time of radiosynthesis from the end of bombardment, including formulation, was about 30 min with >98% radiochemical purity. Second, the synthetic approach to [11C]1 was optimized using 5,6-diaminouracil sulfate (3) with [11C]COCl2 in the presence of 1,8-bis(dimethylamino)naphthalene. [11C]1 was synthesized in 36 ± 6% radiochemical yield, 89-142 GBq/μmol of specific radioactivities, and 98% radiochemical purity by this method (n = 5). This allowed the synthesis of [11C]1 to be carried out repeatedly and the radiochemical yield, specific radioactivities, average time of synthesis, and radiochemical purity of [11C]1 were similar to those obtained using 2. PET studies in rats showed large differences in the accumulation of radioligand in the limbs under normal and hyperuricemic conditions. Thus, an efficient and convenient automated synthesis of [11C]1 has been developed, and preliminary PET evaluation of [11C]1 confirmed the increased accumulation of radioactivity in the limbs of a rat model of hyperuricemia. © 2011 Elsevier Ltd. All rights reserved