ADAR2-dependent RNA editing of GluR2 is involved in thiamine deficiency-induced alteration of calcium dynamics

BACKGROUND: Thiamine (vitamin B1) deficiency (TD) causes mild impairment of oxidative metabolism and region-selective neuronal loss in the central nervous system (CNS). TD in animals has been used to model aging-associated neurodegeneration in the brain. The mechanisms of TD-induced neuron death are complex, and it is likely multiple mechanisms interplay and contribute to the action of TD. In this study, we demonstrated that TD significantly increased intracellular calcium concentrations [Ca2+]i in cultured cortical neurons. RESULTS: TD drastically potentiated AMPA-triggered calcium influx and inhibited pre-mRNA editing of GluR2, a Ca2+-permeable subtype of AMPA receptors. The Ca2+ permeability of GluR2 is regulated by RNA editing at the Q/R site. Edited GluR2 (R) subunits form Ca2+-impermeable channels, whereas unedited GluR2 (Q) channels are permeable to Ca2+ flow. TD inhibited Q/R editing of GluR2 and increased the ratio of unedited GluR2. The Q/R editing of GluR2 is mediated by adenosine deaminase acting on RNA 2 (ADAR2). TD selectively decreased ADAR2 expression and its self-editing ability without affecting ADAR1 in cultured neurons and in the brain tissue. Over-expression of ADAR2 reduced AMPA-mediated rise of [Ca2+]i and protected cortical neurons against TD-induced cytotoxicity, whereas down-regulation of ADAR2 increased AMPA-elicited Ca2+ influx and exacerbated TD-induced death of cortical neurons. CONCLUSIONS: Our findings suggest that TD-induced neuronal damage may be mediated by the modulation of ADAR2-dependent RNA Editing of GluR2

Influence of Two Common Polymorphisms in the EPHX1 Gene on Warfarin Maintenance Dosage: A Meta-Analysis

We conducted a meta-analysis to investigate the influence of two common single nucleotide polymorphisms (SNPs) (rs2292566 G>A and rs4653436 A>G) in the EPHX1 gene on warfarin maintenance dosages. Relevant literatures were searched using the PubMed, Embase, Web of Science, Cochrane Library, CISCOM, CINAHL, Google Scholar, CBM, and CNKI databases without any language restrictions. STATA Version 12.0 software (Stata Corporation, College Station, TX, USA) was used for this meta-analysis. Standard mean difference and its corresponding 95% confidence interval (95% CI) were calculated. Seven studies met the inclusion criteria, including 2,063 warfarin-treated patients. Meta-analysis results illustrated that EPHX1 rs2292566 G>A polymorphism might be strongly correlated with a higher maintenance dose of warfarin. However, no interaction of EPHX1 rs4653436 A>G polymorphism with warfarin maintenance dosage was detected. A further subgroup analysis based on stratification by ethnicity indicated that EPHX1 rs2292566 G>A polymorphism was positively correlated with warfarin maintenance dosage among Caucasians, but not Asians. No associations were observed between EPHX1 rs4653436 A>G polymorphism warfarin maintenance dosage among both Caucasians and Asians. Our meta-analysis provides robust and unambiguous evidence that EPHX1 rs2292566 polymorphism may affect the maintenance dose of warfarin in Caucasians

Clinical and Radiological Features of Wallerian Degeneration of the Middle Cerebellar Peduncles Secondary to Pontine Infarction

Background: Wallerian degeneration (WD) of bilateral middle cerebellar peduncles (MCPs) can occur following pontine infarction, but its characteristics have not yet been clarified because of the low incidence. Thus, the present study discussed the clinical and radiological features to improve the awareness of this disease. Methods: Clinical and radiological information from consecutive individuals diagnosed with WD of bilateral MCPs following pontine infarction in three hospitals over the past 4 years between October 2012 and October 2016 were retrospectively investigated and compared with a control group (patients with pontine infarction had no secondary WD). Results: This study involved 30 patients with WD of MCPs, with a detection rate of only 4.9%. The primary infarctions (χ2 =24.791, P = 0.001, vs. control group) were located in the paramedian pons in 21 cases (70.0%), and ventrolateral pons in nine cases (30.0%). WD of the MCPs was detected 8–24 weeks after pons infarction using conventional magnetic resonance imaging (MRI); all secondary WDs were asymptomatic and detected incidentally. All WD lesions exhibited bilateral, symmetrical, and boundary blurring on MRI. The signal features were hypointense on T1-weighted imaging, hyperintense on T2-weighted imaging and fluid-attenuated inversion recovery, and slightly hyperintense or isointense on diffusion-weighted imaging and apparent diffusion coefficient maps. Secondary brainstem atrophy was found in six (20.0%) cases. A Modified Rankin Scale score 0–2 was found in 10 (33.3%) cases and score >2 in 20 (66.7%) cases at 90 days after discharge, and the short-term prognosis was worse than that in control group (χ2 =12.814, P = 0.001). Conclusions: Despite the rarity of bilateral and symmetrical lesions of MCPs, secondary WD should be highly suspected if these lesions occur within 6 months after pontine infarction, particularly paramedian pons. Conventional MRI appears to be a relatively sensitive method for detecting WD of MCPs, which might affect the short-term prognosis

Study of the swirling flow field induced by guide vanes using electrical resistance tomography and numerical simulations

In this work, the swirling flow field induced by guide vanes was studied using electrical resistance tomography (ERT) and numerical simulations. The results show that the two-phase water and oil mixture moves in the same axial direction for this type of flow field, which is very unlike the flow behavior of a traditional hydrocyclone with a tangential inlet. In the pipe behind the guide vanes, the smallest axial velocity and tangential velocity are located at the center of the pipe. From the pipe center to the pipe wall, both pressure and velocity increase gradually. Downstream of guide vanes, the maximal oil volume fraction is observed at the center of the pipe. From the center of the pipe to the inner wall, the oil volume fraction gradually decreases. Moreover, ERT can precisely show the oil distribution in the pipe section. These studies prove the possibility of efficient oil and water mixture separation by guide vanes, and the results may be very important for guiding the optimal design of vane-type pipe separators

Plaques of Nonstenotic Basilar Arteries with Isolated Pontine Infarction on Three-dimensional High Isotropic Resolution Magnetic Resonance Imaging

Background: There are few studies for evaluating plaque characteristics of nonstenotic basilar arteries (BA). Our aim was to determine entire BA plaques with a three-dimensional volumetric isotropic turbo spin-echo acquisition (VISTA) and investigate the differences between the patients with and without isolated pontine infarction (IPI). Methods: Twenty-four consecutive symptomatic patients with nonstenotic BA on time of flight magnetic resonance angiography (TOF MRA) were enrolled from China-Japan Friendship Hospital between January 2014 and December 2014. BA was classified as "normal" or "irregular" based on TOF MRA, and "normal wall", "slight wall-thickening", and "plaque" based on three-dimensional VISTA images. Outcomes from MRA and VISTA were compared. Patients were categorized as IPI and non-IPI groups based on the diffusion-weighted imaging. Clinical and plaque characteristics were compared between the two groups. Results: A total of 1024 image slices including 311 (30.37%) plaque slices, 427 (41.70%) slight wall-thickening slices, and 286 (27.93%) normal wall slices for the entire BA from 23 patients were finally included for analysis. VISTA images detected plaques in all the 9 (100%) irregular MRA patients and 7 of 14 (50%) normal MRA patients. IPI was found in 11 (47.83%) patients. Compared to non-IPI group, the IPI group had a higher percentage of plaque slices (P = 0.001) and lower percentage of normal wall slices (P = 0.014) than non-IPI group. Conclusions: Three-dimensional VISTA images enable detection of BA plaques not visualized by MRA. BA plaques could be found in both the IPI and non-IPI group. However, IPI group showed plaques more extensively in BA than the non-IPI group