The first Irish genome and ways of improving sequence accuracy

Whole-genome sequencing of an Irish person reveals hundreds of thousands of novel genomic variants. Imputation using previous known information improves the accuracy of low-read-depth sequencing

NFATc1 regulates the transcription of DNA damage-induced apoptosis suppressor

AbstractDNA damage induced apoptosis suppressor (DDIAS), or human Noxin (hNoxin), is strongly expressed in lung cancers. DDIAS knockdown induced apoptosis in non-small cell lung carcinoma A549 cells in response to DNA damage, indicating DDIAS as a potential therapeutic target in lung cancer. To understand the transcriptional regulation of DDIAS, we determined the transcription start site, promoter region, and transcription factor. We found that DDIAS transcription begins at nucleotide 212 upstream of the DDIAS translation start site. We cloned the DDIAS promoter region and identified NFAT2 as a major transcription factor (Im et al., 2016 [1]). We demonstrated that NFATc1 regulates DDIAS expression in both pancreatic cancer Panc-1 cells and lung cancer cells

Performance evaluation of water-repellent combat uniforms using a static manikin and human subjects under a rainfall tower system

The purpose of the present study was to evaluate the water-repellent properties of newly-developed combat uniforms using a rainfall tower system. Two types of water-repellent- combat uniforms with an identical level of water repellency through textile tests (WR_M and WR_T) were compared with an untreated-combat uniform (Control). A static manikin was used to evaluate water-repellent properties in a standing position and eight male subjects participated to test walking effects under artificial rainfall. The results showed that it took to saturate the upper body was longer for WR_T than WR_M and Control in the standing position for both normal and heavy rain conditions (P < 0.05). The lower body in WR_T was rarely wet in the standing position after 60 min, whereas the lower body was partially wet while walking within 30 min. Changes in clothing weight after the rainfall test were 729 ± 21, 256 ± 36 and 137 ± 25 g per trial for Control, WR_M, and WR_T, respectively (P < 0.001). Subjects expressed better tactile, less colder, less heavier, and less humid sensations and less uncomfortable feeling for WR_T than Control or WR_M (P < 0.05), while WR_M was better only for tactile sensation and heaviness than Control (P < 0.05). Ten-time-washes had not impaired the water-repellent properties of WR_M or WR_T. These results indicated that the rainfall tower test is valid to verify water-repellent property of clothing ensemble and suggest a possibility of classifying the water repellency of clothing ensemble into sub-levels of an excellent and a fair class. Further studies on wider range of experimental conditions to validate the current results are required.This study is funded by Defense Agency for Technology and Quality (20190907EA7-00

Menthol Enhances an Antiproliferative Activity of 1α,25-Dihydroxyvitamin D3 in LNCaP Cells

1α,25-dihydroxyvitamin D3 [1α,25(OH)2D3], the most active form of vitamin D3, and its analogues have therapeutic benefits for prostate cancer treatment. However, the development of hypercalcemia is an obstacle to clinical applications of 1α,25(OH)2D3 for cancer therapy. In this study, we provide evidence that menthol, a key component of peppermint oil, increases an anti-proliferation activity of 1α,25(OH)2D3 in LNCaP prostate cancer cells. We found that menthol per se does not exhibit antiproliferative activity, but it is able to enhance 1α,25(OH)2D3-mediated growth inhibition in LNCaP cells. Fluorometric assays using Fura-2 showed that 1α,25(OH)2D3 does not induce acute Ca2+ response, whereas menthol evokes an increase in [Ca2+]i, which suggests that cross-talks of menthol-induced Ca2+ signaling with 1α,25(OH)2D3-mediated growth inhibition pathways. In addition, Western blot analysis revealed that 1α,25(OH)2D3 and menthol cooperatively modulate the expression of bcl-2 and p21 which provides the insight into the molecular mechanisms underlying the enhanced 1α,25(OH)2D3-mediated growth inhibition by menthol. Thus, our findings suggest that menthol may be a useful natural compound to enhance therapeutic effects of 1α,25(OH)2D3

Limaprost and the Risk of Bleeding: A Self-Controlled Case Series Study

Objective To investigate the association between the use of limaprost and the risk of bleeding. Methods A self-controlled case series analysis was conducted using the National Health Insurance Service-National Sample Cohort database in South Korea. We identified patients aged 18 years or older who had at least one prescription of limaprost and were diagnosed with at least one case of bleeding between 2003 and 2019. The incidence rate ratio (IRR) of bleeding was calculated by dividing the incidence rate in the exposed period to limaprost by that in the unexposed period and adjusted for age using conditional Poisson regression model. Results Among 72,860 patients with limaprost prescriptions and bleeding diagnoses, there were 184,732 events of bleeding. After adjusting for age, the IRR was 1.47 (95% confidence interval [CI], 1.43–1.50), wherein the IRR was the highest during the 0–7 days after limaprost initiation (IRR, 2.11; 95% CI, 2.03–2.18). Risk of bleeding was higher when limaprost was concomitantly used with antithrombotics or other drugs for spinal stenosis treatment, and when higher daily doses of limaprost were administered. Conclusion Our findings suggest that the risk of bleeding increased by 1.5-fold in periods of limaprost exposure compared to unexposed periods, with particularly higher risks observed during the first week after limaprost initiation, with concomitant drugs related to bleeding, and with a higher daily dose. A careful risk-benefit assessment is warranted when initiating limaprost, especially when administered with other medications or in higher daily doses

Breathing silicon anodes for durable high-power operations

Silicon anode materials have been developed to achieve high capacity lithium ion batteries for operating smart phones and driving electric vehicles for longer time. Serious volume expansion induced by lithiation, which is the main drawback of silicon, has been challenged by multi-faceted approaches. Mechanically rigid and stiff polymers (e.g. alginate and carboxymethyl cellulose) were considered as the good choices of binders for silicon because they grab silicon particles in a tight and rigid way so that pulverization and then break-away of the active mass from electric pathways are suppressed. Contrary to the public wisdom, in this work, we demonstrate that electrochemical performances are secured better by letting silicon electrodes breathe in and out lithium ions with volume change rather than by fixing their dimensions. The breathing electrodes were achieved by using a polysaccharide (pullulan), the conformation of which is modulated from chair to boat during elongation. The conformational transition of pullulan was originated from its a glycosidic linkages while the conventional rigid polysaccharide binders have beta linkagesopen1

Tetramethyl-O-scutellarin isolated from peels of immature Shiranuhi fruit exhibits anti-inflammatory effects on LPSinduced RAW264.7 cells

Purpose: To investigate the anti-inflammatory activity of the ethanol extract of the immature fruit of a citrus, Shiranuhi, and to identify the active ingredient.Methods: The immature Shiranuhi peel was extracted with 80 % ethanol, and the extract was fractionated with solvents (n-hexane, ethyl acetate and n-butanol) to afford the corresponding fractions and water residue. Among them, the EtOAc-soluble portion was subjected to medium pressure liquid chromatography (MPLC) over a reversed-phase SiO2 column to give compound 1. The isolated compound was identified based on the proton and carbon nuclear magnetic resonance (NMR) spectra. The release of nitric oxide, prostaglandin (PG)E2, tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6 secreted by mouse macrophages was measured using RAW264.7 cell culture supernatant.Results: Shiranuhi (Korean name, Hallabong) is an important citrus species cultivated in Jeju Island, Korea. A polymethoxyflavonoid (PMF), tetramethyl-O-scutellarin (1), was isolated from the peels of immature Shiranuhi fruit. Upon the evaluation of anti-inflammatory effects, the flavonoid 1 decreased the nitric oxide production in macrophage cells with high efficiency, viz, 50 % inhibition concentration, IC50 of 57.4 μM. Subsequent studies demonstrated that PMF 1 effectively inhibited the generation of PGE2, TNF-α, IL-1β, and IL-6 cytokine in a dose-dependent manner.Conclusion: Tetramethyl-O-scutellarin (1) has been successfully isolated from Shiranuhi species for the first time. Thus, Shiranuhi fruit peel extract containing PMF 1 can potentially be applied as an antiinflammatory ingredient in food or cosmetic industries.Keywords: Shiranuhi fruit, Nitric oxide, Tetramethyl-O-scutellarin, Anti-inflammator

Obsessive-Compulsive Behavior Disappearing after Left Capsular Genu Infarction

This case report describes a 74-year-old woman with obsessive-compulsive behaviors that disappeared following a left capsular genu infarction. The patient's capsular genu infarction likely resulted in thalamocortical disconnection in the cortico-basal ganglia-thalamocortical loop, which may have caused the disappearance of her obsessive-compulsive symptoms. The fact that anterior capsulotomy has been demonstrated to be effective for treating refractory obsessive-compulsive disorder further supports this hypothesis

Chlorin e6 Prevents ADP-Induced Platelet Aggregation by Decreasing PI3K-Akt Phosphorylation and Promoting cAMP Production

A number of reagents that prevent thrombosis have been developed but were found to have serious side effects. Therefore, we sought to identify complementary and alternative medicinal materials that are safe and have long-term efficacy. In the present studies, we have assessed the ability of chlorine e6 (CE6) to inhibit ADP-induced aggregation of rat platelets and elucidated the underlying mechanism. CE6 inhibited platelet aggregation induced by 10 µM ADP in a concentration-dependent manner and decreased intracellular calcium mobilization and granule secretion (i.e., ATP and serotonin release). Western blotting revealed that CE6 strongly inhibited the phosphorylations of PI3K, Akt, c-Jun N-terminal kinase (JNK), and different mitogen-activated protein kinases (MAPKs) including extracellular signal-regulated kinase 1/2 (ERK1/2) as well as p38-MAPK. Our study also demonstrated that CE6 significantly elevated intracellular cAMP levels and decreased thromboxane A2 formation in a concentration-dependent manner. Furthermore, we determined that CE6 initiated the activation of PKA, an effector of cAMP. Taken together, our findings indicate that CE6 may inhibit ADP-induced platelet activation by elevating cAMP levels and suppressing PI3K/Akt activity. Finally, these results suggest that CE6 could be developed as therapeutic agent that helps prevent thrombosis and ischemia