Role of the pleckstrin homology domain of PLCγ1 in its interaction with the insulin receptor

A thiol-reactive membrane-associated protein (TRAP) binds covalently to the cytoplasmic domain of the human insulin receptor (IR) β-subunit when cells are treated with the homobifunctional cross-linker reagent 1,6-bismaleimidohexane. Here, TRAP was found to be phospholipase C γ1 (PLCγ1) by mass spectrometry analysis. PLCγ1 associated with the IR both in cultured cell lines and in a primary culture of rat hepatocytes. Insulin increased PLCγ1 tyrosine phosphorylation at Tyr-783 and its colocalization with the IR in punctated structures enriched in cortical actin at the dorsal plasma membrane. This association was found to be independent of PLCγ1 Src homology 2 domains, and instead required the pleckstrin homology (PH)–EF-hand domain. Expression of the PH–EF construct blocked endogenous PLCγ1 binding to the IR and inhibited insulin-dependent phosphorylation of mitogen-activated protein kinase (MAPK), but not AKT. Silencing PLCγ1 expression using small interfering RNA markedly reduced insulin-dependent MAPK regulation in HepG2 cells. Conversely, reconstitution of PLCγ1 in PLCγ1−/− fibroblasts improved MAPK activation by insulin. Our results show that PLCγ1 is a thiol-reactive protein whose association with the IR could contribute to the activation of MAPK signaling by insulin

Discrimination of cultivation ages and cultivars of ginseng leaves using Fourier transform infrared spectroscopy combined with multivariate analysis

AbstractTo determine whether Fourier transform (FT)-IR spectral analysis combined with multivariate analysis of whole-cell extracts from ginseng leaves can be applied as a high-throughput discrimination system of cultivation ages and cultivars, a total of total 480 leaf samples belonging to 12 categories corresponding to four different cultivars (Yunpung, Kumpung, Chunpung, and an open-pollinated variety) and three different cultivation ages (1 yr, 2 yr, and 3 yr) were subjected to FT-IR. The spectral data were analyzed by principal component analysis and partial least squares-discriminant analysis. A dendrogram based on hierarchical clustering analysis of the FT-IR spectral data on ginseng leaves showed that leaf samples were initially segregated into three groups in a cultivation age-dependent manner. Then, within the same cultivation age group, leaf samples were clustered into four subgroups in a cultivar-dependent manner. The overall prediction accuracy for discrimination of cultivars and cultivation ages was 94.8% in a cross-validation test. These results clearly show that the FT-IR spectra combined with multivariate analysis from ginseng leaves can be applied as an alternative tool for discriminating of ginseng cultivars and cultivation ages. Therefore, we suggest that this result could be used as a rapid and reliable F1 hybrid seed-screening tool for accelerating the conventional breeding of ginseng

Динаміка та аналіз виробничого травматизму та професійних захворювань в Україні

Кожного року в Україні на виробництві травмується понад 10 тис. людей, з них гине понад 600 осіб. Оптимістична, на перший погляд, статистика, за якою травматизм на виробництві за роки незалежності України зменшився в десять разів, виявляється не такою вже й оптимістичною, коли аналізуються конкретні цифри

Severe Aortic Coarctation in a 75-Year-Old Woman: Total Simultaneous Repair of Aortic Coarctation and Severe Aortic Stenosis

Aortic coarctation is usually diagnosed and repaired in childhood and early adulthood. Survival of a patient with an uncorrected coarctation to more than 70 years of age is extremely unusual, and management strategies for these cases remain controversial. We present a case of a 75-year-old woman who was first diagnosed with aortic coarctation and severe aortic valve stenosis 5 years ago and who underwent a successful one-stage repair involving valve replacement and insertion of an extra-anatomical bypass graft from the ascending to the descending aorta

System of integrating biosignals during hemodialysis: the CONTINUAL (Continuous mOnitoriNg viTal sIgN dUring hemodiALysis) registry

Background Appropriate monitoring of intradialytic biosignals is essential to minimize adverse outcomes because intradialytic hypotension and arrhythmia are associated with cardiovascular risk in hemodialysis patients. However, a continuous monitoring system for intradialytic biosignals has not yet been developed. Methods This study investigated a cloud system that hosted a prospective, open-source registry to monitor and collect intradialytic biosignals, which was named the CONTINUAL (Continuous mOnitoriNg viTal sIgN dUring hemodiALysis) registry. This registry was based on real-time multimodal data acquisition, such as blood pressure, heart rate, electrocardiogram, and photoplethysmogram results. Results We analyzed session information from this system for the initial 8 months, including data for some cases with hemodynamic complications such as intradialytic hypotension and arrhythmia. Conclusion This biosignal registry provides valuable data that can be applied to conduct epidemiological surveys on hemodynamic complications during hemodialysis and develop artificial intelligence models that predict biosignal changes which can improve patient outcomes

High-performance and scalable metal-chalcogenide semiconductors and devices via chalco-gel routes

We report a general strategy for obtaining high-quality, large-areametal-chalcogenide semiconductor films from precursors combining chelated metal salts with chalcoureas or chalcoamides. Using conventional organic solvents, such precursors enable the expeditious formation of chalco-gels,which are easily transformed into the corresponding highperformance metal-chalcogenide thin films with large, uniform areas. Diverse metal chalcogenides and their alloys (MQx: M = Zn, Cd, In, Sb, Pb; Q = S, Se, Te) are successfully synthesized at relatively low processing temperatures (<400°C). The versatility of this scalable route is demonstrated by the fabrication of large-area thin-film transistors (TFTs), optoelectronic devices, and integrated circuits on a 4-inch Si wafer and 2.5-inch borosilicate glass substrates in ambient air using CdS, CdSe, and In2Se3 active layers. The CdSe TFTs exhibit a maximum field-effect mobility greater than 300 cm2 V-1 s-1 with an on/off current ratio of >107 and good operational stability (threshold voltage shift < 0.5 V at a positive gate bias stress of 10 ks). In addition,metal chalcogenide-based phototransistors with a photodetectivity of >1013 Jones and seven-stage ring oscillators operating at a speed of ∼2.6 MHz (propagation delay of < 27 ns per stage) are demonstrated. © 2018 The Authors.1

Longitudinal trajectory of acidosis and mortality in acute kidney injury requiring continuous renal replacement therapy

Abstract Background Acidosis frequently occurs in severe acute kidney injury (AKI), and continuous renal replacement therapy (CRRT) can control this pathologic condition. Nevertheless, acidosis may be aggravated; thus, monitoring is essential after starting CRRT. Herein, we addressed the longitudinal trajectory of acidosis on CRRT and its relationship with worse outcomes. Methods The latent growth mixture model was applied to classify the trajectories of pH during the first 24 hours and those of C-reactive protein (CRP) after 24 hours on CRRT due to AKI (n = 1815). Cox proportional hazard models were used to calculate hazard ratios of all-cause mortality after adjusting multiple variables or matching their propensity scores. Results The patients could be classified into 5 clusters, including the normally maintained groups (1st cluster, pH = 7.4; and 2nd cluster, pH = 7.3), recovering group (3rd cluster with pH values from 7.2 to 7.3), aggravating group (4th cluster with pH values from 7.3 to 7.2), and ill-being group (5th cluster, pH < 7.2). The pH clusters had different trends of C-reactive protein (CRP) after 24 hours; the 1st and 2nd pH clusters had lower levels, but the 3rd to 5th pH clusters had an increasing trend of CRP. The 1st pH cluster had the best survival rates, and the 3rd to 5th pH clusters had the worst survival rates. This survival difference was significant despite adjusting for other variables or matching propensity scores. Conclusions Initial trajectories of acidosis determine subsequent worse outcomes, such as mortality and inflammation, in patients undergoing CRRT due to AKI