Validation of a rapid, non-radioactive method to quantify internalisation of G-protein coupled receptors

Agonist exposure can cause internalisation of G-protein coupled receptors (GPCRs), which may be a part of desensitisation but also of cellular signaling. Previous methods to study internalisation have been tedious or only poorly quantitative. Therefore, we have developed and validated a quantitative method using a sphingosine-1-phosphate (S1P) receptor as a model. Because of a lack of suitable binding studies, it has been difficult to study S1P receptor internalisation. Using a N-terminal HisG-tag, S1P1 receptors on the cell membrane can be visualised via immunocytochemistry with a specific anti-HisG antibody. S1P-induced internalisation was concentration dependent and was quantified using a microplate reader, detecting either absorbance, a fluorescent or luminescent signal, depending on the antibodies used. Among those, the fluorescence detection method was the most convenient to use. The relative ease of this method makes it suitable to measure a large number of data points, e.g. to compare the potency and efficacy of receptor ligands

Prevalence and long-term outcomes of patients with coronary artery ectasia presenting with acute myocardial infarction

Coronary artery ectasia (CAE) is described in 5% of patients undergoing coronary angiography. Previous studies have shown controversial results regarding the prognostic impact of CAE. The prevalence and prognostic value of CAE in patients with acute myocardial infarction (AMI) remain unknown. In 4788 patients presenting with AMI referred for coronary angiography the presence of CAE (defined as dilation of a coronary segment with a diameter >= 1.5 times of the adjacent normal segment) was confirmed in 174 (3.6%) patients (age 62 + 12 years; 81% male), and was present in the culprit vessel in 79.9%. Multivessel CAE was frequent (67%). CAE patients were more frequently male, had high thrombus burden and were treated more often with thrombectomy and less often was stent implantation. Markis I was the most frequent angiographic phenotype (43%). During a median follow-up of 4 years (1-7), 1243 patients (26%) experienced a major adverse cardiovascular event (MACE): 282 (6%) died from a cardiac cause, 358 (8%) had a myocardial infarction, 945 (20%) underwent coronary revascularization and 58 (1%) presented with a stroke. Patients with CAE showed higher rates of MACE as compared to those without CAE (36.8% versus 25.6%; p <0.001). On multivariable analysis, CAE was associated with MACE (HR 1.597; 95% CI 1.238-2.060; p <0.001) after adjusting for risk factors, type of AMI and number of narrowed coronary arteries. In conclusion, the prevalence of CAE in patients presenting with AMI is relatively low but was independently associated with an increased risk of MACE at follow-up. (c) 2021 The Author(s). Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/) (Am J Cardiol 2021;156:9-15)Cardiolog

Atomistic origins of high-performance in hybrid halide perovskite solar cells

The performance of organometallic perovskite solar cells has rapidly surpassed that of both conventional dye-sensitised and organic photovoltaics. High power conversion efficiency can be realised in both mesoporous and thin-film device architectures. We address the origin of this success in the context of the materials chemistry and physics of the bulk perovskite as described by electronic structure calculations. In addition to the basic optoelectronic properties essential for an efficient photovoltaic device (spectrally suitable band gap, high optical absorption, low carrier effective masses), the materials are structurally and compositionally flexible. As we show, hybrid perovskites exhibit spontaneous electric polarisation; we also suggest ways in which this can be tuned through judicious choice of the organic cation. The presence of ferroelectric domains will result in internal junctions that may aid separation of photoexcited electron and hole pairs, and reduction of recombination through segregation of charge carriers. The combination of high dielectric constant and low effective mass promotes both Wannier-Mott exciton separation and effective ionisation of donor and acceptor defects. The photoferroic effect could be exploited in nanostructured films to generate a higher open circuit voltage and may contribute to the current-voltage hysteresis observed in perovskite solar cells.Comment: 6 pages, 5 figure

Male antene: postupci smanjivanja izmjera i primjene

The paper presents research results in the field of small antennas obtained at the Department of Wireless Communications, Faculty of Electrical Engineering and Computing, University of Zagreb. A study comparing the application of several miniaturization techniques on a shorted patch antenna is presented. Single and dual band shorted patch antennas with notches and/or slot are introduced. A PIFA designed for application in mobile GSM terminals is described. The application of stacked shorted patches as array elements for a mobile communication base station as well as for electromagnetic field sensor is presented. The design of single and dual band folded monopoles is described. Prototypes of the presented antennas have been manufactured and their characteristics were verified by measurements.U radu su prikazani rezultati istraživanja u području malih antena ostvareni na Zavodu za Radiokomunikacije, Sveučilišta u Zagrebu Fakulteta elektrotehnike i računarstva. Prikazana je primjena više postupaka za smanjivanje izmjera skraćene mikrotrakaste antene. Opisane su izvedbe skraćenih mikrotrakastih antena s urezima i prorezom za rad u jednom i u dva frekvencijska područja. Prikazana je izvedba planarne invertirane F-antene (PIFA) za primjenu u ručnim terminalima sustava pokretnih komunikacija GSM. Višeslojne skraćene mikrotrakaste antene uporabljene su za izvedbu antenskog niza za baznu postaju sustava pokretnih komunikacija te kao elementi osjetila za mjerenje jakosti elektromagnetskog polja. Prikazana je izvedba savijenih monopolnih antena za rad u jednom te u dva frekvencijska pojasa. Izrađeni su prototipovi opisanih antena i mjerenjima su ispitane njihove osobine

Labor markets and cultural values: Evidence from Japanese and American views about caregiving immigrants

One overlooked reason for the persistence of distinct cultural values across rich democracies, we argue, is a country's labor market structure. Parents seeking to position their children for long‐term success would do well to instill values consistent with requirements of the labor market in the country where their children are likely to work. To the extent that labor markets are fluid, as in the United States, parents should teach their children to be resourceful and creative. In countries like Japan with relatively rigid labor markets, where workers have one chance to land a long‐term contract with a leading company, parents instead should instill the values of hard work and respect for authority. We find evidence consistent with this argument in survey experiments about attitudes in the United States and Japan about the desirability of employing immigrants for care work, and what values the immigrant care workers should hold. We also find evidence of indirect norm creation. American and Japanese respondents prefer immigrants—not just caregiving immigrants—whose values align with their country's type of valued human capital

Prognostic value of nonalcoholic fatty liver disease in patients with severe aortic stenosis who underwent transcatheter aortic valve implantation

Nonalcoholic fatty liver disease (NAFLD) is associated with an increased risk of cardiovascular events. Although the association between NAFLD and aortic valve sclerosis has been described, the prevalence and prognostic implications of NAFLD among patients with severe aortic stenosis (AS) have not been described. In addition, the effect of the presence of severe tricuspid regurgitation (TR) on the prevalence of NAFLD remains unexplored. Accordingly, we investigated the prognostic implications of NAFLD among patients with severe AS with and without concomitant significant TR. A total of 538 patients (aged 80 +/- 7 y, 49.6% men) who underwent noncontrast computed tomography before transcatheter aortic valve implantation (TAVI) between 2007 and 2019 were included. NAFLD was defined as a liver-to-spleen attenuation ratio Thoracic Surger

Vasorelaxant activity of indole alkaloids from Tabernaemontana dichotoma.

The aim of this study was to search for bioactive natural products from medicinal plants targeting vasorelaxant activity and we found the methanol extract from bark of Tabernaemontana dichotoma showed vasorelaxant activity on rat aorta. We isolated eight indole alkaloids including 10-methoxyalstonerine (1), a new macroline type indole alkaloid, from bark of T. dichotoma. These were respectively identified as 10-methoxyaffinisine (2), lochnerine (3), cathafoline (4), (−)-alstonerine (5), 19,20-dehydro-10-methoxytalcarpine (6), alstonisine (7), and alstonal (8) based on spectroscopic analysis. Among them, sarpagine type (2 and 3), akuammiline type (4), and macroline oxindole type (7 and 8) showed potent vasorelaxant activity. Mechanism of action on vasorelaxant activity of 10-methoxyaffinisine (2), cathafoline (4), and alstonisine (7) was clarified. Effects of 10-methoxyaffinisine (2), cathafoline (4), and alstonisine (7) were partially mediated the NO release from endothelial cells. Furthermore, 10-methoxyaffinisine (2) and alstonisine (7) attribute to the inhibitory effect of VDC and ROC, and cathafoline (4) have inhibitory effect on Ca2+ influx via ROC. In addition, 10-methoxyaffinisine (2) as a major compound from bark of T. dichotoma showed hypotensive effect on normotensive rats in vivo