Unsaturated Fatty Acids Repress the Expression of ATP-Binding Cassette Transporter A1 in HepG2 and FHs 74 Int Cells

Adenosine triphosphate–binding cassette transporter A1 (ABCA1) plays a critical role in the formation and metabolism of high-density lipoproteins (HDLs). Adenosine triphosphate–binding cassette transporter A1 in the liver and small intestine, in particular, accounts for approximately 90% of plasma HDL cholesterol. Therefore, any alterations in the hepatic and intestinal expression of ABCA1 could have a large impact on HDL biogenesis. We tested the hypothesis that ABCA1 expression is regulated differentially by different types of fatty acids in the liver and small intestine. Human hepatoma HepG2 and human small intestine epithelial FHs 74 Int cells were used as an in vitro model. Cells were incubated with saturated and unsaturated fatty acids in the presence or absence of T0901317, a synthetic agonist of liver X receptor. Unsaturated fatty acids decreased ABCA1 protein levels at 100 μmol/L of concentration regardless of the agonist with a minimal effect on messenger RNA abundance. Incubation of HepG2 and FHs 74 Int cells with rottlerin, a protein kinase C δ (PKCδ) inhibitor, increased ABCA1 protein but did not abolish linoleic acid–induced decrease in ABCA1 protein levels. Depletion of PKCδ using small interfering RNA showed decreased ABCA1 protein levels in control, palmitic acid–, and linoleic acid–treated cells, but the repressive effect of linoleic acid was sustained. In conclusion, our results indicate that unsaturated fatty acids regulate ABCA1 expression in HepG2 and FHs 74 Int cells at the posttranscriptional level, and PKCδ is likely to be involved in maintaining ABCA1 protein levels

Designing a Mobile Crowdsourcing System for Campus Safety

Safety on college campuses remains a dire issue. Current reporting methods are still cumbersome and include no enhancing social aspect. Given the unique opportunity that universities are required to publish their safety report logs, we conducted a preliminary data analysis of a university's safety report log. The analysis allowed us to detect relevant trends in reporting behavior, specifically pertaining to where, when, and how soon the community would report safety incidents. Motivated by these findings and by literature promoting interactive reporting systems, we designed a novel mobile app which aims to enable the spread of crowdsourced public safety information. This app allows for immediate mass sharing of self-reported safety incidents, as well as the opportunity for witness reporting. Feedback from a paper prototype interview study indicated that these qualities would facilitate increased interactivity among its user community, and ultimately promote awareness of campus safety.ye

Hypocholesterolemic effect of \u3ci\u3eNostoc commune\u3c/i\u3e var. \u3ci\u3esphaeroides\u3c/i\u3e Kützing, an edible blue-green alga

Background Intake of an edible blue-green alga Nostoc commune var. sphaeroides Kützing (N. commune) has been shown to lower plasma total cholesterol concentration, but the mechanisms behind the hypocholesterolemic effect have not been elucidated. Aim of the study To elucidate the mechanisms underlying the cholesterol-lowering effect of N. commune in mice. Methods Male C57BL/6J mice were fed the AIN-93 M diet supplemented with 0 or 5% (wt/wt) dried N. commune for 4 weeks. Lipid levels in the plasma and liver, intestinal cholesterol absorption, and fecal sterol excretion were measured. Expression of hepatic and intestinal genes involved in cholesterol metabolism was evaluated by quantitative realtime PCR. Results N. commune supplementation significantly reduced total plasma cholesterol and triglyceride concentrations by ~20% compared to controls. Intestinal cholesterol absorption was significantly decreased, while fecal neutral sterol output was significantly increased in N. commune–fed mice. mRNA levels of the cholesterol transporters such as Niemann Pick C1 Like 1, scavenger receptor class B type 1, ATP-binding cassette transporters G5 and A1 in small intestine were not significantly different between two groups. Hepatic lipid contents including total cholesterol, triglyceride and free cholesterol in N. commune–fed mice were not significantly altered. However, the expression of cholesterol-modulating genes including sterol regulatory element binding protein-2 and 3-hydroxy-3-methylglutaryl coenzyme A reductase were significantly increased in mice fed N. commune. Conclusions N. commune supplementation exerted a hypocholesterolemic effect in mice, largely in part, by reducing intestinal cholesterol absorption and promoting fecal neutral sterol excretion

The Infrared Imaging Spectrograph (IRIS) for TMT: Instrument Overview

We present an overview of the design of IRIS, an infrared (0.84 - 2.4 micron) integral field spectrograph and imaging camera for the Thirty Meter Telescope (TMT). With extremely low wavefront error (<30 nm) and on-board wavefront sensors, IRIS will take advantage of the high angular resolution of the narrow field infrared adaptive optics system (NFIRAOS) to dissect the sky at the diffraction limit of the 30-meter aperture. With a primary spectral resolution of 4000 and spatial sampling starting at 4 milliarcseconds, the instrument will create an unparalleled ability to explore high redshift galaxies, the Galactic center, star forming regions and virtually any astrophysical object. This paper summarizes the entire design and basic capabilities. Among the design innovations is the combination of lenslet and slicer integral field units, new 4Kx4k detectors, extremely precise atmospheric dispersion correction, infrared wavefront sensors, and a very large vacuum cryogenic system.Comment: Proceedings of the SPIE, 9147-76 (2014

Bioavailability of the amino acid-attached prodrug as a new anti-HIV agent in rats

The primary objective of this study was to compare the pharmacokinetics of a new anti-human immunodeficiency virus agent 1-(2-amino-pyridin-4-ylmethyl)-6-(3,5-dimethyl-benzoyl)-5-isopropyl-1H-pyrimidine-2,4-dione (VP-0502) with its amino acid prodrug alanine amide of VP-0502 (VP-0502AL), following intravenous and oral administrations to rats. The plasma concentrations of both analytes were analyzed via high-performance liquid chromatography coupled with photodiode-array detection (HPLC-DAD). When VP-0502 was intravenously administered at 20 mg/kg, the analyte appeared in low levels with an AUC of 0.3 µg · h/ml, and C0 of 0.2 µg/ml in plasma. However, both the prodrug VP-0502AL and its metabolite VP-0502 appeared at comparatively higher levels following intravenous injection of VP-0502AL at the same dose. VP-0502AL's pharmacokinetic parameters were Vd: 4.6 l/kg; AUC: 3 µg · h/ml; t1/2: 0.5 h; C0: 6 µg/ml; CLtot: 7 l/h/kg; and MRT: 0.6 h. Following oral administration of VP-0502 (100 mg/kg), it was not detectable in plasma (<50 ng/ml), while after the oral administration of VP-0502AL, VP-0502 was quantitatively detected as an active metabolite for the first 7 h, with a maximum plasma concentration (Cmax) of 0.8 µg/ml, and an area under the concentration-time curve (AUC) of 2 µg · h/ml. The oral pharmaco-kinetic parameters of VP-0502AL were calculated to be: maximum concentration time (tmax) 2.7 h; Cmax 0.2 µg/ml; elimination half-life (t1/2): 0.8 h; and AUC 0.5 µg · h/ml. Overall the findings indicate that VP-0502AL has a favorable pharmacokinetic profile as a prodrug with rapid transformation into the active metabolite, and that the attachment of the amino acid alanine to VP-0502 is an effective approach to improve its oral bioavailability. VP-0502AL is predicted to become a new highly bioavailable anti-AIDS drug candidate and/or lead compound

On the Role of Higher Twist in Polarized Deep Inelastic Scattering

The higher twist corrections $h^N(x)/Q^2$ to the spin dependent proton and neutron structure functions $g_1^N(x, Q^2)$ are extracted in a model independent way from experimental data on $g_1^N$ and found to be non-negligible. It is shown that the NLO QCD polarized parton densities determined from the data on g1, including higher twist effects, are in good agreement with those found earlier from our analysis of the data on g1/F1 and A1 where higher twist effects are negligible. On the contrary, the LO QCD polarized parton densities obtained from the data on g1, including higher twist, differ significantly from our previous results.Comment: 18 pages, latex, 6 figures, final version which will be published in Phys. Rev. D, fig. 5 is changed, misprints in Table 2 are remove

Cardiac CT and MRI guide surgery in impending left ventricular rupture after acute myocardial infarction

We report the case of a 67 year-old patient who presented with worsening chest pain and shortness of breath, four days post acute myocardial infarction. Contrast enhanced computed tomography of the chest ruled out a pulmonary embolus but revealed an unexpected small subepicardial aneurysm (SEA) in the lateral left ventricular wall which was confirmed on cardiac magnetic resonance imaging. Intraoperative palpation of the left lateral wall was guided by the cardiac MRI and CT findings and confirmed the presence of focally thinned and weakened myocardium, covered by epicardial fat. An aneurysmorrhaphy was subsequently performed in addition to coronary bypass surgery and a mitral valve repair. The patient was discharged home on post operative day eight in good condition and is feeling well 2 years after surgery

The Assembly of Individual Chaplin Peptides from Streptomyces coelicolor into Functional Amyloid Fibrils

The self-association of proteins into amyloid fibrils offers an alternative to the natively folded state of many polypeptides. Although commonly associated with disease, amyloid fibrils represent the natural functional state of some proteins, such as the chaplins from the soil-dwelling bacterium Streptomyces coelicolor, which coat the aerial mycelium and spores rendering them hydrophobic. We have undertaken a biophysical characterisation of the five short chaplin peptides ChpD-H to probe the mechanism by which these peptides self-assemble in solution to form fibrils. Each of the five chaplin peptides produced synthetically or isolated from the cell wall is individually surface-active and capable of forming fibrils under a range of solution conditions in vitro. These fibrils contain a highly similar cross-β core structure and a secondary structure that resembles fibrils formed in vivo on the spore and mycelium surface. They can also restore the growth of aerial hyphae to a chaplin mutant strain. We show that cysteine residues are not required for fibril formation in vitro and propose a role for the cysteine residues conserved in four of the five short chaplin peptides

Thermal behaviour of Anopheles stephensi in response to infection with malaria and fungal entomopathogens

<p>Abstract</p> <p>Background</p> <p>Temperature is a critical determinant of the development of malaria parasites in mosquitoes, and hence the geographic distribution of malaria risk, but little is known about the thermal preferences of <it>Anopheles</it>. A number of other insects modify their thermal behaviour in response to infection. These alterations can be beneficial for the insect or for the infectious agent. Given current interest in developing fungal biopesticides for control of mosquitoes, <it>Anopheles stephensi </it>were examined to test whether mosquitoes showed thermally-mediated behaviour in response to infection with fungal entomopathogens and the rodent malaria, <it>Plasmodium yoelii</it>.</p> <p>Methods</p> <p>Over two experiments, groups of <it>An. stephensi </it>were infected with one of three entomopathogenic fungi, and/or <it>P. yoelii</it>. Infected and uninfected mosquitoes were released on to a thermal gradient (14 – 38°C) for "snapshot" assessments of thermal preference during the first five days post-infection. Mosquito survival was monitored for eight days and, where appropriate, oocyst prevalence and intensity was assessed.</p> <p>Results and conclusion</p> <p>Both infected and uninfected <it>An. stephensi </it>showed a non-random distribution on the gradient, indicating some capacity to behaviourally thermoregulate. However, chosen resting temperatures were not altered by any of the infections. There is thus no evidence that thermally-mediated behaviours play a role in determining malaria prevalence or that they will influence the performance of fungal biopesticides against adult <it>Anopheles</it>.</p