Mboat7 down-regulation by hyper-insulinemia induces fat accumulation in hepatocytes

BACKGROUND: Naturally occurring variation in Membrane-bound O-acyltransferase domain-containing 7 (MBOAT7), encoding for an enzyme involved in phosphatidylinositol acyl-chain remodelling, has been associated with fatty liver and hepatic disorders. Here, we examined the relationship between hepatic Mboat7 down-regulation and fat accumulation. METHODS: Hepatic MBOAT7 expression was surveyed in 119 obese individuals and in experimental models. MBOAT7 was acutely silenced by antisense oligonucleotides in C57Bl/6 mice, and by CRISPR/Cas9 in HepG2 hepatocytes. FINDINGS: In obese individuals, hepatic MBOAT7 mRNA decreased from normal liver to steatohepatitis, independently of diabetes, inflammation and MBOAT7 genotype. Hepatic MBOAT7 levels were reduced in murine models of fatty liver, and by hyper-insulinemia. In wild-type mice, Mboat7 was down-regulated by refeeding and insulin, concomitantly with insulin signalling activation. Acute hepatic Mboat7 silencing promoted hepatic steatosis in vivo and enhanced expression of fatty acid transporter Fatp1. MBOAT7 deletion in hepatocytes reduced the incorporation of arachidonic acid into phosphatidylinositol, consistently with decreased enzymatic activity, determining the accumulation of saturated triglycerides, enhanced lipogenesis and FATP1 expression, while FATP1 deletion rescued the phenotype. INTERPRETATION: MBOAT7 down-regulation by hyper-insulinemia contributes to hepatic fat accumulation, impairing phosphatidylinositol remodelling and up-regulating FATP1. FUNDING: LV was supported by MyFirst Grant AIRC n.16888, Ricerca Finalizzata Ministero della Salute RF-2016-02,364,358, Ricerca corrente Fondazione IRCCS Ca\u27 Granda Ospedale Maggiore Policlinico; LV and AG received funding from the European Union Programme Horizon 2020 (No. 777,377) for the project LITMUS- Liver Investigation: Testing Marker Utility in Steatohepatitis . MM was supported by Fondazione Italiana per lo Studio del Fegato (AISF) \u27Mario Coppo\u27 fellowship

Strange quark asymmetry in the nucleon and the NuTeV anomaly

The NuTeV anomaly of a non-universal value of the fundamental parameter sin^2\theta_W in the electroweak theory has been interpreted as an indication for new physics beyond the Standard Model. However, the observed quantity depends on a possible asymmetry in the momentum distributions of strange quarks and antiquarks in the nucleon. This asymmetry occurs naturally in a phenomenologically successful physical model for such parton distributions, which reduces the NuTeV result to only about two standard deviations from the Standard Model.Comment: 4 pages, 5 figures, RevTex4. Updated with new references and extended discussion. v.3: Minor corrections mad

Storing images in warm atomic vapor

Reversible and coherent storage of light in atomic medium is a key-stone of future quantum information applications. In this work, arbitrary two-dimensional images are slowed and stored in warm atomic vapor for up to 30 $\mu$s, utilizing electromagnetically induced transparency. Both the intensity and the phase patterns of the optical field are maintained. The main limitation on the storage resolution and duration is found to be the diffusion of atoms. A techniqueanalogous to phase-shift lithography is employed to diminish the effect of diffusion on the visibility of the reconstructed image

A Formulaic Analysis of Samples Taken from the Shahnama of Firdowsi

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Sequence organization of feline leukemis virus DNA in infected cells

A restriction site map has been deduced of unintegrated and integrated FeLV viral DNA found in human RD cells after experimental infection with the Gardner-Arnstein strain of FeLV. Restriction fragments were ordered by single and double enzyme digests followed by Southern transfer (1) and hybridization with 32P-labeled viral cDNA probes. The restriction map was oriented with respect to the 5' and 3' ends of viral RNA by using a 3' specific hybridization probe. The major form of unintegrated viral DNA found was a 8.7 kb linear DNA molecule bearing a 450 bp direct long terminal redundancy (LTR) derived from both 5' and 3' viral RNA sequences. Minor, circular forms, 8.7 kb and 8.2 kb in length were also detected, the larger one probably containing two adjacent copies of the LTR and the smaller one containing one copy of the LTR. Integrated copies of FeLV are colinear with the unintegrated linear form and contain the KpnI and SmaI sites found in each LTR

Neoclassical realism and the collapse of the 1994 Agreed Framework

The collapse of the 1994 Agreed Framework in early 2003 has had far reaching consequences for the diplomatic relationship of the United States and North Korea. In the following thesis, neoclassical realist theory is applied to the collapse of the Agreed Framework in an effort to gain insight on the importance of domestic level variables in the successful implementation of foreign policy. The thesis also provides a roadmap for American policy makers toward the successful construction of a lasting nuclear agreement between the United States and Democratic People\u27s Republic of Korea

Measurement of Dicke Narrowing in Electromagnetically Induced Transparency

Dicke narrowing is a phenomena that dramatically reduces the Doppler width of spectral lines, due to frequent velocity-changing collisions. A similar phenomena occurs for electromagnetically induced transparency (EIT) resonances, and facilitates ultra-narrow spectral features in room-temperature vapor. We directly measure the Dicke-like narrowing by studying EIT line-shapes as a function of the angle between the pump and the probe beams. The measurements are in good agreement with an analytic theory with no fit parameters. The results show that Dicke narrowing can increase substantially the tolerance of hot-vapor EIT to angular deviations. We demonstrate the importance of this effect for applications such as imaging and spatial solitons using a single-shot imaging experiment, and discuss the implications on the feasibility of storing images in atomic vapor.Comment: Introduction revise