Role of angiopoietin-like protein 3 in sugar-induced dyslipidemia in rhesus macaques: suppression by fish oil or RNAi.

Angiopoietin-like protein 3 (ANGPTL3) inhibits lipid clearance and is a promising target for managing cardiovascular disease. Here we investigated the effects of a high-sugar (high-fructose) diet on circulating ANGPTL3 concentrations in rhesus macaques. Plasma ANGPTL3 concentrations increased ∼30% to 40% after 1 and 3 months of a high-fructose diet (both P < 0.001 vs. baseline). During fructose-induced metabolic dysregulation, plasma ANGPTL3 concentrations were positively correlated with circulating indices of insulin resistance [assessed with fasting insulin and the homeostatic model assessment of insulin resistance (HOMA-IR)], hypertriglyceridemia, adiposity (assessed as leptin), and systemic inflammation [C-reactive peptide (CRP)] and negatively correlated with plasma levels of the insulin-sensitizing hormone adropin. Multiple regression analyses identified a strong association between circulating APOC3 and ANGPTL3 concentrations. Higher baseline plasma levels of both ANGPTL3 and APOC3 were associated with an increased risk for fructose-induced insulin resistance. Fish oil previously shown to prevent insulin resistance and hypertriglyceridemia in this model prevented increases of ANGPTL3 without affecting systemic inflammation (increased plasma CRP and interleukin-6 concentrations). ANGPTL3 RNAi lowered plasma concentrations of ANGPTL3, triglycerides (TGs), VLDL-C, APOC3, and APOE. These decreases were consistent with a reduced risk of atherosclerosis. In summary, dietary sugar-induced increases of circulating ANGPTL3 concentrations after metabolic dysregulation correlated positively with leptin levels, HOMA-IR, and dyslipidemia. Targeting ANGPTL3 expression with RNAi inhibited dyslipidemia by lowering plasma TGs, VLDL-C, APOC3, and APOE levels in rhesus macaques

Patient-specific 3D printed model of biliary ducts with congenital cyst

Background: 3D printing has shown great promise in medical applications, with increasing reports in liver diseases. However, research on 3D printing in biliary disease is limited with lack of studies on validation of model accuracy. In this study, we presented our experience of creating a realistic 3D printed model of biliary ducts with congenital cyst. Measurements of anatomical landmarks were compared at different stages of model generation to determine dimensional accuracy. Methods: Contrast-enhanced computed tomography (CT) images of a patient diagnosed with congenital cyst in the common bile duct with dilated hepatic ducts were used to create the 3D printed model. The 3D printed model was scanned on a 64-slice CT scanner using the similar abdominal CT protocol. Measurements of anatomical structures including common hepatic duct (CHD), right hepatic duct (RHD), left hepatic duct (LHD) and the cyst at left to right and anterior to posterior dimensions were performed and compared between original CT images, the standard tessellation language (STL) image and CT images of the 3D model. Results: The 3D printing model was successfully generated with replication of biliary ducts and cyst. Significant differences in measurements of these landmarks were found between the STL and the original CT images, and the CT images of the 3D printed model and the original CT images (

Genomic characterization of Gli-activator targets in sonic hedgehog-mediated neural patterning

Sonic hedgehog (Shh) acts as a morphogen to mediate the specification of distinct cell identities in the ventral neural tube through a Gli-mediated (Gli1-3) transcriptional network. Identifying Gli targets in a systematic fashion is central to the understanding of the action of Shh. We examined this issue in differentiating neural progenitors in mouse. An epitope-tagged Gli-activator protein was used to directly isolate cis-regulatory sequences by chromatin immunoprecipitation (ChIP). ChIP products were then used to screen custom genomic tiling arrays of putative Hedgehog (Hh) targets predicted from transcriptional profiling studies, surveying 50-150 kb of non-transcribed sequence for each candidate. In addition to identifying expected Gli-target sites, the data predicted a number of unreported direct targets of Shh action. Transgenic analysis of binding regions in Nkx2.2, Nkx2.1 (Titf1) and Rab34 established these as direct Hh targets. These data also facilitated the generation of an algorithm that improved in silico predictions of Hh target genes. Together, these approaches provide significant new insights into both tissue-specific and general transcriptional targets in a crucial Shh-mediated patterning process

Demonstrating Photon Ring Existence with Single-Baseline Polarimetry

Images of supermassive black hole accretion flows contain features of both curved spacetime and plasma structure. Inferring properties of the spacetime from images requires modeling the plasma properties, and vice versa. The Event Horizon Telescope Collaboration has imaged near-horizon millimeter emission from both Messier 87* (M87*) and Sagittarius A* (Sgr A*) with very-long-baseline interferometry (VLBI) and has found a preference for magnetically arrested disk (MAD) accretion in each case. MAD accretion enables spacetime measurements through future observations of the photon ring, the image feature composed of near-orbiting photons. The ordered fields and relatively weak Faraday rotation of MADs yield rotationally symmetric polarization when viewed at modest inclination. In this letter, we utilize this symmetry along with parallel transport symmetries to construct a gain-robust interferometric quantity that detects the transition between the weakly lensed accretion flow image and the strongly lensed photon ring. We predict a shift in polarimetric phases on long baselines and demonstrate that the photon rings in M87* and Sgr A* can be unambiguously detected {with sensitive, long-baseline measurements. For M87* we find that photon ring detection in snapshot observations requires $\sim1$ mJy sensitivity on $>15$ G$\lambda$ baselines at 230 GHz and above, which could be achieved with space-VLBI or higher-frequency ground-based VLBI. For Sgr A*, we find that interstellar scattering inhibits photon ring detectability at 230 GHz, but $\sim10$ mJy sensitivity on $>12$ G$\lambda$ baselines at 345 GHz is sufficient, which is accessible from the ground. For both sources, these sensitivity requirements may be relaxed by repeated observations and averaging.Comment: 14 pages, 7 figures, Accepted to ApJ

Quantitative relationships between benthic diatom assemblages and water chemistry in Macquarie Island lakes and their potential for reconstructing past environmental changes

This study is the first published survey of diatom-environment relationships Oil sub-Antarctic Macquarie Island. Fifty-eight sites in 50 coastal and inland lakes were sampled for benthic diatoms and water chemistry. 208 diatom species from 34 genera were identified. Multivariate analyses indicated that the lakes were distributed along nutrient and conductivity gradients. Conductivity, pH, phosphate (SRP), silicate and temperature all explained independent portions of the variance in the diatom data. Transfer functions provide a quantitative basis for palaeolimnological studies of past climate change and human impacts, and can be used to establish baseline conditions for assessing the impacts of recent climate change and the introduction of non-native plants and animals. Statistically robust diatom transfer functions for conductivity, phosphate and silicate were developed, while pH and temperature transfer functions performed less well. The lower predictive abilities of the pH and temperature transfer functions probably reflect the broad pH tolerance range of diatoms on Macquarie Island and uneven distribution of lakes along the temperature gradient. This study contributes to understanding the current ecological distribution of Macquarie Island diatoms and provides transfer functions that will be applied in studies of diatoms in lake sediment cores to quantitatively reconstruct past environmental changes