Cardiac 4D phase-contrast CMR at 9.4 T using self-gated ultra-short echo time (UTE) imaging

Background: Time resolved 4D phase contrast (PC) cardiovascular magnetic resonance (CMR) in mice is challenging due to long scan times, small animal ECG-gating and the rapid blood flow and cardiac motion of small rodents. To overcome several of these technical challenges we implemented a retrospectively self-gated 4D PC radial ultra-short echo-time (UTE) acquisition scheme and assessed its performance in healthy mice by comparing the results with those obtained with an ECG-triggered 4D PC fast low angle shot (FLASH) sequence. Methods: Cardiac 4D PC CMR images were acquired at 9.4 T in healthy mice using the proposed self-gated radial center-out UTE acquisition scheme (TE/TR of 0.5 ms/3.1 ms) and a standard Cartesian 4D PC imaging sequence (TE/TR of 2.1 ms/5.0 ms) with a four-point Hadamard flow encoding scheme. To validate the proposed UTE flow imaging technique, experiments on a flow phantom with variable pump rates were performed. Results: The anatomical images and flow velocity maps of the proposed 4D PC UTE technique showed reduced artifacts and an improved SNR (left ventricular cavity (LV): 8.9 +/- 2.5, myocardium (MC): 15.7 +/- 1.9) compared to those obtained using a typical Cartesian FLASH sequence (LV: 5.6 +/- 1.2, MC: 10.1 +/- 1.4) that was used as a reference. With both sequences comparable flow velocities were obtained in the flow phantom as well as in the ascending aorta (UTE: 132.8 +/- 18.3 cm/s, FLASH: 134.7 +/- 13.4 cm/s) and pulmonary artery (UTE: 78.5 +/- 15.4 cm/s, FLASH: 86.6 +/- 6. 2 cm/s) of the animals. Self-gated navigator signals derived from information of the oversampled k-space center were successfully extracted for all animals with a higher gating efficiency of time spent on acquiring gated data versus total measurement time (UTE: 61.8 +/- 11.5%, FLASH: 48.5 +/- 4.9%). Conclusions: The proposed self-gated 4D PC UTE sequence enables robust and accurate flow velocity mapping of the mouse heart in vivo at high magnetic fields. At the same time SNR, gating efficiency, flow artifacts and image quality all improved compared to the images obtained using the well-established, ECG-triggered, 4D PC FLASH sequenc

Multigram Synthesis of Isobutyl-β-<i>C</i>-galactoside as a Substitute of Isopropylthiogalactoside for Exogenous Gene Induction in Mammalian Cells

Herein we report that isobutyl-β-<i>C</i>-galactoside (IBCG) is also a promising inducer of gene expression in mammalian cells and report a new synthetic route to the compound that should make obtaining the multigram quantities of material required for animal studies more feasible. A convenient synthesis of IBCG, an inducer of genes controlled by the <i>lac</i> operon system in bacterial cells, was achieved in 5 steps from galactose in 81% overall yield without any chromatographic separation steps. An optimized microwave-assisted reaction at high concentration was key to making the <i>C-</i>glycosidic linkage. A Wittig reaction on a per<i>-O</i>-silylated rather than per-<i>O</i>-acetylated or -benzylated substrate proved most effective in installing the final carbon atom

Structure of the no-go mRNA decay complex Dom34-Hbs1 bound to a stalled 80S ribosome

No-go decay (NGD) is a mRNA quality-control mechanism in eukaryotic cells that leads to degradation of mRNAs stalled during translational elongation. The key factors triggering NGD are Dom34 and Hbs1. We used cryo-EM to visualize NGD intermediates resulting from binding of the Dom34-Hbs1 complex to stalled ribosomes. At subnanometer resolution, all domains of Dom34 and Hbs1 were identified, allowing the docking of crystal structures and homology models. Moreover, the close structural similarity of Dom34 and Hbs1 to eukaryotic release factors (eRFs) enabled us to propose a model for the ribosome-bound eRF1-eRF3 complex. Collectively, our data provide structural insights into how stalled mRNA is recognized on the ribosome and how the eRF complex can simultaneously recognize stop codons and catalyze peptide release