Background: Tau protein is believed to be stationary while bound to microtubules. Results: Tau molecules can diffuse along microtubules over distances up to several micrometers. Conclusion: Tau diffusion on microtubules is a novel mechanism for Tau dispersion in cells. Significance: Modulation of Tau binding and diffusion on microtubules by local modifications of microtubules can provide a tool to target Tau to specific cellular compartments.

SummaryThe mitotic spindle in eukaryotic cells is composed of a bipolar array of microtubules (MTs) and associated proteins that are required during mitosis for the correct partitioning of the two sets of chromosomes to the daughter cells. In addition to the well-established functions of MT-associated proteins (MAPs) and MT-based motors in cell division, there is increasing evidence that the F-actin-based myosin motors are important mediators of F-actin-MT interactions during mitosis. Here, we report the functional characterization of the long-tailed class-1 myosin myosin-1C from Dictyostelium discoideum during mitosis. Our data reveal that myosin-1C binds to MTs and has a role in maintenance of spindle stability for accurate chromosome separation. Both myosin-1C motor function and taildomain-mediated MT-F-actin interactions are required for the cell-cycle-dependent relocalization of the protein from the cell periphery to the spindle. We show that the association of myosin-1C with MTs is mediated through the tail domain. The myosin-1C tail can inhibit kinesin motor activity, increase the stability of MTs, and form crosslinks between MTs and F-actin. These data illustrate that myosin-1C is involved in the regulation of MT function during mitosis in D. discoideum.

Purpose To evaluate the feasibility and effect of an approach to adrenal venous sampling (AVS) analysis by combining established selective cortisol and aldosterone indices with the acquisition of a collimated C-arm CT(CACTColl). Methods Overall, 107 consecutive patients (45f,62 m; 54 ± 10 years) undergoing 111 AVS procedures without hormonal stimulation from 7/13 to 2/20 in a single institution were retrospectively analysed. Hormone levels were measured in sequential samples of the suspected adrenal veins and right iliac vein, and selectivity indices (SI) computed. Stand-alone SICortisol and/or SIAldosterone ≥ 2.0 as well as SICortisol and/or SIAldosterone ≥ 1.1 combined with positive right-sided CACTColl of the adrenals (n = 80; opacified right adrenal vein) were defined as a successful AVS procedure. Radiation exposure of CACT was measured via dose area product (DAP) and weighed against an age-/weight-matched cohort (n = 66). Results Preliminary success rates (SICortisol and/or SIAldosterone ≥ 2.0) were 99.1% (left) and 72.1% (right). These could be significantly increased to a 90.1% success rate on the right, by combining an adjusted SI of 1.1 with a positive CACTColl proving the correct sampling position. Sensitivity for stand-alone collimated CACT (CACTColl) was 0.93, with 74/80 acquired CACTColl confirming selective cannulation by adrenal vein enhancement. Mean DAPColl_CACT measured 2414 ± 958 μGyxm2, while mean DAPFull-FOV_CACT in the matched cohort measured 8766 ± 1956 μGyxm2 (p < 0.001). Conclusion Collimated CACT in AVS procedures is feasible and leads to a significant increase in success rates of (right-sided) selective cannulation and may in combination with adapted hormone indices, offer a successful alternative to previously published AVS analysis algorithms with lower radiation exposure compared to a full-FOV CACT.

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Pulmonary arteriovenous malformations (PAVMs) are low-resistance, high-flow vascular structures that create a shunt in the pulmonary circulation. This shunting affects regional and systemic hemodynamics in Hereditary Hemorrhagic Telangiectasia (HHT). We hypothesized that this could lead to differential cardiac presentations in this setting. Thus, we investigated the cardiac structural and functional differences between HHT patients with PAVMs (HHT-P) compared to other presentations of HHT (HHT-O). Materials and Methods: We conducted a retrospective, crosssectional, single-center study of HHT patients who underwent transthoracic echocardiograms (TTE) between 2005 and 2020. HHT diagnosis was determined by Curacao score of !3 or positive genetic testing. PAVM diagnosis was made by angiography. Results: 176 HHT-O and 125 HHT-P patients were included. HHT-O patients had severely dilated right ventricles (RVIDD) and reduced tricuspid annular plane systolic excursion (TAPSE), a parameter of right ventricular (RV) function. In the left heart, HHT-O patients had larger left atriums (LASD) and increased mitral E/e' ratios, signifying elevated left sided filling pressures. HHT-O patients also had larger left ventricular diameters (LVEDD), lengths (LVEDL), and septal and posterior wall thicknesses (IVSd and LVPW). Cardiac output (CO) and stroke volumes were not significantly different (Table ). Conclusions: In our study, HHT patients without PAVMs had differences in right and left ventricular structure and function suggestive of a potential trend toward adverse remodeling as indicated by large right ventricles and thicker walls. PAVMs may therefore have a cardioprotective effect in HHT. Longitudinal studies should investigate these changes in cardiac structure/function to understand potential cardiovascular effects of PAVM embolization in this setting.