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Plasmonic catalysis in the colloidal phase requires robust surface ligands that prevent particles from aggregation in adverse chemical environments and allow carrier flow from reagents to nanoparticles. This work describes the use of a water-soluble conjugated polymer comprising a thiophene moiety as a surface ligand for gold nanoparticles to create a hybrid system that, under the action of visible light, drives the conversion of the biorelevant NAD+ to its highly energetic reduced form NADH. A combination of advanced microscopy techniques and numerical simulations revealed that the robust metal–polymer heterojunction, rich in sulfonate functional groups, directs the interaction of electron-donor molecules with the plasmonic photocatalyst. The tight binding of polymer to the gold surface precludes the need for conventional transition-metal surface cocatalysts, which were previously shown to be essential for photocatalytic NAD+ reduction but are known to hinder the optical properties of plasmonic nanocrystals. Moreover, computational studies indicated that the coating polymer fosters a closer interaction between the sacrificial electron-donor triethanolamine and the nanoparticles, thus enhancing the reactivity., This work was supported by grant PID2019-111772RB-I00 funded by MCIN/AEI/10.13039/501100011033 and grant IT 1254-19 funded by Basque Government. The authors acknowledge the financial support of the European Commission (EUSMI, Grant 731019). S.B. is grateful to the European Research Council (ERC-CoG-2019 815128).

PURPOSE The dimensional accuracy of three-dimensional (3D) printed anatomical models is essential to correctly understand spatial relationships and enable safe presurgical planning. Most recent accuracy studies focused on 3D printing of a single pathology for surgical planning. This study evaluated the accuracy of medical models across multiple pathologies, using desktop inverted vat photopolymerization (VP) to 3D print anatomic models using both rigid and elastic materials. METHODS In the primary study, we 3D printed seven models (six anatomic models and one reference cube) with volumes ranging from ~2 to ~209 cc. The anatomic models spanned multiple pathologies (neurological, cardiovascular, abdominal, musculoskeletal). Two solid measurement landing blocks were strategically created around the pathology to allow high-resolution measurement using a digital micrometer and/or caliper. The physical measurements were compared to the designed dimensions, and further analysis was conducted regarding the observed patterns in accuracy. All of the models were printed in three resins: Elastic, Clear, and Grey Pro in the primary experiments. A full factorial block experimental design was employed and a total of 42 models were 3D printed in 21 print runs. In the secondary study, we 3D printed two of the anatomic models in triplicates selected from the previous six to evaluate the effect of 0.1 mm vs 0.05 mm layer height on the accuracy. RESULTS In the primary experiment, all dimensional errors were less than 1 mm. The average dimensional error across the 42 models was 0.238 ± 0.219 mm and the relative error was 1.10 ± 1.13%. Results from the secondary experiments were similar with an average dimensional error of 0.252 ± 0.213 mm and relative error of 1.52% ± 1.28% across 18 models. There was a statistically significant difference in the relative errors between the Elastic resin and Clear resin groups. We explained this difference by evaluating inverted VP 3D printing peel forces. There was a significant difference between the Solid and Hollow group of models. There was a significant difference between measurement landing blocks oriented Horizontally and Vertically. In the secondary experiments, there was no difference in accuracy between the 0.10 and 0.05 mm layer heights. CONCLUSIONS The maximum measured error was less than 1 mm across all models, and the mean error was less than 0.26mm. Therefore, inverted VP 3D printing technology is suitable for medical 3D printing if 1 mm is considered the cutoff for clinical use cases. The 0.1 mm layer height is suitable for 3D printing accurate anatomical models for presurgical planning in a majority of cases. Elastic models, models oriented horizontally, and models that are hollow tend to have relatively higher deviation as seen from experimental results and mathematical model predictions. While clinically insignificant using a 1 mm cutoff, further research is needed to better understand the complex physical interactions in VP 3D printing which influence model accuracy.

Summary: Tubulin glutamylation is a reversible posttranslational modification that accumulates on stable microtubules (MTs). While abnormally high levels of this modification lead to a number of disorders such as male sterility, retinal degeneration, and neurodegeneration, very little is known about the molecular mechanisms underlying the regulation of glutamylase activity. Here, we found that CSAP forms a complex with TTLL5, and we demonstrate that the two proteins regulate their reciprocal abundance. Moreover, we show that CSAP increases TTLL5-mediated glutamylation and identify the TTLL5-interacting domain. Deletion of this domain leads to complete loss of CSAP activating function without impacting its MT binding. Binding of CSAP to TTLL5 promotes relocalization of TTLL5 toward MTs. Finally, we show that CSAP binds and activates all of the remaining autonomously active TTLL glutamylases. As such, we present CSAP as a major regulator of tubulin glutamylation and associated functions. : Bompard et al. describe an activator of tubulin glutamylases that modify the microtubule-based cytoskeleton. They find that CSAP forms a complex with TTLL5, which controls its localization and activity on microtubules. Keywords: posttranslational modification, MAPs, microtubule dynamics, severing, brain, tubulin code

BMP10 is highly expressed in the developing heart and plays essential roles in cardiogenesis. BMP10 deletion in mice results in embryonic lethality because of impaired cardiac development. In adults, BMP10 expression is restricted to the right atrium, though ventricular hypertrophy is accompanied by increased BMP10 expression in a rat hypertension model. However, reports of BMP10 activity in the circulation are inconclusive. In particular, it is not known whether in vivo secreted BMP10 is active or whether additional factors are required to achieve its bioactivity. It has been shown that high-affinity binding of the BMP10 prodomain to the mature ligand inhibits BMP10 signaling activity in C2C12 cells, and it was proposed that prodomain-bound BMP10 (pBMP10) complex is latent. In this study, we demonstrated that the BMP10 prodomain did not inhibit BMP10 signaling activity in multiple endothelial cells, and that recombinant human pBMP10 complex, expressed in mammalian cells and purified under native conditions, was fully active. In addition, both BMP10 in human plasma and BMP10 secreted from the mouse right atrium were fully active. Finally, we confirmed that active BMP10 secreted from mouse right atrium was in the prodomain-bound form. Our data suggest that circulating BMP10 in adults is fully active and that the reported vascular quiescence function of BMP10 in vivo is due to the direct activity of pBMP10 and does not require an additional activation step. Moreover, being an active ligand, recombinant pBMP10 may have therapeutic potential as an endothelial-selective BMP ligand, in conditions characterized by loss of BMP9/10 signaling.

SummaryMicrotubules are filamentous polymers essential for cell viability. Microtubule plus-end tracking proteins (+TIPs) associate with growing microtubule plus ends and control microtubule dynamics and interactions with different cellular structures during cell division, migration, and morphogenesis. EB1 and its homologs are highly conserved proteins that play an important role in the targeting of +TIPs to microtubule ends, but the underlying molecular mechanism remains elusive. By using live cell experiments and in vitro reconstitution assays, we demonstrate that a short polypeptide motif, Ser-x-Ile-Pro (SxIP), is used by numerous +TIPs, including the tumor suppressor APC, the transmembrane protein STIM1, and the kinesin MCAK, for localization to microtubule tips in an EB1-dependent manner. Structural and biochemical data reveal the molecular basis of the EB1-SxIP interaction and explain its negative regulation by phosphorylation. Our findings establish a general “microtubule tip localization signal” (MtLS) and delineate a unifying mechanism for this subcellular protein targeting process.