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Abstract Background With increased attention to the importance of integrating the One Health approach into zoonotic disease surveillance and response, a greater understanding of the mechanisms to support effective communication and information sharing across animal and human health sectors is needed. The objectives of this qualitative case study were to describe the communication channels used between human and animal health stakeholders and to identify the elements that have enabled the integration of the One Health approach. Methods We combined documentary research with interviews with fifteen stakeholders to map the communication channels used in human and swine influenza surveillance in Alberta, Canada, as well as in the response to a human case of H1N2v in 2020. A thematic analysis of the interviews was also used to identify the barriers and facilitators to communication among stakeholders from the animal and human health sectors. Results When a human case of swine influenza emerged, the response led by the provincial Chief Medical Officer of Health involved players at various levels of government and in the human and animal health sectors. The collaboration of public and animal health laboratories and of the swine sector, in addition to the information available through the surveillance systems in place, was swift and effective. Elements identified as enabling smooth communication between the human and animal health systems included preexisting relationships between the various stakeholders, a relationship of trust between them (e.g., the swine sector and their perception of government structures), the presence of stakeholders acting as permanent liaisons between the ministries of health and agriculture, and stakeholders' understanding of the importance of the One Health approach. Conclusions Information flows through formal and informal channels and both structural and relational features that can support rapid and effective communication in infectious disease surveillance and outbreak response.

Heart failure with preserved ejection fraction (HFpEF) is a complex syndrome associated with increased myocardial stiffness and cardiac filling abnormalities. Prior studies implicated increased α-tubulin detyrosination, which is catalyzed by the vasohibin enzymes, as a contributor to increased stabilization of the cardiomyocyte microtubule network (MTN) and stiffness in failing human hearts. We explored whether increased MTN detyrosination contributed to impaired diastolic function in the ZSF1 obese rat model of HFpEF and designed a small-molecule vasohibin inhibitor to ablate MTN detyrosination in vivo. Compared with ZSF1 lean and Wistar Kyoto rats, obese rats exhibited increased tubulin detyrosination concomitant with diastolic dysfunction, left atrial enlargement, and cardiac hypertrophy with a preserved left ventricle ejection fraction, consistent with an HFpEF phenotype. Ex vivo myocardial phenotyping assessed cardiomyocyte mechanics and contractility. Vasohibin inhibitor treatment of isolated cardiomyocytes from obese rats resulted in reduced stiffness and faster relaxation. Acute in vivo treatment with vasohibin inhibitor improved diastolic relaxation in ZSF1 obese rats compared with ZSF1 lean and Wistar Kyoto rats. Vasohibin inhibition also improved relaxation in isolated human cardiomyocytes from both failing and nonfailing hearts. Our data suggest the therapeutic potential for vasohibin inhibition to reduce myocardial stiffness and improve relaxation in HFpEF.

The two related members of the vasohibin family, VASH1 and VASH2, encode human tubulin detyrosinases. Here we demonstrate that, in contrast to VASH1, which requires binding of small vasohibin binding protein (SVBP), VASH2 has autonomous tubulin detyrosinating activity. Moreover, we demonstrate that SVBP acts as a bona fide activator of both enzymes. Phylogenetic analysis of the vasohibin family revealed that regulatory diversification of VASH-mediated tubulin detyrosination coincided with early vertebrate evolution. Thus, as a model organism for functional analysis, we used Trypanosoma brucei (Tb), an evolutionarily early-branched eukaryote that possesses a single VASH and encodes a terminal tyrosine on both α- and β-tubulin tails, both subject to removal. Remarkably, although detyrosination levels are high in the flagellum, TbVASH knockout parasites did not present any noticeable flagellar abnormalities. In contrast, we observed reduced proliferation associated with profound morphological and mitotic defects, underscoring the importance of tubulin detyrosination in cell division., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

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., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)