Regulator of calcineurin-2 is a centriolar protein with a role in cilia length control

Almost every cell in the human body extends a primary cilium. Defective cilia function leads to a set of disorders known as ciliopathies characterised by debilitating developmental defects affecting many tissues. Here we report a new role for regulator of calcineurin 2, RCAN2, in primary cilia function. It localises to centrioles and the basal body and is required to maintain normal cilia length. RCAN2 was identified as the most strongly upregulated gene from a comparative RNAseq analysis of cells in which expression of the Golgi matrix protein giantin had been abolished by gene editing. In contrast to previous work where we showed that depletion of giantin by RNAi results in defects in ciliogenesis and in cilia length control, giantin knockout cells generate normal cilia on serum withdrawal. Furthermore, giantin knockout zebrafish show increased expression of RCAN2. Importantly, suppression of RCAN2 expression in giantin knockout cells results in the same defects in cilia length control seen on RNAi of giantin itself. Together these data define RCAN2 as a regulator of cilia function that can compensate for loss of giantin function.</jats:p

Non-Standard Errors

In statistics, samples are drawn from a population in a data-generating process (DGP). Standard errors measure the uncertainty in estimates of population parameters. In science, evidence is generated to test hypotheses in an evidence-generating process (EGP). We claim that EGP variation across researchers adds uncertainty: Non-standard errors (NSEs). We study NSEs by letting 164 teams test the same hypotheses on the same data. NSEs turn out to be sizable, but smaller for better reproducible or higher rated research. Adding peer-review stages reduces NSEs. We further find that this type of uncertainty is underestimated by participants

Using Vaccinia virus as a model system to understand microtubule-based transport

Vaccinia virus is a great model system for studying the cell cytoskeleton as it efficiently hijacks both the actin and microtubule network during infection. Intracellular mature virions (IMV) are the first infectious form of the virus produced during replication and are released when the cell undergoes lysis. A subset of IMV undergo envelopment at the Golgi to become intracellular enveloped virions (IEV) which recruit kinesin-1 to undergo microtubule-based transport from their perinuclear site of assembly to the plasma membrane. Limited work indicates that IMV can also be transported on microtubules. However, we have little or no molecular understanding of how this is achieved. This understudied area of vaccinia virus cell biology is surprising given that IMV comprise the majority of infectious virions formed during infection. I have now used a combination of cell-based and in vitro approaches to gain insights into IMV motility. Unexpectedly, I found that IMV also recruit kinesin-1 to move on microtubules in infected cells, although at a much lower levels compared to IEV. Using CRISPR/Cas9 genome edited cells expressing endogenously GFP-tagged kinesin-1, I have determined the number of kinesin-1 motors on virions and find that IMV recruit on average ~50% fewer motors than IEV. Additionally, for the first time, I have shown that these motors remain stably attached to the virus for long periods without undergoing turnover. I have also reconstituted IMV motility on purified microtubules in vitro using extracts from infected cells. In this system, IMV virions are very processive, typically moving to the very ends of the microtubule. Using polarity-marked microtubules, I found that IMV are exclusively plus-end directed, moving at an average velocity of ~0.65 μm/s. Furthermore, there is near complete loss of IMV motility in vitro in the absence of kinesin-1. Consistent with this, there is also a defect in intracellular IMV spread in cells lacking kinesin-1. My observations now demonstrate that kinesin-1 transports IMV as well as IEV during vaccinia infection. Moreover, reconstitution of vaccinia virus microtubule-based motility in vitro provides a useful new tool to investigate kinesin-1 driven transport of IMV and IEV in a system that is both biochemically accessible and tuneable to the user requirements

Findings from a qualitative study

Pinto Lopes, D., Rita, P., & Treiblmaier, H. (2021). The impact of blockchain on the aviation industry: Findings from a qualitative study. Research in Transportation Business and Management, 41(December), 1-12. [100669]. https://doi.org/10.1016/j.rtbm.2021.100669The aviation industry is searching for innovative solutions to boost its business in a sector that operates on a financial knife-edge driven by fierce competition. This paper seeks to identify how blockchain, an immutable and append-only data ledger, can impact the aviation industry. This study presents the results from 18 interviews with industry experts. Text mining and a thematic data analysis were combined to investigate the likelihood of the airline industry adopting a disruptive technology that has the potential to affect various stakeholders and replace current platforms. The connection between the key terms and emergent themes is visualised and discussed in detail. The current attitude as well as the expectations and uncertainties of the aviation industry towards blockchain are systematised. The five core topics determining the adoption of blockchain by the industry are specific adoption factors, the replacement of current centralised platforms, customer loyalty, adoption barriers and a general lack of awareness. All topics are discussed in detail, and concrete propositions for future academic research are put forward.authorsversionpublishe

Animal models reveal role for tau phosphorylation in human disease

Many proteins that are implicated in human disease are posttranslationally modified. This includes the microtubule-associated protein tau that is deposited in a hyperphosphorylated form in brains of Alzheimer's disease patients. The focus of this review article is on the physiological and pathological phosphorylation of tau; the relevance of aberrant phosphorylation for disease; the role of kinases and phosphatases in this process; its modeling in transgenic mice, flies, and worms; and implications of phosphorylation for therapeutic intervention

Non-Standard Errors

In statistics, samples are drawn from a population in a data-generating process (DGP). Standard errors measure the uncertainty in estimates of population parameters. In science, evidence is generated to test hypotheses in an evidence-generating process (EGP). We claim that EGP variation across researchers adds uncertainty: Non-standard errors (NSEs). We study NSEs by letting 164 teams test the same hypotheses on the same data. NSEs turn out to be sizable, but smaller for better reproducible or higher rated research. Adding peer-review stages reduces NSEs. We further find that this type of uncertainty is underestimated by participants

Non-Standard Errors

In statistics, samples are drawn from a population in a data-generating process (DGP). Standard errors measure the uncertainty in sample estimates of population parameters. In science, evidence is generated to test hypotheses in an evidence-generating process (EGP). We claim that EGP variation across researchers adds uncertainty: non-standard errors. To study them, we let 164 teams test six hypotheses on the same sample. We find that non-standard errors are sizeable, on par with standard errors. Their size (i) co-varies only weakly with team merits, reproducibility, or peer rating, (ii) declines significantly after peer-feedback, and (iii) is underestimated by participants