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The TAM tyrosine kinases, Axl and MerTK, play an important role in rheumatoid arthritis (RA). Here, using a unique synovial tissue bioresource of patients with RA matched for disease stage and treatment exposure, we assessed how Axl and MerTK relate to synovial histopathology and disease activity, and their topographical expression and longitudinal modulation by targeted treatments. We show that in treatment-naive patients, high AXL levels are associated with pauci-immune histology and low disease activity and inversely correlate with the expression levels of pro-inflammatory genes. We define the location of Axl/MerTK in rheumatoid synovium using immunohistochemistry/fluorescence and digital spatial profiling and show that Axl is preferentially expressed in the lining layer. Moreover, its ectodomain, released in the synovial fluid, is associated with synovial histopathology. We also show that Toll-like-receptor 4-stimulated synovial fibroblasts from patients with RA modulate MerTK shedding by macrophages. Lastly, Axl/MerTK synovial expression is influenced by disease stage and therapeutic intervention, notably by IL-6 inhibition. These findings suggest that Axl/MerTK are a dynamic axis modulated by synovial cellular features, disease stage and treatment. The TAM tyrosine kinases, Axl and MerTK, have been implicated in rheumatoid arthritis (RA). Here, using a synovial tissue bioresource of patients with RA, the authors describe how Axl and MerTK expression and function are linked to synovial histopathology, disease activity, and therapeutic intervention with IL-6 inhibitors.

Efficient long-range axonal transport is essential for maintaining neuronal function, and perturbations in this process underlie severe neurological diseases. We have previously demonstrated that signalling endosomes are transported in vivo at comparable speeds across motor neurons (MNs) innervating different hindlimb muscles, as well as between forelimb and hindlimb peripheral nerves. In contrast, axonal transport is faster in MNs compared to sensory neurons innervating the same muscle. Found periodically across the myelin sheath, Nodes of Ranvier (NoR) are short uncovered axonal domains that facilitate action potential propagation. Currently, it remains unresolved how the distinct molecular structures of the NoR impact axonal transport dynamics. Here, using intravital time-lapse microscopy of sciatic nerves in live, anaesthetised mice, we assessed diverse organelle dynamics at the NoR. We first observed that axonal morphologies were similar between fast and slow MNs, and found that signalling endosomes and mitochondria accumulate on the distal side of the NoR in both motor neuron subtypes. Assessment of axonal transport of signalling endosomes and mitochondria revealed a decrease in velocity and increase in pausing as the organelles transit through the NoR, followed by an increase in speed in the adjacent intranodal region. Collectively, this study has established axonal transport dynamics of two independent organelles at the NoR in vivo, and has relevance for several pathologies affecting peripheral nerves and the NoR, such as peripheral neuropathy, motor neuron diseases, and/or multiple sclerosis.

How can cognitive biases affect the birth and evolution of entrepreneurial ventures? In Entrepreneurial Decision Making (EDM), this lively research question remains largely unaddressed when the world of Unicorns, as a per se entrepreneurial species, is considered. Thus, through this conceptual article, we aim to contribute toward knowledge creation in this context. We start by proposing a conceptual framework of Unicorns’ EDM based on a behavioral approach. Through three propositions, this novel framework advances how the birth, transition, and consolidation of a Unicorn may be explained by the sequentially intertwined occurrence of biases, from which establishment and legitimization eventually emerge. We complement the framework with examples from the social media industry and then discuss its main implications for theory and practice.

Purpose Unicorn companies, such as Facebook, Uber, and Airbnb, significantly impact our economies. This happens although they had a dramatic initial start – at least in terms of financial performance – that would have let any other “conventional” business close. In other words, Unicorns challenge the start-ups’ problems traditionally associated with early failure (liability of newness). This paper aims to understand what helps Unicorn firms initially survive despite huge losses. Design/methodology/approach By adopting a behavioral lens, this historical case study article focuses on key strategic decisions regarding the famous social media Unicorn Snapchat from 2011 to 2022. The case combines secondary data and a thematic analysis of Snapchat founders’ and investors’ interviews/comments to identify the behavioral antecedents leading to Snapchat’s honeymoon. Findings Snapchat network effect triggered cognitive biases of Snapchat founders’ and investors’ decisions, leading them to provide initial assets (i.e. beliefs/goodwill, trust, financial resources and psychological commitment) to the nascent Unicorn. Therefore, the network effect and biases resulted in significant antecedents for Snapchat’s honeymoon. Originality/value The authors propose a general, theoretical framework advancing the possible impact of biases on Unicorns’ initial survival. The authors argue that some biases of the Unicorns’ founders and investors can positively support a honeymoon period for these new ventures. This is one of the first case studies drawing on a behavioral approach in general and on biases in particular to investigate the liability of newness in the Unicorns’ context.