JAK inhibition differentially affects NK cell and ILC1 homeostasis

Janus kinase (JAK) inhibitors are widely used in the treatment of multiple autoimmune and inflammatory diseases. Immunologic and transcriptomic profiling have revealed major alterations on natural killer (NK) cell homeostasis associated with JAK inhibitions, while information on other innate lymphoid cells (ILCs) is still lacking. Herein, we observed that, in mice, the homeostatic pool of liver ILC1 was less affected by JAK inhibitors compared to the pool of NK cells present in the liver, spleen and bone marrow. JAK inhibition had overlapping effects on the transcriptome of both subsets, mainly affecting genes regulating cell cycle and apoptosis. However, the differential impact of JAK inhibition was linked to the high levels of the antiapoptotic gene Bcl2 expressed by ILC1. Our findings provide mechanistic explanations for the effects of JAK inhibitors on NK cells and ILC1 which could be of major clinically relevance

Spatial and temporal modulation of cell instructive cues in a filamentous supramolecular biomaterial

Supramolecular materials provide unique opportunities to mimic both the structure and mechanics of the biopolymer networks that compose the extracellular matrix. However, strategies to modify their filamentous structures in space and time in 3D cell culture to study cell behavior as encountered in development and disease are lacking. We herein disclose a multicomponent squaramide-based supramolecular material whose mechanics and bioactivity can be controlled by light through co-assembly of a 1,2-dithiolane (DT) monomer that forms disulfide cross-links. Remarkably, increases in storage modulus from ∼200 Pa to >10 kPa after stepwise photo-cross-linking can be realized without an initiator while retaining colorlessness and clarity. Moreover, viscoelasticity and plasticity of the supramolecular networks decrease upon photo-irradiation, reducing cellular protrusion formation and motility when performed at the onset of cell culture. When applied during 3D cell culture, force-mediated manipulation is impeded and cells move primarily along earlier formed channels in the materials. Additionally, we show photopatterning of peptide cues in 3D using either a photomask or direct laser writing. We demonstrate that these squaramide-based filamentous materials can be applied to the development of synthetic and biomimetic 3D in vitro cell and disease models, where their secondary cross-linking enables mechanical heterogeneity and shaping at multiple length scales

Macro level factors influencing strategic responses to emergent pandemics: a scoping review

Background: Strategic planning is critical for successful pandemic management. This study aimed to identify and review the scope and analytic depth of situation analyses conducted to understand their utility, and capture the documented macro-level factors impacting pandemic management. Methods: To synthesise this disparate body of literature, we adopted a two-step search and review process. A systematic search of the literature was conducted to identify all studies since 2000, that have 1) employed a situation analysis; and 2) examined contextual factors influencing pandemic management. The included studies are analysed using a seven-domain systems approach from the discipline of strategic management. Results: Nineteen studies were included in the final review ranging from single country (6) to regional, multi-country studies (13). Fourteen studies had a single disease focus, with 5 studies evaluating responses to one or more of COVID-19, Severe Acute Respiratory Syndrome (SARS), Middle East Respiratory Syndrome (MERS), Influenza A (H1N1), Ebola virus disease, and Zika virus disease pandemics. Six studies examined a single domain from political, economic, sociological, technological, ecological or wider industry (PESTELI), 5 studies examined two to four domains, and 8 studies examined five or more domains. Methods employed were predominantly literature reviews. The recommendations focus predominantly on addressing inhibitors in the sociological and technological domains with few recommendations articulated in the political domain. Overall, the legislative domain is least represented. Conclusions: Ex-post analysis using the seven-domain strategic management framework provides further opportunities for a planned systematic response to pandemics which remains critical as the current COVID-19 pandemic evolves

Macro level factors influencing strategic responses to emergent pandemics: A scoping review.

BackgroundStrategic planning is critical for successful pandemic management. This study aimed to identify and review the scope and analytic depth of situation analyses conducted to understand their utility, and capture the documented macro-level factors impacting pandemic management.MethodsTo synthesise this disparate body of literature, we adopted a two-step search and review process. A systematic search of the literature was conducted to identify all studies since 2000, that have 1) employed a situation analysis; and 2) examined contextual factors influencing pandemic management. The included studies are analysed using a seven-domain systems approach from the discipline of strategic management.ResultsNineteen studies were included in the final review ranging from single country (6) to regional, multi-country studies (13). Fourteen studies had a single disease focus, with 5 studies evaluating responses to one or more of COVID-19, Severe Acute Respiratory Syndrome (SARS), Middle East Respiratory Syndrome (MERS), Influenza A (H1N1), Ebola virus disease, and Zika virus disease pandemics. Six studies examined a single domain from political, economic, sociological, technological, ecological or wider industry (PESTELI), 5 studies examined two to four domains, and 8 studies examined five or more domains. Methods employed were predominantly literature reviews. The recommendations focus predominantly on addressing inhibitors in the sociological and technological domains with few recommendations articulated in the political domain. Overall, the legislative domain is least represented.ConclusionsEx-post analysis using the seven-domain strategic management framework provides further opportunities for a planned systematic response to pandemics which remains critical as the current COVID-19 pandemic evolves

A Fast pH-Switchable and Self-Healing Supramolecular Hydrogel Carrier for Guided, Local Catheter Injection in the Infarcted Myocardium

Minimally invasive intervention strategies after myocardial infarction use state-of-the-art catheter systems that are able to combine mapping of the infarcted area with precise, local injection of drugs. To this end, catheter delivery of drugs that are not immediately pumped out of the heart is still challenging, and requires a carrier matrix that in the solution state can be injected through a long catheter, and instantaneously gelates at the site of injection. To address this unmet need, a pH-switchable supramolecular hydrogel is developed. The supramolecular hydrogel is switched into a liquid at pH > 8.5, with a viscosity low enough to enable passage through a 1-m long catheter while rapidly forming a hydrogel in contact with tissue. The hydrogel has self-healing properties taking care of adjustment to the injection site. Growth factors are delivered from the hydrogel thereby clearly showing a reduction of infarct scar in a pig myocardial infarction model