The Effect of Shelter on Oxidative Stress and Aggressive Behavior in Crested Newt Larvae (Triturus spp.)

Shelters are important for animal survival. Provision of adequate hiding places allow animals to express their natural sheltering behavior and it can have different positive effects on cortisol levels, physiological processes and mental performance. Although the absence of a refuge activates some stress response, its effect on oxidative stress has not been adequately examined. This study investigated whether the presence/absence of a shelter modifies the oxidative status (the antioxidant system and oxidative damage) and aggressive behavior of crested newt larvae (Triturus macedonicus and its hybrid with T. ivanbureschi). Our results show that individuals reared with shelters had lower values of the tested antioxidant parameters (catalase, glutathione peroxidase, glutathione S-transferase and glutathione), indicating a lower production of reactive species than individuals reared without shelter. The same pattern was observed in both T. macedonicus and its hybrid. Contrary to the activation of some physiological pathways, shelter availability did not significantly affect the rate of intraspecific aggressive behavior. The physiological benefits of shelter use can be manifested as a lower requirement for investment in the energy necessary for the maintenance of the upregulated antioxidant defenses, activation of repair systems and synthesis of endogenous antioxidants. This study highlights the importance of shelter provision, which may be valuable in habitat restoration and animal conservation studies

Lung epithelial tip progenitors integrate glucocorticoid- and STAT3-mediated signals to control progeny fate.

Insufficient alveolar gas exchange capacity is a major contributor to lung disease. During lung development, a population of distal epithelial progenitors first produce bronchiolar-fated and subsequently alveolar-fated progeny. The mechanisms controlling this bronchiolar-to-alveolar developmental transition remain largely unknown. We developed a novel grafting assay to test if lung epithelial progenitors are intrinsically programmed or if alveolar cell identity is determined by environmental factors. These experiments revealed that embryonic lung epithelial identity is extrinsically determined. We show that both glucocorticoid and STAT3 signalling can control the timing of alveolar initiation, but that neither pathway is absolutely required for alveolar fate specification; rather, glucocorticoid receptor and STAT3 work in parallel to promote alveolar differentiation. Thus, developmental acquisition of lung alveolar fate is a robust process controlled by at least two independent extrinsic signalling inputs. Further elucidation of these pathways might provide therapeutic opportunities for restoring alveolar capacity.Medical Research Council (G0900424, ER), the March of Dimes (5-FY11-119, ER), the Wellcome Trust (093029, ER), Newton Trust (14.07h, ER), Wellcome Trust PhD programme for Clinicians (MN), Postdoctoral Fellowship from the Government of the Basque Country (UL), MRC studentship (RVR), British Heart Foundation Studentship (EJB), COST BM1201. Core grants from the Wellcome Trust (092096) and Cancer Research UK (C6946/A14492).This is the final version of the article. It first appeared from the Company of Biologists at http://dx.doi.org/10.1242/dev.134023

From the pathophysiology of the human lung alveolus to epigenetic editing: Congress 2018 highlights from ERS Assembly 3 "Basic and Translational Science."

The European Respiratory Society (ERS) International Congress is the largest respiratory congress and brings together leading experts in all fields of respiratory medicine and research. ERS Assembly 3 shapes the basic and translational science aspects of this congress, aiming to combine cutting-edge novel developments in basic research with novel clinical findings. In this article, we summarise a selection of the scientific highlights from the perspective of the three groups within Assembly 3. In particular, we discuss new insights into the pathophysiology of the human alveolus, novel tools in organoid development and (epi)genome editing, as well as insights from the presented abstracts on novel therapeutic targets being identified for idiopathic pulmonary fibrosis.S

Noninterventional statistical comparison of BTS and CHEST guidelines for size and severity in primary pneumothorax.

Hilar rather than apical interpleural distance more accurately predicts need for intercostal chest drain insertion http://ow.ly/JvKFYThe study was funded by the East Anglian Thoracic Society. M.Z. Nikolić is a Wellcome Trust PhD Programme for Clinicians Fellow at the University of Cambridge. S.J. Marciniak is a Medical Research Council Senior Clinical Fellow. J. Wason is funded by the Cambridge Biomedical Research Centre. Funding information for this article has been deposited with FundRef.This is the final version of the article. It first appeared from the European Respiratory Society via http://dx.doi.org/10.1183/09031936.0011861

Biological basis for novel mesothelioma therapies

Funder: British Lung Foundation (BLF); doi: https://doi.org/10.13039/501100000351Funder: Royal Society through a University Research Fellowship and the Engineering and Physical Sciences Research Council (EPRSC)Funder: China Scholarship Council (CSC); doi: https://doi.org/10.13039/501100004543Abstract: Mesothelioma is an aggressive cancer that is associated with exposure to asbestos. Although asbestos is banned in several countries, including the UK, an epidemic of mesothelioma is predicted to affect middle-income countries during this century owing to their heavy consumption of asbestos. The prognosis for patients with mesothelioma is poor, reflecting a failure of conventional chemotherapy that has ultimately resulted from an inadequate understanding of its biology. However, recent work has revolutionised the study of mesothelioma, identifying genetic and pathophysiological vulnerabilities, including the loss of tumour suppressors, epigenetic dysregulation and susceptibility to nutrient stress. We discuss how this knowledge, combined with advances in immunotherapy, is enabling the development of novel targeted therapies

Human embryonic lung epithelial tips are multipotent progenitors that can be expanded in vitro as long-term self-renewing organoids.

The embryonic mouse lung is a widely used substitute for human lung development. For example, attempts to differentiate human pluripotent stem cells to lung epithelium rely on passing through progenitor states that have only been described in mouse. The tip epithelium of the branching mouse lung is a multipotent progenitor pool that self-renews and produces differentiating descendants. We hypothesized that the human distal tip epithelium is an analogous progenitor population and tested this by examining morphology, gene expression and in vitro self-renewal and differentiation capacity of human tips. These experiments confirm that human and mouse tips are analogous and identify signalling pathways that are sufficient for long-term self-renewal of human tips as differentiation-competent organoids. Moreover, we identify mouse-human differences, including markers that define progenitor states and signalling requirements for long-term self-renewal. Our organoid system provides a genetically-tractable tool that will allow these human-specific features of lung development to be investigated

Mapping interindividual dynamics of innate immune response at single-cell resolution

Common genetic variants across individuals modulate the cellular response to pathogens and are implicated in diverse immune pathologies, yet how they dynamically alter the response upon infection is not well understood. Here, we triggered antiviral responses in human fibroblasts from 68 healthy donors, and profiled tens of thousands of cells using single-cell RNA-sequencing. We developed GASPACHO (GAuSsian Processes for Association mapping leveraging Cell HeterOgeneity), a statistical approach designed to identify nonlinear dynamic genetic effects across transcriptional trajectories of cells. This approach identified 1,275 expression quantitative trait loci (local false discovery rate 10%) that manifested during the responses, many of which were colocalized with susceptibility loci identified by genome-wide association studies of infectious and autoimmune diseases, including the OAS1 splicing quantitative trait locus in a COVID-19 susceptibility locus. In summary, our analytical approach provides a unique framework for delineation of the genetic variants that shape a wide spectrum of transcriptional responses at single-cell resolution

Early human lung immune cell development and its role in epithelial cell fate

Studies of human lung development have focused on epithelial and mesenchymal cell types and function, but much less is known about the developing lung immune cells, even though the airways are a major site of mucosal immunity after birth. An unanswered question is whether tissue-resident immune cells play a role in shaping the tissue as it develops in utero. Here, we profiled human embryonic and fetal lung immune cells using scRNA-seq, smFISH, and immunohistochemistry. At the embryonic stage, we observed an early wave of innate immune cells, including innate lymphoid cells, natural killer cells, myeloid cells, and lineage progenitors. By the canalicular stage, we detected naive T lymphocytes expressing high levels of cytotoxicity genes and the presence of mature B lymphocytes, including B-1 cells. Our analysis suggests that fetal lungs provide a niche for full B cell maturation. Given the presence and diversity of immune cells during development, we also investigated their possible effect on epithelial maturation. We found that IL-1β drives epithelial progenitor exit from self-renewal and differentiation to basal cells in vitro. In vivo, IL-1β-producing myeloid cells were found throughout the lung and adjacent to epithelial tips, suggesting that immune cells may direct human lung epithelial development

A spatially resolved atlas of the human lung characterizes a gland-associated immune niche

Single-cell transcriptomics has allowed unprecedented resolution of cell types/states in the human lung, but their spatial context is less well defined. To (re)define tissue architecture of lung and airways, we profiled five proximal-to-distal locations of healthy human lungs in depth using multi-omic single cell/nuclei and spatial transcriptomics (queryable at lungcellatlas.org ). Using computational data integration and analysis, we extend beyond the suspension cell paradigm and discover macro and micro-anatomical tissue compartments including previously unannotated cell types in the epithelial, vascular, stromal and nerve bundle micro-environments. We identify and implicate peribronchial fibroblasts in lung disease. Importantly, we discover and validate a survival niche for IgA plasma cells in the airway submucosal glands (SMG). We show that gland epithelial cells recruit B cells and IgA plasma cells, and promote longevity and antibody secretion locally through expression of CCL28, APRIL and IL-6. This new 'gland-associated immune niche' has implications for respiratory health

Single-cell multi-omics analysis of the immune response in COVID-19

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