Lung epithelial cells interact with immune cells and bacteria to shape the microenvironment in tuberculosis

The lung epithelium has long been overlooked as a key player in tuberculosis disease. In addition to acting as a direct barrier to Mycobacterium tuberculosis (Mtb), epithelial cells (EC) of the airways and alveoli act as first responders during Mtb infections; they directly sense and respond to Mtb by producing mediators such as cytokines, chemokines and antimicrobials. Interactions of EC with innate and adaptive immune cells further shape the immune response against Mtb. These three essential components, epithelium, immune cells and Mtb, are rarely studied in conjunction, owing in part to difficulties in coculturing them. Recent advances in cell culture technologies offer the opportunity to model the lung microenvironment more closely. Herein, we discuss the interplay between lung EC, immune cells and Mtb and argue that modelling these interactions is of key importance to unravel early events during Mtb infection.

Risky interpretations across the length scales: continuum vs. discrete models for soft tissue mechanobiology

Modelling and simulation in mechanobiology play an increasingly important role to unravel the complex mechanisms that allow resident cells to sense and respond to mechanical cues. Many of the in vivo mechanical loads occur on the tissue length scale, thus raising the essential question how the resulting macroscopic strains and stresses are transferred across the scales down to the cellular and subcellular levels. Since cells anchor to the collagen fibres within the extracellular matrix, the reliable representation of fibre deformation is a prerequisite for models that aim at linking tissue biomechanics and cell mechanobiology. In this paper, we consider the two-scale mechanical response of an affine structural model as an example of a continuum mechanical approach and compare it with the results of a discrete fibre network model. In particular, we shed light on the crucially different mechanical properties of the ‘fibres’ in these two approaches. While assessing the capability of the affine structural approach to capture the fibre kinematics in real tissues is beyond the scope of our study, our results clearly show that neither the macroscopic tissue response nor the microscopic fibre orientation statistics can clarify the question of affinity.

Revitalizing Strategic Agility in a Turbulent Environment: A Conceptual Discourse

This paper conceptually examined revitalizing strategic agility in a turbulent environment. In the current turbulent and highly competitive environment of today, agility, that is the ability of organizations to quickly sense and respond to environmental changes, is an important determinant of organizational success. With the advancement of information technologies, company strategy focuses nowadays on sustainable competitive advantage, and gives importance to short-term advantages of flexibility and fast response. In the unpredictable and competitive world of today, organizations must have different competitive features to compete; otherwise, they will move towards annihilation. One of the capabilities that organizations need in the turbulent environments of today is agility. Strategic agility is the ability to continuously and adequately adjust and adapt in appropriate time the strategic direction in core business in relation to changing circumstances. Agility provides the organization with the possibility of quick response and compatibility with environment and allows the organization to improve its efficiency. The paper is largely conceptual in nature and adopts a desk research methodology in reviewing extant literature. This study concludes that firms operating in dynamic environments must realize the need for change and adaptation and thereby stimulate their in developing agility that can better respond to a dynamic environment.

Two-Component Systems of S. aureus: Signaling and Sensing Mechanisms

Staphylococcus aureus encodes 16 two-component systems (TCSs) that enable the bacteria to sense and respond to changing environmental conditions. Considering the function of these TCSs in bacterial survival and their potential role as drug targets, it is important to understand the exact mechanisms underlying signal perception. The differences between the sensing of appropriate signals and the transcriptional activation of the TCS system are often not well described, and the signaling mechanisms are only partially understood. Here, we review present insights into which signals are sensed by histidine kinases in S. aureus to promote appropriate gene expression in response to diverse environmental challenges.

Xenobiotic receptors and the regulation of intestinal homeostasis - harnessing the chemical output of the intestinal microbiota

The commensal bacteria that reside in the gastrointestinal tract exist in a symbiotic relationship with the host, driving the development of the immune system and maintaining metabolic and tissue homeostasis in the local environment. The intestinal microbiota has the capacity to generate a wide array of chemical metabolites to which the cells of the intestinal mucosa are exposed. Host cells express xenobiotic receptors, such as the aryl hydrocarbon receptor (AhR) and pregnane X receptor (PXR), that can sense and respond to chemicals that are generated by non-host pathways. In this review, we will outline the physiological and immunological processes within the intestinal environment that are regulated by microbial metabolites through the activation of the AhR and PXR, with a focus on ligands generated by the step-wise catabolism of tryptophan.

The ColR/S two-component system is a conserved determinant of host association across Pseudomonas species

Members of the bacterial genus Pseudomonas form mutualistic, commensal and pathogenic associations with diverse hosts. The prevalence of host association across the genus suggests that symbiosis may be a conserved ancestral trait and that distinct symbiotic lifestyles may be more recently evolved. Here we show that the ColR/S two-component system, part of the Pseudomonas core genome, is functionally conserved between Pseudomonas aeruginosa and Pseudomonas fluorescens. Using plant rhizosphere colonization and virulence in a murine abscess model, we show that colR is required for commensalism with plants and virulence in animals. Comparative transcriptomics revealed that the ColR regulon has diverged between P. aeruginosa and P. fluorescens and deleting components of the ColR regulon revealed strain-specific, but not host specific, requirements for ColR-dependent genes. Collectively, our results suggest that ColR/S allows Pseudomonas to sense and respond to a host, but that the ColR-regulon has diverged between Pseudomonas strains with distinct lifestyles.

Transcriptome Reveals the Dynamic Response Mechanism of Pearl Millet Roots under Drought Stress

Drought is a major threat to global agricultural production that limits the growth, development and survival rate of plants, leading to tremendous losses in yield. Pearl millet (Cenchrus americanus (L.) Morrone) has an excellent drought tolerance, and is an ideal plant material for studying the drought resistance of cereal crops. The roots are crucial organs of plants that experience drought stress, and the roots can sense and respond to such conditions. In this study, we explored the mechanism of drought tolerance of pearl millet by comparing transcriptomic data under normal conditions and drought treatment at four time points (24 h, 48 h, 96 h, and 144 h) in the roots during the seedling stage. A total of 1297, 2814, 7401, and 14,480 differentially expressed genes (DEGs) were found at 24 h, 48 h, 96 h, and 144 h, respectively. Based on Kyoto Encyclopedia of Genes and Genomes and Gene Ontology enrichment analyses, we found that many DEGs participated in plant hormone-related signaling pathways and the “oxidoreductase activity” pathway. These results should provide a theoretical basis to enhance drought resistance in other plant species.

The role of cell-matrix interactions in connective tissue mechanics

Living tissue is able to withstand large stresses in everyday life, yet it also actively adapts to dynamic loads. This remarkable mechanical behaviour emerges from the interplay between living cells and their non-living extracellular environment. Here we review recent insights into the biophysical mechanisms involved in the reciprocal interplay between cells and the extracellular matrix and how this interplay determines tissue mechanics, with a focus on connective tissues. We first describe the roles of the main macromolecular components of the extracellular matrix in regards to tissue mechanics. We then proceed to highlight the main routes via which cells sense and respond to their biochemical and mechanical extracellular environment. Next we introduce the three main routes via which cells can modify their extracellular environment: exertion of contractile forces, secretion and deposition of matrix components, and matrix degradation. Finally we discuss how recent insights in the mechanobiology of cell-matrix interactions are furthering our understanding of the pathophysiology of connective tissue diseases and cancer, and facilitating the design of novel strategies for tissue engineering.

Emerging Microfluidic Approaches for Platelet Mechanobiology and Interplay With Circulatory Systems

Understanding how platelets can sense and respond to hemodynamic forces in disturbed blood flow and complexed vasculature is crucial to the development of more effective and safer antithrombotic therapeutics. By incorporating diverse structural and functional designs, microfluidic technologies have emerged to mimic microvascular anatomies and hemodynamic microenvironments, which open the floodgates for fascinating platelet mechanobiology investigations. The latest endothelialized microfluidics can even recapitulate the crosstalk between platelets and the circulatory system, including the vessel walls and plasma proteins such as von Willebrand factor. Hereby, we highlight these exciting microfluidic applications to platelet mechanobiology and platelet–circulatory system interplay as implicated in thrombosis. Last but not least, we discuss the need for microfluidic standardization and summarize the commercially available microfluidic platforms for researchers to obtain reproducible and consistent results in the field.

Hidden structure in disordered proteins is adaptive to intracellular changes

Intrinsically disordered protein regions (IDRs) are ubiquitous in all proteomes and essential to cellular function. Unlike folded domains, IDRs exist in an ensemble of rapidly changing conformations. The sequence-encoded structural biases in IDR ensembles are important for function, but are difficult to resolve. Here, we reveal hidden structural preferences in IDR ensembles in vitro with two orthogonal structural methods (SAXS and FRET), and demonstrate that these structural preferences persist in cells using live cell microscopy. Importantly, we demonstrate that some IDRs have structural preferences that can adaptively respond to even mild intracellular environment changes, while other IDRs may display a remarkable structural resilience. We propose that the ability to sense and respond to changes in cellular physicochemical composition, or to resist such changes, is a sequence-dependent property of IDRs in organisms across all kingdoms of life.