Crystal ribcage: a platform for probing real-time lung function at cellular resolution.

Understanding the dynamic pathogenesis and treatment response in pulmonary diseases requires probing the lung at cellular resolution in real time. Despite advances in intravital imaging, optical imaging of the lung during active respiration and circulation has remained challenging. Here, we introduce the crystal ribcage: a transparent ribcage that allows multiscale optical imaging of the functioning lung from whole-organ to single-cell level.

Intravital measurements of solid stresses in tumours reveal length-scale and microenvironmentally dependent force transmission.

In cancer, solid stresses impede the delivery of therapeutics to tumours and the trafficking and tumour infiltration of immune cells. Understanding such consequences and the origin of solid stresses requires their probing in vivo at the cellular scale. Here we report a method for performing volumetric and longitudinal measurements of solid stresses in vivo, and findings from its applicability to tumours.

Modeling the influence of gravity and the mechanical properties of elastin and collagen fibers on alveolar and lung pressure-volume curves.

The relationship between pressure (P) and volume (V) in the human lung has been extensively studied. However, the combined effects of gravity and the mechanical properties of elastin and collagen on alveolar and lung P-V curves during breathing are not well understood. Here, we extended a previously established thick-walled spherical model of a single alveolus with wavy collagen fibers during positive pressure inflation.

MCL-1 Inhibition by Selective BH3 Mimetics Disrupts Mitochondrial Dynamics Causing Loss of Viability and Functionality of Human Cardiomyocytes.

MCL-1 is a well-characterized inhibitor of cell death that has also been shown to be a regulator of mitochondrial dynamics in human pluripotent stem cells. We used cardiomyocytes derived from human-induced pluripotent stem cells (hiPSC-CMs) to uncover whether MCL-1 is crucial for cardiac function and survival. Inhibition of MCL-1 by BH3 mimetics resulted in the disruption of mitochondrial morphology and dynamics as well as disorganization of the actin cytoskeleton.

Deletion of Tet proteins results in quantitative disparities during ESC differentiation partially attributable to alterations in gene expression.

Background: The Tet protein family (Tet1, Tet2, and Tet3) regulate DNA methylation through conversion of 5-methylcytosine to 5-hydroxymethylcytosine which can ultimately result in DNA demethylation and play a critical role during early mammalian development and pluripotency. While multiple groups have generated knockouts combining loss of different Tet proteins in murine embryonic stem cells (ESCs), differences in genetic background and approaches has made it difficult to directly compare results and discern the direct mechanism by which Tet proteins regulate the transcriptome. To address this concern, we utilized genomic editing in an isogenic pluripotent background which permitted a quantitative, flow-cytometry based measurement of pluripotency in combination with genome-wide assessment of gene expression and DNA methylation changes.

TGF-β1 along with other platelet contents augments Treg cells to suppress anti-FVIII immune responses in hemophilia A mice.

Platelets are a rich source of many cytokines and chemokines including transforming growth factor β 1 (TGF-β1). TGF-β1 is required to convert conventional CD4 T (Tconv) cells into induced regulatory T (iTreg) cells that express the transcription factor Foxp3. Whether platelet contents will affect Treg cell properties has not been explored.