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      Metabolically driven maturation of human-induced-pluripotent-stem-cell-derived cardiac microtissues on microfluidic chips

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          Ultra-sensitive fluorescent proteins for imaging neuronal activity

          Summary Fluorescent calcium sensors are widely used to image neural activity. Using structure-based mutagenesis and neuron-based screening, we developed a family of ultra-sensitive protein calcium sensors (GCaMP6) that outperformed other sensors in cultured neurons and in zebrafish, flies, and mice in vivo. In layer 2/3 pyramidal neurons of the mouse visual cortex, GCaMP6 reliably detected single action potentials in neuronal somata and orientation-tuned synaptic calcium transients in individual dendritic spines. The orientation tuning of structurally persistent spines was largely stable over timescales of weeks. Orientation tuning averaged across spine populations predicted the tuning of their parent cell. Although the somata of GABAergic neurons showed little orientation tuning, their dendrites included highly tuned dendritic segments (5 - 40 micrometers long). GCaMP6 sensors thus provide new windows into the organization and dynamics of neural circuits over multiple spatial and temporal scales.
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            Metadata matters: access to image data in the real world

            Data sharing is important in the biological sciences to prevent duplication of effort, to promote scientific integrity, and to facilitate and disseminate scientific discovery. Sharing requires centralized repositories, and submission to and utility of these resources require common data formats. This is particularly challenging for multidimensional microscopy image data, which are acquired from a variety of platforms with a myriad of proprietary file formats (PFFs). In this paper, we describe an open standard format that we have developed for microscopy image data. We call on the community to use open image data standards and to insist that all imaging platforms support these file formats. This will build the foundation for an open image data repository.
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              Advanced maturation of human cardiac tissue grown from pluripotent stem cells

              Cardiac tissues generated from human induced pluripotent stem (iPS) cells can serve as platforms for patient-specific studies of physiology and disease 1–6 . The predictive power of these models remains limited by their immature state 1,2,5,6 . We show that this fundamental limitation could be overcome if cardiac tissues are formed from early iPS-derived cardiomyocytes (iPS-CM), soon after the initiation of spontaneous contractions, and subjected to physical conditioning of an increasing intensity. After only 4 weeks of culture, these tissues displayed adult-like gene expression profiles, remarkably organized ultrastructure, physiologic sarcomere length (2.2 μm) and density of mitochondria (30%), the presence of transverse tubules (t-tubules), oxidative metabolism, positive force-frequency relationship, and functional calcium handling for all iPS cell lines studied. Electromechanical properties developed more slowly and did not achieve the stage of maturity seen in adult human myocardium. Tissue maturity was necessary for achieving physiologic responses to isoproterenol and recapitulating pathological hypertrophy, in support of the utility of this tissue model for studies of cardiac development and disease.
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                Author and article information

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                Journal
                Nature Biomedical Engineering
                Nat. Biomed. Eng
                Springer Science and Business Media LLC
                2157-846X
                April 2022
                April 27 2022
                April 2022
                : 6
                : 4
                : 372-388
                Article
                10.1038/s41551-022-00884-4
                35478228
                4a9a4139-56a2-4160-b07a-c67dfbadfcc9
                © 2022

                https://www.springer.com/tdm

                https://www.springer.com/tdm

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