The large intestine, with its array of crypts lining the epithelium and diverse luminal contents, regulates homeostasis throughout the body. In vitro crypts formed from primary human intestinal epithelial stem cells on a 3D shaped hydrogel scaffold replicate the functional and architectural features of in vivo crypts. Collagen scaffolding assembly methods are provided, along with the microfabrication and soft lithography…
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Characterizing Viral Infection by Electron Microscopy

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, causing coronavirus disease 2019 (COVID-19), has presented many challenges and spurred intense investigations into the pathogenesis of this disease. In addition to respiratory disease, many patients with SARS-CoV-2 infection are experiencing systemic illnesses, including kidney failure, heart failure, liver injury, neurologic dysfunction, and skin manifestations (eg, COVID toe). The etiology and…
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The SARS-CoV-2 virus is causing a global pandemic and cases continue to rise. Most infected individuals experience mildly symptomatic coronavirus disease 2019 (COVID-19), but it is unknown whether this can induce persistent immune memory that could contribute to immunity. We performed a longitudinal assessment of individuals recovered from mild COVID-19 to determine if they develop and sustain multifaceted SARS-CoV-2-specific immunological…
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While the effect of bacterial molecules on the host immune system is well studied, how host factors affect the expression of bacterial molecules is less appreciated. Here we uncover the impact of inflammasome activation and type 1 interferon on the expression of bacterial flagellin. Flagellin induces NLRC4 inflammasome-mediated pyroptosis causing clearance of Salmonella. We show that inflammasome activation also produces lysophospholipids…
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AMD3100 (plerixafor) is a vital component of many clinical and pre-clinical transplant protocols, facilitating harvest of hematopoietic stem and progenitor cells through mobilization into the peripheral blood circulation. Repeat mobilization with AMD3100 is also necessary for many patients with suboptimal first stem cell collection or those requiring repeat transplantation. In this study we investigated the mobilization efficacy of repeated AMD3100…
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Rhabdomyosarcoma (RMS) is a devastating pediatric sarcoma. The survival outcomes remain poor for patients with relapsed or metastatic disease. Effective targeted therapy is lacking due to our limited knowledge of the underlying cellular and molecular mechanisms leading to disease progression. In this study, we used functional assays in vitro and in vivo (zebrafish and xenograft mouse models) to demonstrate the…
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Neurons are frequently classified into distinct types on the basis of structural, physiological, or genetic attributes. To better constrain the definition of neuronal cell types, we characterized the transcriptomes and intrinsic physiological properties of over 4,200 mouse visual cortical GABAergic interneurons and reconstructed the local morphologies of 517 of those neurons. We find that most transcriptomic types (t-types) occupy specific…
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Our study highlights an important limitation of most current cfDNA or "liquid biopsy" testing for men with prostate cancer. We found that blood cell mutations were commonly detected in blood plasma, and that these mutations could be misinterpreted as coming from prostate cancer. The results have important implications for guiding therapy with a newer class of cancer drugs called PARP inhibitors.
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Understanding the trajectory of a developing human requires an understanding of how genes are regulated and expressed. Two papers now present a pooled approach using three levels of combinatorial indexing to examine the single-cell gene expression and chromatin landscapes from 15 organs in fetal samples. Cao et al. focus on measurements of RNA in broadly distributed cell types and provide insights into…
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Understanding the trajectory of a developing human requires an understanding of how genes are regulated and expressed. Two papers now present a pooled approach using three levels of combinatorial indexing to examine the single-cell gene expression and chromatin landscapes from 15 organs in fetal samples. Cao et al. focus on measurements of RNA in broadly distributed cell types and provide insights into…
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