During cancer metastasis, tumor cells penetrate tissues through tight interstitial spaces, requiring extensive deformation of the cell and its nucleus. Here, we investigated tumor cell migration in confining microenvironments in vitro and in vivo. Nuclear deformation caused localized loss of nuclear envelope (NE) integrity, which led to the uncontrolled exchange of nucleo-cytoplasmic content, herniation of chromatin across the NE, and DNA damage. The incidence of NE rupture increased with cell confinement and with depletion of nuclear lamins, NE proteins that structurally support the nucleus. Cells restored NE integrity using components of the endosomal sorting complexes required for transport-III (ESCRT-III) machinery. Our findings indicate that cell migration incurs substantial physical stress on the NE and its content, requiring efficient NE and DNA damage repair for survival.
Ultraviolet germicidal irradiation (UVGI) systems can be used to decontaminate filtering facepiece respirators that are in short supply during the current COVID-19 pandemic, but are costly and scarce. n Custom-built UVGI systems can be easily and affordably created using common items found in hardware stores and within research institutions. n Health care workers and administrators should consider this setup as a cost-effective option to combat personal protective equipment (PPE) shortages during the current pandemic. n Academic institutions should consider fostering collaborations with local health care institutions to provide idle resources to front line health care workers facing PPE shortages.
The Hei photoelectron and vacuum ultraviolet spectra up to about 20 eV of CF3Be, CF2Br2, and CF2BrCl have been measured. In both spectra, we find bands at energies lower than in the corresponding chlorine derivatives. Otherwise, the spectra can be interpreted along similar lines. The lowest ionization potentials and the lowest frequency bands in the ultraviolet spectra are due to transitions from the bromine lone pair orbitals.
Congenital diaphragmatic hernia (CDH) is a developmental disorder associated with diaphragm defects and lung hypoplasia. The etiology of CDH is complex and its clinical presentation is variable. We investigated the role of the pulmonary mesothelium in dysregulated lung growth noted in the Wt1 knockout mouse model of CDH. Loss of WT1 leads to intrafetal effusions, altered lung growth, and branching defects prior to normal closure of the diaphragm. We found significant differences in key genes; however, when Wt1 null lungs were cultured ex vivo, growth and branching were indistinguishable from wild-type littermates. Micro-CT imaging of embryos in situ within the uterus revealed a near absence of space in the dorsal chest cavity, but no difference in total chest cavity volume in Wt1 null embryos, indicating a redistribution of pleural space. The altered space and normal ex vivo growth suggest that physical constraints are contributing to the CDH lung phenotype observed in this mouse model. These studies emphasize the importance of examining the mesothelium and chest cavity as a whole, rather than focusing on single organs in isolation to understand early CDH etiology.
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