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Search indexed NASA NTRS and DOE OSTI research on propulsion, heat transfer, battery materials and energy systems. Follow report and document links to the original sources.

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At least 145 records · Page 8
All sourcesNASA NTRSDOE OSTI
DOE OSTI2022

EMC3 regulates mesenchymal cell survival via control of the mitotic spindle assembly

Eukaryotic cells transit through the cell cycle to produce two daughter cells. Dysregulation of the cell cycle leads to cell death or tumorigenesis. Herein, we found a subunit of the ER membrane complex, EMC3, as a key regulator of cell cycle. Conditional deletion of Emc3 in mouse embryonic mesoderm led to reduced size and patterning defects of multiple organs. Emc3 deficiency impaired cell proliferation, causing spindle assembly defects, chromosome mis-segregation, cell cycle arrest at G2/M, and apoptosis. Upon entry into mitosis, mesenchymal cells upregulate EMC3 protein levels and localize EMC3 to the mitotic centrosomes. Further analysis indicated that EMC3 works together with VCP to tightly regulate the levels and activity of Aurora A, an essential factor for centrosome function and mitotic spindle assembly: while overexpression of EMC3 or VCP degraded Aurora A, their loss led to increased Aurora A stability but reduced Aurora A phosphorylation in mitosis.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2021

Surviving Under Pressure: The Role of Solvent, Crystal Size, and Morphology During Pelletization of Metal–Organic Frameworks

As metal–organic frameworks (MOFs) gain traction for applications, such as hydrogen storage, it is essential to form the as-synthesized powder materials into shaped bodies with high packing densities to maximize their volumetric performance. Mechanical compaction, which involves compressing the materials at high pressure, has been reported to yield high monolith density but often results in a significant loss in accessible porosity. Herein, we sought to systematically control (1) crystal size, (2) solvation, and (3) compacting pressure in the pelletization process to achieve high packing density without compromising the porosity that makes MOFs functional. It was determined that solvation is the most critical factor among the three factors examined. Solvation that exceeds the pore volume prevents the framework from collapsing, allowing for porosity to be maintained through pelletization. Higher pelletization pressure results in higher packing density, with extensive loss of porosity being observed at a higher pressure if the solvation is below the pore volume. Lastly, we observed that the morphology and size of the MOF particles result in variation in the highest achievable packing efficiency, but these numbers (75%) are still greater than many existing techniques used to form MOFs. Furthermore, we concluded that the application of pressure through pelletization is a suitable and widely applicable technique for forming high-density MOF-monoliths.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2024

Adaptative Survival of Aspergillus fumigatus to Echinocandins Arises from Cell Wall Remodeling Beyond β-1,3-glucan Synthesis Inhibition

Antifungal echinocandins inhibit the biosynthesis of β-1,3-glucan, a major and essential polysaccharide component of the fungal cell wall. However, the efficacy of echinocandins against the pathogen Aspergillus fumigatus is limited. Here, we use solid-state nuclear magnetic resonance (ssNMR) and other techniques to show that echinocandins induce dynamic changes in the assembly of mobile and rigid polymers within the A. fumigatus cell wall. The reduction of β-1,3- glucan induced by echinocandins is accompanied by a concurrent increase in levels of chitin, chitosan and highly polymorphic α-1,3-glucans, whose physical association with chitin maintains cell wall integrity and modulates water permeability. The rearrangement of the macromolecular network is dynamic and controls the permeability and circulation of the drug throughout the cell wall. Thus, our results indicate that echinocandin treatment triggers compensatory rearrangements in the cell wall that may help A. fumigatus to tolerate the drugs’ antifungal effects.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2024

A gene desert required for regulatory control of pleiotropic Shox2 expression and embryonic survival

Approximately a quarter of the human genome consists of gene deserts, large regions devoid of genes often located adjacent to developmental genes and thought to contribute to their regulation. However, defining the regulatory functions embedded within these deserts is challenging due to their large size. Here, we explore the cis-regulatory architecture of a gene desert flanking the Shox2 gene, which encodes a transcription factor indispensable for proximal limb, craniofacial, and cardiac pacemaker development. We identify the gene desert as a regulatory hub containing more than 15 distinct enhancers recapitulating anatomical subdomains of Shox2 expression. Ablation of the gene desert leads to embryonic lethality due to Shox2 depletion in the cardiac sinus venosus, caused in part by the loss of a specific distal enhancer. The gene desert is also required for stylopod morphogenesis, mediated via distributed proximal limb enhancers. In summary, our study establishes a multi-layered role of the Shox2 gene desert in orchestrating pleiotropic developmental expression through modular arrangement and coordinated dynamics of tissue-specific enhancers.

59 BASIC BIOLOGICAL SCIENCES↗