In
recent years, the importance of safety in academic research
laboratories has gained considerable attention nationwide. The University
of Chicago Joint Research Safety Initiative (JRSI) is a community
of graduate students, postdoctoral researchers, and research assistants
in the Department of Chemistry and Pritzker School of Molecular Engineering,
whose focus is to facilitate a sustainable lab safety culture by providing
educational tools, training, and resources that are presented in an
organized, clear, and centralized fashion. Our organization was established
in Fall 2017 to address the safety needs of our research community
with a bottom-up approach. Here, we provide a brief account of how
the JRSI designed activities around five themes: (1) Developing Organizational
Structure, (2) Evaluating Safety Culture and Organizational Effectiveness,
(3) Facilitating Open Dialogues and Collaborations, (4) Defragmenting
Safety Efforts and Resources, and (5) Educating Researchers, Teachers,
and Safety Contacts. In each of these areas, we discuss programs and
highlight lessons learned that can assist in analogous student-led
implementation strategies. This Case Study does not provide an exhaustive
list of solutions for all safety-related deficiencies; rather, it
strives to bring special attention to the general background, core
ideas, reflections, and encountered challenges when forming a new
researcher-led safety initiative.
While -Synuclein, an intrinsically disordered protein linked to Parkinson's disease, has been shown to associate with membrane organelles, its overall cellular function remains nebulous. -Synuclein binds to membranes through its amino-terminal domain (first ~ 100 residues), but there is no This article is protected by copyright. All rights reserved. 2 consensus on the biophysical function of the carboxyl-terminal domain (last ~ 40 residues) due, in part, to its lack of strong interaction partners and persisting intrinsic disorder even when membranebound. Here, by directly applying force on -Synuclein bound to spherical nanoparticle-supported lipid bilayers (SSLBs) and tracking higher-order structural changes through small-angle X-ray scattering, we present strong evidence that -Synuclein sterically stabilizes membrane surfaces through its carboxyl-terminal domain. Full-length -Synuclein dramatically increases the critical osmotic pressure at which SSLBs cluster (P C ~ 1.3 x 10 5 Pa) compared to -Synuclein without the carboxyl-terminal domain (P C ~ 1.9 x 10 4 Pa) at physiological salt and temperature conditions. We show this clustering of -Synuclein-bound SSLBs to be reversible and sensitive to monovalent/divalent salt, both features of grafted polyelectrolyte-mediated steric stabilization. In elucidating the biophysical function of -Synuclein in the framework of polymer science, we demonstrate that the carboxyl-terminal domain can potentially utilize its persisting intrinsic disorder to functionalize membrane surfaces.
The title compound, C9H7FO, crystallizes with two independent molecules in the asymmetric unit, in which corresponding bond lengths are the same within experimental error. The five-membered ring in each molecule is almost planar, with r.m.s. deviations of 0.016 and 0.029 Å. In the crystal, molecules form sheets parallel to (1 0 0) via C—H⋯O and C—H⋯F interactions with F⋯F contacts [3.1788 (16) and 3.2490 (16) Å] between the sheets.
A primary target in cancer research, the p53 tumor suppressor protein, is a transcription activator playing an integral role in the regulation of the cell cycle. Through binding to DNA, the protein has the ability to “turn on” other repair proteins to mend damaged DNA, inhibit cellular division, and initiate apoptosis in cells that are damaged beyond repair. Most inactive p53 mutants contain changes primarily localized to the DNA binding domain (DBD). While intensive research has been conducted on different p53 mutants, previous studies have not yet focused on the capability for the system to exhibit direct and indirect readout among various genomic sites. Consequently, the L1 loop, a structural feature of the DBD, participates in binding to sequences exhibiting differences in the readout mechanism. This study aims to characterize the dynamic properties of the p53 binding event. Hydrogen bonding as direct readout will be ascertained from additive energy models and DNA deformation mechanics will be explored as indirect readout from molecular dynamics (MD) simulations. Additionally, this experiment illuminates the contribution of the L1 loop to the p53/DNA binding interface. Molecular models of p53 with DNA expected to have differing hydrogen bonding patterns are constructed and simulated using the Amber12 MD suite. Results from this study inform rational design of novel therapeutics to combat the changes that are hypothesized to cause over 50% of tumorous cancers.
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