Development of Multivalent Conjugates with a Single Non-Canonical Amino Acid.

Proteins represent powerful biomacromolecules due to their unique functionality and broad utility both in the cell and in non-biological applications. The genetic encoding of non-canonical amino acids (ncAAs) facilitates functional diversification of these already powerful proteins. Specifically, ncAAs have been demonstrated to provide unique functional handles to bioorthogonally introduce novel functionality via conjugation reactions. Herein we examine the ability of a single ncAA to serve as a handle to generate multivalent bioconjugates to introduce two or more additional components to a protein, yielding a multivalent conjugate. To accomplish this aim, p-bromopropargyloxyphenyalanine (pBrPrF) was genetically encoded into both superfolder green fluorescent protein (sfGFP) and ubiquitin model proteins to serve as a conjugation handle. A sequential bioconjugation sequence involving a copper-assisted cycloaddition reaction coupled with a subsequent Sonogashira cross-coupling was then optimized. The linkage of two additional molecules to the model protein via these reactions yielded the desired multivalent bioconjugate. This domino approach using a single ncAA has a plethora of applications in both therapeutics and diagnostics as multiple unique moieties can be introduced into proteins in a highly controlled fashion.

Getting unstuck: The effects of growth mindsets about the self and job on happiness at work.

Past research on growth mindsets has focused on the benefits of viewing the self as flexible rather than fixed. We propose that employees can make more substantial agentic changes to their work experiences if they also hold growth mindsets about their job designs. We introduce the concept of dual-growth mindset-viewing both the self and job as malleable-and examine its impact on employee happiness over time. We hypothesize that fostering a dual-growth mindset yields relatively durable gains in happiness, while fostering a growth mindset about either the self or job is insufficient for sustainable increases in happiness. We tested these predictions using two experimental studies: a field quasi-experiment in a Fortune 500 technology company and a controlled experiment with employees in a variety of organizations and occupations. Across the two experiments, fostering dual-growth mindset yielded gains in self-reported and observer-rated happiness that lasted at least 6 months. Fostering growth mindsets about either the self or job alone did not generate lasting increases in happiness. Supplementary mediation analyses suggest dual-growth mindsets boosted happiness by enabling employees to plan more substantial job crafting. Our research suggests that durable gains in happiness at work depend on holding flexible mindsets about the job, not only the self. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Tips and tools for safe opioid prescribing.

This review-with tables summarizing opioid options, dosing considerations, and recommendations for tapering-will help you provide rigorous Tx for noncancer pain while ensuring patient safety.