Probing delivery of a lipid nanoparticle encapsulated self-amplifying mRNA vaccine using coherent Raman microscopy and multiphoton imaging.

The COVID-19 pandemic triggered the resurgence of synthetic RNA vaccine platforms allowing rapid, scalable, low-cost manufacturing, and safe administration of therapeutic vaccines. Self-amplifying mRNA (SAM), which self-replicates upon delivery into the cellular cytoplasm, leads to a strong and sustained immune response. Such mRNAs are encapsulated within lipid nanoparticles (LNPs) that act as a vehicle for delivery to the cell cytoplasm. A better understanding of LNP-mediated SAM uptake and release mechanisms in different types of cells is critical for designing effective vaccines. Here, we investigated the cellular uptake of a SAM-LNP formulation and subsequent intracellular expression of SAM in baby hamster kidney (BHK-21) cells using hyperspectral coherent anti-Stokes Raman scattering (HS-CARS) microscopy and multiphoton-excited fluorescence lifetime imaging microscopy (FLIM). Cell classification pipelines based on HS-CARS and FLIM features were developed to obtain insights on spectral and metabolic changes associated with SAM-LNPs uptake. We observed elevated lipid intensities with the HS-CARS modality in cells treated with LNPs versus PBS-treated cells, and simultaneous fluorescence images revealed SAM expression inside BHK-21 cell nuclei and cytoplasm within 5 h of treatment. In a separate experiment, we observed a strong correlation between the SAM expression and mean fluorescence lifetime of the bound NAD(P)H population. This work demonstrates the ability and significance of multimodal optical imaging techniques to assess the cellular uptake of SAM-LNPs and the subsequent changes occurring in the cellular microenvironment following the vaccine expression.

My manager endorsed my coworkers' voice: Understanding observers' positive and negative reactions to managerial endorsement of coworker voice.

Research on managerial voice endorsement has primarily focused on the processes and conditions through which voicers receive their managers' endorsement. We shift this focus away from the voicers, focusing instead on the dual reactions that endorsement generates for observing employees. Drawing from an approach-avoidance framework, we propose that managerial endorsement of coworker voice could be perceived as a positive and negative stimulus for observers, prompting them to approach opportunities and avoid threats, respectively. Results from a preregistered experiment and a multiwave, multisource field study revealed that managerial endorsement of coworker voice was positively related to observers' voice instrumentality, thus prompting them to engage in approach behaviors (i.e., voice). We also found that managerial endorsement of coworker voice was positively related to observers' voice threat, triggering avoidant behaviors (i.e., avoidance-oriented counterproductive work behaviors). Further, we found that the avoidant reactions more pronounced for observers with higher (vs. lower) neuroticism. Overall, our research extends theory by demonstrating the rippling effects that voice endorsement can ignite throughout the workgroup. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Distances and directions: An emotional journey into the recovery process.

Positive emotions stemming from leisure activities are often promoted as a way to achieve a state of recovery, in particular by counteracting negative emotions experienced throughout the workday. Yet the recovery literature frequently takes an undifferentiated view of both the positive emotions employees experience as well as the negative emotions employees are recovering from. This implicitly assumes that all positive emotions are equally effective in facilitating recovery from all negative emotions. Drawing from theory treating emotional movements as a metaphorical journey, we develop a framework for understanding recovery that highlights the importance of the distance and direction that individuals "travel" when moving from negative emotions to positive emotions during the recovery process. We argue that the negative emotions that people start with from work-that is, their emotional origin-as well as the positive emotions that people end with following leisure activities-that is, their emotional destination-jointly influence the state of being recovered. Across two studies using experience-sampling methodologies, we find that "shorter" journeys consisting of emotional destinations that match the activation level of emotional origins (e.g., experiencing high activation positive emotion [HAP] to counter high activation negative emotion) are effective in promoting recovery, while "longer" journeys consisting of mismatches (e.g., experiencing HAP to counter low activation negative emotion) are ineffective for recovery. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Biodegradable Polyester Nanoparticle Vaccines Deliver Self-Amplifying mRNA in Mice at Low Doses.

Delivery of self-amplifying mRNA (SAM) has high potential for infectious disease vaccination due its self-adjuvating and dose-sparing properties. Yet a challenge is the susceptibility of SAM to degradation and the need for SAM to reach the cytosol fully intact to enable self-amplification. Lipid nanoparticles have been successfully deployed at incredible speed for mRNA vaccination, but aspects such as cold storage, manufacturing, efficiency of delivery, and the therapeutic window would benefit from further improvement. To investigate alternatives to lipid nanoparticles, we developed a class of >200 biodegradable end-capped lipophilic poly(beta-amino ester)s (PBAEs) that enable efficient delivery of SAM in vitro and in vivo as assessed by measuring expression of SAM encoding reporter proteins. We evaluated the ability of these polymers to deliver SAM intramuscularly in mice, and identified a polymer-based formulation that yielded up to 37-fold higher intramuscular (IM) expression of SAM compared to injected naked SAM. Using the same nanoparticle formulation to deliver a SAM encoding rabies virus glycoprotein, the vaccine elicited superior immunogenicity compared to naked SAM delivery, leading to seroconversion in mice at low RNA injection doses. These biodegradable nanomaterials may be useful in the development of next-generation RNA vaccines for infectious diseases.

The PCMT model of organizational support: Scale development and theoretical application.

The PCMT model of organizational support conceptualizes organizational support as consisting of four forms that differ in terms of their perceived target and ascribed motive. Across six studies (n = 1,853), we create and validate a psychometrically reliable scale that captures these four forms of organizational support, as well as offer a theoretical advancement to the organizational support literature. In particular, the first five studies involve content validation; assessment of factor analytic structure; tests of test-retest reliability and measurement invariance; and establishment of discriminant, convergent, and predictive validity. The final study involves deployment of the validated, 24-item scale in the field and illustrates that the four different forms of organizational support differentially predict the discrete dimensions of job burnout, the effects of which spillover and crossover into the home domain. This investigation thus offers both empirical and theoretical contributions. Empirically, we provide applied psychologists with an instrument for measuring the four forms of organizational support, enabling the emergence of new lines of research. Theoretically, we illustrate that the content and characteristics associated with the different forms of organizational support are important considerations as conceptual alignment between the type of organizational support perceived and the well-being outcome under study enhances the support's predictive validity. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Lower Extremity Inverse Kinematics Results Differ Between Inertial Measurement Unit- and Marker-Derived Gait Data.

In-lab, marker-based gait analyses may not represent real-world gait. Real-world gait analyses may be feasible using inertial measurement units (IMUs) in combination with open-source data processing pipelines (OpenSense). Before using OpenSense to study real-world gait, we must determine whether these methods estimate joint kinematics similarly to traditional marker-based motion capture (MoCap) and differentiate groups with clinically different gait mechanics. Healthy young and older adults and older adults with knee osteoarthritis completed this study. We captured MoCap and IMU data during overground walking at 2 speeds. MoCap and IMU kinematics were computed with OpenSim workflows. We tested whether sagittal kinematics differed between MoCap and IMU, whether tools detected between-group differences similarly, and whether kinematics differed between tools by speed. MoCap showed more anterior pelvic tilt (0%-100% stride) and joint flexion than IMU (hip: 0%-38% and 61%-100% stride; knee: 0%-38%, 58%-89%, and 95%-99% stride; and ankle: 6%-99% stride). There were no significant tool-by-group interactions. We found significant tool-by-speed interactions for all angles. While MoCap- and IMU-derived kinematics differed, the lack of tool-by-group interactions suggests consistent tracking across clinical cohorts. Results of the current study suggest that IMU-derived kinematics with OpenSense may enable reliable evaluation of gait in real-world settings.

Keeping Employees Safe During Health Crises: The Effects of Media Exposure, HR Practices, and Age.

Occupational health and safety are critical in promoting the wellness of organizations and employees. The COVID-19 pandemic is one of the most life-threatening viruses encountered in recent history, providing a unique opportunity for research to examine factors that drive employee safety behavior. Drawing from terror management theory, we propose and test a moderated mediation model using data collected from employees working during a peak of the pandemic. We identify two sources of influence - one external (i.e., media exposure), and one internal (i.e., HR practices) to the organization - that shape employees' mortality salience and safety behaviors. We find that COVID-19 HR practices significantly moderate the relationship between daily COVID-19 media exposure and mortality salience, with media exposure positively associated with mortality salience at lower levels of HR practices but its effects substituted by higher levels of HR practices. Moreover, our results also show that mortality salience spurs safety behaviors, with age moderating this relationship such that younger - but not older - employees are more likely to engage in safety behaviors due to mortality salience. Taken together, we offer theoretical implications for the safety behavior literature and practical implications for organizations faced with health crises or having employees who commonly work in hazardous conditions.