Examining SRP pathway function in mRNA localization to the endoplasmic reticulum.

Signal recognition particle (SRP) pathway function in protein translocation across the endoplasmic reticulum (ER) is well established; its role in RNA localization to the ER remains, however, unclear. In current models, mRNAs undergo translation- and SRP-dependent trafficking to the ER, with ER localization mediated via interactions between SRP-bound translating ribosomes and the ER-resident SRP receptor (SR), a heterodimeric complex comprising SRA, the SRP-binding subunit, and SRB, an integral membrane ER protein. To study SRP pathway function in RNA localization, SR knockout (KO) mammalian cell lines were generated and the consequences of SR KO on steady-state and dynamic mRNA localization examined. CRISPR/Cas9-mediated SRPRB KO resulted in profound destabilization of SRA. Pairing siRNA silencing of SRPRA in SRPRB KO cells yielded viable SR KO cells. Steady-state mRNA compositions and ER-localization patterns in parental and SR KO cells were determined by cell fractionation and deep sequencing. Notably, steady-state cytosol and ER mRNA compositions and partitioning patterns were largely unaltered by loss of SR expression. To examine SRP pathway function in RNA localization dynamics, the subcellular trafficking itineraries of newly exported mRNAs were determined by 4-thiouridine (4SU) pulse-labeling/4SU-seq/cell fractionation. Newly exported mRNAs were distinguished by high ER enrichment, with ER localization being SR-independent. Intriguingly, under conditions of translation initiation inhibition, the ER was the default localization site for all newly exported mRNAs. These data demonstrate that mRNA localization to the ER can be uncoupled from the SRP pathway function and reopen questions regarding the mechanism of RNA localization to the ER.

No evidence for unethical amnesia for imagined actions: A failed replication and extension.

In a recent study, Kouchaki and Gino (2016) suggest that memory for unethical actions is impaired, regardless of whether such actions are real or imagined. However, as we argue in the current study, their claim that people develop "unethical amnesia" confuses two distinct and dissociable memory deficits: one affecting the phenomenology of remembering and another affecting memory accuracy. To further investigate whether unethical amnesia affects memory accuracy, we conducted three studies exploring unethical amnesia for imagined ethical violations. The first study (N = 228) attempts to directly replicate the only study from Kouchaki and Gino (2016) that includes a measure of memory accuracy. The second study (N = 232) attempts again to replicate these accuracy effects from Kouchaki and Gino (2016), while including several additional variables meant to potentially help in finding the effect. The third study (N = 228) is an attempted conceptual replication using the same paradigm as Kouchaki and Gino (2016), but with a new vignette describing a different moral violation. We did not find an unethical amnesia effect involving memory accuracy in any of our three studies. These results cast doubt upon the claim that memory accuracy is impaired for imagined unethical actions. Suggestions for further ways to study memory for moral and immoral actions are discussed.

The foreign body response: emerging cell types and considerations for targeted therapeutics.

The foreign body response (FBR) remains a clinical challenge in the field of biomaterials due to its ability to elicit a chronic and sustained immune response. Modulating the immune response to materials is a modern paradigm in tissue engineering to enhance repair while limiting fibrous encapsulation and implant isolation. Though the classical mediators of the FBR are well-characterized, recent studies highlight that our understanding of the cell types that shape the FBR may be incomplete. In this review, we discuss the emerging role of T cells, stromal-immune cell interactions, and senescent cells in the biomaterial response, particularly to synthetic materials. We emphasize future studies that will deepen the field's understanding of these cell types in the FBR, with the goal of identifying therapeutic targets that will improve implant integration. Finally, we briefly review several considerations that may influence our understanding of the FBR in humans, including rodent models, aging, gut microbiota, and sex differences. A better understanding of the heterogeneous host cell response during the FBR can enable the design and development of immunomodulatory materials that favor healing.

Age-associated Senescent - T Cell Signaling Promotes Type 3 Immunity that Inhibits the Biomaterial Regenerative Response.

Aging is associated with immunological changes that compromise response to infections and vaccines, exacerbate inflammatory diseases and can potentially mitigate tissue repair. Even so, age-related changes to the immune response to tissue damage and regenerative medicine therapies remain unknown. Here, it is characterized how aging induces changes in immunological signatures that inhibit tissue repair and therapeutic response to a clinical regenerative biological scaffold derived from extracellular matrix. Signatures of inflammation and interleukin (IL)-17 signaling increased with injury and treatment both locally and regionally in aged animals, and computational analysis uncovered age-associated senescent-T cell communication that promotes type 3 immunity in T cells. Local inhibition of type 3 immune activation using IL17-neutralizing antibodies improves healing and restores therapeutic response to the regenerative biomaterial, promoting muscle repair in older animals. These results provide insights into tissue immune dysregulation that occurs with aging that can be targeted to rejuvenate repair.

A comparison of memories of fiction and autobiographical memories.

People consume, remember, and discuss not only memories of lived experiences, but also events from works of fiction, such as books, movies, and TV shows. We argue that these memories of fiction represent an important category of event memory, best understood within an autobiographical memory framework. How do fictional events yield psychological realities even when they are known to be invented? We explored this question in three studies by comparing the memory content, phenomenological qualities, and functional roles of naturally occurring personal memories to memories of fiction. In Studies 1 and 2, we characterized the subjective experience of memories of fiction by adapting established measures of autobiographical remembering, such as the Autobiographical Memory Questionnaire (Rubin et al., 2003), Centrality of Event Scale (Berntsen & Rubin, 2006), and items from the Thinking About Life Experiences Scale (Bluck et al., 2005; Pillemer et al., 2015). In Study 3, we investigated similarities and differences in personal memories and memories of fiction for events from childhood or the recent past. In doing so, we observed the impact of a unique property of memories of fiction: their ability to be repeatedly reexperienced in their original form. Taken together, we argue that memories of fiction can be considered similar to other forms of autobiographical remembering and describe a theoretical framework for understanding memories of fiction in the context of other event memories. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

3D microfluidic gradient generator for combination antimicrobial susceptibility testing.

Microfluidic concentration gradient generators (µ-CGGs) have been utilized to identify optimal drug compositions through antimicrobial susceptibility testing (AST) for the treatment of antimicrobial-resistant (AMR) infections. Conventional µ-CGGs fabricated via photolithography-based micromachining processes, however, are fundamentally limited to two-dimensional fluidic routing, such that only two distinct antimicrobial drugs can be tested at once. This work addresses this limitation by employing Multijet-3D-printed microchannel networks capable of fluidic routing in three dimensions to generate symmetric multidrug concentration gradients. The three-fluid gradient generation characteristics of the fabricated 3D µ-CGG prototype were quantified through both theoretical simulations and experimental validations. Furthermore, the antimicrobial effects of three highly clinically relevant antibiotic drugs, tetracycline, ciprofloxacin, and amikacin, were evaluated via experimental single-antibiotic minimum inhibitory concentration (MIC) and pairwise and three-way antibiotic combination drug screening (CDS) studies against model antibiotic-resistant Escherichia coli bacteria. As such, this 3D µ-CGG platform has great potential to enable expedited combination AST screening for various biomedical and diagnostic applications.

Using Testing as a Learning Tool.

Objective. The purpose of this review is to discuss some principles from cognitive psychology regarding the benefits of testing and translate those findings into practical applications for instruction and studying. Findings. Testing or retrieval practice is superior to re-study for promoting long-term retention. The benefits of testing can be see with open-ended responses (eg, cued or free recall) and multiple choice questions. The use of multiple-choice questions during testing may have an additional benefit as it may stabilize information that is stored in memory but temporarily inaccessible due to disuse (eg, marginal knowledge). Summary. Testing can have multiple learning benefits. We emphasize that incorporating opportunities for retrieval after teaching is an essential component of lasting learning. In addition, retrieval practice can be incorporated in all aspects of instruction.

Development of an Online Experiment Platform for High School Biology.

We developed a novel online platform, Rex (Real experiments) that immerses students in a scientific investigative process. Rex is a virtual web-based biological science experiment platform, hosted by real scientists, and uses actual lab experiments that generate real data for students to collect, analyze, and interpret. Seven neuroscience experiments use zebrafish and rats as model systems to study the effects of drugs such as tetrahydrocannabinol (THC), caffeine, alcohol, and cigarette smoke, which are of interest to high school students. We carried out a small field-test of Rex in a variety of high school biology classrooms (e.g., standard, honors, AP, anatomy/physiology) to obtain student and teacher feedback about the implementation and usability of the program. We also assessed student situational interest (SI) to determine whether the Rex experiment captured students' attention, and whether it was an enjoyable and meaningful experience. Overall, students reported a moderate level of SI after participating in the Rex experiments. Situational interest did not differ across teachers, class section, class level, or the type of experiment. In addition, we present details of the technical issues encountered in the classroom, and we provide guidance to readers who may want to use the resource in their classrooms.

Intramyocardial injection of a fully synthetic hydrogel attenuates left ventricular remodeling post myocardial infarction.

Intramyocardial hydrogel injection is an innovative and promising treatment for myocardial infarction (MI) and has recently entered clinical trials. By providing mechanical support to the ventricular wall, hydrogel injectate may act to preserve cardiac function and slow the remodeling process that leads to heart failure. However, improved outcomes will likely depend on the use of hydrogels specifically designed for this unique application, and better understanding of the mechanisms affected by the intervention. In this work, we present the first large animal study achieving functional and geometrical improvements in treating MI using a relatively stiff, fully synthetic hydrogel designed for intramyocardial injection. In addition, the renin-angiotensin system coincided with the mechanical effects of hydrogel injection and attenuated left ventricular remodeling, even after significant hydrogel degradation had occurred in vivo. These results may inspire further optimization of hydrogel materials used in intramyocardial hydrogel injection therapy and a better description of physiologic pathways affected by its implementation to facilitate successful clinical translation.

Reasons probably won't change your mind: The role of reasons in revising moral decisions.

Although many philosophers argue that making and revising moral decisions ought to be a matter of deliberating over reasons, the extent to which the consideration of reasons informs people's moral decisions and prompts them to change their decisions remains unclear. Here, after making an initial decision in 2-option moral dilemmas, participants examined reasons for only the option initially chosen (affirming reasons), reasons for only the option not initially chosen (opposing reasons), or reasons for both options. Although participants were more likely to change their initial decisions when presented with only opposing reasons compared with only affirming reasons, these effect sizes were consistently small. After evaluating reasons, participants were significantly more likely not to change their initial decisions than to change them, regardless of the set of reasons they considered. The initial decision accounted for most of the variance in predicting the final decision, whereas the reasons evaluated accounted for a relatively small proportion of the variance in predicting the final decision. This resistance to changing moral decisions is at least partly attributable to a biased, motivated evaluation of the available reasons: participants rated the reasons supporting their initial decisions more favorably than the reasons opposing their initial decisions, regardless of the reported strategy used to make the initial decision. Overall, our results suggest that the consideration of reasons rarely induces people to change their initial decisions in moral dilemmas. (PsycINFO Database Record