Lithium Chloride Sensitivity Connects the Activity of PEX11 and RIM20 to PGM2 translation

Lithium chloride (LiCl) is a widely used and extensively researched drug for the treatment of bipolar disorder (BD). As a result, LiCl has been the subject of research studying its toxicity, mode of action, and downstream cellular responses. LiCl has been shown to influence cell signalling and signalling transduction pathways through protein kinase C and glycogen synthase kinase-3 in mammalian cells. LiCl's significant downstream effects on the translational pathway necessitate further investigation. In yeast, LiCl is found to lower the activity and alter the expression of PGM2, a gene encoding a sugar-metabolism phosphoglucomutase. When phosphoglucomutase activity is reduced in the presence of galactose, intermediates of galactose metabolism aggregate, causing cell sensitivity to LiCl. In this study, we identified that deleting the genes PEX11 and RIM20 increases yeast LiCl sensitivity. We further show that PEX11 and RIM20 regulate the expression of PGM2 mRNA at the translation level. The observed alteration of translation seems to target the structured 5′-untranslated region (5′-UTR) of the PGM2 mRNA.

Orchestrating serine/threonine phosphorylation and elucidating downstream effects by short linear motifs

Cellular function is based on protein–protein interactions. A large proportion of these interactions involves the binding of short linear motifs (SLiMs) by folded globular domains. These interactions are regulated by post-translational modifications, such as phosphorylation, that create and break motif binding sites or tune the affinity of the interactions. In addition, motif-based interactions are involved in targeting serine/threonine kinases and phosphatases to their substrate and contribute to the specificity of the enzymatic actions regulating which sites are phosphorylated. Here, we review how SLiM-based interactions assist in determining the specificity of serine/threonine kinases and phosphatases, and how phosphorylation, in turn, affects motif-based interactions. We provide examples of SLiM-based interactions that are turned on/off, or are tuned by serine/threonine phosphorylation and exemplify how this affects SLiM-based protein complex formation.

Articulating the Pueblo Cubano: Women’s Politicization and Productivity in Revolutionary Cuba, 1959 to 1969

How do political actors forge social solidarity across preexisting axes of social difference? This article investigates how political elites undertaking projects of political articulation—understood as linking together diverse constituencies to create integrated political blocs—contend with preexisting cultural constraints embedded in the social fabric. I do so by tracing how the post-1959 Cuban regime attempted to build a population-wide revolutionary identity despite persisting cultural understandings of women primarily as apolitical housewives. Through systematic analysis of a large corpus of state discourse in the form of speeches and women’s magazines, I show how regime leaders negotiated, with varying degrees of success over time, the cultural constraints that gender posed to their unifying project. Ultimately, the regime’s initiatives to politicize women through including them in mass campaigns and radicalizing their traditional household tasks were relatively successful, but cultural backlash against women’s increasing presence in the labor force prompted the institutionalization of a gendered division of labor in the economy that traditionalized their initially radical entry into the workplace. Analyzing how political elites confront and manage social differences within political blocs promises to contribute to a better understanding of the political production of social solidarity and its downstream effects on categorical inequalities.

IL-38 Alleviates Inflammation in Sepsis in Mice by Inhibiting Macrophage Apoptosis and Activation of the NLRP3 Inflammasome

Interleukin- (IL-) 38 is an emerging cytokine with multiple functions involved in infection and immunity. However, the potential role of IL-38 in the host immune response during sepsis remains elusive. Herein, we investigated if macrophages in septic mice express IL-38, the molecular mechanisms behind its expression, and the downstream effects of its expression. In mouse peritoneal macrophages, lipopolysaccharide (LPS) upregulated IL-38 and its receptor IL-36R, and the resulting IL-38 shifted macrophages from a M1 to M2 phenotype. Moreover, exposure to IL-38 alone was sufficient to inhibit macrophage apoptosis and LPS-driven activation of the NOD-, LRR-, and pyrin domain-containing 3 (NLRP3) inflammasome. These effects were partly abrogated by IL-38 downregulation. In septic mice, IL-38 markedly lowered serum concentrations of proinflammatory cytokines and greatly improved survival. Conversely, IL-38 blockade aggravated their mortality. Collectively, these findings present IL-38 as a potent immune modulator that restrains the inflammatory response by suppressing macrophage apoptosis and activation of the NLRP3 inflammasome. IL-38 may help protect organs from sepsis-related injury.

The Psychology of Status Competitions within Organizations

Status hierarchies, which represent how individuals stack up based on the amount of influence and respect they have relative to others, develop quickly as group members make judgments and inferences about others’ competencies or expected contributions to the group. While quick to emerge, one’s place in the hierarchy is not entirely fixed. Because occupying higher status offers a number of rewards and benefits, people vie with others to achieve the higher status positions, and seek to maintain them by engaging in behaviors that have downstream effects on group and individual outcomes. Scholars have directed increasing attention to the unique psychology associated with status seeking to understand the consequences of hierarchical competitions. This emerging body of work highlights the dual concerns (i.e., self-oriented and other-oriented concerns) inherent in the pursuit of status and offers new insights to aid our understanding of status competitions. In this chapter, the authors first review the literature that explores the mixed-motive psychology of status striving, noting the potentially beneficial and destructive behavioral outcomes that status competitions can elicit within workgroups. Next, the authors detail some of the structural, temporal, relational, and individual properties that may exacerbate people’s self-interested status concerns. The chapter concludes by discussing some of the organizational implications of this body of work and reviewing potentially rich opportunities for future research on status competitions.

Human Granulocytic Anaplasmosis as a COVID-19 Mimicker

Introduction: Human granulocytic anaplasmosis (HGA) is a tick-borne illness caused by the bacterium Anaplasma phagocytophilum. HGA has a widely variable clinical presentation and can be life-threatening. Case description: A 77-year-old man was transferred from an outside facility with altered mental status, a fever of up to 40.5°C, and shortness of breath. Laboratory analysis revealed a progressively worsening pro-inflammatory state and abnormalities in the patient’s coagulation studies. With clinical and laboratory evidence concerning for potential COVID-19 infection, the patient was placed in isolation as a precaution. The results of two COVID-19 tests, given approximately 24 hours apart, were negative. The patient’s spouse confirmed a bug bite to his upper extremity while working outdoors. His symptoms resolved completely after a 10-day course of empiric doxycycline. Discussion: The diverse clinical presentations of HGA necessitate a broad differential diagnosis, including viral, bacterial and non-infectious aetiologies. In severe cases, a cytokine-mediated immune cascade can occur (namely, cytokine storm) leading to devastating downstream effects. This cytokine storm can be seen in many other diseases, but most recently it has been demonstrated in the novel coronavirus disease 2019 (COVID-19). Conclusion: Here we present a case of HGA in which diagnosis was delayed due to mimicry of COVID-19 infection. This case highlights the importance of taking clinical and social histories, seasonality and geography into account during diagnosis, and maintaining a broad differential with non-specific symptoms. Despite the current COVID-19 pandemic, we recommend that HGA remains in the differential diagnosis of a pro-inflammatory state with an atypical respiratory presentation.

The Impacts of COVID-19 on Technology Use and Experience Across Generations

Among its many downstream effects, the COVID-19 pandemic has influenced how people think about and interact with technology. With limitations and restrictions around in-person interactions and use of public spaces, people are increasingly relying on technology to support everyday activities including work, communication and care. Results from the survey series showed an increased adoption of and interest in home, health and communication technologies. The changes may be long-lived, with the majority of the new adopters saying that they will continue to use the technologies that they started using in response to the pandemic. A generational comparison showed that while baby boomers and the silent generation were less likely than younger adults to have made recent adoptions, the older generations did not significantly differ in terms of interest in using new technologies. This presentation will also report on how COVID-19-related changes in technology experience varied by other demographic and socio-economic characteristics.

The Bumpy Road towards mTOR Inhibition in Glioblastoma: Quo Vadis?

Glioblastoma multiforme (GBM), a grade IV astrocytoma, is a lethal brain tumor with a poor prognosis. Despite recent advances in the molecular biology of GBM, neuro-oncologists have very limited treatment options available to improve the survival of GBM patients. A prominent signaling pathway implicated in GBM pathogenesis is that of the mechanistic target of rapamycin (mTOR). Attempts to target the mTOR pathway with first-generation mTOR inhibitors appeared promising in the preclinical stage; however, results have been disappointing in clinical trials, owing to the heterogeneous nature of GBM, escape mechanisms against treatment, the blood–brain barrier, drug-related toxicities, and the imperfect design of clinical trials, among others. The development of next-generation mTOR inhibitors and their current evaluation in clinical trials have sparked new hope to realize the clinical potential of mTOR inhibitors in GBM. Meanwhile, studies are continuously furthering our understanding of mTOR signaling dysregulation, its downstream effects, and interplay with other signaling pathways in GBM tumors. Therefore, it remains to be seen whether targeting mTOR in GBM will eventually prove to be fruitful or futile.

Populated Places and Conspicuous Consumption: High Population Density Cues Predict Consumers’ Luxury-Linked Brand Attitudes

Population density has been identified as an ecological factor with considerable behavioral implications. The present research aimed to examine whether the mere perception of more (vs. less) populated places can change consumers’ luxury-linked brand attitudes. To this end, we experimentally manipulated consumers’ perceptions of population density using pictorial exposure to high (vs. low) population density cues. The results revealed a significant interaction between manipulated population density and perceived brand luxury on brand attitudes. Specifically, exposure to high rather than low population density cues resulted in more positive (negative) attitudes toward brands deemed to be more (less) luxurious. These findings support our prediction that high population density cues can shift people’s perceptions in consumption contexts linked to luxury. Our work contributes to the growing stream of literature on population density and suggests that this (geo-) demographic factor can exert important downstream effects on consumer behavior.

Humanization and policy support: A replication-extension on group-composition framing

Evaluations of beneficiary groups matter for individual levels of policy support. A variety of cues and heuristics shape evaluations. One particularly consequential heuristic concerns the beneficiary’s perceived level of humanity. Recent work shows that individuals, individuals within groups (group compositions), and unitary groups evoke different levels of perceived humanity, and that these differences have downstream effects on sympathy and willingness to help. We replicate these findings, and then extend them to government policy support. We find that individuals and group compositions evoke higher levels of support than groups, and that perceived humanity explains this effect. We focus on the Roma, a tough, critical test given pervasive dehumanization and anti-Roma prejudice. Finally, we demonstrate the value of cross-disciplinary extension-replications.