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Sea sponges are the largest marine source of small-molecule natural products described to date. Sponge-derived molecules, such as the chemotherapeutic eribulin, the calcium-channel blocker manoalide, and antimalarial compound kalihinol A, are renowned for their impressive medicinal, chemical, and biological properties. Sponges contain microbiomes that control the production of many natural products isolated from these marine invertebrates. In fact, all genomic studies to date investigating the metabolic origins of sponge-derived small molecules concluded that microbes-not the sponge animal host-are the biosynthetic producers. However, early cell-sorting studies suggested the sponge animal host may play a role particularly in the production of terpenoid molecules. To investigate the genetic underpinnings of sponge terpenoid biosynthesis, we sequenced the metagenome and transcriptome of an isonitrile sesquiterpenoid-containing sponge of the order Bubarida. Using bioinformatic searches and biochemical validation, we identified a group of type I terpene synthases (TSs) from this sponge and multiple other species, the first of this enzyme class characterized from the sponge holobiome. The Bubarida TS-associated contigs consist of intron-containing genes homologous to sponge genes and feature GC percentage and coverage consistent with other eukaryotic sequences. We identified and characterized TS homologs from five different sponge species isolated from geographically distant locations, thereby suggesting a broad distribution amongst sponges. This work sheds light on the role of sponges in secondary metabolite production and speaks to the possibility that other sponge-specific molecules originate from the animal host.

The development of dendritic cells (DCs) depends on signaling via the FMS‐like tyrosine kinase 3 (Flt3) receptor. How Flt3 signaling impacts terminally differentiated DC function is unknown. This is important given the increasing interest in exploiting Flt3 for vaccination and tumor immunotherapy. Here, we examined DCs in mice harboring constitutively activated Flt3 (Flt3‐ITD). Flt3ITD/ITD mice possessed expanded splenic DC subsets including plasmacytoid DC, conventional DC (cDC)1, cDC2, double positive (DP) cDC1 (CD11c+ CD8+ CD11b− CD103+ CD86+), noncanonical (NC) cDC1 (CD11c+ CD8+ CD11b− CD103− CD86−) and single positive (SP) cDC1 (CD11c+ CD8+ CD11b− CD103− CD86+). Outcomes of constitutive Flt3 signaling differed depending on the cDC subset examined. In comparison with wild type (WT) DCs, all Flt3ITD/ITD cDCs displayed an altered surface phenotype with changes in costimulatory molecules, major histocompatibility complex class I (MHC I) and II (MHC II). Cytokine secretion patterns, antigen uptake, antigen proteolysis and antigen presenting function differed between WT and Flt3ITD/ITD subsets, particularly cDC2. In summary, Flt3 signaling impacts the function of terminally differentiated cDCs with important consequences for antigen presentation. [ABSTRACT FROM AUTHOR]

Savoring is a positive emotion up‐regulation technique that can increase electrocortical and self‐reported valence and arousal to positive and neutral pictures, with effects persisting to increase response to the same stimuli when encountered later. Outside of the lab, emotion regulation techniques that persist to affect not just encounters with the same stimuli but also encounters with similar, but previously unencountered stimuli should save individuals time and effort. Here, we used event‐related potentials and picture ratings to test whether savoring would generalize to similar, but previously unseen positive pictures. To this end, 89 participants (56 female; M age = 18.96 years, SD = 1.87) were asked to savor positive pictures from one category (e.g., happy people) and to view positive pictures from another category (e.g., cute animals), as well as to view neutral pictures (e.g., plants). In a subsequent passive picture viewing task, participants viewed novel pictures from all three categories (i.e., happy people, cute animals, plants). In the first task, savoring was effective for pictures of animals throughout picture presentation, but only for pictures of people during the later part of picture presentation. In the second task, savoring generalized to novel pictures of animals, though this was only evident in the early portion of picture processing (and for self‐reported ratings). Therefore, savoring holds promise as a useful technique for increasing positive emotion in everyday life, though more work is needed to understand whether effects may vary depending on different types of picture content. We tested whether savoring, a technique for increasing positive emotion, would generalize to novel, similar stimuli, thereby saving individuals time and effort. Participants performed a savor and view task, before viewing similar pictures in a passive view task. Results showed that pictures resembling those that had previously been savored elicited increased late positive potentials and more emotional ratings than pictures resembling those that had been viewed. Nonetheless, effects were specific to certain picture content. [ABSTRACT FROM AUTHOR]

Naïve CD8+ T cells need to undergo a complex and coordinated differentiation program to gain the capacity to control virus infections. This not only involves the acquisition of effector functions, but also regulates the development of a subset of effector CD8+ T cells into long-lived and protective memory cells. Microbiotaderivedmetabolites have recently gained interest for their influence on T cells, but much remains unclear about their role in CD8+ T cell differentiation. In this study, we investigated the role of the G protein-coupled receptors (GPR)41 and GPR43 that can bind microbiota-derived short chain fatty acids (SCFAs) in CD8+ T cell priming following epicutaneous herpes simplex virus type 1 (HSV-1) infection. We found that HSV-specificCD8+ T cells in GPR41/43-deficientmicewere impaired in the antigen-elicited production of interferon-gamma (IFN-g), tumour necrosis factor-alpha (TNF-a), granzyme B and perforin, and failed to differentiate effectively into memory precursors. The defect in controlling HSV-1 at the site of infection could be restored when GPR41 and GPR43were expressed exclusively by HSV-specific CD8+ T cells. Our findings therefore highlight roles for GPR41 and GPR43 in CD8+ T cell differentiation, emphasising the importance of metabolite sensing in fine-tuning anti-viral CD8+ T cell priming. [ABSTRACT FROM AUTHOR]

Isonitrile‐containing natural products have garnered attention for their manifold bioactivities but are difficult to detect and isolate due to the chemical lability of the isonitrile functional group. Here, we used the isonitrile‐chlorooxime ligation (INC) in a reactivity‐based screening (RBS) protocol for the detection and isolation of alkaloid and terpene isonitriles in the cyanobacterium Fischerella ambigua and a marine sponge of the order Bubarida, respectively. A trifunctional probe bearing a chlorooxime moiety, a UV active aromatic moiety, and a bromine label facilitated the chemoselective reaction with isonitriles, UV‐Vis spectroscopic detection, and mass spectrometric analysis. The INC‐based RBS allowed for the detection, isolation, and structural elucidation of isonitriles in microgram quantities. [ABSTRACT FROM AUTHOR]

Early embryogenesis requires the establishment of fields of progenitor cells with distinct molecular signatures. A balance of intrinsic and extrinsic cues determines the boundaries of embryonic territories and pushes progenitor cells toward different fates. This process involves multiple layers of regulation, including signaling systems, transcriptional networks, and post‐transcriptional control. In recent years, microRNAs (miRNAs) have emerged as undisputed regulators of developmental processes. Here, we discuss how miRNAs regulate pattern formation during vertebrate embryogenesis. We survey how miRNAs modulate the activity of signaling pathways to optimize transcriptional responses in embryonic cells. We also examine how localized RNA interference can generate spatial complexity during early development. Unraveling the complex crosstalk between miRNAs, signaling systems and cell fate decisions will be crucial for our understanding of developmental outcomes and disease. [ABSTRACT FROM AUTHOR]

Introduction: Administering large volumes of crystalloids to trauma patients has been shown to exacerbate metabolic complications of hemorrhage including dilutional coagulopathy and worsening acidosis The aim of this study was to evaluate crystalloid administration volumes in trauma patients after replacing 1 L IV containers with 500 mL IV containers in the emergency department trauma resuscitation bay.Materials and Methods: This was a single-center, IRB-approved, retrospective cohort evaluation of adult trauma patients conducted at an 864-bed community tertiary referral center located in the southeastern United States. Patterns of crystalloid administration were examined before and after the trauma resuscitation bay began to exclusively stock 500 mL IV containers. The primary outcome was mean total crystalloid volume infused from time of injury to hospital admission. Secondary outcomes included mean total crystalloid volume infused prior to administration of blood products, proportion of patients who received less than 2 L total of crystalloids, time to initiation of blood products, and mortality in both the emergency department and in-hospital.Results: Patient characteristics were largely similar between both groups including age, mechanism of injury, and Injury Severity Score. For the primary outcome, the mean total crystalloid volume infused from time of injury to hospital administration, patients in the 500 mL IV fluid container group were administered 555 mL less crystalloid when compared to the 1 L IV fluid container group, 1048 mL vs 1603 mL (p < 0.01; 95% CI 406 mL - 704 mL), respectively. After conversion to the 500 mL IV container bags, there was a 27.5% increase in the proportion of patients receiving less than 2 L of crystalloid, 90.5% vs 63.0% in the 500 mL IV fluid container and 1 L IV fluid container groups, respectively (p < 0.01).Conclusions: Due to reduced mortality, expanding literature and guidelines clearly support minimizing IV crystalloid resuscitation. Institutions must now work to minimize use of IV crystalloids to hemorrhaging trauma patients and a simple solution of using smaller IV fluid bags was shown to improve adherence to this practice. [ABSTRACT FROM AUTHOR]

This treatise represents the lived experiences of an assistant professor of social work/MSW admissions director and three first year MSW students as they navigated the COVID-19 pandemic and participated in an online instructional platform. The experiences and adaptive skills of the MSW students are presented in their own voice. The disappointments, distractions, disruptions in family relationships, and absence of actual human interaction with peers and professors are relayed from each contributor's perspective. Adaptive techniques employed by each student and the assistant professor are discussed from a locus of control perspective. Recommendations for future research are offered as they relate to the emotional and physical concerns experienced by faculty and students during the pandemic. [ABSTRACT FROM AUTHOR]

Naïve CD8 + T cells need to undergo a complex and coordinated differentiation program to gain the capacity to control virus infections. This not only involves the acquisition of effector functions, but also regulates the development of a subset of effector CD8 + T cells into long-lived and protective memory cells. Microbiota-derived metabolites have recently gained interest for their influence on T cells, but much remains unclear about their role in CD8 + T cell differentiation. In this study, we investigated the role of the G protein-coupled receptors (GPR)41 and GPR43 that can bind microbiota-derived short chain fatty acids (SCFAs) in CD8 + T cell priming following epicutaneous herpes simplex virus type 1 (HSV-1) infection. We found that HSV-specific CD8 + T cells in GPR41/43-deficient mice were impaired in the antigen-elicited production of interferon-gamma (IFN-γ), tumour necrosis factor-alpha (TNF-α), granzyme B and perforin, and failed to differentiate effectively into memory precursors. The defect in controlling HSV-1 at the site of infection could be restored when GPR41 and GPR43 were expressed exclusively by HSV-specific CD8 + T cells. Our findings therefore highlight roles for GPR41 and GPR43 in CD8 + T cell differentiation, emphasising the importance of metabolite sensing in fine-tuning anti-viral CD8 + T cell priming., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Lee, Wilson, Clarke, Engel, Tscharke, Gebhardt, Bedoui and Bachem.)

Background: Fear and anxiety are distinct dimensions of psychopathology that may be characterized by differences in dimensional threat reactivity. Heightened response to predictable threat is hypothesized to underlie fear symptomatology, whereas increased response to unpredictable threat may underlie anxiety. Despite widespread acceptance of this model, these purported associations have rarely been tested, and the prognostic value of predictable and unpredictable threat responding is unclear. Here we examined multilevel indicators of predictable and unpredictable threat response as cross-sectional correlates and prospective predictors of transdiagnostic fear and anxiety., Methods: Fifty-two individuals with varying levels of internalizing psychopathology (31 female) performed the no-threat, predictable threat, and unpredictable threat task. Transdiagnostic fear and anxiety were assessed at baseline (time 1) and approximately 1.5 years later (time 2). We used event-related potential, the stimulus-preceding negativity, as a measure of threat anticipation and startle eyeblink as a measure of defensive reactivity during the no-threat, predictable threat, and unpredictable threat task. These probes were assessed as cross-sectional correlates and prospective predictors of fear and anxiety., Results: Participants with larger time 1 stimulus-preceding negativities to predictable threat were characterized by greater time 1 fear. Larger time 1 stimulus-preceding negativities to unpredictable threat were associated with greater increases in time 2 anxiety. Heightened time 1 startle to predictable threat predicted larger increases in time 2 fear., Conclusions: Results validate predictable and unpredictable threat responding as dimensional correlates of transdiagnostic fear versus anxiety and suggest that psychophysiological measures of predictable and unpredictable threat response hold promise as prospective predictors of trajectories of fear and anxiety., (© 2022 The Authors.)