People constrain their semantic associations when talking to both friends and strangers.

During conversations, people face a trade-off between establishing understanding and making interesting and unique contributions. How do people balance this when deciding which concepts to reference, and does it matter how well they know their conversation partner? In the present work, participants made stream-of-consciousness word associations either with a partner or alone-simplified versions of dialogue and monologue. Participants made semantically narrower and more predictable word associations with a stranger than alone (Study 1), suggesting that they constrain their associations to establish mutual understanding. Increasing closeness (Study 2) or having a prior relationship (Study 3) did not moderate this effect. Thus, even during a task that does not depend on establishing mutual understanding, people sacrifice being interesting for the sake of being understood. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Measures of Anxiety Disorder Symptoms in Adolescents.

This study examines select psychometric properties (i.e., internal reliability, and factorial, convergent, discriminant, and criterion validity) of three commonly-used measures of anxiety disorder symptoms in adolescents in the context of multi-trait, multi-method matrix analyses. A sample of 331 adolescents (age M = 17.1; 75.3% white; 71.0% female) completed three self-report scales that assess symptoms of separation anxiety, social anxiety, panic, and generalized anxiety, as well as measures of depression, experiential avoidance, and intolerance of uncertainty. Measures of panic disorder symptoms showed poor factorial, convergent, and discriminant validity. A multi-trait, multi-method matrix model to understand the relationships among the measures of separation anxiety, social anxiety, and generalized anxiety symptoms provided a reasonable fit to the data. Measures of separation anxiety showed poor discriminant and criterion validity, suggesting limited relevance of separation anxiety in this adolescent sample. Measures of social anxiety generally showed evidence of adequate-to-good factorial, convergent, and discriminant validity. Measures of generalized anxiety showed adequate -to-good factorial and convergent validity, and poor-to-adequate discriminant validity. The associations of measures of social and generalized anxiety with measures of depression, experiential avoidance, and intolerance of uncertainty were at least partially independent of method variance. The findings of this study add to the growing literature that evaluates the strengths and limitations of these scales for clinical practice and research.

Competencies and Milestones for Bioethics Trainees: Beyond ASBH's Healthcare Ethics Certification and Core Competencies.

Clinical ethics training programs are responsible for preparing their trainees to be competent ethics consultants worthy of the trust of patients, families, surrogates, and healthcare professionals. While the American Society for Bioethics and Humanities (ASBH) offers a certification examination for healthcare ethics consultants, no tools exist for the formal evaluation of ethics trainees to assess their progress toward competency. Medical specialties accredited by the Accreditation Council for Graduate Medical Education (ACGME) use milestones to report trainees' progress along a continuum of professional development as a means of "operationalizing and implementing" medical competencies. Utilizing the Core Competencies for Healthcare Ethics Consultation and the ACGME and American Board of Pediatrics' (ABP) Pediatric Milestones Project, we developed milestones for 17 subcompetencies in clinical ethics consultation and academic bioethics. As the field of clinical ethics becomes more standardized, such tools will be needed to promote the development of robust training programs and to certify that their graduates are competent practitioners.

Living with the Unknown: A Qualitative Study of Parental Experience of Prognostic Uncertainty in the Neonatal Intensive Care Unit.

OBJECTIVE: This study aims to characterize the experience of prognostic uncertainty for neonatal intensive care unit (NICU) parents. STUDY DESIGN: We conducted a qualitative interview study of current and former NICU parents regarding their experience with prognostic uncertainty in the NICU. Interviews were transcribed and analyzed using a grounded theory methodology. RESULTS: Twenty-four parents were interviewed before achieving thematic saturation. Three phases of the parental experience of prognostic uncertainty emerged: shock, gray daze, and looking forward. These phases often, but not always, occurred sequentially. In shock, parents felt overwhelmed by uncertainty and were unable to visualize a future for their family. In gray daze, parents felt frustrated by the continued uncertainty. While accepting the possibility of a future for their family, they could not conceptualize a path by which to achieve it. In looking forward, parents accepted uncertainty as inevitable and incorporated it into their vision of the future. CONCLUSION: While each parent experienced the prognostic uncertainty in the neonatal intensive care unit in their own way, we found three common experiential phases. By understanding how a parent experiences prognostic uncertainty in these phases, providers may become better able to communicate and form therapeutic relationships with parents.

Anxiety sensitivity, disgust sensitivity and aversive reactions to four stimuli.

BACKGROUND: Prior theory and research has implicated disgust as relevant to some, but not all phobias. AIMS: The current study examined whether anxiety sensitivity is more relevant to certain specific phobias and whether disgust sensitivity is more relevant to other specific phobias. METHOD: Participants (n = 201) completed measures of anxiety sensitivity, disgust sensitivity and measures of aversive reactions in the presence of two fear-relevant stimuli (i.e. heights and small, enclosed spaces) and two disgust-relevant stimuli (i.e. spiders and blood/injury). RESULTS: Results of multiple linear regression analyses revealed that disgust sensitivity showed significant associations with aversive reactions in all four stimulus domains after controlling for anxiety sensitivity. After controlling for disgust sensitivity, anxiety sensitivity showed associations with the two fear-relevant phobias but not with the two disgust-relevant phobias included in this study. Anxiety sensitivity also showed an association with variance specific to one of the two fear-relevant specific phobias included in the study. Disgust sensitivity also showed associations with variance specific to both of the disgust-relevant phobias included in the study but not with variance specific to either of the fear-relevant specific phobias. CONCLUSIONS: These results provide evidence that the distinction between fear-relevant and disgust-relevant specific phobias is meaningful and also implicate disgust sensitivity as relevant to aversive reactions to all stimuli included in this study.

Cytoplasmic Polyadenylation Element Binding Proteins CPEB1 and CPEB3 Regulate the Translation of FosB and Are Required for Maintaining Addiction-Like Behaviors Induced by Cocaine.

A recurrent and devastating feature of addiction to a drug of abuse is its persistence, which is mediated by maladaptive long-term memories of the highly pleasurable experience initially associated with the consumption of the drug. We have recently found that members of the CPEB family of proteins (Cytoplasmic Polyadenylation Element-Binding Proteins) are involved in the maintenance of spatial memory. However, their possible role in the maintenance of memories that sustain addictive behavior has yet to be explored. Little is known about any of the mechanisms for maintaining memories for addictive behavior. To address the mechanisms whereby addictive behavior is maintained over time, we utilized a conditional transgenic mouse model expressing a dominant-negative version of CPEB1 that abolishes the activity in the forebrain of two of the four CPEB isoforms (CPEB1 and CPEB3). We found that, following cocaine administration, these dominant-negative (DN) CPEB mice showed a significant decrease, when compared to wild type (WT) mice, in both locomotor sensitizations and conditioned place preference (CPP), two indices of addictive behavior. Supporting these behavioral results, we also found a difference between WT and DN-CPEB1-3 mice in the cocaine-induced synaptic depression in the core of the Nucleus Accumbens (NAc). Finally, we found that (1) CPEB is reduced in transgenic mice following cocaine injections and that (2) FosB, known for its contribution to establishing the addictive phenotype, when its expression in the striatum is increased by drug administration, is a novel target of CPEBs molecules. Thus, our study highlights how CPEB1 and CPEB3 act on target mRNAs to build the neuroadaptative implicit memory responses that lead to the development of the cocaine addictive phenotypes in mammals.

Reassurance seeking and spoiled answers on academic tests.

Background: The current study examined whether test-related reassurance seeking is associated with lower scores on a high stakes, standardized test (i.e., the ACT) after controlling for academic performance in high school, and with spoiled answers (i.e., changing correct answers to incorrect) on a subsequent academic exam. Method: Students (N = 59) completed measures of test-related reassurance seeking behavior, other test anxiety-related constructs, and social anxiety-related constructs prior to taking the last in-class exam in their introductory psychology courses. Erasure marks on the bubble answer sheets were inspected to identify the number of spoiled answers. Results: Replicating results from a prior study, reassurance seeking predicted underperformance on the ACT. In addition, reassurance seeking predicted the number of spoiled answers on the in-class exam. Reassurance seeking did not predict irrelevant changes or corrections. Conclusions: Overall, these results provide additional evidence that test-related reassurance seeking is associated with performance on academic tests, and novel evidence that test-related reassurance seeking is associated with spoiling answers.

Proximodistal Heterogeneity of Hippocampal CA3 Pyramidal Neuron Intrinsic Properties, Connectivity, and Reactivation during Memory Recall.

The hippocampal CA3 region is classically viewed as a homogeneous autoassociative network critical for associative memory and pattern completion. However, recent evidence has demonstrated a striking heterogeneity along the transverse, or proximodistal, axis of CA3 in spatial encoding and memory. Here we report the presence of striking proximodistal gradients in intrinsic membrane properties and synaptic connectivity for dorsal CA3. A decreasing gradient of mossy fiber synaptic strength along the proximodistal axis is mirrored by an increasing gradient of direct synaptic excitation from entorhinal cortex. Furthermore, we uncovered a nonuniform pattern of reactivation of fear memory traces, with the most robust reactivation during memory retrieval occurring in mid-CA3 (CA3b), the region showing the strongest net recurrent excitation. Our results suggest that heterogeneity in both intrinsic properties and synaptic connectivity may contribute to the distinct spatial encoding and behavioral role of CA3 subregions along the proximodistal axis.

Social Involvement Modulates the Response to Novel and Adverse Life Events in Mice.

Epidemiological findings suggest that social involvement plays a major role in establishing resilience to adversity, however, the neurobiology by which social involvement confers protection is not well understood. Hypothesizing that social involvement confers resilience by changing the way adverse life events are encoded, we designed a series of behavioral tests in mice that utilize the presence or absence of conspecific cage mates in measuring response to novel and adverse events. We found that the presence of cage mates increased movement after exposure to a novel environment, increased time spent in the open arms of the elevated plus maze, and decreased freezing time after a foot shock as well as expedited fear extinction, therefore significantly changing the response to adversity. This is a first description of a mouse model for the effects of social involvement on adverse life events. Understanding how social involvement provides resilience to adversity may contribute to the future treatment and prevention of mental and physical illness.

A Unique Set of the Burkholderia Collagen-Like Proteins Provides Insight into Pathogenesis, Genome Evolution and Niche Adaptation, and Infection Detection.

Burkholderia pseudomallei and Burkholderia mallei, classified as category B priority pathogens, are significant human and animal pathogens that are highly infectious and broad-spectrum antibiotic resistant. Currently, the pathogenicity mechanisms utilized by Burkholderia are not fully understood, and correct diagnosis of B. pseudomallei and B. mallei infection remains a challenge due to limited detection methods. Here, we provide a comprehensive analysis of a set of 13 novel Burkholderia collagen-like proteins (Bucl) that were identified among B. pseudomallei and B. mallei select agents. We infer that several Bucl proteins participate in pathogenesis based on their noncollagenous domains that are associated with the components of a type III secretion apparatus and membrane transport systems. Homology modeling of the outer membrane efflux domain of Bucl8 points to a role in multi-drug resistance. We determined that bucl genes are widespread in B. pseudomallei and B. mallei; Fischer's exact test and Cramer's V2 values indicate that the majority of bucl genes are highly associated with these pathogenic species versus nonpathogenic B. thailandensis. We designed a bucl-based quantitative PCR assay which was able to detect B. pseudomallei infection in a mouse with a detection limit of 50 CFU. Finally, chromosomal mapping and phylogenetic analysis of bucl loci revealed considerable genomic plasticity and adaptation of Burkholderia spp. to host and environmental niches. In this study, we identified a large set of phylogenetically unrelated bucl genes commonly found in Burkholderia select agents, encoding predicted pathogenicity factors, detection targets, and vaccine candidates.

SUMOylation Is an Inhibitory Constraint that Regulates the Prion-like Aggregation and Activity of CPEB3.

Protein synthesis is crucial for the maintenance of long-term-memory-related synaptic plasticity. The prion-like cytoplasmic polyadenylation element-binding protein 3 (CPEB3) regulates the translation of several mRNAs important for long-term synaptic plasticity in the hippocampus. Here, we provide evidence that the prion-like aggregation and activity of CPEB3 is controlled by SUMOylation. In the basal state, CPEB3 is a repressor and is soluble. Under these circumstances, CPEB3 is SUMOylated in hippocampal neurons both in vitro and in vivo. Following neuronal stimulation, CPEB3 is converted into an active form that promotes the translation of target mRNAs, and this is associated with a decrease of SUMOylation and an increase of aggregation. A chimeric CPEB3 protein fused to SUMO cannot form aggregates and cannot activate the translation of target mRNAs. These findings suggest a model whereby SUMO regulates translation of mRNAs and structural synaptic plasticity by modulating the aggregation of the prion-like protein CPEB3.

"Wigglesworthia morsitans" Folate (Vitamin B9) Biosynthesis Contributes to Tsetse Host Fitness.

Closely related ancient endosymbionts may retain minor genomic distinctions through evolutionary time, yet the biological relevance of these small pockets of unique loci remains unknown. The tsetse fly (Diptera: Glossinidae), the sole vector of lethal African trypanosomes (Trypanosoma spp.), maintains an ancient and obligate mutualism with species belonging to the gammaproteobacterium Wigglesworthia. Extensive concordant evolution with associated Wigglesworthia species has occurred through tsetse species radiation. Accordingly, the retention of unique symbiont loci between Wigglesworthia genomes may prove instrumental toward host species-specific biological traits. Genome distinctions between "Wigglesworthia morsitans" (harbored within Glossina morsitans bacteriomes) and the basal species Wigglesworthia glossinidia (harbored within Glossina brevipalpis bacteriomes) include the retention of chorismate and downstream folate (vitamin B9) biosynthesis capabilities, contributing to distinct symbiont metabolomes. Here, we demonstrate that these W. morsitans pathways remain functionally intact, with folate likely being systemically disseminated through a synchronously expressed tsetse folate transporter within bacteriomes. The folate produced by W. morsitans is demonstrated to be pivotal for G. morsitans sexual maturation and reproduction. Modest differences between ancient symbiont genomes may still play key roles in the evolution of their host species, particularly if loci are involved in shaping host physiology and ecology. Enhanced knowledge of the Wigglesworthia-tsetse mutualism may also provide novel and specific avenues for vector control.

Aspergillus collagen-like genes (acl): identification, sequence polymorphism, and assessment for PCR-based pathogen detection.

The genus Aspergillus is a burden to public health due to its ubiquitous presence in the environment, its production of allergens, and wide demographic susceptibility among cystic fibrosis, asthmatic, and immunosuppressed patients. Current methods of detection of Aspergillus colonization and infection rely on lengthy morphological characterization or nonstandardized serological assays that are restricted to identifying a fungal etiology. Collagen-like genes have been shown to exhibit species-specific conservation across the noncollagenous regions as well as strain-specific polymorphism in the collagen-like regions. Here we assess the conserved region of the Aspergillus collagen-like (acl) genes and explore the application of PCR amplicon size-based discrimination among the five most common etiologic species of the Aspergillus genus, including Aspergillus fumigatus, A. flavus, A. nidulans, A. niger, and A. terreus. Genetic polymorphism and phylogenetic analysis of the aclF1 gene were additionally examined among the available strains. Furthermore, the applicability of the PCR-based assay to identification of these five species in cultures derived from sputum and bronchoalveolar fluid from 19 clinical samples was explored. Application of capillary electrophoresis on nanogels was additionally demonstrated to improve the discrimination between Aspergillus species. Overall, this study demonstrated that Aspergillus acl genes could be used as PCR targets to discriminate between clinically relevant Aspergillus species. Future studies aim to utilize the detection of Aspergillus acl genes in PCR and microfluidic applications to determine the sensitivity and specificity for the identification of Aspergillus colonization and invasive aspergillosis in immunocompromised subjects.

Interwoven biology of the tsetse holobiont.

Microbial symbionts can be instrumental to the evolutionary success of their hosts. Here, we discuss medically significant tsetse flies (Diptera: Glossinidae), a group comprised of over 30 species, and their use as a valuable model system to study the evolution of the holobiont (i.e., the host and associated microbes). We first describe the tsetse microbiota, which, despite its simplicity, harbors a diverse range of associations. The maternally transmitted microbes consistently include two Gammaproteobacteria, the obligate mutualists Wigglesworthia spp. and the commensal Sodalis glossinidius, along with the parasitic Alphaproteobacteria Wolbachia. These associations differ in their establishment times, making them unique and distinct from previously characterized symbioses, where multiple microbial partners have associated with their host for a significant portion of its evolution. We then expand into discussing the functional roles and intracommunity dynamics within this holobiont, which enhances our understanding of tsetse biology to encompass the vital functions and interactions of the microbial community. Potential disturbances influencing the tsetse microbiome, including salivary gland hypertrophy virus and trypanosome infections, are highlighted. While previous studies have described evolutionary consequences of host association for symbionts, the initial steps facilitating their incorporation into a holobiont and integration of partner biology have only begun to be explored. Research on the tsetse holobiont will contribute to the understanding of how microbial metabolic integration and interdependency initially may develop within hosts, elucidating mechanisms driving adaptations leading to cooperation and coresidence within the microbial community. Lastly, increased knowledge of the tsetse holobiont may also contribute to generating novel African trypanosomiasis disease control strategies.

The tsetse fly obligate mutualist Wigglesworthia morsitans alters gene expression and population density via exogenous nutrient provisioning.

The obligate mutualist Wigglesworthia morsitans provisions nutrients to tsetse flies. The symbiont's response to thiamine (B(1)) supplementation of blood meals, specifically towards the regulation of thiamine biosynthesis and population density, is described. Despite an ancient symbiosis and associated genome tailoring, Wigglesworthia responds to nutrient availability, potentially accommodating a decreased need.

Insight into the transmission biology and species-specific functional capabilities of tsetse (Diptera: glossinidae) obligate symbiont Wigglesworthia.

UNLABELLED: Ancient endosymbionts have been associated with extreme genome structural stability with little differentiation in gene inventory between sister species. Tsetse flies (Diptera: Glossinidae) harbor an obligate endosymbiont, Wigglesworthia, which has coevolved with the Glossina radiation. We report on the ~720-kb Wigglesworthia genome and its associated plasmid from Glossina morsitans morsitans and compare them to those of the symbiont from Glossina brevipalpis. While there was overall high synteny between the two genomes, a large inversion was noted. Furthermore, symbiont transcriptional analyses demonstrated host tissue and development-specific gene expression supporting robust transcriptional regulation in Wigglesworthia, an unprecedented observation in other obligate mutualist endosymbionts. Expression and immunohistochemistry confirmed the role of flagella during the vertical transmission process from mother to intrauterine progeny. The expression of nutrient provisioning genes (thiC and hemH) suggests that Wigglesworthia may function in dietary supplementation tailored toward host development. Furthermore, despite extensive conservation, unique genes were identified within both symbiont genomes that may result in distinct metabolomes impacting host physiology. One of these differences involves the chorismate, phenylalanine, and folate biosynthetic pathways, which are uniquely present in Wigglesworthia morsitans. Interestingly, African trypanosomes are auxotrophs for phenylalanine and folate and salvage both exogenously. It is possible that W. morsitans contributes to the higher parasite susceptibility of its host species. IMPORTANCE: Genomic stasis has historically been associated with obligate endosymbionts and their sister species. Here we characterize the Wigglesworthia genome of the tsetse fly species Glossina morsitans and compare it to its sister genome within G. brevipalpis. The similarity and variation between the genomes enabled specific hypotheses regarding functional biology. Expression analyses indicate significant levels of transcriptional regulation and support development- and tissue-specific functional roles for the symbiosis previously not observed in obligate mutualist symbionts. Retention of the genetically expensive flagella within these small genomes was demonstrated to be significant in symbiont transmission and tailored to the unique tsetse fly reproductive biology. Distinctions in metabolomes were also observed. We speculate an additional role for Wigglesworthia symbiosis where infections with pathogenic trypanosomes may depend upon symbiont species-specific metabolic products and thus influence the vector competence traits of different tsetse fly host species.

The phylogeny of Sodalis-like symbionts as reconstructed using surface-encoding loci.

Phylogenetic analyses of 16S rRNA support close relationships between the Gammaproteobacteria Sodalis glossinidius, a tsetse (Diptera: Glossinidae) symbiont, and bacteria infecting diverse insect orders. To further examine the evolutionary relationships of these Sodalis-like symbionts, phylogenetic trees were constructed for a subset of putative surface-encoding genes (i.e. ompA, spr, slyB, rcsF, ycfM, and ompC). The ompA and ompC loci were used toward examining the intra- and interspecific diversity of Sodalis within tsetse, respectively. Intraspecific analyses of ompA support elevated nonsynonymous (dN) polymorphism with an excess of singletons, indicating diversifying selection, specifically within the tsetse Glossina morsitans. Additionally, interspecific ompC comparisons between Sodalis and Escherichia coli demonstrate deviation from neutrality, with higher fixed dN observed at sites associated with extracellular loops. Surface-encoding genes varied in their phylogenetic resolution of Sodalis and related bacteria, suggesting conserved vs. host-specific roles. Moreover, Sodalis and its close relatives exhibit genetic divergence at the rcsF, ompA, and ompC loci, indicative of initial molecular divergence. The application of outer membrane genes as markers for further delineating the systematics of recently diverged bacteria is discussed. These results increase our understanding of insect symbiont evolution, while also identifying early genome alterations occurring upon integration of microorganisms with eukaryotic hosts.

Use of the Internal Transcribed Spacer (ITS) Regions to Examine Symbiont Divergence and as a Diagnostic Tool for Sodalis-Related Bacteria.

Bacteria excel in most ecological niches, including insect symbioses. A cluster of bacterial symbionts, established within a broad range of insects, share high 16S rRNA similarities with the secondary symbiont of the tsetse fly (Diptera: Glossinidae), Sodalis glossinidius. Although 16S rRNA has proven informative towards characterization of this clade, the gene is insufficient for examining recent divergence due to selective constraints. Here, we assess the application of the internal transcribed spacer (ITS) regions, specifically the ITS(glu) and ITS(ala,ile), used in conjunction with 16S rRNA to enhance the phylogenetic resolution of Sodalis-allied bacteria. The 16S rRNA + ITS regions of Sodalis and allied bacteria demonstrated significant divergence and were robust towards phylogenetic resolution. A monophyletic clade of Sodalis isolates from tsetse species, distinct from other Enterobacteriaceae, was consistently observed suggesting diversification due to host adaptation. In contrast, the phylogenetic distribution of symbionts isolated from hippoboscid flies and various Hemiptera and Coleoptera were intertwined suggesting either horizontal transfer or a recent establishment from an environmental source. Lineage splitting of Sodalis-allied bacteria into symbiotic and free-living sister groups was also observed. Additionally, we propose an ITS region as a diagnostic marker for the identification of additional Sodalis-allied symbionts in the field. These results expand our knowledge of informative genome regions to assess genetic divergence since splitting from the last common ancestor, of this versatile insect symbiont clade that have become increasingly recognized as valuable towards our understanding of the evolution of symbiosis. These facultative and recently associated symbionts may provide a novel source of traits adaptable to the dynamic ecologies encountered by diverse host backgrounds.

Nutrient provisioning facilitates homeostasis between tsetse fly (Diptera: Glossinidae) symbionts.

Host-associated microbial interactions may involve genome complementation, driving-enhanced communal efficiency and stability. The tsetse fly (Diptera: Glossinidae), the obligate vector of African trypanosomes (Trypanosoma brucei subspp.), harbours two enteric Gammaproteobacteria symbionts: Wigglesworthia glossinidia and Sodalis glossinidius. Host coevolution has streamlined the Wigglesworthia genome to complement the exclusively sanguivorous tsetse lifestyle. Comparative genomics reveal that the Sodalis genome contains the majority of Wigglesworthia genes. This significant genomic overlap calls into question why tsetse maintains the coresidence of both symbionts and, furthermore, how symbiont homeostasis is maintained. One of the few distinctions between the Wigglesworthia and Sodalis genomes lies in thiamine biosynthesis. While Wigglesworthia can synthesize thiamine, Sodalis lacks this capability but retains a thiamine ABC transporter (tbpAthiPQ) believed to salvage thiamine. This genetic complementation may represent the early convergence of metabolic pathways that may act to retain Wigglesworthia and evade species antagonism. We show that thiamine monophosphate, the specific thiamine derivative putatively synthesized by Wigglesworthia, impacts Sodalis thiamine transporter expression, proliferation and intracellular localization. A greater understanding of tsetse symbiont interactions may generate alternative control strategies for this significant medical and agricultural pest, while also providing insight into the evolution of microbial associations within hosts.