Infection of Aedes aegypti Mosquitoes with Midgut-Attenuated Sindbis Virus Reduces, but Does Not Eliminate, Disseminated Infection.

Arboviruses are transmitted by specific vectors, and the reasons for this specificity are not fully understood. One contributing factor is the existence of tissue barriers within the vector such as the midgut escape barrier. We used microRNA (miRNA) targeting of Sindbis virus (SINV) to study how replication in midgut cells contributes to overcoming this barrier in the mosquito Aedes aegypti. SINV constructs were designed to be attenuated specifically in midgut cells by inserting binding sites for midgut-specific miRNAs into either the 3' untranslated region (MRE3'miRT) or the structural open reading frame (MRE-ORFmiRT) of the SINV genome. Both miRNA-targeted viruses replicated less efficiently than control viruses in the presence of these miRNAs. When mosquitoes were given infectious blood meals containing miRNA-targeted viruses, only around 20% (MRE3'miRT) or 40% (MRE-ORFmiRT) of mosquitoes developed disseminated infection. In contrast, dissemination occurred in almost all mosquitoes fed control viruses. Deep sequencing of virus populations from individual mosquitoes ruled out selection for mutations in the inserted target sequences as the cause for dissemination in these mosquitoes. In mosquitoes that became infected with miRNA-targeted viruses, titers were equivalent to those of mosquitoes infected with control virus in both the midgut and the carcass, and there was no evidence of a threshold titer necessary for dissemination. Instead, it appeared that if infection was successfully established in the midgut, replication and dissemination were largely normal. Our results support the hypothesis that replication is an important factor in allowing SINV to overcome the midgut escape barrier but hint that other factors are also likely involved. IMPORTANCE When a mosquito ingests an arbovirus during a blood meal, the arbovirus must escape from the midgut of the vector and infect the salivary glands in order to be transmitted to a new host. We used tissue-specific miRNA targeting to examine the requirement for Sindbis virus (SINV) to replicate in midgut epithelium in order to cause disseminated infection in the mosquito Aedes aegypti. Our results indicate that specifically reducing the ability of SINV to replicate in the mosquito midgut reduces its overall ability to establish infection in the mosquito, but if infection is established, replication and dissemination occur normally. These results are consistent with an importance for replication in the midgut epithelium in aiding arboviruses in crossing the midgut barrier.

Reinstatement of item-specific contextual details during retrieval supports recombination-related false memories.

Flexible retrieval mechanisms that allow us to infer relationships across events may also lead to memory errors or distortion when details of one event are misattributed to the related event. Here, we tested how making successful inferences alters representation of overlapping events, leading to false memories. Participants encoded overlapping associations ('AB' and 'BC'), each of which was superimposed on different indoor and outdoor scenes that were pre-exposed prior to associative learning. Participants were subsequently tested on both the directly learned pairs ('AB' and 'BC') and inferred relationships across pairs ('AC'). We predicted that when people make a correct inference, features associated with overlapping events may become integrated in memory. To test this hypothesis, participants completed a final detailed retrieval test, in which they had to recall the scene associated with initially learned 'AB' pairs (or 'BC' pairs). We found that the outcome of inference decisions impacted the degree to which neural patterns elicited during detailed 'AB' retrieval reflected reinstatement of the scene associated with the overlapping 'BC' event. After successful inference, neural patterns in the anterior hippocampus, posterior medial prefrontal cortex, and our content-reinstatement region (left inferior temporal gyrus) were more similar to the overlapping, yet incorrect 'BC' context relative to after unsuccessful inference. Further, greater hippocampal activity during inference was associated with greater reinstatement of the incorrect, overlapping context in our content-reinstatement region, which in turn tracked contextual misattributions during detailed retrieval. These results suggest recombining memories during successful inference can lead to misattribution of contextual details across related events, resulting in false memories.

Constructive episodic simulation, flexible recombination, and memory errors.

According to Mahr & Csibra (M&C), the view that the constructive nature of episodic memory is related to its role in simulating future events has difficulty explaining why memory is often accurate. We hold this view, but disagree with their conclusion. Here we consider ideas and evidence regarding flexible recombination processes in episodic retrieval that accommodate both accuracy and distortion.

Cellulose nanomaterials in water treatment technologies.

Cellulose nanomaterials are naturally occurring with unique structural, mechanical and optical properties. While the paper and packaging, automotive, personal care, construction, and textiles industries have recognized cellulose nanomaterials' potential, we suggest cellulose nanomaterials have great untapped potential in water treatment technologies. In this review, we gather evidence of cellulose nanomaterials' beneficial role in environmental remediation and membranes for water filtration, including their high surface area-to-volume ratio, low environmental impact, high strength, functionalizability, and sustainability. We make direct comparison between cellulose nanomaterials and carbon nanotubes (CNTs) in terms of physical and chemical properties, production costs, use and disposal in order to show the potential of cellulose nanomaterials as a sustainable replacement for CNTs in water treatment technologies. Finally, we comment on the need for improved communication and collaboration across the myriad industries invested in cellulose nanomaterials production and development to achieve an efficient means to commercialization.

Enhanced Biogas Production from Nanoscale Zero Valent Iron-Amended Anaerobic Bioreactors.

Addition of nanoscale zero valent iron (NZVI) to anaerobic batch reactors to enhance methanogenic activity is described. Two NZVI systems were tested: a commercially available NZVI (cNZVI) slurry and a freshly synthesized NZVI (sNZVI) suspension that was prepared immediately before addition to the reactors. In both systems, the addition of NZVI increased pH and decreased oxidation/reduction potential compared with unamended control reactors. Biodegradation of a model brewery wastewater was enhanced as indicated by an increase in chemical oxygen demand removal with both sNZVI and cNZVI amendments at all concentrations tested (1.25-5.0 g Fe/L). Methane production increased for all NZVI-amended bioreactors, with a maximum increase of 28% achieved on the addition of 2.5 and 5.0 g/L cNZVI. Addition of bulk zero-valent iron resulted in only a 5% increase in methane, indicating the advantage of using the nanoscale particles. NZVI amendments further improved produced biogas by decreasing the amount of CO2 released from the bioreactor by approximately 58%. Overall, addition of cNZVI proved more beneficial than the sNZVI at equal iron concentrations, due to decreased colloidal stability and larger effective particle size of sNZVI. Although some have reported cytotoxicity of NZVI to anaerobic microorganisms, work presented here suggests that NZVI of a certain particle size and reactivity can serve as an amendment to anaerobic digesters to enhance degradation and increase the value of the produced biogas, yielding a more energy-efficient anaerobic method for wastewater treatment.

Spindle cell cutaneous epitheliotropic T-cell lymphoma in an American Bulldog.

An 8-year-old American Bulldog developed coalescing exophytic bulbous nodules that grew rapidly on the left pinna and a single cutaneous mass on the left flank. Histological examination of the pinnal biopsy by a diagnostic laboratory revealed a densely cellular neoplasm with haphazardly arranged round to spindle cells with high mitotic activity and epitheliotropism. The initial diagnosis was a poorly differentiated malignant neoplasm with differential diagnoses including melanoma, tumour of histiocytic origin and, less likely, a pleomorphic lymphoma. A panel of melanoma immunohistochemical markers and immunolabelling for CD18 were pursued. Neoplastic cells were immunopositive for CD18 but negative for Melan-A, PNL2, TRP-1 and TRP-2, suggestive of a histiocytic tumour or lymphoma. The left ear masses recurred, and more masses developed on the body. The pinnectomized ear was submitted to the University of Missouri Veterinary Medical Diagnostic Laboratory. Similar cells were seen and were immunolabelled for CD18 and CD3 but were immunonegative for SOX10, CD79a and CD20. PCR for antigen receptor rearrangements revealed a clonal rearrangement of T-cell receptor gamma. These findings enabled a final diagnosis of epitheliotropic T-cell lymphoma with spindle cell morphology. Lymphoma should be considered as a potential differential diagnosis for cutaneous nodules of spindle cell morphology and lymphocytic immunohistochemical markers should be included in diagnostic panels.

Disseminated pleomorphic rhabdomyosarcoma in a horse.

An 8-y-old National Show Horse mare was presented for evaluation of pneumonia and laminitis. Harsh bronchovesicular sounds were auscultated throughout both lung fields, and the mare had signs of moderately painful laminitis. Thoracic ultrasonography revealed lung consolidation throughout the dorsal aspect of both lungs, and radiography revealed an extensive diffuse-to-patchy bronchointerstitial lung pattern. The mare's clinical condition rapidly deteriorated, and euthanasia was elected. On postmortem examination, the lungs, omentum, spleen, liver, adrenal glands, kidneys, and femur contained 0.5-2.5-cm, firm, tan nodules. Histologically, the lungs, spleen, liver, kidneys, adrenal glands, omentum, left eye, and femur were infiltrated by bundles and nests of pleomorphic polygonal-to-spindloid cells intermixed with frequent multinucleate cells. Lymphatic vessels in the affected tissues were frequently distended with tumor emboli. Neoplastic cells were diffusely positive for vimentin, desmin, sarcomeric actin, myoblastic differentiation protein 1, and myogenin, supportive of the diagnosis of rhabdomyosarcoma (RMS), which is a rare neoplasm in horses. Cross-striations were not evident with H&E or phosphotungstic acid-hematoxylin stains. Markedly pleomorphic neoplastic cells, multinucleate cells, and lack of cross-striations suggested the subclassification of pleomorphic RMS.

Nitric oxide release: part II. Therapeutic applications.

A wide range of nitric oxide (NO)-releasing materials has emerged as potential therapeutics that exploit NO's vast biological roles. Macromolecular NO-releasing scaffolds are particularly promising due to their ability to store and deliver larger NO payloads in a more controlled and effective manner compared to low molecular weight NO donors. While a variety of scaffolds (e.g., particles, dendrimers, and polymers/films) have been cleverly designed, the ultimate clinical utility of most NO-releasing macromolecules remains unrealized. Although not wholly predictive of clinical success, in vitro and in vivo investigations have enabled a preliminary evaluation of the therapeutic potential of such materials. In this tutorial review, we review the application of macromolecular NO therapies for cardiovascular disease, cancer, bacterial infections, and wound healing.

Factors Affecting Arbovirus Midgut Escape in Mosquitoes.

Arboviral diseases spread by mosquitoes cause significant morbidity and mortality throughout much of the world. The treatment and prevention of these diseases through medication and vaccination is often limited, which makes controlling arboviruses at the level of the vector ideal. One way to prevent the spread of an arbovirus would be to stop its vector from developing a disseminated infection, which is required for the virus to make its way to the saliva of the mosquito to be potentially transmitted to a new host. The midgut of the mosquito provides one such opportunity to stop an arbovirus in its tracks. It has been known for many years that in certain arbovirus-vector combinations, or under certain circumstances, an arbovirus can infect and replicate in the midgut but is unable to escape from the tissue to cause disseminated infection. This situation is known as a midgut escape barrier. If we better understand why this barrier occurs, it might aid in the development of more informed control strategies. In this review, we discuss how the midgut escape barrier contributes to virus-vector specificity and possible mechanisms that may allow this barrier to be overcome in successful virus-vector combinations. We also discuss several of the known factors that either increase or decrease the likelihood of midgut escape.

Prevalence and genetic characterization of Toxoplasma gondii strains isolated from 31 wild Passeriformes collected in North-Central Oklahoma.

Passerine birds are widely distributed and adapted to various habitats, therefore they are commonly exposed to, and infected with Toxoplasma gondii. The purpose of our project was to determine the prevalence and genotypes of T. gondii in 31 different species of passerines collected as mortalities due to window collisions in North-Central Oklahoma. DNA was extracted from breast tissue and subjected to PCR with primers that amplify a portion of the T. gondii B1 gene. Genotyping was based on a portion of the infected birds based on a multiplex PCR followed by RFLP of 12 T . gondii markers. Of 103 birds comprising 31 species, the overall prevalence (95% confidence interval) of T. gondii infection was 33.0% (24.1‒42.6%). Significant differences in the proportion of T. gondii in birds according to sex or weight were not observed. However, sample sizes of each species were small and prevented a robust analysis of T. gondii according to those biological variables. Genotyping of T. gondii in a subset of 13 infected individuals of 7 species revealed 4 genotypes, according to the Toxoplasma Data Base: #54, #139, #20, and #220. Our results, while hampered by a small sample size for each bird species, suggest that infection with T. gondii in Oklahoma, is common in both migrant and resident passerines.

Dual action antimicrobials: nitric oxide release from quaternary ammonium-functionalized silica nanoparticles.

The synthesis of quaternary ammonium (QA)-functionalized silica nanoparticles with and without nitric oxide (NO) release capabilities is described. Glycidyltrialkylammonium chlorides of varied alkyl chain lengths (i.e., methyl, butyl, octyl, and dodecyl) were tethered to the surface of amine-containing silica nanoparticles via a ring-opening reaction. Secondary amines throughout the particle were then functionalized with N-diazeniumdiolate NO donors to yield dual functional nanomaterials with surface QAs and total NO payloads of 0.3 µmol/mg. The bactericidal activities of singly (i.e., only NO-releasing or only QA-functionalized) and dual (i.e., NO-releasing and QA-functionalized) functional nanoparticles were tested against Gram-positive Staphylococcus aureus and Gram-negative Pseudomonas aeruginosa . Particles with only NO release capabilities alone were found to be more effective against P. aeruginosa , while particles with only QA-functionalities exhibited greater toxicity toward S. aureus . The minimum bactericidal concentrations (MBC) of QA-functionalized particles decreased with increasing alkyl chain length against both microbes tested. Combining NO release and QA-functionalities on the same particle resulted in an increase in bactericidal efficacy against S. aureus ; however, no change in activity against P. aeruginosa was observed compared to NO-releasing particles alone.

Expressing the Pro-Apoptotic Reaper Protein via Insertion into the Structural Open Reading Frame of Sindbis Virus Reduces the Ability to Infect Aedes aegypti Mosquitoes.

Arboviruses continue to threaten a significant portion of the human population, and a better understanding is needed of the determinants of successful arbovirus infection of arthropod vectors. Avoiding apoptosis has been shown to be one such determinant. Previous work showed that a Sindbis virus (SINV) construct called MRE/rpr that expresses the Drosophila pro-apoptotic protein Reaper via a duplicated subgenomic promoter had a reduced ability to orally infect Aedes aegypti mosquitoes at 3 days post-blood meal (PBM), but this difference diminished over time as virus variants containing deletions in the inserted reaper gene rapidly predominated. In order to further clarify the effect of midgut apoptosis on disseminated infection in Ae. aegypti, we constructed MRE/rprORF, a version of SINV containing reaper inserted into the structural open reading frame (ORF) as an in-frame fusion. MRE/rprORF successfully expressed Reaper, replicated similarly to MRE/rpr in cell lines, induced apoptosis in cultured cells, and caused increased effector caspase activity in mosquito midgut tissue. Mosquitoes that fed on blood containing MRE/rprORF developed significantly less midgut and disseminated infection when compared to MRE/rpr or a control virus up to at least 7 days PBM, when less than 50% of mosquitoes that ingested MRE/rprORF had detectable disseminated infection, compared with around 80% or more of mosquitoes fed with MRE/rpr or control virus. However, virus titer in the minority of mosquitoes that became infected with MRE/rprORF was not significantly different from control virus. Deep sequencing of virus populations from ten mosquitoes infected with MRE/rprORF indicated that the reaper insert was stable, with only a small number of point mutations and no deletions being observed at frequencies greater than 1%. Our results indicate that expression of Reaper by this method significantly reduces infection prevalence, but if infection is established then Reaper expression has limited ability to continue to suppress replication.

TOXOPLASMA GONDII PREVALENCE, PARTIAL GENOTYPES, AND SPATIAL VARIATION IN NORTH AMERICAN RIVER OTTERS (LONTRA CANADENSIS) IN THE UPPER PENINSULA OF MICHIGAN, USA.

Toxoplasma gondii is a ubiquitous parasitic protozoan that poses a health threat to wildlife and human health worldwide. Oocysts shed into the environment in felid host feces may persist for several years. Runoff from rainfall and snowmelt may carry the oocysts into waterways. Semiaquatic mammals such as the Northern American river otter (Lontra canadensis) are particularly at risk of exposure, as they may encounter infective stages in both terrestrial and aquatic environments. Despite this risk, only a small number of studies have examined the prevalence of T. gondii in US river otter populations. Tongue tissue was sampled from 124 otters from the Upper Peninsula of Michigan submitted by trappers to the Michigan Department of Natural Resources in the 2018-19 harvest season. Following DNA extraction, a portion of the B1 T. gondii gene was amplified with PCR. A subset of positive samples was genotyped for comparison with known T. gondii sequences. Of the 124 tongue samples, 35 (28%) were positive for T. gondii. Prevalence did not differ significantly between sexes or age classes across the entire study area. Most (53.8%) of the genotyped samples were type 4 (type 12), a genotype commonly found in North American wildlife. Genotypes 127 and 197 were also found. Three clusters of T. gondii prevalence were identified through SaTScan analysis, although they were not significant. When modeling prevalence of T. gondii with covariates at individual otter locations, the top three models included the presence of Sarcocystis, area of exotic plants, area of agriculture, and sex of the otter. Our results suggest that T. gondii is widespread in otter populations in the Upper Peninsula of Michigan.

Safety and immunogenicity of a prefusion non-stabilized spike protein mRNA COVID-19 vaccine: a phase I trial.

Effective mRNA SARS-CoV-2 vaccines are available but need to be stored in freezers, limiting their use to countries that have appropriate storage capacity. ChulaCov19 is a prefusion non-stabilized SARS-CoV-2 spike-protein-encoding, nucleoside-modified mRNA, lipid nanoparticle encapsulated vaccine that we report to be stable when stored at 2-8 °C for up to 3 months. Here we report safety and immunogenicity data from a phase I open-label, dose escalation, first-in-human trial of the ChulaCov19 vaccine (NCT04566276). Seventy-two eligible volunteers, 36 of whom were aged 18-55 (adults) and 36 aged 56-75 (elderly), were enroled. Two doses of vaccine were administered 21 d apart at 10, 25 or 50 µg per dose (12 per group). The primary outcome was safety and the secondary outcome was immunogenicity. All three dosages of ChulaCov19 were well tolerated and elicited robust dose-dependent and age-dependent B- and T-cell responses. Transient mild/moderate injection site pain, fever, chills, fatigue and headache were more common after the second dose. Four weeks after the second dose, in the adult cohort, MicroVNT-50 geometric mean titre against wild-type SARS-CoV-2 was 848 (95% CI, 483-1,489), 736 (459-1,183) and 1,140 (854-1,522) IU ml-1 at 10, 25 and 50 µg doses, respectively, versus 285 (196-413) IU ml-1 for human convalescent sera. All dose levels elicited 100% seroconversion, with geometric mean titre ratios 4-8-fold higher than for human convalescent sera (P < 0.01), and high IFNγ spot-forming cells per million peripheral blood mononuclear cells. The 50 µg dose induced better cross-neutralization against Alpha, Beta, Gamma and Delta variants than lower doses. ChulaCov19 at 50 µg is well tolerated and elicited higher neutralizing antibodies than human convalescent sera, with strong T-cell responses. These antibodies cross-neutralized four variants of concern. ChulaCov19 has proceeded to phase 2 clinical trials. We conclude that the mRNA vaccine expressing a prefusion non-stabilized spike protein is safe and highly immunogenic.

Nitric oxide-releasing silica nanoparticle inhibition of ovarian cancer cell growth.

Although the potent antitumor activity of nitric oxide (NO) supports its promise as an antineoplastic agent, effective and selective delivery and action on tumor and not normal cells remains a limiting factor. Nanoparticle-based delivery of NO has been considered as one approach to overcome these limitations. Therefore, we determined the utility of NO delivery using silica nanoparticles and evaluated their antitumor efficacy against human ovarian tumor and nontumor cells. The NO-releasing nanoparticles exhibited enhanced growth inhibition of ovarian tumor cells when compared to both control nanoparticles and a previously reported small molecule NO donor, PYRRO/NO. In addition, the NO-releasing nanoparticles showed greater inhibition of the anchorage-independent growth of tumor-derived and Ras-transformed ovarian cells. Confocal microscopy analysis revealed that fluorescently labeled NO-releasing nanoparticles entered the cytosol of the cell and localized to late endosomes and lysosomes. Furthermore, we observed a nanoparticle size dependency on efficacy against normal versus transformed ovarian cells. Our study provides the first application of nanoparticle-derived NO as an antitumor therapy and merits future studies examining nanoparticle formulation for in vivo applications.

False memories, false preferences: Flexible retrieval mechanisms supporting successful inference bias novel decisions.

Prior research suggests that episodic memory can guide value-based decisions when single episodes are encoded in relation to the specific reward-context in which they were experienced. The current experiments examine the role that a flexible recombination-related retrieval mechanism that allows one to link together distinct events plays in the misattribution of specific reward-contexts across distinct episodes. To determine whether the same recombination-related retrieval mechanism supports both successful inference and transfer of reward-context across episodes, we developed a modified version of an associative inference paradigm in which participants encoded overlapping associations (AB, BC) that could later be linked to support inferential retrieval (AC), where one element ("A") was tied to reward. Our key experimental manipulation concerned whether value memory (Experiments 1 and 2) or decision bias tests (Experiment 3) were probed before or after the associative inference test, thereby allowing us to assess whether false value transfer and decision bias scores increased after as compared to before successful versus unsuccessful inference. Results revealed that participants more frequently misattributed the specific reward-context ("A") to unrewarded items ("C;" Experiments 1 and 2) and showed higher decision bias scores when asked to choose between two previously unrewarded items ("C;" Experiment 3) for successful compared with unsuccessful inference, but only when the value memory and decision bias tests were given after the associative inference test. These results suggest that a recombination-related retrieval mechanism that supports successful inference also contributes to the misattribution of reward-context in memory and further biases participants' novel value-based decisions. (PsycINFO Database Record

Flexible retrieval mechanisms supporting successful inference produce false memories in younger but not older adults.

Episodic memory involves flexible retrieval processes that allow a person to link elements of distinct episodes in order to make novel inferences across events. In younger adults, we recently found that the same retrieval-related recombination mechanism that supports successful associative inference produces source misattributions as a consequence of erroneous binding of contextual elements from distinct episodes. In the current experiment, we found that older adults, in contrast to younger adults, did not show an increase in source misattributions following successful associative inference. We observed this pattern both when (a) younger and older adults were tested under identical experimental conditions and (b) younger and older adults were matched on associative inference accuracy and overall source memory errors. We suggest that the differing patterns of results are a consequence of age-related deficits in associative binding during successful inferential retrieval. (PsycINFO Database Record

Are eyewitness accounts biased? Evaluating false memories for crimes involving in-group or out-group conflict.

Eyewitness testimony has been shown to be unreliable and susceptible to false memories. Whether eyewitness memory errors are influenced by the victim's group membership (relative to both the eyewitness and perpetrator) is underexplored. The current study used complementary behavioral and neuroimaging approaches to test the hypothesis that intragroup conflict heightens participants' susceptibility to subsequent false memories. Healthy young adults witnessed and later answered questions about events in which the perpetrator and victim were either 1) identified as in-group members relative to each other and the eyewitness, 2) out-group members relative to the eyewitness, but not each other, or 3) out-group members relative to each other (Experiments 1a and 1b). When perpetrators and victims were in-group members (intragroup conflict), participants showed heightened false memory rates. Moreover, false memories increased upon crime realization. Neuroimaging data analysis revealed that salient (as compared to ambiguous) intragroup conflict elicited heightened activation in neural regions associated with resolving cognitive conflict (anterior cingulate cortex; ACC). Increased functional connectivity between the ACC and dorsomedial prefrontal cortex was associated with subsequent false memories (Experiment 2). Results suggest that the social salience of the intragroup conflict may have been associated with participants' increased susceptibility to false memories.

Remembering and imagining alternative versions of the personal past.

Although autobiographical memory and episodic simulations recruit similar core brain regions, episodic simulations engage additional neural recruitment in the frontoparietal control network due to greater demands on constructive processes. However, previous functional neuroimaging studies showing differences in remembering and episodic simulation have focused on veridical retrieval of past experiences, and thus have not fully considered how retrieving the past in different ways from how it was originally experienced may also place similar demands on constructive processes. Here we examined how alternative versions of the past are constructed when adopting different egocentric perspectives during autobiographical memory retrieval compared to simulating hypothetical events from the personal past that could have occurred, or episodic counterfactual thinking. Participants were asked to generate titles for specific autobiographical memories from the last five years, and then, during functional magnetic resonance (fMRI) scanning, were asked to repeatedly retrieve autobiographical memories or imagine counterfactual events cued by the titles. We used an fMRI adaptation paradigm in order to isolate neural regions that were sensitive to adopting alternative egocentric perspectives and counterfactual simulations of the personal past. The fMRI results revealed that voxels within left posterior inferior parietal and ventrolateral frontal cortices were sensitive to novel visual perspectives and counterfactual simulations. Our findings suggest that the neural regions supporting remembering become more similar to those underlying episodic simulation when we adopt alternative egocentric perspectives of the veridical past.

Flexible retrieval: When true inferences produce false memories.

Episodic memory involves flexible retrieval processes that allow us to link together distinct episodes, make novel inferences across overlapping events, and recombine elements of past experiences when imagining future events. However, the same flexible retrieval and recombination processes that underpin these adaptive functions may also leave memory prone to error or distortion, such as source misattributions in which details of one event are mistakenly attributed to another related event. To determine whether the same recombination-related retrieval mechanism supports both successful inference and source memory errors, we developed a modified version of an associative inference paradigm in which participants encoded everyday scenes comprised of people, objects, and other contextual details. These scenes contained overlapping elements (AB, BC) that could later be linked to support novel inferential retrieval regarding elements that had not appeared together previously (AC). Our critical experimental manipulation concerned whether contextual details were probed before or after the associative inference test, thereby allowing us to assess whether (a) false memories increased for successful versus unsuccessful inferences, and (b) any such effects were specific to after compared with before participants received the inference test. In each of 4 experiments that used variants of this paradigm, participants were more susceptible to false memories for contextual details after successful than unsuccessful inferential retrieval, but only when contextual details were probed after the associative inference test. These results suggest that the retrieval-mediated recombination mechanism that underlies associative inference also contributes to source misattributions that result from combining elements of distinct episodes. (PsycINFO Database Record