Proximity-dependent mapping of the HCMV US28 interactome identifies RhoGEF signaling as a requirement for efficient viral reactivation.

Human cytomegalovirus (HCMV) encodes multiple putative G protein-coupled receptors (GPCRs). US28 functions as a viral chemokine receptor and is expressed during both latent and lytic phases of virus infection. US28 actively promotes cellular migration, transformation, and plays a major role in mediating viral latency and reactivation; however, knowledge about the interaction partners involved in these processes is still incomplete. Herein, we utilized a proximity-dependent biotinylating enzyme (TurboID) to characterize the US28 interactome when expressed in isolation, and during both latent (CD34+ hematopoietic progenitor cells) and lytic (fibroblasts) HCMV infection. Our analyses indicate that the US28 signalosome converges with RhoA and EGFR signal transduction pathways, sharing multiple mediators that are major actors in processes such as cellular proliferation and differentiation. Integral members of the US28 signaling complex were validated in functional assays by immunoblot and small-molecule inhibitors. Importantly, we identified RhoGEFs as key US28 signaling intermediaries. In vitro latency and reactivation assays utilizing primary CD34+ hematopoietic progenitor cells (HPCs) treated with the small-molecule inhibitors Rhosin or Y16 indicated that US28 -RhoGEF interactions are required for efficient viral reactivation. These findings were recapitulated in vivo using a humanized mouse model where inhibition of RhoGEFs resulted in a failure of the virus to reactivate. Together, our data identifies multiple new proteins in the US28 interactome that play major roles in viral latency and reactivation, highlights the utility of proximity-sensor labeling to characterize protein interactomes, and provides insight into targets for the development of novel anti-HCMV therapeutics.

Recalling fake news during real news corrections can impair or enhance memory updating: the role of recollection-based retrieval.

Fake news can impair memory leading to societal controversies such as COVID-19 vaccine efficacy. The pernicious influence of fake news is clear when ineffective corrections leave memories outdated. A key theoretical issue is whether people should recall fake news while reading corrections with contradictory details. The familiarity backfire view proposes that recalling fake news increases its familiarity, leading to interference. However, the integrative encoding view proposes that recalling fake news promotes co-activation and binding of contradictory details, leading to facilitation. Two experiments examined if one theory better accounts for memory updating after participants recalled actual fake news details when reading headlines that corrected misinformation. In Phase 1, participants read real and fake news headlines of unclear veracity taken from various internet sources. In Phase 2, participants read real news headlines that reaffirmed real news and corrected fake news from Phase 1. When they detected that Phase 2 real news corrected fake news, they attempted to recall Phase 1 fake news. In Phase 3, participants first recalled real news details. When they remembered that those details were corrections from Phase 2, they attempted to recall fake news from Phase 1. Recalling fake news when noticing corrections in Phase 2 led to better memory for real news in Phase 3 when fake news was recalled again and worse memory for real news in Phase 3 when fake news was not recalled again. Both views explain part of the memory differences associated with recalling fake news during corrections, but only when considering whether people recollected that fake news had been corrected.

Erratum: Chest radiographs of cardiac devices (Part 1): Cardiovascular implantable electronic devices, cardiac valve prostheses and Amplatzer occluder devices.

[This corrects the article DOI: 10.4102/sajr.v23i1.1730.].

The role of prior-event retrieval in encoding changed event features.

When people experience everyday activities, their comprehension can be shaped by expectations that derive from similar recent experiences, which can affect the encoding of a new experience into memory. When a new experience includes changes-such as a driving route being blocked by construction-this can lead to interference in subsequent memory. One potential mechanism of effective encoding of event changes is the retrieval of related features from previous events. Another such mechanism is the generation of a prediction error when a predicted feature is contradicted. In two experiments, we tested for effects of these two mechanisms on memory for changed features in movies of everyday activities. Participants viewed movies of an actor performing everyday activities across two fictitious days. Some event features changed across the days, and some features violated viewers' predictions. Retrieval of previous event features while viewing the second movie was associated with better subsequent memory, providing evidence for the retrieval mechanism. Contrary to our hypotheses, there was no support for the error mechanism: Prediction error was not associated with better memory when it was observed correlationally (Experiment 1) or directly manipulated (Experiment 2). These results support a key role for episodic retrieval in the encoding of new events. They also indicate boundary conditions on the role of prediction errors in driving new learning. Both findings have clear implications for theories of event memory.

Rat and human cytomegalovirus ORF116 encodes a virion envelope glycoprotein required for infectivity.

Herpesviruses encode multiple glycoproteins required for different stages of viral attachment, fusion, and envelopment. The protein encoded by the human cytomegalovirus (HCMV) open reading frame UL116 forms a stable complex with glycoprotein H that is incorporated into virions. However, the function of this complex remains unknown. Herein, we characterize R116, the rat CMV (RCMV) putative homolog of UL116. Two R116 transcripts were identified in fibroblasts with three proteins expressed with molecular weights of 42, 58, and 82 kDa. R116 is N-glycosylated, expressed with late viral gene kinetics, and is incorporated into the virion envelope. RCMV lacking R116 failed to result in productive infection of fibroblasts and siRNA knockdown of R116 substantially reduced RCMV infectivity. Complementation in trans of an R116-deficient virus restored ability of the virus to infect fibroblasts. Finally, UL116 knockdown also decreased HCMV infectivity indicating that R116 and UL116 both contribute to viral infectivity.

Reminders of Everyday Misinformation Statements Can Enhance Memory for and Beliefs in Corrections of Those Statements in the Short Term.

Fake-news exposure can cause misinformation to be mistakenly remembered and believed. In two experiments (Ns = 96), we examined whether reminders of misinformation could improve memory for and beliefs in corrections. Subjects read factual statements and misinformation statements taken from news websites and then read statements that corrected the misinformation. Misinformation reminders appeared before some corrections but not others. Subjects then attempted to recall facts, indicated their belief in those recalls, and indicated whether they remembered corrections and misinformation. In Experiment 1, we did not constrain subjects' report criteria. But in Experiment 2, we encouraged conservative reporting by instructing subjects to report only information they believed to be true. Reminders increased recall and belief accuracy. These benefits were greater both when misinformation was recollected and when subjects remembered that corrections had occurred. These findings demonstrate one situation in which misinformation reminders can diminish the negative effects of fake-news exposure in the short term.

Abdominal and pelvic radiographs of medical devices and materials- part 2: neurologic and genitourinary devices and materials.

Radiographs of the abdomen and pelvis are routinely obtained as a standard part of clinical care for the abdomen and pelvis. Brisk advances in technology over the last few decades have resulted in a multitude of medical devices and materials. Recognizing and evaluating these devices on abdominal and pelvic radiographs are critical, yet increasingly a difficult endeavor. In addition, multiple devices serving different purposes may have a similar radiographic appearance and position causing confusion for the interpreting radiologist. The role of the radiologist is to not only identify accurately these medical objects, but also to confirm for their accurate placement and to recognize any complications that could affect patient care, management or even be potentially life threatening. An extensive online search of literature showed our review article to be the most comprehensive work on medical devices and materials of the abdomen and pelvis, and in this second part of our two-part series, we discuss in depth about the neurologic and genitourinary devices seen on abdominal and pelvic radiographs.

Abdominal and pelvic radiographs of medical devices and materials-Part 1: gastrointestinal and vascular devices and materials.

When compared with chest radiographs, medical devices of the abdomen and pelvis are less frequently seen. However, with recent advances in technology the interpreting radiologists are seeing more medical objects on these radiographs. The identification of these devices and materials are crucial for not only enabling the radiologist to understand the underlying background pathology but also for evaluating any related complications. An online survey of literature showed our review article to be the most detailed. In this first part of our two-part series, we discuss about the various gastrointestinal and vascular devices and materials seen on abdominal and pelvic radiographs.

Erratum: Chest radiographs - Lines, tubes, non-cardiac medical devices and materials.

[This corrects the article DOI: 10.4102/sajr.v23i1.1729.].

Chest radiographs of cardiac devices (Part 1): Lines, tubes, non-cardiac medical devices and materials.

Chest radiographs (CXRs) are the most common imaging investigations undertaken because of their value in evaluating the cardiorespiratory system. They play a vital role in intensive care units for evaluating the critically ill. It is therefore very common for the radiologist to encounter tubes, lines, medical devices and materials on a daily basis. It is important for the interpreting radiologist not only to identify these iatrogenic objects, but also to look for their accurate placement as well as for any complications related to their placement, which may be seen either on the immediate post-procedural CXR or on a follow-up CXR. In this article, we discussed and illustrated the routinely encountered tubes and lines that one may see on a CXR as well as some of their complications. In addition, we also provide a brief overview of other important non-cardiac medical devices and materials that may be seen on CXRs.

Chest radiographs of cardiac devices (Part 1): Cardiovascular implantable electronic devices, cardiac valve prostheses and Amplatzer occluder devices.

Several new innovative cardiac devices have been created over the last few decades. Chest radiographs (CXRs) are the most common imaging investigations undertaken because of their value in evaluating the cardiorespiratory system. It is important for the interpreting radiologist to not only identify these iatrogenic objects but also to assess for their accurate placement, as well as for any complications related to their placement, which may be seen either on the immediate post-procedural CXR or on a follow-up CXR.

Chest radiographs of cardiac devices (Part 2): Ventricular assist devices.

Heart failure is considered a worldwide pandemic affecting 26 million people globally. Patients who are unfit or waiting for cardiac transplantation may benefit from alternate mechanical support therapies using ventricular assist devices. It is not uncommon for radiologists, especially those working in institutions with a high volume of cardiac transplantations, to be presented with radiographs containing these devices. The role of the radiologist is not only to accurately identify these devices, but also to evaluate for any complications.

Interpolated retrieval effects on list isolation: Individual differences in working memory capacity.

We examined the effects of interpolated retrieval from long-term memory (LTM) and short-term memory (STM) on list isolation in dual-list free recall and whether individual differences in working memory capacity (WMC) moderated those effects. Ninety-seven subjects completed study-test trials that included two study lists separated by either an exemplar generation task (LTM retrieval) or a two-back task (STM retrieval). Subjects then completed an externalized free recall task that allowed for the examination of response accessibility and monitoring. Individual differences in WMC were assessed using three complex span tasks: operation span, reading span, and rotation span. Correct recall and intratrial intrusion summary scores showed no effect of interpolated retrieval on either response accessibility or monitoring. However, serial-position curves for correct recall of List 1 showed larger primacy in the two-back than in the exemplar generation task for high-WMC subjects. We interpreted these results from a context change perspective, as showing that interpolated LTM retrieval accelerated context change for subjects who processed the context more effectively. We consider the implications of these findings for models of memory.

Interactive responses of primary producers and grazers to pollution on temperate rocky reefs.

Macroalgal beds provide important habitat structure and support primary production for rocky reef communities, but are increasingly degraded as a result of human pressures. Various sources of pollution can have both direct and interactive effects on stressed ecosystems. In particular, interactions involving invertebrate grazers could potentially weaken or strengthen the overall impact of pollution on macroalgal beds. Using a paired impact-control experimental design, we tested the effects of multiple pollution sources (fish farms, marinas, sewerage, and stormwater) on translocated and locally established algal assemblages, while also considering the influence of invertebrate grazers. Marinas directly affected algal assemblages and also reduced densities of amphipods and other invertebrate mesograzers. Fish farms and sewerage outfalls tended to directly increase local establishment of foliose and leathery algae without any indication of changes in herbivory. Overall, pollution impacts on algae did not appear to be strongly mediated by changes in grazer abundance. Instead, mesograzer abundance was closely linked to availability of more complex algal forms, with populations likely to decline concurrently with loss of complex algal habitats. Macrograzers, such as sea urchins, showed no signs of a negative impact from any pollution source; hence, the influence of this group on algal dynamics is probably persistent and independent of moderate pollution levels, potentially adding to the direct impacts of pollution on algal beds in urbanised environments.

Counter-intuitive moral judgement following traumatic brain injury.

Several neurological patient populations, including traumatic brain injury (TBI), appear to produce an abnormally 'utilitarian' pattern of judgements to moral dilemmas; they tend to make judgements that maximize the welfare of the majority, rather than deontological judgements based on the following of moral rules (e.g., do not harm others). However, this patient research has always used extreme dilemmas with highly valued moral rules (e.g., do not kill). Data from healthy participants, however, suggest that when a wider range of dilemmas are employed, involving less valued moral rules (e.g., do not lie), moral judgements demonstrate sensitivity to the psychological intuitiveness of the judgements, rather than their deontological or utilitarian content (Kahane et al., Social Cognitive and Affective Neuroscience, 7, 2011, 393). We sought the moral judgements of 30 TBI participants and 30 controls on moral dilemmas where content (utilitarian/deontological) and intuition (intuitive/counter-intuitive) were measured concurrently. Overall TBI participants made utilitarian judgements in equal proportions to controls; disproportionately favouring utilitarian judgements only when they were counter-intuitive, and deontological judgements only when they were counter-intuitive. These results speak against the view that TBI causes a specific utilitarian bias, suggesting instead that moral intuition is broadly disrupted following TBI.

Abundance and local-scale processes contribute to multi-phyla gradients in global marine diversity.

Among the most enduring ecological challenges is an integrated theory explaining the latitudinal biodiversity gradient, including discrepancies observed at different spatial scales. Analysis of Reef Life Survey data for 4127 marine species at 2406 coral and rocky sites worldwide confirms that the total ecoregion richness peaks in low latitudes, near +15°N and -15°S. However, although richness at survey sites is maximal near the equator for vertebrates, it peaks at high latitudes for large mobile invertebrates. Site richness for different groups is dependent on abundance, which is in turn correlated with temperature for fishes and nutrients for macroinvertebrates. We suggest that temperature-mediated fish predation and herbivory have constrained mobile macroinvertebrate diversity at the site scale across the tropics. Conversely, at the ecoregion scale, richness responds positively to coral reef area, highlighting potentially huge global biodiversity losses with coral decline. Improved conservation outcomes require management frameworks, informed by hierarchical monitoring, that cover differing site- and regional-scale processes across diverse taxa, including attention to invertebrate species, which appear disproportionately threatened by warming seas.

Cognitive correlates of pragmatic language comprehension in adult traumatic brain injury: A systematic review and meta-analyses.

Effective pragmatic comprehension of language is critical for successful communication and interaction, but this ability is routinely impaired following Traumatic Brain Injury (TBI) (1,2). Individual studies have investigated the cognitive domains associated with impaired pragmatic comprehension, but there remains little understanding of the relative importance of these domains in contributing to pragmatic comprehension impairment following TBI. This paper presents a systematic meta-analytic review of the observed correlations between pragmatic comprehension and cognitive processes following TBI. Five meta-analyses were computed, which quantified the relationship between pragmatic comprehension and five key cognitive constructs (declarative memory; working memory; attention; executive functions; social cognition). Significant moderate-to-strong correlations were found between all cognitive measures and pragmatic comprehension, where declarative memory was the strongest correlate. Thus, our findings indicate that pragmatic comprehension in TBI is associated with an array of domain general cognitive processes, and as such deficits in these cognitive domains may underlie pragmatic comprehension difficulties following TBI. The clinical implications of these findings are discussed.

Relating trophic resources to community structure: a predictive index of food availability.

The abundance and the distribution of trophic resources available for consumers influence the productivity and the diversity of natural communities. Nevertheless, assessment of the actual abundance of food items available for individual trophic groups has been constrained by differences in methods and metrics used by various authors. Here we develop an index of food abundance, the framework of which can be adapted for different ecosystems. The relative available food index (RAFI) is computed by considering standard resource conditions of a habitat and the influence of various generalized anthropogenic and natural factors. RAFI was developed using published literature on food abundance and validated by comparison of predictions versus observed trophic resources across various marine sites. RAFI tables here proposed can be applied to a range of marine ecosystems for predictions of the potential abundance of food available for each trophic group, hence permitting exploration of ecological theories by focusing on the deviation from the observed to the expected.

Does eutrophication-driven evolution change aquatic ecosystems?

Eutrophication increases primary production and changes the relative abundance, taxonomic composition and spatial distribution of primary producers within an aquatic ecosystem. The changes in composition and location of resources alter the distribution and flow of energy and biomass throughout the food web. Changes in productivity also alter the physico-chemical environment, which has further effects on the biota. Such ecological changes influence the direction and strength of natural and sexual selection experienced by populations. Besides altering selection, they can also erode the habitat gradients and/or behavioural mechanisms that maintain ecological separation and reproductive isolation among species. Consequently, eutrophication of lakes commonly results in reduced ecological specialization as well as genetic and phenotypic homogenization among lakes and among niches within lakes. We argue that the associated loss in functional diversity and niche differentiation may lead to decreased carrying capacity and lower resource-use efficiency by consumers. We show that in central European whitefish species radiations, the functional diversity affected by eutrophication-induced speciation reversal correlates with community-wide trophic transfer efficiency (fisheries yield per unit phosphorus). We take this as an example of how evolutionary dynamics driven by anthropogenic environmental change can have lasting effects on biodiversity and ecosystem functioning.This article is part of the themed issue 'Human influences on evolution, and the ecological and societal consequences'.

Reef Fishes at All Trophic Levels Respond Positively to Effective Marine Protected Areas.

Marine Protected Areas (MPAs) offer a unique opportunity to test the assumption that fishing pressure affects some trophic groups more than others. Removal of larger predators through fishing is often suggested to have positive flow-on effects for some lower trophic groups, in which case protection from fishing should result in suppression of lower trophic groups as predator populations recover. We tested this by assessing differences in the trophic structure of reef fish communities associated with 79 MPAs and open-access sites worldwide, using a standardised quantitative dataset on reef fish community structure. The biomass of all major trophic groups (higher carnivores, benthic carnivores, planktivores and herbivores) was significantly greater (by 40% - 200%) in effective no-take MPAs relative to fished open-access areas. This effect was most pronounced for individuals in large size classes, but with no size class of any trophic group showing signs of depressed biomass in MPAs, as predicted from higher predator abundance. Thus, greater biomass in effective MPAs implies that exploitation on shallow rocky and coral reefs negatively affects biomass of all fish trophic groups and size classes. These direct effects of fishing on trophic structure appear stronger than any top down effects on lower trophic levels that would be imposed by intact predator populations. We propose that exploitation affects fish assemblages at all trophic levels, and that local ecosystem function is generally modified by fishing.