Successful Replication Research Articles

Recruitment Strategies Bias Sampling and Shape Replicability.

Replicating psychological research has become a central concern for psychologists. Although attention has been paid to the possibility of heterogeneous populations driving replication success/failure, the heterogeneous recruitment strategies researchers use to draw samples from those populations are often overlooked. Yet recruitment strategies may bias the participants who show up and shape replication results. We examine this idea through several unique paradigms (sampling North American university students, Ntotal = 1,009). First, subtle manipulations of recruitment strategies (i.e., mentioning cash, expedient credit, fun, or a study narrative) were differentially appealing to individuals varying on experiential versus reward-based motivations (Experiment 1). Second, employing different recruitment strategies biased the motivational styles of actual participant show-ups, and sometimes even shaped the success of several replication studies (Experiment 2-3). We conclude that recruitment strategies may sometimes alter the degree of successful replication.

An increase of lysosomes through EGF-triggered endocytosis attenuated zinc-mediated lysosomal membrane permeabilization and neuronal cell death

In the context of acute brain injuries, where zinc neurotoxicity and oxidative stress are acknowledged contributors to neuronal damage, we investigated the pivotal role of lysosomes as a potential protective mechanism. Our research commenced with an exploration of epidermal growth factor (EGF) and its impact on lysosomal dynamics, particularly its neuroprotective potential against zinc-induced cytotoxicity. Using primary mouse cerebrocortical cultures, we observed the rapid induction of EGFR endocytosis triggered by EGF, resulting in a transient increase in lysosomal vesicles. Furthermore, EGF stimulated lysosomal biogenesis, evident through elevated expression of lysosomal-associated membrane protein 1 (LAMP-1) and the induction and activation of prominent lysosomal proteases, particularly cathepsin B (CTSB). This process of EGFR endocytosis was found to promote lysosomal augmentation, thus conferring protection against zinc-induced lysosomal membrane permeabilization (LMP) and subsequent neuronal death. Notably, the neuroprotective effects and lysosomal enhancement induced by EGF were almost completely reversed by the inhibition of clathrin-mediated and caveolin-mediated endocytosis pathways, along with the disruption of retrograde trafficking. Furthermore, tyrosine kinase inhibition of EGFR nullified EGFR endocytosis, resulting in the abrogation of EGF-induced lysosomal upregulation and neuroprotection. An intriguing aspect of our study is the successful replication of EGF’s neuroprotective effects through the overexpression of LAMP-1, which significantly reduced zinc-induced LMP and cell death, demonstrated in both primary mouse cerebrocortical neuronal cultures and human embryonic kidney (HEK) cells. Our research extended beyond zinc-induced neurotoxicity, as we observed EGF’s protective effects against other oxidative stressors linked to intracellular zinc release, including hydrogen peroxide (H2O2) and 1-methyl-4-phenylpyridinium ion (MPP+). Collectively, our findings unveil the intricate interplay between EGF-triggered EGFR endocytosis, lysosomal upregulation, an increase in the regulatory capacity for zinc homeostasis, and the subsequent alleviation of zinc-induced neurotoxicity. These results present promising avenues for therapeutic interventions to enhance neuroprotection by targeting lysosomal augmentation.

Evaluating the Replicability of Social Priming Studies

To assess the replicability of social priming findings we reviewed the extant close replication attempts in the field. In total, we found 70 close replications, that replicated 49 unique findings. Ninety-four percent of the replications had effect sizes smaller than the effect they replicated and only 17% of the replications reported a significant p-value in the original direction. The strongest predictor of replication success was whether or not the replication team included at least one of the authors of the original paper. Twelve of the 18 replications with at least one original author produced a significant effect in the original direction and the meta-analytic average of these studies suggest a significant priming effect (d = 0.40, 95% CI[0.23; 0.58]). In stark contrast, none of the 52 replications by independent research teams produced a significant effect in the original direction and the meta-analytic average was virtually zero (d = 0.002, 95% CI[-0.03; 0.03]). We argue that these results have shifted the burden of proof back onto advocates of social priming. Successful replications from independent research teams will likely be required to convince sceptics that social priming exists at all.

Identification of critical residues for RNA binding of nairovirus nucleoprotein.

We sought to identify the important residues for RNA binding of nairovirus nucleoprotein using Orthonairovirus hazaraense, a surrogate model for Orthonairovirus haemorrhagiae. The four basic amino acid residues of Orthonairovirus hazaraense nucleoprotein were critical for RNA binding. Sufficient RNA-binding capacity of nucleoprotein was essential for successful virus replication. This study provides new insights into a detailed binding model between nairovirus nucleoprotein and its genomic RNA.

Reducing the replication time for structural estimations: A successful replication of “An Anatomy of International Trade” using GPU computing

AbstractEaton, Kortum, and Kramarz (2011) (EKK) discovered empirical patterns from French manufacturing firms that a baseline firm heterogeneity model could not explain. The authors proposed and estimated a model that closely matches the patterns observed in French data. This paper successfully replicates their findings using author‐provided data, re‐implementing their algorithms in Python and leveraging graphics processing unit computing to significantly boost computational speed. Applying the model to Chinese manufacturing data, despite differences in context, showed that the model explains most observed patterns well.

Decreasing of Trimethylamine N-Oxide by Cecal Microbiota and Choline-Trimethylamine Lyase are Associated with Sishen Pill on Diarrhea with Kidney-Yang Deficiency Syndrome.

Sishen Pill (SSP) is a traditional Chinese medicine prescription commonly used to treat diarrhea with kidney-yang deficiency syndrome. The aim was to investigate the underlying mechanisms of SSP's therapeutic effects, providing experimental evidence for its mechanism of action. A mouse model of diarrhea with kidney-yang deficiency syndrome was induced using adenine combined with Folium sennae. After successful model replication, SSP decoction was administered. CutC activity, TMAO, IL-6, TNF-α levels, and cecal content microbiota were measured. SSP significantly improved the general behavioral characteristics of diarrhea mice, and reduced CutC activity, TMAO and IL-6 levels. Sequencing results indicated significant changes at the phylum and genus levels. Correlation analysis revealed a positive correlation between CutC activity and Faecalibaculum (p<0.05) and Chryseobacterium (p<0.05), and a significant negative correlation with Prevotellaceae UCG-001, Rikenella (p<0.05), Acinetobacter (p<0.05), Parasutterella (p<0.05), and Lacticaseibacillus (p<0.05). TNF-α levels showed a significant negative correlation with Lacticaseibacillus (p<0.05), Prevotellaceae UCG-001 (p<0.01), Parasutterella (p<0.05), and Candidatus Saccharimonas (p<0.05). IL-6 levels exhibited a significant negative correlation with Rikenella (p<0.05), Acinetobacter (p<0.05), Prevotellaceae UCG-001 (p<0.05), Lacticaseibacillus (p<0.01), and Parasutterella (p<0.05), and a significant positive correlation with Faecalibaculum (p<0.05), Chryseobacterium (p<0.01), and A2. Serum TMAO levels showed a significant positive correlation with Faecalibaculum (p<0.05) and Chryseobacterium (p<0.01), and hepatic TMAO levels exhibited a significant positive correlation with Chryseobacterium (p<0.05). SSP significantly alleviated the symptoms of diarrhea with kidney-yang deficiency syndrome by modulating the cecal microbiota, downregulating CutC activity, and reducing TMAO and inflammatory factor levels. The cecal microbiota-CutC-TMAO-inflammatory cytokine axis may be a key mechanism underlying the therapeutic effects of SSP.

Prior familiarity enhances recognition memory of faces, not just images of faces, when accompanied by conceptual information.

A recent paper reported that recognition discriminability was improved for faces that were familiarized prior to study, but only if that familiarization protocol included conceptual information, like a name (Akan & Benjamin, Journal of Memory and Language,131, 104,433, 2023). In those experiments, familiarity with each facial identity was gained through exposures to the same facial image prior to study, and memory for each facial identity was tested using the same images across study and test. That design characteristic has a serious constraint on generality, since it is possible that prior conceptual information enhances memory for images (of faces), but not for the representation of the face itself. Here we evaluated whether this finding generalizes to a paradigm in which each exposure of a face is a novel image. In two experiments, faces were familiarized with orienting tasks that induced more perceptual or more conceptual processing prior to study and test phases. Results from recognition tests replicated the results from Akan and Benjamin (2023): (1) Discriminability was enhanced when prior familiarity involved conceptual processing but not when it involved perceptual processing, and (2) familiarity gained through either perceptual or conceptual processing led to an increase in both correct and false identifications. This successful replication in a design with exclusively novel images indicates that the discriminability advantage provided by conceptual familiarity goes beyond memory for facial images and applies to memory for faces. These findings have implications in practical contexts, such as eyewitness identification situations involving suspects who are previously known or familiar to the witness.

Measurement of the social investment impact of the bahtera segara program using the social return on investment method (SROI)

PT Pertamina Patra Niaga Integrated Terminal Semarang conducted this study to analyze the impact of the BAHTERA SEGARA (Bahagia Sejahtera Nelayan Pesisir Semarang Utara) Program, aiming to enhance the program's quality in the future. This research employs the SROI method to measure the impact of all activities carried out by PT Pertamina Patra Niaga Integrated Terminal Semarang within the framework of the BAHTERA SEGARA (Bahagia Sejahtera Nelayan Pesisir Pesisir Semarang Utara) Program. Based on the study results of the BAHTERA SEGARA Program (Bahagia Sejahtera Nelayan Pesisir Semarang Utara), this program has proven to be effective and has a significant positive impact. The program has succeeded in improving the economic, social, and environmental welfare of the target community groups and communities that replicate it independently. Increasing SROI scores from 2020 to 2023 indicate that the program is increasingly effective in delivering benefits, particularly through the replication of food crop cultivation and increased fish processing productivity. The program also contributes to the reduction of greenhouse gas emissions and supports climate change adaptation efforts. The program's successful replication demonstrates the effectiveness of BAHTERA SEGARA as a collective learning tool, as well as its potential for replication in other areas with similar conditions.

Towards the Development of a Minigenome Assay for Species A Rotaviruses.

RNA virus polymerases carry out multiple functions necessary for successful genome replication and transcription. A key tool for molecular studies of viral RNA-dependent RNA polymerases (RdRps) is a 'minigenome' or 'minireplicon' assay, in which viral RdRps are reconstituted in cells in the absence of full virus infection. Typically, plasmids expressing the viral polymerase protein(s) and other co-factors are co-transfected, along with a plasmid expressing an RNA encoding a fluorescent or luminescent reporter gene flanked by viral untranslated regions containing cis-acting elements required for viral RdRp recognition. This reconstitutes the viral transcription/replication machinery and allows the viral RdRp activity to be measured as a correlate of the reporter protein signal. Here, we report on the development of a 'first-generation' plasmid-based minigenome assay for species A rotavirus using a firefly luciferase reporter gene.

Classifying the Breadth of Knowledge Management Frameworks

This study aims to analyze Knowledge Management frameworks and categorize them based on their specification breadth. A total of 27 frameworks, selected from the temporal spectrum spanning 1995 to 2016 and representative of the field of Knowledge Management, were examined using content analysis. This research employs a qualitative, exploratory, descriptive, and bibliographic approach. Among the 27 frameworks examined, 12 were identified as descriptive, while 15 exhibited hybrid characteristics. Additionally, existing typologies lack sufficient detail for successful replication. Consequently, it is imperative to develop structures underpinned by a conjunctive approach. Such structures should provide both a comprehensive overview and detailed prescriptions of the “what,” “why,” “who,” “how,” and “when” aspects of implementing and operationalizing Knowledge Management. The prevalence of hybrid frameworks is notable within the examined set, highlighting the need for an integrated approach that combines breadth and depth. Organizations require a sufficiently comprehensive and detailed roadmap to implement Knowledge Management effectively. This analysis expands upon prior research concerning the classification of Knowledge Management frameworks and introduces a novel and anticipated approach to classifying specification breadth.

Discovery of Living Optical Networks in Orchid Leaves as Inspiration for Light Harvesting and Redistribution in Soft, Curvilinear Material Formats

AbstractPlants and animals produce highly evolved, hierarchical systems that combine physicochemical material parameters with functional micro‐ and nanostructures to manage energy, motion, and species survival. These systems, besides providing cues on bottom‐up manufacturing of technological structures, can give insight on strategies for efficient energy management. Here is reported the observation of an optically interconnected network formed by the cells of the leaves of the Macodes petola jewel orchid that provides light harvesting and redistribution across its surface. The planar redistribution of light incident on the leaf is enabled by the distinctively rounded shape of the outer epidermal cells and by their arrangement in a short‐range ordered hexagonal lattice. Successful replication of a live leaf in a free‐standing biopolymer film validates the observation and opens avenues for the exploration of non‐traditional energy harvesting interfaces that are soft, conformal, and curvilinear.

Targeting Monkeypox Virus Methyltransferase: Virtual Screening of Natural Compounds from Middle-Eastern Medicinal Plants.

Monkeypox is an infectious disease resulting from the monkeypox virus, and its fatality rate varies depending on the virus clade and the location of the outbreak. In monkeypox virus, methyltransferase (MTase) plays a crucial role in modifying the cap structure of viral mRNA. This alteration assists the virus in evading the host's immune system, enhances viral protein synthesis, and ultimately enables successful infection and replication within host cells. Given the significance of MTase in viral infection and spread within the host, our study aimed to identify a natural inhibitor for this enzyme using docking and molecular dynamic (MD) simulations. We collected a total of 12,971 natural compounds from 200 medicinal plants in the Middle East. After eliminating duplicate compounds, we had 5,749 unique ligand conformers, which we then subjected to high-throughput virtual screening against MTase. The most promising hits were further evaluated using the extra-precision (XP) tool. The affinity of these hits was also assessed by Prime-Molecular Mechanics/Generalized Born Surface Area (MMGBSA) tool. The analysis revealed that two standard controls (sinefungin and TO1119) and two Middle-Eastern compounds (folic acid and 1,2,4,6-tetragalloylglucose) exhibited the best XP docking scores. According to Prime MMGBSA calculations, the Middle-Eastern compounds showed higher affinities, with values of -60.61 kcal/mol for 1,2,4,6-tetragalloylglucose and -51.87 kcal/mol for folic acid, surpassing the controls (TO1119 at -35.71 kcal/mol and sinefungin at -31.51 kcal/mol). In the majority of Molecular dynamic (MD) simulations, folic acid exhibited demonstrated greater stability than sinefungin. Further investigation revealed that folic acid occupied a critical position in the active site of MTase, which reduced its interaction with the mRNA substrate. Based on these findings, it can be concluded that folic acid is a highly promising natural compound for potential use in the cost-effective treatment of monkeypox virus. The identification of folic acid as a potential antiviral agent highlights the importance of nature in providing new therapeutic uses that have significant implications for global health, particularly in regions where monkeypox viral outbreaks are prevalent. However, it is essential to note that further wet-lab validations are necessary to confirm its efficacy for treatment in a medical context.

Unlocking the Economic Potential of Cultural Heritage: Women's Empowerment in the Creative Economy of Developing Countries

This literature review explores how empowering women in a culture-based creative economy can preserve cultural heritage while encouraging economic competitiveness in developing countries. Through a systematic analysis of 44 studies, key findings emerged. First, cultural heritage offers economic opportunities through sustainable tourism and creative entrepreneurship. Second, women face challenges such as marginalization, limited resources, and socio-cultural obstacles in conservation efforts. Third, integrating traditional wisdom into creative products, entrepreneurship training, and marketing can empower women economically. Fourth, government policy, financial support, use of digital technology, and multi-stakeholder involvement are important factors. Fifth, best practices from various countries demonstrate successful replication models. The review concludes that empowering women to preserve cultural heritage opens up sustainable economic development by leveraging local strengths, thus requiring synergistic efforts from the government, stakeholders, and women. Preserving cultural heritage through empowering women is a dual opportunity for developing countries to maintain their identity while driving economic progress.

Time-resolved scRNA-seq reveals transcription dynamics of polarized macrophages with influenza A virus infection and antigen presentation to T cells

Throughout history, the influenza A virus has caused numerous devastating global pandemics. Macrophages, as pivotal innate immune cells, exhibit a wide range of immune functions characterized by distinct polarization states, reflecting their intricate heterogeneity. In this study, we employed the time-resolved single-cell sequencing technique coupled with metabolic RNA labelling to elucidate the dynamic transcriptional changes in distinct polarized states of bone marrow-derived macrophages (BMDMs) upon infection with the influenza A virus. Our approach not only captures the temporal dimension of transcriptional activity, which is lacking in conventional scRNA-seq methods, but also reveals that M2-polarized Arg1_macrophages is the sole state supporting successful replication of influenza A virus. Furthermore, we identified distinct antigen presentation capabilities to CD4 + T and CD8 + T cells across diverse polarized states of macrophages. Notably, the M1 phenotype, exhibited by both bone marrow-derived macrophages (BMDMs) and murine alveolar macrophages (AMs), demonstrated superior conventional and cross-presentation abilities for exogenous antigens, with a particular emphasis on cross-presentation capacity. Additionally, as CD8 + T cell differentiation progressed, M1 polarization exhibited an enhanced capacity for cross-presentation. All three phenotypes of BMDMs, including M1, demonstrated robust presentation of CD4 + regulatory T cells, while displaying limited ability to present naive CD4+ T cells. These findings offer novel insights into the immunological regulatory mechanisms governing distinct polarized states of macrophages, particularly their roles in restricting the replication of influenza A virus and modulating antigen-specific T cell responses through innate immunity.

Brucella NpeA is a secreted Type IV effector containing an N-WASP-binding short linear motif that promotes niche formation.

The modulation of actin polymerization is a common theme among microbial pathogens. Even though microorganisms show a wide repertoire of strategies to subvert the activity of actin, most of them converge in the ones that activate nucleating factors, such as the Arp2/3 complex. Brucella spp. are intracellular pathogens capable of establishing chronic infections in their hosts. The ability to subvert the host cell response is dependent on the capacity of the bacterium to attach, invade, avoid degradation in the phagocytic compartment, replicate in an endoplasmic reticulum-derived compartment and egress. Even though a significant number of mechanisms deployed by Brucella in these different phases have been identified and characterized, none of them have been described to target actin as a cellular component. In this manuscript, we describe the identification of a novel virulence factor (NpeA) that promotes niche formation. NpeA harbors a short linear motif (SLiM) present within an amphipathic alpha helix that has been described to bind the GTPase-binding domain (GBD) of N-WASP and stabilizes the autoinhibited state. Our results show that NpeA is secreted in a Type IV secretion system-dependent manner and that deletion of the gene diminishes the intracellular replication capacity of the bacterium. In vitro and ex vivo experiments demonstrate that NpeA binds N-WASP and that the short linear motif is required for the biological activity of the protein.IMPORTANCEThe modulation of actin-binding effectors that regulate the activity of this fundamental cellular protein is a common theme among bacterial pathogens. The neural Wiskott-Aldrich syndrome protein (N-WASP) is a protein that several pathogens target to hijack actin dynamics. The highly adapted intracellular bacterium Brucella has evolved a wide repertoire of virulence factors that modulate many activities of the host cell to establish successful intracellular replication niches, but, to date, no effector proteins have been implicated in the modulation of actin dynamics. We present here the identification of a virulence factor that harbors a short linear motif (SLiM) present within an amphipathic alpha helix that has been described to bind the GTPase-binding domain (GBD) of N-WASP stabilizing its autoinhibited state. We demonstrate that this protein is a Type IV secretion effector that targets N-WASP-promoting intracellular survival and niche formation.

Does empathy promote helping by activating altruistic motivation or concern about social evaluation? A direct replication of Fultz et al. (1986).

When people experience empathy for a needy stranger, efforts to help are often not far behind. But does empathy actually cause prosocial behavior? And if so, does it activate genuine concern or more self-interested motivations? To rule out the alternative hypothesis that empathy motivates prosocial behavior by generating fear of social disapproval for acting selfishly, Fultz et al. (1986) manipulated empathy for a lonely stranger using perspective-taking instructions; they also manipulated whether subjects believed their decision to help would remain anonymous. However, Fultz et al. conducted their experiment decades ago, with few subjects, and before some potentially important cultural changes in college students' values and social lives. Here, in a preregistered replication with 280 undergraduates, we tested Fultz et al.'s key assertions. The perspective-taking and social evaluation manipulations influenced scores on the manipulation check measures mostly in theory-consistent ways but did not significantly influence helping. Consistent with theory, empathy was positively associated with prosocial behavior. We also found evidence that endorsement of the principle of care reflects genuine concern for needy strangers and that moral identity symbolization reflects a desire to help in order to avoid social disapproval. We consider these results a partially successful replication of key tenets of the empathy-altruism hypothesis, though questions remain about the conditions under which perspective-taking promotes prosocial behavior and about the generalizability of our findings to populations beyond undergraduate women circa 1986. Our results also help illuminate the motivational underpinnings of two individual differences that predicted prosocial behavior in previous research. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Norovirus NS1/2 protein increases glutaminolysis for efficient viral replication.

Viruses are obligate intracellular parasites that rely on host cell metabolism for successful replication. Thus, viruses rewire host cell pathways involved in central carbon metabolism to increase the availability of building blocks for successful propagation. However, the underlying mechanisms of virus-induced alterations to host metabolism are largely unknown. Noroviruses (NoVs) are highly prevalent pathogens that cause sporadic and epidemic viral gastroenteritis. In the present study, we uncovered several strain-specific and shared host cell metabolic requirements of three murine norovirus (MNV) strains, MNV-1, CR3, and CR6. While all three strains required glycolysis, glutaminolysis, and the pentose phosphate pathway for optimal infection of macrophages, only MNV-1 relied on host oxidative phosphorylation. Furthermore, the first metabolic flux analysis of NoV-infected cells revealed that both glycolysis and glutaminolysis are upregulated during MNV-1 infection of macrophages. Glutamine deprivation affected the viral lifecycle at the stage of genome replication, resulting in decreased non-structural and structural protein synthesis, viral assembly, and egress. Mechanistic studies further showed that MNV infection and overexpression of the non-structural protein NS1/2 increased the enzymatic activity of the rate-limiting enzyme glutaminase. In conclusion, the inaugural investigation of NoV-induced alterations to host glutaminolysis identified NS1/2 as the first viral molecule for RNA viruses that regulates glutaminolysis either directly or indirectly. This increases our fundamental understanding of virus-induced metabolic alterations and may lead to improvements in the cultivation of human NoVs.

Transfection of a Molecular Clone of Naegleria gruberi rDNA into N. gruberi Trophozoites.

All ribosomal genes of Naegleria trophozoites are maintained in a closed circular extrachromosomal ribosomal DNA (rDNA) containing element (CERE). While little is known about the CERE, a complete genome sequence analysis of three Naegleria species clearly demonstrates that there are no rDNA cistrons in the nuclear genome. Furthermore, a single DNA origin of replication has been mapped in the N. gruberi CERE, supporting the hypothesis that CERE replicates independently of the nuclear genome. This CERE characteristic suggests that it may be possible to use engineered CERE to introduce foreign proteins into Naegleria trophozoites. As the first step in exploring the use of a CERE as a vector in Naegleria, we developed a protocol to transfect N. gruberi with a molecular clone of the N. gruberi CERE cloned into pGEM7zf+ (pGRUB). Following transfection, pGRUB was readily detected in N. gruberi trophozoites for at least seven passages, as well as through encystment and excystment. As a control, trophozoites were transfected with the backbone vector, pGEM7zf+, without the N. gruberi sequences (pGEM). pGEM was not detected after the first passage following transfection into N. gruberi, indicating its inability to replicate in a eukaryotic organism. These studies describe a transfection protocol for Naegleria trophozoites and demonstrate that the bacterial plasmid sequence in pGRUB does not inhibit successful transfection and replication of the transfected CERE clone. Furthermore, this transfection protocol will be critical in understanding the minimal sequence of the CERE that drives its replication in trophozoites, as well as identifying regulatory regions in the non-ribosomal sequence (NRS).

Attentional mechanisms of the date/delay effect in intertemporal choice: An eye-tracking study.

Temporal discounting refers to the tendency to discount future rewards as a function of time until receipt of rewards. The discount rate can be reduced by experimentally manipulating time framing, an example being the date/delay effect: Specifically, if time until receipt of the reward is presented as a date (e.g., August 21, 2022) rather than as a delay (e.g., 136 days), temporal discounting is reduced. While this effect has been replicated several times, its underlying cognitive mechanisms are not well understood. Therefore, we used eye tracking to examine the role of attention in the date/delay effect. Participants completed both a delay and date condition of the Monetary Choice Questionnaire, while eye movements were recorded (N = 54). Results revealed a successful replication of the date/delay effect (p < .001, gav = 0.48). Eye tracking showed that participants compared time attributes (relative to reward attributes) more and fixated them longer in the date compared to the delay condition. Moreover, the absolute difference in reward values of choice options was more predictive of choosing the delayed reward in the date compared to the delay condition. Finally, explorative correlations revealed a stronger date/delay effect in participants who paid more attention to time than reward attributes in the delay condition and who used a more integrative search strategy. Our findings suggest that the date manipulation causes participants to weight rewards more strongly in their decision process than in the delay condition, ultimately reducing temporal discounting. Computation of time intervals in the date condition could possibly reflect an adaptation lowering the date/delay effect. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Nervous necrosis virus capsid protein and Protein A dynamically modulate the fish cGAS-mediated IFN signal pathway to facilitate viral evasion.

Nervous necrosis virus (NNV), an aquatic RNA virus belonging to Betanodavirus, infects a variety of marine and freshwater fishes, leading to massive mortality of cultured larvae and juveniles and substantial economic losses. The enzyme cyclic guanosine monophosphate-adenosine monophosphate synthase (cGAS) is widely recognized as a central component in the innate immune response to cytosolic DNA derived from different pathogens. However, little is known about the response of cGAS to aquatic RNA viruses. This study found that Epinephelus coioides cGAS (EccGAS) overexpression inhibited NNV replication, whereas EccGAS silencing promoted NNV replication. The anti-NNV activity of EccGAS was involved in interferon (IFN) signaling activation including tumor necrosis factor receptor-associated factor family member-associated NF-kappa-B activator-binding kinase 1 (TBK1) phosphorylation, interferon regulatory factor 3 (IRF3) nuclear translocation, and the subsequent induction of IFNc and ISGs. Interestingly, NNV employed its capsid protein (CP) or Protein A (ProA) to negatively or positively modulate EccGAS-mediated IFN signaling by simultaneously targeting EccGAS. CP interacted with EccGAS via the arm-P, S-P, and SD structural domains and promoted its polyubiquitination with K48 and K63 linkages in an EcUBE3C (the ubiquitin ligase)-dependent manner, ultimately leading to EccGAS degradation. Conversely, ProA bound to EccGAS and inhibited its ubiquitination and degradation. In regulating EccGAS protein content, CP's inhibitory action was more pronounced than ProA's protective effect, allowing successful NNV replication. These novel findings suggest that NNV CP and ProA dynamically modulate the EccGAS-mediated IFN signaling pathway to facilitate the immune escape of NNV. Our findings shed light on a novel mechanism of virus-host interaction and provide a theoretical basis for the prevention and control of NNV.IMPORTANCEAs a well-known DNA sensor, cGAS is a pivotal component in innate anti-viral immunity to anti-DNA viruses. Although there is growing evidence regarding the function of cGAS in the resistance to RNA viruses, the mechanisms by which cGAS participates in RNA virus-induced immune responses in fish and how aquatic viruses evade cGAS-mediated immune surveillance remain elusive. Here, we investigated the detailed mechanism by which EccGAS positively regulates the anti-NNV response. Furthermore, NNV CP and ProA interacted with EccGAS, regulating its protein levels through ubiquitin-proteasome pathways, to dynamically modulate the EccGAS-mediated IFN signaling pathway and facilitate viral evasion. Notably, NNV CP was identified to promote the ubiquitination of EccGAS via ubiquitin ligase EcUBE3C. These findings unveil a novel strategy for aquatic RNA viruses to evade cGAS-mediated innate immunity, enhancing our understanding of virus-host interactions.