Intensionality is more cognitively demanding than false belief in adults: evidence from a non-inferential sentence-reading task.

Children are said to understand false belief if they can appreciate an agent's wrong description of an object as a result of misinformation, and intensionality if they can appreciate and switch between alternative descriptions from different epistemic viewpoints. Most previous studies have investigated the developmental trajectories of these capacities in the age range from 3 to 10 years aiming to discern their conceptual nature. The present research examines whether intensionality incurs lower performance accuracies and longer response times than false belief in adults, using a task in which participants read sentences that explicitly state an agent's beliefs. Experiment 1 showed that participants were less accurate in rejecting verbal probes that contradicted an agent's alternative than false thoughts about objects. Experiments 2 and 3 replicated this finding using thoughts about object identities but not properties. These results suggest that compared to false belief, intensionality is cognitively demanding for adults to process because of the availability of more than one identity candidate under the agent's perspective.

Measures of individual differences in adult theory of mind: A systematic review.

Theory of mind (ToM), the ability to understand and reason about mental states, has been extensively studied in young children and clinical populations. A growing interest in examining ToM in adults has emerged over the past two decades, but the extent to which existing measures are suitable for studying adults, especially in detecting individual differences, remains understudied. In this systematic review of 273 studies, 75 measures used to investigate individual differences in adults' ToM were identified. Their sensitivity to individual differences, reliability, and validity were examined. Results suggest that ceiling effects were prevalent, and there was limited evidence to establish the reliability or validity of these measures due to the lack of reports of psychometric properties. Interrelations among measures were inconsistent. These findings highlight the need for future empirical and theoretical work to broaden the evidence base regarding psychometric properties of measures, to develop new measures, and to lay out more specific hypotheses about the relevance of ToM for different social outcomes.

Gene regulatory networks shape developmental plasticity of root cell types under water extremes in rice.

Understanding how roots modulate development under varied irrigation or rainfall is crucial for development of climate-resilient crops. We established a toolbox of tagged rice lines to profile translating mRNAs and chromatin accessibility within specific cell populations. We used these to study roots in a range of environments: plates in the lab, controlled greenhouse stress and recovery conditions, and outdoors in a paddy. Integration of chromatin and mRNA data resolves regulatory networks of the following: cycle genes in proliferating cells that attenuate DNA synthesis under submergence; genes involved in auxin signaling, the circadian clock, and small RNA regulation in ground tissue; and suberin biosynthesis, iron transporters, and nitrogen assimilation in endodermal/exodermal cells modulated with water availability. By applying a systems approach, we identify known and candidate driver transcription factors of water-deficit responses and xylem development plasticity. Collectively, this resource will facilitate genetic improvements in root systems for optimal climate resilience.

Flood resilience loci SUBMERGENCE 1 and ANAEROBIC GERMINATION 1 interact in seedlings established underwater.

Crops with resilience to multiple climatic stresses are essential for increased yield stability. Here, we evaluate the interaction between two loci associated with flooding survival in rice (Oryza sativa L.). ANAEROBIC GERMINATION 1 (AG1), encoding trehalose 6-phosphate phosphatase 7 (TPP7), promotes mobilization of endosperm reserves to enhance the elongation of a hollow coleoptile in seeds that are seeded directly into shallow paddies. SUBMERGENCE 1 (SUB1), encoding the ethylene-responsive transcription factor SUB1A-1, confers tolerance to complete submergence by dampening carbohydrate catabolism, to enhance recovery upon desubmergence. Interactions between AG1/TPP7 and SUB1/SUB1A-1 were investigated under three flooding scenarios using four near-isogenic lines by surveying growth and survival. Pyramiding of the two loci does not negatively affect anaerobic germination or vegetative-stage submergence tolerance. However, the pyramided AG1 SUB1 genotype displays reduced survival when seeds are planted underwater and maintained under submergence for 16 d. To better understand the roles of TPP7 and SUB1A-1 and their interaction, temporal changes in carbohydrates and shoot transcriptomes were monitored in the four genotypes varying at the two loci at four developmental timeponts, from day 2 after seeding through day 14 of complete submergence. TPP7 enhances early coleoptile elongation, whereas SUB1A-1 promotes precocious photoautotrophy and then restricts underwater elongation. By contrast, pyramiding of the AG1 and SUB1 slows elongation growth, the transition to photoautotrophy, and survival. mRNA-sequencing highlights time-dependent and genotype-specific regulation of mRNAs associated with DNA repair, cell cycle, chromatin modification, plastid biogenesis, carbohydrate catabolism and transport, elongation growth, and other processes. These results suggest that interactions between AG1/TPP7 and SUB1/SUB1A-1 could impact seedling establishment if paddy depth is not effectively managed after direct seeding.

After The Deluge: Plant Revival Post-Flooding.

Increasing flooding events have detrimentally impacted food security amid a growing global population. Complete submergence of plants represents the most severe flooding stress and studies have identified underwater responses to low oxygen and light availability. However, knowledge on plant responses during the post-submergence phase is limited. It is important to consider how plants can resume vegetative growth after enduring submergence and post-submergence stress. This review highlights current knowledge on physiological and molecular adaptations following desubmergence. Interplays of reactive oxygen species (ROS), energy depletion, photoinhibition, desiccation stress, and hormonal signaling have been characterized as components of the post-submergence stress response. Active elucidation of key genes and traits enhancing post-submergence adaptations is highly relevant for the improvement of submergence tolerance and ultimately crop yield.

A stress recovery signaling network for enhanced flooding tolerance in Arabidopsis thaliana.

Abiotic stresses in plants are often transient, and the recovery phase following stress removal is critical. Flooding, a major abiotic stress that negatively impacts plant biodiversity and agriculture, is a sequential stress where tolerance is strongly dependent on viability underwater and during the postflooding period. Here we show that in Arabidopsis thaliana accessions (Bay-0 and Lp2-6), different rates of submergence recovery correlate with submergence tolerance and fecundity. A genome-wide assessment of ribosome-associated transcripts in Bay-0 and Lp2-6 revealed a signaling network regulating recovery processes. Differential recovery between the accessions was related to the activity of three genes: RESPIRATORY BURST OXIDASE HOMOLOG D, SENESCENCE-ASSOCIATED GENE113, and ORESARA1, which function in a regulatory network involving a reactive oxygen species (ROS) burst upon desubmergence and the hormones abscisic acid and ethylene. This regulatory module controls ROS homeostasis, stomatal aperture, and chlorophyll degradation during submergence recovery. This work uncovers a signaling network that regulates recovery processes following flooding to hasten the return to prestress homeostasis.

Signal Dynamics and Interactions during Flooding Stress.

Flooding is detrimental for nearly all higher plants, including crops. The compound stress elicited by slow gas exchange and low light levels under water is responsible for both a carbon and an energy crisis ultimately leading to plant death. The endogenous concentrations of four gaseous compounds, oxygen, carbon dioxide, ethylene, and nitric oxide, change during the submergence of plant organs in water. These gases play a pivotal role in signal transduction cascades, leading to adaptive processes such as metabolic adjustments and anatomical features. Of these gases, ethylene is seen as the most consistent, pervasive, and reliable signal of early flooding stress, most likely in tight interaction with the other gases. The production of reactive oxygen species (ROS) in plant cells during flooding and directly after subsidence, during which the plant is confronted with high light and oxygen levels, is characteristic for this abiotic stress. Low, well-controlled levels of ROS are essential for adaptive signaling pathways, in interaction with the other gaseous flooding signals. On the other hand, excessive uncontrolled bursts of ROS can be highly damaging for plants. Therefore, a fine-tuned balance is important, with a major role for ROS production and scavenging. Our understanding of the temporal dynamics of the four gases and ROS is basal, whereas it is likely that they form a signature readout of prevailing flooding conditions and subsequent adaptive responses.

Reliability of EUS indices to detect inflammation in ulcerative colitis.

BACKGROUND AND AIMS: EUS is a potentially useful modality to assess severity of inflammation in ulcerative colitis (UC). We assessed the reliability of existing EUS indices and correlated them with endoscopic and histologic scores. METHODS: Four blinded endosonographers assessed 58 endoscopic and EUS videos in triplicate, from patients with UC. Intrarater and interrater reliability of the hyperemia and Tsuga scores were estimated by using intra-class correlation coefficients (ICCs). Correlation with the Mayo endoscopy score, modified Baron score (MBS), Ulcerative Colitis Endoscopic Index of Severity (UCEIS), and Geboes histopathology score (GHS) were calculated by using bootstrapping methods. A RAND consensus process led to development of standardized definitions and a revised EUS-UC score. RESULTS: ICCs for intrarater reliability were 0.76 (95% confidence interval [CI], 0.71-0.80) for the hyperemia score and 0.85 (95% CI, 0.79-0.89) for the Tsuga score. Corresponding values for interrater reliability were 0.34 (95% CI, 0.25-0.42) and 0.36 (95% CI, 0.24-0.46). Correlation between hyperemia and Tsuga scores to Mayo scoring system, MBS, UCEIS, and the GHS were 0.39 (95% CI, 0.15-0.61) and 0.28 (95% CI, 0.04-0.51), 0.38 (95% CI, 0.16-0.57) and 0.25 (95% CI, -0.01-0.48), 0.41 (95% CI, 0.16-0.62) and 0.27 (95% CI, 0.01-0.50), 0.37 (95% CI, -0.01-0.48) and 0.24 (95% CI, 0.13-0.57), respectively. The revised EUS-UC score included bowel wall thickening, depth of inflammation, and hyperemia. CONCLUSIONS: Although substantial to almost perfect intrarater agreement existed for EUS indices in UC, interrater agreement was fair. Standardization of item definitions with development of a revised evaluative instrument has potential application as an evaluative and prognostic tool for UC. (Clinical trial registration number: NCT01852760.).

Regional differences in use of endoscopic ultrasonography in Ontario: a population-based retrospective cohort study.

BACKGROUND: Endoscopic ultrasonography is a safe and accurate modality for evaluating and managing hepatobiliary and gastrointestinal conditions (malignant and nonmalignant); its use is increasing. The aim of this study was to describe regional trends in the use of endoscopic ultrasonography in Ontario. METHODS: We conducted a population-based retrospective cohort study using health administrative databases. We identified all patients who underwent an endoscopic ultrasound procedure in Ontario from 2003 to 2011 using physician billing data. Patient, physician and institution characteristics were examined. The primary outcome was use of endoscopic ultrasonography. RESULTS: We identified 9076 endoscopic ultrasound procedures performed in 8001 patients (3858 women [48.2%]; median patient age at first procedure 59 years). A total of 3066 procedures (33.8%) involved fine-needle aspiration. Use of endoscopic ultrasonography increased 17-fold over the study period. In 2011, people living in the health region with the highest rate of use of endoscopic ultrasonography were more than 4 times more likely to undergo the procedure than people living in the health region with the lowest rate of use (standardized rate 61.6 v. 12.9 per 100 000). About 7 in 10 endoscopic ultrasound procedures were performed in an academic institution or regional cancer centre. All 17 endoscopists performing endoscopic ultrasonography during the study period practised in urban areas. INTERPRETATION: Although the use of endoscopic ultrasonography increased over time in Ontario, there were marked regional differences in use. Provincial needs- and evidence-based initiatives may be needed to narrow the regional gaps in provision of endoscopic ultrasound services in the province.

The submergence tolerance gene SUB1A delays leaf senescence under prolonged darkness through hormonal regulation in rice.

Leaf senescence is a natural age-dependent process that is induced prematurely by various environmental stresses. Typical alterations during leaf senescence include breakdown of chlorophyll, a shift to catabolism of energy reserves, and induction of senescence-associated genes, all of which can occur during submergence, drought, and constant darkness. Here, we evaluated the influence of the submergence tolerance regulator, SUBMERGENCE1A (SUB1A), in the acclimation responses during leaf senescence caused by prolonged darkness in rice (Oryza sativa). SUB1A messenger RNA was highly induced by prolonged darkness in a near-isogenic line containing SUB1A. Genotypes with conditional and ectopic overexpression of SUB1A significantly delayed loss of leaf color and enhanced recovery from dark stress. Physiological analysis revealed that SUB1A postpones dark-induced senescence through the maintenance of chlorophyll and carbohydrate reserves in photosynthetic tissue. This delay allowed leaves of SUB1A genotypes to recover photosynthetic activity more quickly upon reexposure to light. SUB1A also restricted the transcript accumulation of representative senescence-associated genes. Jasmonate and salicylic acid are positive regulators of leaf senescence, but ectopic overexpression of SUB1A dampened responsiveness to both hormones in the context of senescence. We found that ethylene accelerated senescence stimulated by darkness and jasmonate, although SUB1A significantly restrained dark-induced ethylene accumulation. Overall, SUB1A genotypes displayed altered responses to prolonged darkness by limiting ethylene production and responsiveness to jasmonate and salicylic acid, thereby dampening the breakdown of chlorophyll, carbohydrates, and the accumulation of senescence-associated messenger RNAs. A delay of leaf senescence conferred by SUB1A can contribute to the enhancement of tolerance to submergence, drought, and oxidative stress.

The submergence tolerance regulator SUB1A mediates crosstalk between submergence and drought tolerance in rice.

Submergence and drought are major constraints to rice (Oryza sativa) production in rain-fed farmlands, both of which can occur sequentially during a single crop cycle. SUB1A, an ERF transcription factor found in limited rice accessions, dampens ethylene production and gibberellic acid responsiveness during submergence, economizing carbohydrate reserves and significantly prolonging endurance. Here, we evaluated the functional role of SUB1A in acclimation to dehydration. Comparative analysis of genotypes with and without SUB1A revealed that SUB1A enhanced recovery from drought at the vegetative stage through reduction of leaf water loss and lipid peroxidation and increased expression of genes associated with acclimation to dehydration. Overexpression of SUB1A augmented ABA responsiveness, thereby activating stress-inducible gene expression. Paradoxically, vegetative tissue undergoes dehydration upon desubmergence even though the soil contains sufficient water, indicating that leaf desiccation occurs in the natural progression of a flooding event. Desubmergence caused the upregulation of gene transcripts associated with acclimation to dehydration, with higher induction in SUB1A genotypes. SUB1A also restrained accumulation of reactive oxygen species (ROS) in aerial tissue during drought and desubmergence. Consistently, SUB1A increased the abundance of transcripts encoding ROS scavenging enzymes, resulting in enhanced tolerance to oxidative stress. Therefore, in addition to providing robust submergence tolerance, SUB1A improves survival of rapid dehydration following desubmergence and water deficit during drought.

Hepatitis C virus core protein blocks interferon signaling by interaction with the STAT1 SH2 domain.

Emerging data have indicated that hepatitis C virus (HCV) subverts the host antiviral response to ensure its persistence. We previously demonstrated that HCV protein expression suppresses type I interferon (IFN) signaling by leading to the reduction of phosphorylated STAT1 (P-STAT1). We also demonstrated that HCV core protein directly bound to STAT1. However, the detailed mechanisms by which HCV core protein impacts IFN signaling components have not been fully clarified. In this report, we show that the STAT1 interaction domain resides in the N-terminal portion of HCV core (amino acids [aa] 1 to 23). This domain is also required to produce P-STAT1 reduction and inhibit IFN signaling transduction. Conversely, the C-terminal region of STAT1, specifically the SH2 domain (aa 577 to 684), is required for the interaction of HCV core with STAT1. The STAT1 SH2 domain is critical for STAT1 hetero- or homodimerization. We propose a model by which the binding of HCV core to STAT1 results in decreased P-STAT, blocked STAT1 heterodimerization to STAT2, and, therefore, reduced IFN-stimulated gene factor-3 binding to DNA and disrupted IFN-stimulated gene transcription.

Ramipril-associated hepatotoxicity.

CONTEXT: Angiotensin-converting enzyme inhibitors are prescribed for many cardiovascular and renal diseases. Adverse hepatic events, especially cholestasis, have rarely been reported with captopril, enalapril, lisinopril, and fosinopril. To date, hepatic injury associated with ramipril has not been reported. OBJECTIVE: To describe 3 patients who developed hepatitis, with or without jaundice, after receiving ramipril. DESIGN: Medical records and liver biopsies of the 3 patients were reviewed. Clinical, laboratory, and histologic findings were compared with findings in other cases of angiotensin-converting enzyme inhibitor-induced liver injury reported in the literature. RESULTS: The 3 patients were middle-aged men. In 2 patients, jaundice appeared 4 and 8 weeks after starting ramipril. Bilirubin levels peaked at 15.5 and 5 mg/dL, and alkaline phosphatase values peaked at 957 and 507 U/L. Aminotransferase levels were mildly elevated. Endoscopic retrograde cholangiopancreatography and ultrasonography showed no bile duct obstruction. Liver biopsies from the jaundiced patients were similar, with cholestasis, duct necrosis, and extravasation of bile, ductular proliferation, and portal inflammation. Cholestasis improved in 1 patient 6 weeks after stopping ramipril and was prolonged for 14 months in the other, in whom biliary cirrhosis was present on biopsy. The third patient developed hepatitis without jaundice 3 weeks after starting ramipril; symptoms resolved after stopping the drug. Ramipril-associated liver injury is similar to that seen with other angiotensin-converting enzyme inhibitors, but liver biopsy findings of duct necrosis and extravasation of bile have not been reported previously. CONCLUSION: Prolonged cholestatic hepatitis and biliary cirrhosis may result from the use of ramipril. Monitoring of liver enzymes is advisable for patients starting on ramipril.

Monitoring adverse drug reactions to sulfonamide antibiotics in human immunodeficiency virus-infected individuals.

Patients infected with the human immunodeficiency virus (HIV) are at higher risk for adverse drug reactions from trimethoprim-sulfamethoxazole (TMP-SMX) than the HIV-negative population. Studying the HIV-positive population the authors aimed to validate the predictive and diagnostic value of the lymphocyte toxicity assay (LTA) for adverse drug reactions. Patient lymphocytes were analyzed for toxicity to SMX and TMP. Of 35 enrolled HIV patients, 18 had TMP-SMX hypersensitivity syndrome reaction (HSR); 10 tolerated the drug; and 5 had never received the drug. When cases with HSR were compared with controls that tolerated the drugs, cytotoxicity was higher for cases: 29.5% +/- 10.1% versus 19.3% +/- 11.2% for SMX (P < 0.022) and 25.0% +/- 11.9% versus 16.3% +/- 11.0% for TMP (P < 0.04). The authors' proposed threshold value for assigning positive results for TMP and SMX hypersensitivities was 22.5%. The LTA has a strong potential for use as a diagnostic tool to assess TMP-SMX hypersensitivity in HIV-infected individuals. Larger patient populations, as well as in vitro studies are needed to further address the reasons for elevated results in immunocompromised patients and to validate the usefulness of the test.