The Endogenous Th17 Response in NO<inf>2</inf>-Promoted Allergic Airway Disease Is Dispensable for Airway Hyperresponsiveness and Distinct from Th17 Adoptive Transfer

Severe, glucocorticoid-resistant asthma comprises 5-7% of patients with asthma. IL-17 is a biomarker of severe asthma, and the adoptive transfer of Th17 cells in mice is sufficient to induce glucocorticoid-resistant allergic airway disease. Nitrogen dioxide (NO2) is an environmental toxin that correlates with asthma severity, exacerbation, and risk of adverse outcomes. Mice that are allergically sensitized to the antigen ovalbumin by exposure to NO2 exhibit a mixed Th2/Th17 adaptive immune response and eosinophil and neutrophil recruitment to the airway following antigen challenge, a phenotype reminiscent of severe clinical asthma. Because IL-1 receptor (IL-1R) signaling is critical in the generation of the Th17 response in vivo, we hypothesized that the IL-1R/Th17 axis contributes to pulmonary inflammation and airway hyperresponsiveness (AHR) in NO2-promoted allergic airway disease and manifests in glucocorticoid-resistant cytokine production. IL-17A neutralization at the time of antigen challenge or genetic deficiency in IL-1R resulted in decreased neutrophil recruitment to the airway following antigen challenge but did not protect against the development of AHR. Instead, IL-1R-/- mice developed exacerbated AHR compared to WT mice. Lung cells from NO2-allergically inflamed mice that were treated in vitro with dexamethasone (Dex) during antigen restimulation exhibited reduced Th17 cytokine production, whereas Th17 cytokine production by lung cells from recipient mice of in vitro Th17-polarized OTII T-cells was resistant to Dex. These results demonstrate that the IL-1R/Th17 axis does not contribute to AHR development in NO2-promoted allergic airway disease, that Th17 adoptive transfer does not necessarily reflect an endogenously-generated Th17 response, and that functions of Th17 responses are contingent on the experimental conditions in which they are generated. © 2013 Martin et al

Photocatalytic Decomposition of Formic Acid on Mo2C-Containing Catalyst

Soluble components in the peripheral blood from experimental exposure of 14 healthy subjects to filtered air and wood smoke. Samples were collected before (pre), at 24 h and 44 h after exposure, to air and wood smoke. Data are given as medians with interquartile range. (DOCX 62 kb

The Epistemic Status of Processing Fluency as Source for Judgments of Truth

This article combines findings from cognitive psychology on the role of processing fluency in truth judgments with epistemological theory on justification of belief. We first review evidence that repeated exposure to a statement increases the subjective ease with which that statement is processed. This increased processing fluency, in turn, increases the probability that the statement is judged to be true. The basic question discussed here is whether the use of processing fluency as a cue to truth is epistemically justified. In the present analysis, based on Bayes’ Theorem, we adopt the reliable-process account of justification presented by Goldman (1986) and show that fluency is a reliable cue to truth, under the assumption that the majority of statements one has been exposed to are true. In the final section, we broaden the scope of this analysis and discuss how processing fluency as a potentially universal cue to judged truth may contribute to cultural differences in commonsense beliefs

Rapidly Measuring the Speed of Unconscious Learning: Amnesics Learn Quickly and Happy People Slowly

BACKGROUND We introduce a method for quickly determining the rate of implicit learning. METHODOLOGY/PRINCIPAL FINDINGS The task involves making a binary prediction for a probabilistic sequence over 10 minutes; from this it is possible to determine the influence of events of a different number of trials in the past on the current decision. This profile directly reflects the learning rate parameter of a large class of learning algorithms including the delta and Rescorla-Wagner rules. To illustrate the use of the method, we compare a person with amnesia with normal controls and we compare people with induced happy and sad moods. CONCLUSIONS/SIGNIFICANCE Learning on the task is likely both associative and implicit. We argue theoretically and demonstrate empirically that both amnesia and also transient negative moods can be associated with an especially large learning rate: People with amnesia can learn quickly and happy people slowl

Syntactic learning by mere exposure - An ERP study in adult learners

<p>Abstract</p> <p>Background</p> <p>Artificial language studies have revealed the remarkable ability of humans to extract syntactic structures from a continuous sound stream by mere exposure. However, it remains unclear whether the processes acquired in such tasks are comparable to those applied during normal language processing. The present study compares the ERPs to auditory processing of simple Italian sentences in native and non-native speakers after brief exposure to Italian sentences of a similar structure. The sentences contained a non-adjacent dependency between an auxiliary and the morphologically marked suffix of the verb. Participants were presented four alternating learning and testing phases. During learning phases only correct sentences were presented while during testing phases 50 percent of the sentences contained a grammatical violation.</p> <p>Results</p> <p>The non-native speakers successfully learned the dependency and displayed an N400-like negativity and a subsequent anteriorily distributed positivity in response to rule violations. The native Italian group showed an N400 followed by a P600 effect.</p> <p>Conclusion</p> <p>The presence of the P600 suggests that native speakers applied a grammatical rule. In contrast, non-native speakers appeared to use a lexical form-based processing strategy. Thus, the processing mechanisms acquired in the language learning task were only partly comparable to those applied by competent native speakers.</p

Statistical learning leads to persistent memory: evidence for one-year consolidation

Statistical learning is a robust mechanism of the brain that enables the extraction of environmental patterns, which is crucial in perceptual and cognitive domains. However, the dynamical change of processes underlying long-term statistical memory formation has not been tested in an appropriately controlled design. Here we show that a memory trace acquired by statistical learning is resistant to inference as well as to forgetting after one year. Participants performed a statistical learning task and were retested one year later without further practice. The acquired statistical knowledge was resistant to interference, since after one year, participants showed similar memory performance on the previously practiced statistical structure after being tested with a new statistical structure. These results could be key to understand the stability of long-term statistical knowledge

Sources of avoidance motivation: Valence effects from physical effort and mental rotation

When reaching goals, organisms must simultaneously meet the overarching goal of conserving energy. According to the law of least effort, organisms will select the means associated with the least effort. The mechanisms underlying this bias remain unknown. One hypothesis is that organisms come to avoid situations associated with unnecessary effort by generating a negative valence toward the stimuli associated with such situations. Accordingly, merely using a dysfunctional, ‘slow’ computer mouse causes participants to dislike ambient neutral images (Study 1). In Study 2, nonsense shapes were liked less when associated with effortful processing (135° of mental rotation) versus easier processing (45° of rotation). Complementing ‘fluency’ effects found in perceptuo-semantic research, valence emerged from action-related processing in a principled fashion. The findings imply that negative valence associations may underlie avoidance motivations, and have practical implications for educational/workplace contexts in which effort and positive affect are conducive to success

GM-CSF drives dysregulated hematopoietic stem cell activity and pathogenic extramedullary myelopoiesis in experimental spondyloarthritis

Dysregulated hematopoiesis occurs in several chronic inflammatory diseases, but it remains unclear how hematopoietic stem cells (HSCs) in the bone marrow (BM) sense peripheral inflammation and contribute to tissue damage. Here, we show the HSC gene expression program is biased toward myelopoiesis and differentiation skewed toward granulocyte-monocyte progenitors (GMP) during joint and intestinal inflammation in experimental spondyloarthritis (SpA). GM-CSF-receptor is increased on HSC and multipotent progenitors, favoring a striking increase in myelopoiesis at the earliest hematopoietic stages. GMP accumulate in the BM in SpA and, unexpectedly, at extramedulary sites: in the inflamed joints and spleen. Furthermore we show that GM-CSF promotes BM and extramedullary myelopoiesis, tissue-toxic neutrophil accumulation in target organs, and GM-CSF prophylactic or therapeutic blockade substantially decreases SpA severity. Surprisingly, besides CD4 T cells and innate lymphoid cells, mast cells (MC) are a source of GM-CSF in inflammation, and its pathogenic production is promoted by the alarmin IL-33

Preference for facial averageness: evidence for a common mechanism in human and macaque infants

Human adults and infants show a preference for average faces, which could stem from a general processing mechanism and may be shared among primates. However, little is known about preference for facial averageness in monkeys. We used a comparative developmental approach and eye-tracking methodology to assess visual attention in human and macaque infants to faces naturally varying in their distance from a prototypical face. In Experiment 1, we examined the preference for faces relatively close to or far from the prototype in 12-month-old human infants with human adult female faces. Infants preferred faces closer to the average than faces farther from it. In Experiment 2, we measured the looking time of 3-month-old rhesus macaques (Macaca mulatta) viewing macaque faces varying in their distance from the prototype. Like human infants, macaque infants looked longer to faces closer to the average. In Experiments 3 and 4, both species were presented with unfamiliar categories of faces (i.e., macaque infants tested with adult macaque faces; human infants and adults tested with infant macaque faces) and showed no prototype preferences, suggesting that the prototypicality effect is experience-dependent. Overall, the findings suggest a common processing mechanism across species, leading to averageness preferences in primates