Exploring Lysophosphatidylcholine as a Biomarker in Ischemic Stroke: The Plasma-Brain Disjunction.

Lipids and their bioactive metabolites, notably lysophosphatidylcholine (LPC), are increasingly important in ischemic stroke research. Reduced plasma LPC levels have been linked to stroke occurrence and poor outcomes, positioning LPC as a potential prognostic or diagnostic marker. Nonetheless, the connection between plasma LPC levels and stroke severity remains unclear. This study aimed to elucidate this relationship by examining plasma LPC levels in conjunction with brain LPC levels to provide a deeper understanding of the underlying mechanisms. Adult male Sprague-Dawley rats underwent transient middle cerebral artery occlusion and were randomly assigned to different groups (sham-operated, vehicle, LPC supplementation, or LPC inhibition). We measured multiple LPC species in the plasma and brain, alongside assessing sensorimotor dysfunction, cerebral perfusion, lesion volume, and markers of BBB damage, inflammation, apoptosis, and oxidative stress. Among five LPC species, plasma LPC(16:0) and LPC(18:1) showed strong correlations with sensorimotor dysfunction, lesion severity, and mechanistic biomarkers in the rat stroke model. Despite notable discrepancies between plasma and brain LPC levels, both were strongly linked to functional outcomes and mechanistic biomarkers, suggesting that LPC's prognostic value is retained extracranially. This study advances the understanding of LPC as a blood marker in ischemic stroke and highlights directions for future research to further elucidate its association with stroke severity, particularly through investigations in more clinically representative models.

Processing of Emotional Words in Children and Adolescents with Autism Spectrum Disorders.

Individuals with autism spectrum disorder (ASD) have difficulties in understanding emotional language, but little research has discussed the developmental course of the processing of emotional words in the clinical population. Previous studies have revealed distinct processing for emotion-label (e.g., happiness) and emotion-laden (e.g., birthday) words in typically developing (TD) children and adolescents. Extending these findings, the study used event-related potentials (ERPs) to explore the processing of these two types of emotional words in children and adolescents with ASD. The stimuli included two-character Chinese words with factors of word type (emotion-label versus emotion-laden) and valence (positive versus negative). The participants were 11 to 14-year-old children and adolescents with ASD (N = 23) and age-matched TD peers (N = 23). They categorized emotion valence for words while their brain responses were recorded. Both the TD and the ASD groups exhibited emotional processing for all emotional words across the N400 and late positivity component (LPC). The emotional processing was modulated by word type but varied with group and valence. A trend for group differences was observed in processing positive words at 500-600 ms. In particular, the emotion effects of positive emotion-label words were positively correlated with social dysfunction across all participants. These findings suggested that children and adolescents with ASD have a selective impairment in understanding emotional concepts from language. The ERP measurements may reflect atypical emotional word processing for individuals with higher autistic severity in positive valence contexts.

Comparison of peripheral cannula outcomes, ultrasound-guided placement of deep veins versus blind insertion of superficial veins in children aged 0-18 years: A retrospective study.

BACKGROUND: The clinical use of ultrasound has increased the chances of successful insertion of all venous access devices, including short peripheral cannulas (SPC) and long peripheral catheters (LPC). The aim of the study was to compare the clinical performance of peripheral cannulas inserted using the traditional "blind" technique versus those inserted with ultrasound guidance (US). METHODS: In this retrospective study we compared 135 peripheral intravenous cannulations (PIVCs) with ultrasound guidance and 135 PIVCs with blind technique, inserted in children (0-18 years) in the emergency department. All devices were inserted using the catheter-over-needle technique. With the blind technique, superficial arm veins were cannulated using SPCs (1.9 cm, 24G; 2.5 cm, 22G; 3.2 cm, 20G), while with US, deeper non-palpable veins were accessed using SPCs of 3.2 cm, 24G; and LPCs of 6.4 cm, 22G; 6.4 cm, 20G. RESULTS: The accesses were removed electively in 66% of US-PIVCs, with an average duration of the device of 5.3 ± 4.0 days, but only in 30% of Blind-PIVCs, which presented an average duration of 2.5 ± 1.8 days. The longest dwelling time (8.7 ± 5.1 days) was observed in 20G LPCs inserted with US into the basilic vein of the arm; among Blind-PIVCs, the longest duration (3.0 ± 2.1 days) was observed in 22G SPCs inserted into the cephalic vein at the forearm. The most commonly encountered complication in both groups was accidental dislodgment. CONCLUSIONS: PIVCs with ultrasound guidance were apparently more effective than the blind ones, reducing the number of successive cannulations. Additionally, LPCs, with their greater length compared to SPCs, have proven to be more durable and may be recommended as emergency venous access in children requiring peripheral access for 4-15 days. Dislodgement should be reduced by improving the securement of the device.

Cortical oscillations and event-related brain potentials during the preparation and execution of deceptive behavior.

Deception often occurs in response to a preceding cue (e.g., a precarious question) alerting us about the need to subsequently lie. Here, we simulate this process by adapting a previously established paradigm of intentionally false responding, now instructing participants about the need for deception (vs. truthful responses) by means of a simple cue occurring before each response-relevant target. We analyzed event-related brain potentials (ERPs) as well as cortical oscillations recorded from the scalp. In an experimental study (N = 44), we show that a cue signaling the need for deception involves increased attentional selection (P2, P3a, P3b). Moreover, in the period following the cue and leading up to the target, ERP and oscillatory signatures of anticipation and preparation (Contingent Negative Variation, alpha suppression) were found to be increased during trials requiring a deceptive as compared to a truthful response. Additionally, we replicated earlier findings that target processing involves enhanced motivated attention toward words requiring a deceptive response (LPC). Moreover, a signature of integration effort and semantic inhibition (N400) was observed to be larger for words to which responses have to be intentionally false as compared to those to which responses must be truthful. Our findings support the view of the involvement of a series of basic cognitive processes (especially attention and cognitive control) when responses are deliberately wrong instead of right. Moreover, preceding cues signaling the subsequent need for lying already elicit attentional and preparatory mechanisms facilitating the cognitive operations necessary for later successful lying.

Lysophosphatidylcholine Impairs the Mitochondria Homeostasis Leading to Trophoblast Dysfunction in Gestational Diabetes Mellitus.

Gestational diabetes mellitus (GDM) is a common pregnancy disorder associated with an increased risk of pre-eclampsia and macrosomia. Recent research has shown that the buildup of excess lipids within the placental trophoblast impairs mitochondrial function. However, the exact lipids that impact the placental trophoblast and the underlying mechanism remain unclear. GDM cases and healthy controls were recruited at Kaohsiung Medical University Hospital. The placenta and cord blood were taken during birth. Confocal and electron microscopy were utilized to examine the morphology of the placenta and mitochondria. We determined the lipid composition using liquid chromatography-mass spectrometry in data-independent analysis mode (LC/MSE). In vitro studies were carried out on choriocarcinoma cells (JEG3) to investigate the mechanism of trophoblast mitochondrial dysfunction. Results showed that the GDM placenta was distinguished by increased syncytial knots, chorangiosis, lectin-like oxidized low-density lipoprotein (LDL) receptor-1 (LOX-1) overexpression, and mitochondrial dysfunction. Lysophosphatidylcholine (LPC) 16:0 was significantly elevated in the cord blood LDL of GDM patients. In vitro, we demonstrated that LPC dose-dependently disrupts mitochondrial function by increasing reactive oxygen species (ROS) levels and HIF-1α signaling. In conclusion, highly elevated LPC in cord blood plays a pivotal role in GDM, contributing to trophoblast impairment and pregnancy complications.

Modeling demyelination and endogenous remyelination in spinal cord ex vivo rat organotypic slice cultures.

Introduction: Demyelination of the spinal cord is a prominent feature of multiple sclerosis (MS) and spinal cord injuries (SCI), where impaired neuronal communication between the brain and periphery has devastating consequences on neurological function. Demyelination precedes remyelination, an endogenous process in which oligodendrocyte precursor cells (OPCs) differentiate into mature, myelinating oligodendrocytes with the ability to restore the myelin sheath and reinstate functional nerve signaling. However, in MS or SCI, demyelination is more severe, persistent, and inhibitory to OPC-mediated remyelination, leading to a permanent loss of neuronal function. Currently, there are no effective treatments for demyelination, and existing pre-clinical models typically focus on brain tissue with little characterization of demyelination within the spinal cord. Organotypic slice cultures are a useful tool to study neurological disease, providing a more complex 3-dimensional system than standard 2-dimensional in vitro cell cultures. Methods: Building on our previously developed rat brain slice culture protocol, we have extended our findings to develop a rat longitudinal spinal cord ex vivo model of demyelination. Results: We generated rat longitudinal spinal cord slice cultures that remain viable for up to 6 weeks in culture and retain key anatomical features of the spinal cord's cytoarchitecture. We show that treating longitudinal spinal cord slices with lysolecithin (LPC) induced robust demyelination with some endogenous remyelination, which was not seen following exposure to lipopolysaccharide (LPS). Discussion: Our ex vivo organotypic spinal cord slice culture system provides a platform to model demyelination and endogenous remyelination long-term, mimicking that observed in LPC-induced rodent models of demyelination. This platform is suitable for the development and testing of novel therapeutic strategies with ease of manipulation prior to in vivo experimentation.

Dietary LPC-Bound n-3 LCPUFA Protects against Neonatal Brain Injury in Mice but Does Not Enhance Stem Cell Therapy.

Neonatal hypoxic-ischemic (HI) brain injury is a prominent cause of neurological morbidity, urging the development of novel therapies. Interventions with n-3 long-chain polyunsaturated fatty acids (n-3 LCPUFAs) and mesenchymal stem cells (MSCs) provide neuroprotection and neuroregeneration in neonatal HI animal models. While lysophosphatidylcholine (LPC)-bound n-3 LCPUFAs enhance brain incorporation, their effect on HI brain injury remains unstudied. This study investigates the efficacy of oral LPC-n-3 LCPUFAs from Lysoveta following neonatal HI in mice and explores potential additive effects in combination with MSC therapy. HI was induced in 9-day-old C57BL/6 mice and Lysoveta was orally supplemented for 7 subsequent days, with or without intranasal MSCs at 3 days post-HI. At 21-28 days post-HI, functional outcome was determined using cylinder rearing, novel object recognition, and open field tasks, followed by the assessment of gray (MAP2) and white (MBP) matter injury. Oral Lysoveta diminished gray and white matter injury but did not ameliorate functional deficits following HI. Lysoveta did not further enhance the therapeutic potential of MSC therapy. In vitro, Lysoveta protected SH-SY5Y neurons against oxidative stress. In conclusion, short-term oral administration of Lysoveta LPC-n-3 LCPUFAs provides neuroprotection against neonatal HI by mitigating oxidative stress injury but does not augment the efficacy of MSC therapy.

Auditory associative word learning in adults: The effects of musical experience and stimulus ordering.

Evidence for sequential associative word learning in the auditory domain has been identified in infants, while adults have shown difficulties. To better understand which factors may facilitate adult auditory associative word learning, we assessed the role of auditory expertise as a learner-related property and stimulus order as a stimulus-related manipulation in the association of auditory objects and novel labels. We tested in the first experiment auditorily-trained musicians versus athletes (high-level control group) and in the second experiment stimulus ordering, contrasting object-label versus label-object presentation. Learning was evaluated from Event-Related Potentials (ERPs) during training and subsequent testing phases using a cluster-based permutation approach, as well as accuracy-judgement responses during test. Results revealed for musicians a late positive component in the ERP during testing, but neither an N400 (400-800 ms) nor behavioral effects were found at test, while athletes did not show any effect of learning. Moreover, the object-label-ordering group only exhibited emerging association effects during training, while the label-object-ordering group showed a trend-level late ERP effect (800-1200 ms) during test as well as above chance accuracy-judgement scores. Thus, our results suggest the learner-related property of auditory expertise and stimulus-related manipulation of stimulus ordering modulate auditory associative word learning in adults.

Autotaxin-Lysophosphatidate Axis: Promoter of Cancer Development and Possible Therapeutic Implications.

Autotaxin (ATX) is a member of the ectonucleotide pyrophosphate/phosphodiesterase (ENPP) family; it is encoded by the ENPP2 gene. ATX is a secreted glycoprotein and catalyzes the hydrolysis of lysophosphatidylcholine to lysophosphatidic acid (LPA). LPA is responsible for the transduction of various signal pathways through the interaction with at least six G protein-coupled receptors, LPA Receptors 1 to 6 (LPAR1-6). The ATX-LPA axis is involved in various physiological and pathological processes, such as angiogenesis, embryonic development, inflammation, fibrosis, and obesity. However, significant research also reported its connection to carcinogenesis, immune escape, metastasis, tumor microenvironment, cancer stem cells, and therapeutic resistance. Moreover, several studies suggested ATX and LPA as relevant biomarkers and/or therapeutic targets. In this review of the literature, we aimed to deepen knowledge about the role of the ATX-LPA axis as a promoter of cancer development, progression and invasion, and therapeutic resistance. Finally, we explored its potential application as a prognostic/predictive biomarker and therapeutic target for tumor treatment.

"Find Me" and "Eat Me" signals: tools to drive phagocytic processes for modulating antitumor immunity.

Phagocytosis, a vital defense mechanism, involves the recognition and elimination of foreign substances by cells. Phagocytes, such as neutrophils and macrophages, rapidly respond to invaders; macrophages are especially important in later stages of the immune response. They detect "find me" signals to locate apoptotic cells and migrate toward them. Apoptotic cells then send "eat me" signals that are recognized by phagocytes via specific receptors. "Find me" and "eat me" signals can be strategically harnessed to modulate antitumor immunity in support of cancer therapy. These signals, such as calreticulin and phosphatidylserine, mediate potent pro-phagocytic effects, thereby promoting the engulfment of dying cells or their remnants by macrophages, neutrophils, and dendritic cells and inducing tumor cell death. This review summarizes the phagocytic "find me" and "eat me" signals, including their concepts, signaling mechanisms, involved ligands, and functions. Furthermore, we delineate the relationships between "find me" and "eat me" signaling molecules and tumors, especially the roles of these molecules in tumor initiation, progression, diagnosis, and patient prognosis. The interplay of these signals with tumor biology is elucidated, and specific approaches to modulate "find me" and "eat me" signals and enhance antitumor immunity are explored. Additionally, novel therapeutic strategies that combine "find me" and "eat me" signals to better bridge innate and adaptive immunity in the treatment of cancer patients are discussed.

Lysophosphatidylcholine induces oxidative stress and calcium-mediated cell death in human blood platelets.

Platelets are essential component of circulation that plays a major role in hemostasis and thrombosis. During activation and its demise, platelets release platelet-derived microvesicles, with lysophosphatidylcholine (LPC) being a prominent component in their lipid composition. LPC, an oxidized low-density lipoprotein, is involved in cellular metabolism, but its higher level is implicated in pathologies like atherosclerosis, diabetes, and inflammatory disorders. Despite this, its impact on platelet function remains relatively unexplored. To address this, we studied LPC's effects on washed human platelets. A multimode plate reader was employed to measure reactive oxygen species and intracellular calcium using H2DCF-DA and Fluo-4-AM, respectively. Flow cytometry was utilized to measure phosphatidylserine expression, mitochondrial membrane potential (ΔΨm), and mitochondrial permeability transition pore (mPTP) formation using FITC-Annexin V, JC-1, and CoCl2/calcein-AM, respectively. Additionally, platelet morphology and its ultrastructure were observed via phase contrast and electron microscopy. Sonoclot and light transmission aggregometry were employed to examine fibrin formation and platelet aggregation, respectively. The findings demonstrate that LPC induced oxidative stress and increased intracellular calcium in platelets, resulting in increased phosphatidylserine expression and reduced ΔΨm. LPC triggered caspase-independent platelet death and mPTP opening via cytosolic and mitochondrial calcium, along with microvesiculation and reduced platelet counts. LPC increased the platelet's size, adopting a balloon-shaped morphology, causing membrane fragmentation and releasing its cellular contents, while inducing a pro-coagulant phenotype with increased fibrin formation and reduced integrin αIIbß3 activation. Conclusively, this study reveals LPC-induced oxidative stress and calcium-mediated platelet death, necrotic in nature with pro-coagulant properties, potentially impacting inflammation and repair mechanisms during vascular injury.

Validation of a high-performance liquid chromatography method for determining lysophosphatidylcholine content in bovine pulmonary surfactant medication.

Pulmonary surfactant replacement therapy is a promising improvement in neonatal care for infants with respiratory distress syndrome. Lysophosphatidylcholine (LPC) is an undesirable component that can hinder surfactant proteins from enhancing the adsorption of surfactant lipids to balance surface tensions by creating a saturated coating on the interior of the lungs. A novel normal-phase liquid chromatography method utilizing UV detection and non-toxic solvents was developed and validated for the first time to analyze LPC in the complex matrix of pulmonary surfactant medication. The analytical method validation included evaluation of system suitability, repeatability, intermediate precision, linearity, accuracy, limit of detection (LOD), limit of quantification (LOQ), stability and robustness. The method yielded detection and quantification limits of 4.4 and 14.5 µg/ml, respectively. The calibration curve was modified linearly within the LOQ to 1.44 mg/ml range, with a determination coefficient of 0.9999 for standards and 0.9997 for sample solutions. Given the lack of reliable published data on LPC analysis in pulmonary surfactant medications, this newly developed method demonstrates promising results and offers advantages of HPLC methodology, including simplicity, accuracy, specificity, sensitivity and an exceptionally low LOD and LOQ. These attributes contribute to considering this achievement as an innovative method.

Risk factors and metabolomics of mild cognitive impairment in type 2 diabetes mellitus.

Objective: This study aimed to explore the risk factors, metabolic characteristics, and potential biomarkers of mild cognitive impairment in type 2 diabetes mellitus (T2DM-MCI) and to provide potential evidence for the diagnosis, prevention, and treatment of mild cognitive impairment (MCI) in patients with type 2 diabetes mellitus (T2DM). Methods: A total of 103 patients with T2DM were recruited from the Endocrinology Department of The Second Affiliated Hospital of Dalian Medical University for inclusion in the study. The Montreal Cognitive Assessment (MoCA) was utilized to evaluate the cognitive functioning of all patients. Among them, 50 patients were categorized into the T2DM-MCI group (MoCA score < 26 points), while 53 subjects were classified into the T2DM without cognitive impairment (T2DM-NCI) group (MoCA score ≥ 26 points). Serum samples were collected from the subjects, and metabolomics profiling data were generated by Ultra-high performance liquid chromatography-mass spectrometry (UHPLC-MS). These groups were analyzed to investigate the differences in expression of small molecule metabolites, metabolic pathways, and potential specific biomarkers. Results: Comparison between the T2DM-MCI group and T2DM-NCI group revealed significant differences in years of education, history of insulin application, insulin resistance index, insulin-like growth factor-binding protein-3 (IGFBP-3), and creatinine levels. Further binary logistic regression analysis of the variables indicated that low educational level and low serum IGFBP-3 were independent risk factor for T2DM-MCI. Metabolomics analysis revealed that differential expression of 10 metabolites between the T2DM-MCI group and T2DM-NCI group (p < 0.05 and FDR<0.05, VIP>1.5). Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment pathway analysis revealed that fatty acid degradation was the most significant pathway. Receiver operating characteristic (ROC) analysis shows that lysophosphatidylcholine (LPC) 18:0 exhibited greater diagnostic efficiency. Conclusion: This study revealed that a shorter duration of education and lower serum IGFBP-3 levels are independent risk factors for T2DM-MCI. Serum metabolites were found to be altered in both T2DM-MCI and T2DM-NCI groups. T2DM patients with or without MCI can be distinguished by LPC 18:0. Abnormal lipid metabolism plays a significant role in the development of MCI in T2DM patients.

Lipidome is a valuable tool for the severity prediction of coronavirus disease 2019.

Objective: To describe the lipid metabolic profile of different patients with coronavirus disease 2019 (COVID-19) and contribute new evidence on the progression and severity prediction of COVID-19. Methods: This case-control study was conducted in Peking University Third Hospital, China. The laboratory-confirmed COVID-19 patients aged ≥18 years old and diagnosed as pneumonia from December 2022 to January 2023 were included. Serum lipids were detected. The discrimination ability was calculated with the area under the curve (AUC). A random forest (RF) model was conducted to determine the significance of different lipids. Results: Totally, 44 COVID-19 patients were enrolled with 16 mild and 28 severe patients. The top 5 super classes were triacylglycerols (TAG, 55.9%), phosphatidylethanolamines (PE, 10.9%), phosphatidylcholines (PC, 6.8%), diacylglycerols (DAG, 5.9%) and free fatty acids (FFA, 3.6%) among the 778 detected lipids from the serum of COVID-19 patients. Certain lipids, especially lysophosphatidylcholines (LPCs), turned to have significant correlations with certain immune/cytokine indexes. Reduced level of LPC 20:0 was observed in severe patients particularly in acute stage. The AUC of LPC 20:0 reached 0.940 in discriminating mild and severe patients and 0.807 in discriminating acute and recovery stages in the severe patients. The results of RF models also suggested the significance of LPCs in predicting the severity and progression of COVID-19. Conclusion: Lipids probably have the potential to differentiate and forecast the severity, progression, and clinical outcomes of COVID-19 patients, with implications for immune/inflammatory responses. LPC 20:0 might be a potential target in predicting the progression and outcome and the treatment of COVID-19.

Perception of cure in prostate cancer: human-led and artificial intelligence-assisted landscape review and linguistic analysis of literature, social media and policy documents.

BACKGROUND: Understanding stakeholders' perception of cure in prostate cancer (PC) is essential to preparing for effective communication about emerging treatments with curative intent. This study used artificial intelligence (AI) for landscape review and linguistic analysis of definition, context and value of cure among stakeholders in PC. MATERIALS AND METHODS: Subject-matter experts (SMEs) selected cure-related key words using Elicit, a semantic literature search engine, and extracted hits containing the key words from Medline, Sermo and Overton, representing academic researchers, health care providers (HCPs) and policymakers, respectively. NetBase Quid, a social media analytics and natural language processing tool, was used to carry out key word searches in social media (representing the general public). NetBase Quid analysed linguistics of key word-specific hit sets for key word count, geolocation and sentiments. SMEs qualitatively summarised key word-specific insights. Contextual terms frequently occurring with key words were identified and quantified. RESULTS: SMEs identified seven key words applicable to PC (number of acquired hits) across four platforms: Cure (12429), Survivor (6063), Remission (1904), Survivorship (1179), Curative intent (432), No evidence of disease (381) and Complete remission (83). Most commonly used key words were Cure by the general public and HCPs (11815 and 224 hits), Survivorship by academic researchers and Survivor by policymakers (378 hits each). All stakeholders discussed Cure and cure-related key words primarily in early-stage PC and associated them with positive sentiments. All stakeholders defined cure differently but communicated about it in relation to disease measurements (e.g. prostate-specific antigen) or surgery. Stakeholders preferred different terms when discussing cure in PC: Cure (academic researchers), Cure rates (HCPs), Potential cure and Survivor/Survivorship (policymakers) and Cure and Survivor (general public). CONCLUSION: This human-led, AI-assisted large-scale qualitative language-based research revealed that cure was commonly discussed by academic researchers, HCPs, policymakers and the general public, especially in early-stage PC. Stakeholders defined and contextualised cure in their communications differently and associated it with positive value.

Choice overload interferes with early processing and necessitates late compensation: Evidence from electroencephalogram.

Having a multitude of choices can be advantageous, yet an abundance of options can be detrimental to the decision-making process. Based on existing research, the present study combined electroencephalogram and self-reported methodologies to investigate the neural mechanisms underlying the phenomenon of choice overload. Behavioural data suggested that an increase in the number of options led to negative evaluations and avoidance of choice tendencies, even in the absence of time pressure. Event-related potential results indicated that the large choice set interfered with the early visual process, as evidenced by the small P1 amplitude, and failed to attract more attentional resources in the early stage, as evidenced by the small amplitude of P2 and N2. However, the LPC amplitude was increased in the late stage, suggesting greater investment of attentional resources and higher emotional arousal. Multivariate pattern analysis revealed that the difference between small and large choice set began at around 120 ms, and the early and late stages were characterised by opposite activation patterns. This suggested that too many options interfered with early processing and necessitate continued processing at a later stage. In summary, both behavioural and event-related potential (ERP) results confirm the choice overload effect, and it was observed that individuals tend to subjectively exaggerate the choice overload effect.

Can irony regulate negative emotion? Evidence from behaviour and ERPs.

This study used ratings and event-related potentials (ERPs) to compare the mechanisms through which verbal irony and cognitive reappraisal mitigate negative emotion. Verbal irony is when the literal meaning of words contrasts with their intended meaning. Cognitive reappraisal is when we reconsider emotional stimuli to make them less intense. Our hypothesis was that cognitive reappraisal is a potential mechanism through which irony reduces negative emotion. Participants viewed mildly negative pictures first, then read an ironic or literal statement about it in one block, and used cognitive reappraisal of or attending to the picture in the other block. Participants then viewed the picture for a second time, before rating how negative they felt. Behaviourally, irony reduced negative feelings more than literal statements, and reappraisal reduced negative feelings more than attending, with a larger reduction from reappraisal than from irony. In ERPs, irony elicited a prolonged N400 compared to literal, indexing an initial contrast between picture and word affect and sustained processing of their combination. Cognitive reappraisal elicited a larger late positivity compared to attending at the instruction screen. No differences were found during second picture presentation. These findings suggest that irony and cognitive reappraisal can reduce negative affect in different ways.

Brain responses to a lab-evolved artificial language with space-time metaphors.

What is the connection between the cultural evolution of a language and the rapid processing response to that language in the brains of individual learners? In an iterated communication study that was conducted previously, participants were asked to communicate temporal concepts such as "tomorrow," "day after," "year," and "past" using vertical movements recorded on a touch screen. Over time, participants developed simple artificial 'languages' that used space metaphorically to communicate in nuanced ways about time. Some conventions appeared rapidly and universally (e.g., using larger vertical movements to convey greater temporal durations). Other conventions required extensive social interaction and exhibited idiosyncratic variation (e.g., using vertical location to convey past or future). Here we investigate whether the brain's response during acquisition of such a language reflects the process by which the language's conventions originally evolved. We recorded participants' EEG as they learned one of these artificial space-time languages. Overall, the brain response to this artificial communication system was language-like, with, for instance, violations to the system's conventions eliciting an N400-like component. Over the course of learning, participants' brain responses developed in ways that paralleled the process by which the language had originally evolved, with early neural sensitivity to violations of a rapidly-evolving universal convention, and slowly developing neural sensitivity to an idiosyncratic convention that required slow social negotiation to emerge. This study opens up exciting avenues of future work to disentangle how neural biases influence learning and transmission in the emergence of structure in language.

Testosterone Inhibits Secretion of the Pro-Inflammatory Chemokine CXCL1 from Astrocytes.

Astrocytes play an important role in the regulation of the inflammatory response in the CNS, e.g., in demyelinating diseases. Since the chemokine CXCL1 is known to be secreted by astrocytes and to have a pro-inflammatory effect on immune cells in the CNS, we verified the effect of testosterone on its secretion in vitro (in the astrocytic cell line DI TNC1). Testosterone reduced the increase in CXCL1 production caused by the pro-inflammatory agent lysophosphatidylcholine and restored the basal production level of CXCL1. The androgen receptor (present and functional in the studied cell line) was strongly suggested to mediate this effect-its non-steroid ligand flutamide exerted an agonist-like effect, mimicking the activity of testosterone itself on CXCL1 secretion. This novel mechanism has important implications for the known immunomodulatory effect of testosterone and potentially other androgenic hormones. It provides a potential explanation on the molecular level and shows that astrocytes are important players in inflammatory homeostasis in the CNS and its hormonal regulation. Therefore, it suggests new directions for the development of the therapeutic intervention.

The cognitive neural mechanism of trait anxiety influences mind wandering: An ERP study.

Converging evidence from behavioral and neuroscience studies demonstrated that our attention to the external world is influenced by emotion, especially anxiety. However, little is known about how trait anxiety influences neural and behavioral responses during mind wandering. The present study aimed to examine the neural and cognitive time courses of how trait anxiety affects mind wandering. Event-related potentials (ERPs) were recorded from 20 individuals with high trait anxiety and 20 with low trait anxiety when they performed the Sustained Attention to Response Task (SART) in which they were asked to respond to frequent ''nontargets'' (digits 0-6, 8-9) but withhold responses to infrequent ''targets'' (the digit 7). We compared the behavioral performance and electroencephalographic waves between the high and low trait anxiety groups during states of "mind wandering" (fail to withhold a response to the target number) and being "on-task" (correctly withhold a response to the target number). Results showed that a larger late positive component (LPC, 400-950 ms) was elicited when participants were "on task" than when they were mind wandering. Additionally, a larger late slow waveform (LSW, 950-1050 ms) was elicited in the high trait anxiety group than in the low trait anxiety group. Moreover, there was a positive correlation between self-reported trait anxiety scores and the LSW amplitudes during mind wandering. It was proposed that the effect of trait anxiety on the cognitive neural mechanism underlying attentional processing was primarily reflected in a later process involving the redistribution of cognitive resources.