Intestinal lysozyme engagement of Salmonella Typhimurium stimulates the release of barrier-impairing InvE and Lpp1.

Lysozyme is a ß-1,4-glycosidase that hydrolyzes the polysaccharide backbone of bacterial cell walls. With an additional bactericidal function mediated by a separate protein domain, lysozyme is considered a uniquely important antimicrobial molecule contributing to the host's innate immune response to infection. Elevated lysozyme production is found in various inflammatory conditions while patients with genetic risks for inflammatory bowel diseases demonstrate abnormal lysozyme expression, granule packaging, and secretion in Paneth cells. However, it remains unclear how a gain- or loss-of-function in host lysozyme may impact the host inflammatory responses to pathogenic infection. We challenged Lyz1-/- and ectopic Lyz1-expressing (Villin-Lyz1TG) mice with S. Typhimurium and then comprehensively assessed the inflammatory disease progression. We conducted proteomics analysis to identify molecules derived from human lysozyme-mediated processing of live Salmonella. We examined the barrier-impairing effects of these identified molecules in human intestinal epithelial cell monolayer and enteroids. Lyz1-/- mice are protected from infection in terms of morbidity, mortality, and barrier integrity, whereas Villin-Lyz1TG mice demonstrate exacerbated infection and inflammation. The growth and invasion of Salmonella in vitro are not affected by human or chicken lysozyme, whereas lysozyme encountering of live Salmonella stimulates the release of barrier-disrupting factors, InvE-sipC and Lpp1, which directly or indirectly impair the tight junctions. The direct engagement of host intestinal lysozyme with an enteric pathogen such as Salmonella promotes the release of virulence factors that are barrier-impairing and pro-inflammatory. Controlling lysozyme function may help alleviate the inflammatory progression.

Neurophysiological responses to emotional faces predict dynamic fluctuations in affect in adolescents.

The ability to accurately identify and interpret others' emotions is critical for social and emotional functioning during adolescence. Indeed, previous research has identified that laboratory-based indices of facial emotion recognition and engagement with emotional faces predict adolescent mood states. Whether socioemotional information processing relates to real-world affective dynamics using an ecologically sensitive approach, however, has rarely been assessed. In the present study, adolescents (N = 62; ages 13-18) completed a Facial Recognition Task, including happy, angry, and sad stimuli, while EEG data were acquired. Participants also provided ecological momentary assessment (EMA) data probing their current level of happiness, anger, and sadness for 1-week, resulting in indices of emotion (mean-level, inertia, instability). Analyses focused on relations between (1) accuracy for and (2) prolonged engagement with (LPP) emotional faces and EMA-reported emotions. Greater prolonged engagement with happy faces was related to less resistance to changes in happiness (i.e., less happiness inertia), whereas greater prolonged engagement with angry faces associated with more resistance to changes in anger (i.e., greater anger inertia). Results suggest that socioemotional processes captured by laboratory measures have real-world implications for adolescent affective states and highlight potentially actionable targets for novel treatment approaches (e.g., just-in-time interventions). Future studies should continue to assess relations among socioemotional informational processes and dynamic fluctuations in adolescent affective states.

Competition influences outcome processing involving social comparison: An ERP study.

In a complicated social context, outcome evaluation involves not only oneself but also others in relation to the self (i.e., social comparison). Previous event-related potential (ERP) studies have investigated the processing of social comparison-related outcomes when one's interests are independent of the interests of others (i.e., noncompetition circumstances). However, it is unclear how social comparison-related outcomes are processed in the brain when there are conflicts of interest between oneself and others (i.e., competition circumstances). To address this issue, participants in the current study were asked to perform an attentional task with several peers and were subsequently presented with self-related outcomes (i.e., the performance difference between the current trial and several preceding trials) and social comparison-related outcomes (i.e., the performance difference between oneself and their peer). Importantly, rewards and punishments were based on social comparison-related outcomes in the competition condition and on self-related outcomes in the noncompetition condition. ERP results revealed that in the competition condition, positive outcomes involving social comparison elicited a greater P300 response than negative outcomes, whereas this effect was not observed in the noncompetition condition. Additionally, there was generally a larger late positive potential (LPP) response to negative outcomes involving social comparison than to positive outcomes only when one obtained a self-related positive outcome in the competition condition. These findings suggest that competition might strengthen outcome processing involving social comparison at late time ranges relying on self-related outcomes to some extent.

Emotion regulation flexibility: EEG/EMG predictors and consequences of switching between reappraisal and distraction strategies.

Flexible use of emotion regulation (ER) strategies is central to mental health. To advance our understanding of what drives adaptive strategy-switching decisions, in this preregistered study, we used event-related potentials (late positive potential, LPP and stimulus preceding negativity, SPN) and facial electromyography (EMG corrugator activity) to test the antecedents and consequences of switching to an alternative ER strategy. Participants (N = 63, Mage = 24.8 years, all female) passively watched and then implemented an instructed ER strategy (reappraisal or distraction) in response to high-intensity negative pictures that were either easy or difficult to reinterpret (high or low reappraisal affordance, respectively). Next, they decided to "switch from" or "maintain" the instructed strategy and subsequently implemented the chosen strategy. Reappraisal affordance manipulations successfully induced switching. Regarding antecedents, switching was predicted by the reduced ER efficacy of the current strategy (corrugator, but not LPP). Switching to distraction was additionally predicted by increased responses to the stimulus during passive viewing (corrugator and LPP) and increased anticipatory effort in implementing reappraisal (SPN). Concerning consequences, switching to distraction improved, whereas switching to reappraisal impaired post-choice ER effects (LPP). However, starting with reappraisal was overall more effective than starting with distraction, irrespective of the subsequent decision (corrugator). Our results suggest that switching between ER strategies occurs in accordance with situational demands (stimulus affordances) and is predicted by reduced peripheral physiological ER efficacy. However, only switching to distraction leads to improved regulatory effects. These insights provide neurocognitively grounded starting points for developing interventions targeting ER flexibility.

Expectancy and attention bias to spiders: Dissecting anticipation and allocation processes using ERPs.

The current registered report focused on the temporal dynamics of the relationship between expectancy and attention toward threat, to better understand the mechanisms underlying the prioritization of threat detection over expectancy. In the current event-related potentials experiment, a-priori expectancy was manipulated, and attention bias was measured, using a well-validated paradigm. A visual search array was presented, with one of two targets: spiders (threatening) or birds (neutral). A verbal cue stating the likelihood of encountering a target preceded the array, creating congruent and incongruent trials. Following cue presentation, preparatory processes were examined using the contingent negative variation (CNV) component. Following target presentation, two components were measured: early posterior negativity (EPN) and late positive potential (LPP), reflecting early and late stages of natural selective attention toward emotional stimuli, respectively. Behaviorally, spiders were found faster than birds, and congruency effects emerged for both targets. For the CNV, a non-significant trend of more negative amplitudes following spider cues emerged. As expected, EPN and LPP amplitudes were larger for spider targets compared to bird targets. Data-driven, exploratory, topographical analyses revealed different patterns of activation for bird cues compared to spider cues. Furthermore, 400-500 ms post-target, a congruency effect was revealed only for bird targets. Together, these results demonstrate that while expectancy for spider appearance is evident in differential neural preparation, the actual appearance of spider target overrides this expectancy effect and only in later stages of processing does the cueing effect come again into play.

Generalization of savoring to novel positive stimuli.

Savoring is a positive emotion up-regulation technique that can increase electrocortical and self-reported valence and arousal to positive and neutral pictures, with effects persisting to increase response to the same stimuli when encountered later. Outside of the lab, emotion regulation techniques that persist to affect not just encounters with the same stimuli but also encounters with similar, but previously unencountered stimuli should save individuals time and effort. Here, we used event-related potentials and picture ratings to test whether savoring would generalize to similar, but previously unseen positive pictures. To this end, 89 participants (56 female; M age = 18.96 years, SD = 1.87) were asked to savor positive pictures from one category (e.g., happy people) and to view positive pictures from another category (e.g., cute animals), as well as to view neutral pictures (e.g., plants). In a subsequent passive picture viewing task, participants viewed novel pictures from all three categories (i.e., happy people, cute animals, plants). In the first task, savoring was effective for pictures of animals throughout picture presentation, but only for pictures of people during the later part of picture presentation. In the second task, savoring generalized to novel pictures of animals, though this was only evident in the early portion of picture processing (and for self-reported ratings). Therefore, savoring holds promise as a useful technique for increasing positive emotion in everyday life, though more work is needed to understand whether effects may vary depending on different types of picture content.

Case-by-case: neural markers of emotion and task stimulus significance.

The present study assessed the hypothesis that electrophysiological markers of emotional and task stimulus significance can be demonstrated in concert at the level of the individual case. Participants (n = 18, 9 females) viewed low and high-arousing pictures selected from behavior systems of sexual reproduction, disease avoidance, and predator fear. Furthermore, to concurrently manipulate task relevance, participants performed an explicit emotion categorization task with either low or high-arousing pictures alternating as target stimuli in separate experimental blocks. Pooled across behavior systems, event-related components sensitive to emotional significance reached statistical significance in 100% of the tests for the early posterior negativity and in 96% of the tests for the late positive potential. Regarding explicit task relevance, the target P3 effect was significant in 96% of the tests. These findings demonstrate that neural markers of stimulus significance driven by emotional picture content and explicit task demands can be assessed at the individual level. Replicating an effect case-after-case provides strong support for an effect common-to-all and may support individual inferences. Contributions of the case-by-case approach to reveal reproducible effects and implications for the development of neural biomarkers for specific affective and cognitive component processes are discussed.

Predictive utility of the P3 event-related potential (ERP) response to alcohol cues for ecologically assessed alcohol craving and use.

Neural measures of alcohol cue incentive salience have been associated with retrospective reports of riskier alcohol use behaviour and subjective response profiles. This study tested whether the P3 event-related potential (ERP) elicited by alcohol-related cues (ACR-P3) can forecast alcohol use and craving during real-world drinking episodes. Participants (N = 262; Mage = 19.53; 56% female) completed a laboratory task in which they viewed images of everyday objects (Neutral), non-alcohol drinks (NonAlc) and alcohol beverages (Alc) while EEG was recorded and then completed a 21-day ecological momentary assessment (EMA) protocol in which they recorded alcohol craving and consumption. Anthropometrics were used to derive estimated blood alcohol concentration (eBAC) throughout drinking episodes. Multilevel modelling indicated positive associations between P3 amplitudes elicited by all stimuli and within-episode alcohol use measures (e.g., eBAC, cumulative drinks). Focal follow-up analyses indicated a positive association between AlcP3 amplitude and eBAC within episodes: Larger AlcP3 was associated with a steeper rise in eBAC. This association was robust to controlling for the association between NonAlcP3 and eBAC. AlcP3 also was positively associated with episode-level measures (e.g., max drinks, max eBAC). There were no associations between any P3 variables and EMA-based craving measures. Thus, individual differences in neural measures of alcohol cue incentive salience appear to predict the speed and intensity of alcohol consumption but not reports of craving during real-world alcohol use episodes.

The effect of cognitive reappraisal on food craving and consumption: Does working memory capacity influence reappraisal ability? An event-related potential study.

Regulating cravings for unhealthy foods in favour of healthier options is essential for weight management. Cognitive reappraisal, which involves changing the meaning of a stimulus to modify its emotional impact, has shown promise for regulating food craving and consumption. Eighty participants were presented with high-calorie (HC) and low-calorie (LC) food pictures preceded by cues signalling instructions to naturally view the food (i.e., passive viewing; LOOK) or to imagine the future consequences of consuming that food (i.e., cognitive reappraisal; REGULATE). Participants' subjective craving and event-related potentials (ERPs) were measured, and food consumption after the task was assessed. Participants' working memory capacity (WMC) was measured with the automated Operation Span task. During cognitive reappraisal, cravings for HC foods decreased, whereas cravings for LC foods increased, compared to passive viewing. Cravings for LC and HC foods were correlated with consumptions of LC and HC foods, respectively. Occipital N1 (100-200ms) amplitudes were more negative for LC than for HC pictures, but were not modulated by strategy (LOOK or REGULATE), whereas early posterior negativity (EPN; 200-300ms) was not sensitive to food type (HC or LC) or strategy. Late positive potential (LPP; 400-1000ms) ERPs were largest in the HC-REGULATE condition, possibly due to cognitive processes induced by focusing on the consequences of unhealthy foods. Late LPP (1000-3000ms) was not affected by food type or strategy. LPP amplitudes were not correlated with cravings. WMC was weakly correlated with cravings for LC following reappraisal, suggesting that WMC may influence reappraisal ability. In sum, focusing on future consequences of eating may promote healthier food choices through craving regulation. Further research is needed to examine how regulatory effects evolve over time and how they relate to WMC and brain activity.

Cleavage of Braun's lipoprotein Lpp from the bacterial peptidoglycan by a paralog of l,d-transpeptidases, LdtF.

The gram-negative bacterial cell envelope is made up of an outer membrane (OM), an inner membrane (IM) that surrounds the cytoplasm, and a periplasmic space between the two membranes containing peptidoglycan (PG or murein). PG is an elastic polymer that forms a mesh-like sacculus around the IM, protecting cells from turgor and environmental stress conditions. In several bacteria, including Escherichia coli, the OM is tethered to PG by an abundant OM lipoprotein, Lpp (or Braun's lipoprotein), that functions to maintain the structural and functional integrity of the cell envelope. Since its discovery, Lpp has been studied extensively, and although l,d-transpeptidases, the enzymes that catalyze the formation of PG-Lpp linkages, have been earlier identified, it is not known how these linkages are modulated. Here, using genetic and biochemical approaches, we show that LdtF (formerly yafK), a newly identified paralog of l,d-transpeptidases in E. coli, is a murein hydrolytic enzyme that catalyzes cleavage of Lpp from the PG sacculus. LdtF also exhibits glycine-specific carboxypeptidase activity on muropeptides containing a terminal glycine residue. LdtF was earlier presumed to be an l,d-transpeptidase; however, our results show that it is indeed an l,d-endopeptidase that hydrolyzes the products generated by the l,d-transpeptidases. To summarize, this study describes the discovery of a murein endopeptidase with a hitherto unknown catalytic specificity that removes the PG-Lpp cross-links, suggesting a role for LdtF in the regulation of PG-OM linkages to maintain the structural integrity of the bacterial cell envelope.

Processing of food stimuli in anorexia nervosa: An ERP-study comparing adolescents and adults.

BACKGROUND: Anorexia nervosa (AN) is associated with altered processing of disorder-relevant stimuli. Event-related potentials (ERP) - such as the Late Positive Potential (LPP) - give information about the underlying mechanisms of central nervous stimulus processing. METHODS: Patients with AN (22 adolescents, 23 adults) and healthy controls (HCs; 17 adolescents, 24 adults) were included. Neutral, low, and high calorie food-images were rated for valence and arousal; EEG activity was recorded and LPPs (early: 350-700 ms; late: 800-1200 ms) were extracted. Effects of patient status, age group, and stimulus category were analyzed via mixed 2 × 2 × 3-AN(C)OVAs. RESULTS: Patients with AN rated high calorie stimuli lower in valence and higher in arousal than HCs. Controlling for hunger, food stimuli elicited higher early LPPs than neutral ones in patients and HCs. For the late LPP, patients with AN showed larger amplitudes. CONCLUSION: Results suggest a highly automatic attentional bias towards low-calorie foods. Patients with AN seem to have more intense cognitive processing independent of stimulus material. More research is needed to validate and clarify differences between early and late LPP measures as well as the operationalization and relevance of hunger status.

Hierarchical status is rapidly assessed from behaviourally dominant faces.

Recognition of social hierarchy is a key feature that helps us navigate through our complex social environment. Neuroimaging studies have identified brain structures involved in the processing of hierarchical stimuli, but the precise temporal dynamics of brain activity associated with such processing remains largely unknown. In this investigation, we used event-related potentials (ERPs) to examine the effect of social hierarchy on the neural responses elicited by dominant and nondominant faces. Participants played a game where they were led to believe that they were middle-rank players, responding alongside other alleged players, whom they perceived as higher or lower-ranking. ERPs were examined in response to dominant and nondominant faces, and low-resolution electromagnetic tomography (LORETA) was used to identify the implicated brain areas. The results revealed that the amplitude of the N170 component was enhanced for faces of dominant individuals, showing that hierarchy influences the early stages of face processing. A later component, the late positive potential (LPP) appearing between 350-700 ms, also was enhanced for faces of higher-ranking players. Source localisation suggested that the early modulation was due to an enhanced response in limbic regions. These findings provide electrophysiological evidence for enhanced early visual processing of socially dominant faces.

Weathering the storm of emotions: immediate and lasting effects of reinterpretation and distancing on event-related potentials and their association with habitual use of cognitive reappraisal.

Reinterpretation and distancing, two cognitive reappraisal tactics, are known to effectively reduce negative feelings and event-related potentials (ERPs), such as the P300 and the late positive potential (LPP), in the short-term. Less is known about differential and lasting effects on ERPs as well as their association with habitual reappraisal. Fifty-seven participants were instructed to passively view or reappraise (reinterpretation, distancing) pictures that were repeatedly presented with the same instruction (active regulation phase). Thirty minutes later, these pictures were shown again without instruction for the assessment of lasting effects (re-exposure phase). ERPs were recorded and participants rated the intensity of negative feelings following picture presentation. Reappraisal led to an attenuation of the LPP, and both tactics decreased negative feelings during active regulation, whereby reinterpretation had a stronger impact on the subjective level. Passive re-exposure resulted in reduced negative feelings for previously reappraised pictures but had no lasting effects on ERPs. Higher habitual reappraisal was associated with higher P300 and early LPP amplitudes for emotional reactivity during the active regulation phase. During the re-exposure phase, higher habitual reappraisal was not related to ERPs. The current findings emphasize the effectiveness of both tactics in the short-term and lasting effects on the subjective experience of negative feelings. Enhanced emotional reactivity on the electrocortical level in individuals with a more frequent habitual use of reappraisal might indicate a higher preparedness to regulate.

Electrophysiological normative responses to emotional, neutral, and cigarette-related images.

To create reproducible emotional probes, affective scientists rely on sets of standardized pictures that are normed using subjective ratings of valence and emotional arousal. However, when emotional responses are investigated using neurophysiological measures, it might be more appropriate to select pictures integrating information from normative subjective reports and normative neurophysiological responses. Here, we provide electrophysiological normative responses for 323 emotional pictures (215 from the IAPS) covering a wide range of categories (erotica, romantic, appetizing foods, landscapes, people engaged in mundane activities, household objects, disgusting objects, accidents, sad people, violence, mutilations, and cigarette-related contents). Event-related potentials (ERPs) and subjective ratings of pleasure and emotional arousal were collected from 763 individuals (52% females, 41% white) aged between 18 and 65 (mean = 43). For each image, the mean amplitude of the late positive potential (LPP, an electrophysiological index of motivational relevance) and the mean subjective ratings of valence and arousal were calculated. We validated our procedure by showing that the subjective ratings of valence and arousal from this sample were highly correlated to the IAPS' published norms (Pearson r = .97 for pleasure and r = .82 for emotional arousal). LPP responses and subjective ratings of emotional arousal also were correlated (Pearson r = .61), but some categories reported being significantly more arousing than neutral (i.e., food, landscapes, and unpleasant objects) did not evoke LPPs significantly different from those evoked by neutral pictures. Researchers interested in probing the brain's affective systems can use these electrophysiological normative responses to create emotional probes that evoke reliable neuroaffective responses.

Satellite cell-derived exosome-mediated delivery of microRNA-23a/27a/26a cluster ameliorates the renal tubulointerstitial fibrosis in mouse diabetic nephropathy.

Renal tubulointerstitial fibrosis (TIF) is considered as the final convergent pathway of diabetic nephropathy (DN) without effective therapies currently. MiRNAs play a key role in fibrotic diseases and become promising therapeutic targets for kidney diseases, while miRNA clusters, formed by the cluster arrangement of miRNAs on chromosomes, can regulate diverse biological functions alone or synergistically. In this study, we developed clustered miR-23a/27a/26a-loaded skeletal muscle satellite cells-derived exosomes (Exos) engineered with RVG peptide, and investigated their therapeutic efficacy in a murine model of DN. Firstly, we showed that miR-23a-3p, miR-26a-5p and miR-27a-3p were markedly decreased in serum samples of DN patients using miRNA sequencing. Meanwhile, we confirmed that miR-23a-3p, miR-26a-5p and miR-27a-3p were primarily located in proximal renal tubules and highly negatively correlated with TIF in db/db mice at 20 weeks of age. We then engineered RVG-miR-23a/27a/26a cluster loaded Exos derived from muscle satellite cells, which not only enhanced the stability of miR-23a/27a/26a cluster, but also efficiently delivered more miR-23a/27a/26a cluster homing to the injured kidney. More importantly, administration of RVG-miR-23a/27a/26a-Exos (100 µg, i.v., once a week for 8 weeks) significantly ameliorated tubular injury and TIF in db/db mice at 20 weeks of age. We revealed that miR-23a/27a/26a-Exos enhanced antifibrotic effects by repressing miRNA cluster-targeting Lpp simultaneously, as well as miR-27a-3p-targeting Zbtb20 and miR-26a-5p-targeting Klhl42, respectively. Knockdown of Lpp by injection of AAV-Lpp-RNAi effectively ameliorated the progression of TIF in DN mice. Taken together, we established a novel kidney-targeting Exo-based delivery system by manipulating the miRNA-23a/27a/26a cluster to ameliorate TIF in DN, thus providing a promising therapeutic strategy for DN.

A Defect in Lipoprotein Modification by Lgt Leads to Abnormal Morphology and Cell Death in Escherichia coli That Is Independent of Major Lipoprotein Lpp.

Lgt is an essential enzyme in proteobacteria and therefore a potential target for novel antibiotics. The effect of Lgt depletion on growth, morphology, and viability was studied in Escherichia coli to assess whether absence of Lgt leads to cell death. Two Lgt depletion strains were used in which lgt was under the control of an arabinose-inducible promoter that allowed regulation of Lgt protein levels. Reduced levels of Lgt led to severe growth and morphological defects that could be restored by expressing lgt in trans, demonstrating that only Lgt is responsible for the distorted phenotypes. In the absence of major lipoprotein Lpp, growth defects were partially restored when low levels of Lgt were still present; however, lgt could not be deleted in the absence of Lpp. Our results demonstrate that Lpp is not the main cause of cell death under conditions of Lgt depletion and that other lipoproteins are important in cell envelope biogenesis and cell viability. Specific inhibitors of Lgt are thus promising for the development of novel antibiotics. IMPORTANCE Incomplete maturation and envelope mislocalization of lipoproteins, through inhibition or mutations in lipoprotein modification enzymes or transport to the outer membrane, are lethal in proteobacteria. Resistance to small-molecule inhibition or the appearance of suppressor mutations is often directly correlated with the presence of abundant outer membrane lipoprotein Lpp. Our results show that Lgt, the first enzyme of the lipoprotein modification pathway, is still required for growth and viability in the absence of Lpp and thus is necessary for the function of other essential lipoproteins in the cell envelope. This adds credence to the hypothesis that Lgt is essential in proteobacteria and an attractive target for the development of novel antibiotics.

Establishment of Emotional Memories Is Mediated by Vagal Nerve Activation: Evidence from Noninvasive taVNS.

Emotional memories are better remembered than neutral ones, but the mechanisms leading to this memory bias are not well understood in humans yet. Based on animal research, it is suggested that the memory-enhancing effect of emotion is based on central noradrenergic release, which is triggered by afferent vagal nerve activation. To test the causal link between vagus nerve activation and emotional memory in humans, we applied continuous noninvasive transcutaneous auricular vagus nerve stimulation (taVNS) during exposure to emotional arousing and neutral scenes and tested subsequent, long-term recognition memory after 1 week. We found that taVNS, compared with sham, increased recollection-based memory performance for emotional, but not neutral, material. These findings were complemented by larger recollection-related brain potentials (parietal ERP Old/New effect) during retrieval of emotional scenes encoded under taVNS, compared with sham. Furthermore, brain potentials recorded during encoding also revealed that taVNS facilitated early attentional discrimination between emotional and neutral scenes. Extending animal research, our behavioral and neural findings confirm a modulatory influence of the vagus nerve in emotional memory formation in humans.SIGNIFICANCE STATEMENT Emotionally relevant information elicits stronger and more enduring memories than nonrelevant information. Animal research has shown that this memory-enhancing effect of emotion is related to the noradrenergic activation in the brain, which is triggered by afferent fibers of the vagus nerve (VN). In the current study, we show that noninvasive transcutaneous auricular VN stimulation enhances recollection-based memory formation specifically for emotionally relevant information as indicated by behavioral and electrophysiological indices. These human findings give novel insights into the mechanisms underlying the establishment of emotional episodic memories by confirming the causal link between the VN and memory formation which may help understand the neural mechanisms underlying disorders associated with altered memory functions and develop treatment options.

No trait anxiety influences on early and late differential neuronal responses to aversively conditioned faces across three different tasks.

The human brain's ability to quickly detect dangerous stimuli is crucial in selecting appropriate responses to possible threats. Trait anxiety has been suggested to moderate these processes on certain processing stages. To dissociate such different information-processing stages, research using classical conditioning has begun to examine event-related potentials (ERPs) in response to fear-conditioned (CS +) faces. However, the impact of trait anxiety on ERPs to fear-conditioned faces depending on specific task conditions is unknown. In this preregistered study, we measured ERPs to faces paired with aversive loud screams (CS +) or neutral sounds (CS -) in a large sample (N = 80) under three different task conditions. Participants had to discriminate face-irrelevant perceptual information, the gender of the faces, or the CS category. Results showed larger amplitudes in response to aversively conditioned faces for all examined ERPs, whereas interactions with the attended feature occurred for the P1 and the early posterior negativity (EPN). For the P1, larger CS + effects were observed during the perceptual distraction task, while the EPN was increased for CS + faces when deciding about the CS association. Remarkably, we found no significant correlations between ERPs and trait anxiety. Thus, fear-conditioning potentiates all ERP amplitudes, some processing stages being further modulated by the task. However, the finding that these ERP differences were not affected by individual differences in trait anxiety does not support theoretical accounts assuming increased threat processing or reduced threat discrimination depending on trait anxiety.

LPP polymorphisms are risk factors for allergic rhinitis in the Chinese Han population.

BACKGROUND: Lipoma preferred partner (LPP) polymorphisms are related to immune diseases, but the role of LPP gene in the pathogenesis of allergic rhinitis (AR) is unclear. The current study aimed to explore the contribution of LPP variants to AR susceptibility in the Chinese Han population. METHODS: A total of 992 healthy controls and 992 patients with AR were recruited. Agena MassARRAY system was applied for genotyping. Odds ratios (OR) and 95% confidence intervals (CI) adjusted by age, sex, and body mass index (BMI) were calculated to conduct the risk assessment of LPP variants in people with a predisposition to AR. Additionally, multifactor dimensionality reduction (MDR) was applied to identify high-order interaction models for AR risk. RESULTS: We found that rs2030519-G (p = 0.027, OR: 1.15, 95% CI: 1.02-1.31), rs6780858-G (p = 0.019, OR: 1.16, 95% CI: 1.03-1.32), and rs60946162-T (p = 0.014, OR: 1.18, 95% CI: 1.03-1.34) were associated with increased susceptibility to AR. Subgroup analyses indicated the interaction of LPP polymorphisms in terms of age, gender, and BMI with AR susceptibility (p < 0.05, OR > 1). MDR analysis revealed that rs60946162 had the information gain (0.40%) of individual attribute regarding AR. CONCLUSION: Our results first determined that rs2030519, rs6780858, and rs60946162 were correlated with increased susceptibility to AR in the Chinese Han population, which add to our understanding of the impact of LPP gene variants on AR development.

Microenergy acoustic pulse therapy restores urethral wall integrity and continence in a rat model of female stress incontinence.

OBJECTIVE: To determine the outcomes and mechanisms of microenergy acoustic pulse (MAP) therapy in an irreversible rat model of female stress urinary incontinence. MATERIALS AND METHODS: Twenty-four female Sprague-Dawley rats were randomly assigned into four groups: sham control (sham), vaginal balloon dilation and ovariectomy (VBDO), VBDO + ß-aminopropionitrile (BAPN), and VBDO + ß-aminopropionitrile treated with MAP (MAP). MAP therapy was administered twice per week for 4 weeks. After a 1-week washout period, all 24 rats were evaluated with functional and histological studies. The urethral vascular plexus was examined by immunofluorescence staining with antibodies against collagen IV and von Willebrand factor (vWF). The urethral smooth muscle stem/progenitor cells (uSMPCs) were isolated and functionally studied in vivo and in vitro. RESULTS: Functional study with leak point pressure (LPP) measurement showed that the MAP group had significantly higher LPPs compared to VBDO and BAPN groups. MAP ameliorated the decline in urethral wall thickness and increased the amount of extracellular matrix within the urethral wall, especially in the urethral and vaginal elastic fibers. MAP also improved the disruption of the urethral vascular plexus in the treated animals. In addition, MAP enhanced the regeneration of urethral and vaginal smooth muscle, and uSMPCs could be induced by MAP to differentiate into smooth muscle and neuron-like cells in vitro. CONCLUSION: MAP appears to restore urethral wall integrity by increasing muscle content in the urethra and the vagina and by improving the urethral vascular plexus and the extracellular matrix.