Non-classical ProIL-1beta activation during mammary gland infection is pathogen-dependent but caspase-1 independent

Infection of the mammary gland with live bacteria elicits a pathogen-specific host inflammatory response. To study these host-pathogen interactions wild type mice, NF-kappaB reporter mice as well as caspase-1 and IL-1beta knockout mice were intramammarily challenged with Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus). The murine mastitis model allowed to compare the kinetics of the induced cytokine protein profiles and their underlying pathways. In vivo and ex vivo imaging showed that E. coli rapidly induced NF-kappaB inflammatory signaling concomitant with high mammary levels of TNF-alpha, IL-1 alpha and MCP-1 as determined by multiplex analysis. In contrast, an equal number of S. aureus bacteria induced a low NF-kappaB activity concomitant with high mammary levels of the classical IL-1beta fragment. These quantitative and qualitative differences in local inflammatory mediators resulted in an earlier neutrophil influx and in a more extensive alveolar damage post-infection with E. coli compared to S. aureus. Western blot analysis revealed that the inactive proIL-1beta precursor was processed into pathogen-specific IL-1beta fragmentation patterns as confirmed with IL-1beta knockout animals. Additionally, caspase-1 knockout animals allowed to investigate whether IL-1beta maturation depended on the conventional inflammasome pathway. The lack of caspase-1 did not prevent extensive proIL-1beta fragmentation by either of S. aureus or E. coli. These non-classical IL-1beta patterns were likely caused by different proteases and suggest a sentinel function of IL-1beta during mammary gland infection. Thus, a key signaling nodule can be defined in the differential host innate immune defense upon E. coli versus S. aureus mammary gland infection, which is independent of caspase-1

The therapeutic potential of attentional bias modification training for insomnia: study protocol for a randomised controlled trial.

The efficacy of attentional bias modification (ABM) as a treatment for anxiety and depression has been extensively studied with promising results. Despite some evidence of sleep-related attentional biases in insomnia, only a small number of studies, yielding mixed results, have examined the application of ABM in insomnia. This study specifically aims to determine whether ABM can reduce (i) the presence of an attentional bias for sleep-related threatening words; (ii) insomnia symptom severity; (iii) sleep onset latency; and (iv) pre-sleep cognitive arousal amongst individuals with insomnia compared to a non-treatment control group of individuals with insomnia. We propose a randomised controlled trial of 90 individuals from the general population who meet the criteria for Insomnia Disorder. Following an initial examination for the presence of a sleep-related attentional bias using the dot-probe paradigm, participants will be randomised to an online attentional bias modification training condition, or to a standard attentional bias task (non-treatment) control condition. Both conditions will be delivered online by a web platform. All participants allocated to the non-treatment control group will be offered ABM training once the study is complete. The primary outcome will be the attentional bias indices of vigilance and disengagement and self-reported insomnia symptoms, sleep onset latency and pre-sleep cognitive arousal. Attentional bias and insomnia symptoms will be assessed at baseline (day 1) and post-treatment (2 days after the final training session: day 9). Insomnia symptoms will be again assessed at follow-up (day 16). Secondary outcomes include examining whether sleep associated monitoring and worry are related to a sleep-related attentional bias in insomnia, and whether such reports reduce following ABM. All main analyses will be carried out on completion of follow-up assessments. The trial is supported by the Department of Psychology, Sociology and Politics at Sheffield Hallam University. This study will extend the research base examining the efficacy of attentional bias modification for insomnia. ISRCTN ( ISRCTN11643569 , registered on 5 June 2018)

Inhibitory attentional control in anxiety: Manipulating cognitive load in an antisaccade task

Theorists have proposed that heightened anxiety vulnerability is characterised by reduced attentional control performance and have made the prediction in turn that elevating cognitive load will adversely impact attentional control performance for high anxious individuals to a greater degree than low anxious individuals. Critically however, existing attempts to test this prediction have been limited in their methodology and have presented inconsistent findings. Using a methodology capable of overcoming the limitations of previous research, the present study sought to investigate the effect of manipulating cognitive load on inhibitory attentional control performance of high anxious and low anxious individuals. High and low trait anxious participants completed an antisaccade task, requiring the execution of prosaccades towards, or antisaccades away from, emotionally toned stimuli while eye movements were recorded. Participants completed the antisaccade task under conditions that concurrently imposed a lesser cognitive load, or greater cognitive load. Analysis of participants’ saccade latencies revealed high trait anxious participants demonstrated generally poorer inhibitory attentional control performance as compared to low trait anxious participants. Furthermore, conditions imposing greater cognitive load, as compared to lesser cognitive load, resulted in enhanced inhibitory attentional control performance across participants generally. Crucially however, analyses did not reveal an effect of cognitive load condition on anxiety-linked differences in inhibitory attentional control performance, indicating that elevating cognitive load did not adversely impact attentional control performance for high anxious individuals to a greater degree than low anxious individuals. Hence, the present findings are inconsistent with predictions made by some theorists and are in contrast to the findings of earlier investigations. These findings further highlight the need for research into the relationship between anxiety, attentional control, and cognitive load

The role of performance beliefs in the difference between self-report and behavioural measures of attentional control and their relationship with anxiety

While empirical findings closely link poor attentional control with elevated anxiety, this relationship is more consistently evident and stronger when attentional control is measured through self-report than through behaviour. One possible explanation for these diverging findings is that people lack insight into their attentional control capabilities, and people with elevated anxiety hold more negative beliefs about their level of attentional control, resulting in lower self-reported levels of attentional control. In two studies, participants (N = 78 and N = 207) completed the attentional control scale, the attentional network test (ANT), a questionnaire measuring beliefs about attentional control in the ANT, and a measure of anxiety. In both studies, no significant associations were present between beliefs about attentional control in the ANT and participants' performance on the ANT, suggesting a lack of insight in attentional control capabilities. Both studies further demonstrated that only beliefs about attentional control but not performance in the ANT were related to self-reported attentional control and anxiety. We thus show that evidence supporting the relationship between self-reported attentional control and anxiety is driven by biased beliefs about ability to control attention in people with heightened anxiety, and not by behavioural indices of attentional control.</p

Detecting and correcting partial errors: Evidence for efficient control without conscious access

Appropriate reactions to erroneous actions are essential to keeping behavior adaptive. Erring, however, is not an all-or-none process: electromyographic (EMG) recordings of the responding muscles have revealed that covert incorrect response activations (termed "partial errors") occur on a proportion of overtly correct trials. The occurrence of such "partial errors" shows that incorrect response activations could be corrected online, before turning into overt errors. In the present study, we showed that, unlike overt errors, such "partial errors" are poorly consciously detected by participants, who could report only one third of their partial errors. Two parameters of the partial errors were found to predict detection: the surface of the incorrect EMG burst (larger for detected) and the correction time (between the incorrect and correct EMG onsets; longer for detected). These two parameters provided independent information. The correct(ive) responses associated with detected partial errors were larger than the "pure-correct" ones, and this increase was likely a consequence, rather than a cause, of the detection. The respective impacts of the two parameters predicting detection (incorrect surface and correction time), along with the underlying physiological processes subtending partial-error detection, are discussed