Blue-Enriched Light Enhances Alertness but Impairs Accurate Performance in Evening Chronotypes Driving in the Morning

Attention maintenance is highly demanding and typically leads to vigilance decrement along time on task. Therefore, performance in tasks involving vigilance maintenance for long periods, such as driving, tends to deteriorate over time. Cognitive performance has been demonstrated to fluctuate over 24 h of the day (known as circadian oscillations), thus showing peaks and troughs depending on the time of day (leading to optimal and suboptimal times of day, respectively). Consequently, vigilance decrements are more pronounced along time on task when it is performed at suboptimal times of day. According to research, light exposure (especially blue-enriched white) enhances alertness. Thus, it has been proposed to prevent the vigilance decrement under such adverse circumstances. We aimed to explore the effects of blue-enriched white light (vs. dim light) on the performance of a simulated driving task at a suboptimal time of day. A group of evening-types was tested at 8 am, as this chronotype had previously shown their largest vigilance decrement at that time. In the dim light condition, vigilance decrements were expected on both subjective (as increments in the Karolinska Sleepiness Scale scores) and behavioral measures [as slower reaction times (RTs) in the auditory Psychomotor Vigilance Task, slower RTs to unexpected events during driving, and deteriorated driving accuracy along time on task]. Physiological activation was expected to decrease (as indexed by an increase of the distal-proximal temperature gradient, DPG). Under blue-enriched white light, all these trends should be attenuated. Results from the control dim light condition replicated the vigilance decrement in all measures. Most important, the blue-enriched white light attenuated this decrement, leading to both lower DPG and faster RTs. However, it impaired accuracy of driving performance, and did not have any effect on subjective sleepiness. We conclude that exposure to blue-enriched light provides an effective countermeasure to enhance vigilance performance at suboptimal times of day, according to measures such as RTs. However, it should be considered that alerting effects of light could impair accuracy in precision tasks as keeping a proper car position. The current findings provide ergonomic implications for safety and fatigue related management systems.This work was supported by the Spanish and Andalusian Governments to ÁC (MINECO: PSI2014-58041-P, and Proyectos de Excelencia JJAA: SEJ-3054) and to JM (MINECO: SAF2013- 49132-C2-1-R)

The Vigilance Decrement in Executive Function Is Attenuated When Individual Chronotypes Perform at Their Optimal Time of Day

Time of day modulates our cognitive functions, especially those related to executive control, such as the ability to inhibit inappropriate responses. However, the impact of individual differences in time of day preferences (i.e. morning vs. evening chronotype) had not been considered by most studies. It was also unclear whether the vigilance decrement (impaired performance with time on task) depends on both time of day and chronotype. In this study, morning-type and evening-type participants performed a task measuring vigilance and response inhibition (the Sustained Attention to Response Task, SART) in morning and evening sessions. The results showed that the vigilance decrement in inhibitory performance was accentuated at non-optimal as compared to optimal times of day. In the morning-type group, inhibition performance decreased linearly with time on task only in the evening session, whereas in the morning session it remained more accurate and stable over time. In contrast, inhibition performance in the evening-type group showed a linear vigilance decrement in the morning session, whereas in the evening session the vigilance decrement was attenuated, following a quadratic trend. Our findings imply that the negative effects of time on task in executive control can be prevented by scheduling cognitive tasks at the optimal time of day according to specific circadian profiles of individuals. Therefore, time of day and chronotype influences should be considered in research and clinical studies as well as real-word situations demanding executive control for response inhibition.This work was supported by the Spanish Ministerio de Ciencia e Innovación (Ramón y Cajal programme: RYC-2007-00296 and PLAN NACIONAL de I+D+i: PSI2010-15399) and Junta de Andalucía (SEJ-3054)

Epithelial Proinflammatory Response and Curcumin-Mediated Protection from Staphylococcal Toxic Shock Syndrome Toxin-1

Staphylococcus aureus initiates infections and produces virulence factors, including superantigens (SAgs), at mucosal surfaces. The SAg, Toxic Shock Syndrome Toxin-1 (TSST-1) induces cytokine secretion from epithelial cells, antigen presenting cells (APCs) and T lymphocytes, and causes toxic shock syndrome (TSS). This study investigated the mechanism of TSST-1-induced secretion of proinflammatory cytokines from human vaginal epithelial cells (HVECs) and determined if curcumin, an anti-inflammatory agent, could reduce TSST-1-mediated pathology in a rabbit vaginal model of TSS. TSST-1 caused a significant increase in NF-κB-dependent transcription in HVECs that was associated with increased expression of TNF- α, MIP-3α, IL-6 and IL-8. Curcumin, an antagonist of NF-κB-dependent transcription, inhibited IL-8 production from ex vivo porcine vaginal explants at nontoxic doses. In a rabbit model of TSS, co-administration of curcumin with TSST-1 intravaginally reduced lethality by 60% relative to 100% lethality in rabbits receiving TSST-1 alone. In addition, TNF-α was undetectable from serum or vaginal tissue of curcumin treated rabbits that survived. These data suggest that the inflammatory response induced at the mucosal surface by TSST-1 is NF-κB dependent. In addition, the ability of curcumin to prevent TSS in vivo by co-administration with TSST-1 intravaginally suggests that the vaginal mucosal proinflammatory response to TSST-1 is important in the progression of mTSS

Cross-translational studies in human and Drosophila identify markers of sleep loss

Inadequate sleep has become endemic, which imposes a substantial burden for public health and safety. At present, there are no objective tests to determine if an individual has gone without sleep for an extended period of time. Here we describe a novel approach that takes advantage of the evolutionary conservation of sleep to identify markers of sleep loss. To begin, we demonstrate that IL-6 is increased in rats following chronic total sleep deprivation and in humans following 30 h of waking. Discovery experiments were then conducted on saliva taken from sleep-deprived human subjects to identify candidate markers. Given the relationship between sleep and immunity, we used Human Inflammation Low Density Arrays to screen saliva for novel markers of sleep deprivation. Integrin αM (ITGAM) and Anaxin A3 (AnxA3) were significantly elevated following 30 h of sleep loss. To confirm these results, we used QPCR to evaluate ITGAM and AnxA3 in independent samples collected after 24 h of waking; both transcripts were increased. The behavior of these markers was then evaluated further using the power of Drosophila genetics as a cost-effective means to determine whether the marker is associated with vulnerability to sleep loss or other confounding factors (e.g., stress). Transcript profiling in flies indicated that the Drosophila homologues of ITGAM were not predictive of sleep loss. Thus, we examined transcript levels of additional members of the integrin family in flies. Only transcript levels of scab, the Drosophila homologue of Integrin α5 (ITGA5), were associated with vulnerability to extended waking. Since ITGA5 was not included on the Low Density Array, we returned to human samples and found that ITGA5 transcript levels were increased following sleep deprivation. These cross-translational data indicate that fly and human discovery experiments are mutually reinforcing and can be used interchangeably to identify candidate biomarkers of sleep loss

Elite Suppressors Harbor Low Levels of Integrated HIV DNA and High Levels of 2-LTR Circular HIV DNA Compared to HIV+ Patients On and Off HAART

Elite suppressors (ES) are a rare population of HIV-infected individuals that are capable of naturally controlling the infection without the use of highly active anti-retroviral therapy (HAART). Patients on HAART often achieve viral control to similar (undetectable) levels. Accurate and sensitive methods to measure viral burden are needed to elucidate important differences between these two patient populations in order to better understand their mechanisms of control. Viral burden quantification in ES patients has been limited to measurements of total DNA in PBMC, and estimates of Infectious Units per Million cells (IUPM). There appears to be no significant difference in the level of total HIV DNA between cells from ES patients and patients on HAART. However, recovering infectious virus from ES patient samples is much more difficult, suggesting their reservoir size should be much smaller than that in patients on HAART. Here we find that there is a significant difference in the level of integrated HIV DNA in ES patients compared to patients on HAART, providing an explanation for the previous results. When comparing the level of total to integrated HIV DNA in these samples we find ES patients have large excesses of unintegrated HIV DNA. To determine the composition of unintegrated HIV DNA in these samples, we measured circular 2-LTR HIV DNA forms and found ES patients frequently have high levels of 2-LTR circles in PBMC. We further show that these high levels of 2-LTR circles are not the result of inefficient integration in ES cells, since HIV integrates with similar efficiency in ES and normal donor cells. Our findings suggest that measuring integration provides a better surrogate of viral burden than total HIV DNA in ES patients. Moreover, they add significantly to our understanding of the mechanisms that allow viral control and reservoir maintenance in this unique patient population

Gender and release from imprisonment: Convict licensing systems in mid to late 19th century England

This paper draws on the research undertaken into the lives and prison experiences of around 650 male and female convicts who were released on licence (an early form of parole) from sentences of long term imprisonment (three years to life) in England in the mid- to late-nineteenth century. Our project confirmed the patterns of offending seen in other studies of female and male offending, namely, that women were committed to periods of long-term imprisonment overwhelmingly for crimes of larceny and sometimes low-level violence (or their criminal backgrounds indicated this type of low-level disorderly behaviour) and only in the minority for crimes of serious interpersonal violence. Similarly, the majority of men were also committed to the convict system for larceny. Yet how male and female offenders were treated by the prison licensing system did differ significantly. The vast majority of all prisoners, male and female, were released early on licence from their prison terms, even those who had committed very serious offences. All licences had several conditions in them and licence-holders were free so long as they met these conditions. Any breach of the above conditions meant that the individual would be returned to prison to serve out the remainder of their sentence.However, a proportion of female offenders were released slightly earlier than their male counterparts, though not directly into the community but on a conditional licence to Female Refuges. Out of the 288 women researched in our project, 200 of them were released in this manner; under further confinement in a refuge. Women stayed in such refuges for on average between six and nine months, before their final release was then approved by the Directors of the Convict Prisons

"Monstrous and indefensible"? Newspaper accounts of sexual assaults on children in nineteenth-century England and Wales

This material has been published in Women's Criminality in Europe, 1600–1914 edited by Edited by Manon van der Heijden, Marion Pluskota, Sanne Muurling, https://doi.org/10.1017/9781108774543. This version is free to view and download for private research and study only. Not for re-distribution or re-use. © 2020 Cambridge University Press.Popular crime reportage of sexual violence has a long history in England. Despite the fact that from the 1830s onwards newspapers and periodicals – and sometimes even law reports – were increasingly liable to skim over the reporting of sexual offences as ‘unfit for publication’, this does not mean that such reportage vanished entirely. Instead, certain linguistic codes and euphemisms were invoked to maintain a respectable discourse. Given the serious problems with gaps in the surviving archival record for modern criminal justice, newspapers remain an essential tool for understanding the history of sexual violence in nineteenth century England and Wales. Using keyword searches in digitized newspaper databases such as the British Newspaper Archive and Welsh Newspapers Database, this chapter examines the continuities and changes in the reporting of sexual violence against children between 1800 and 1900, and explores what these euphemisms and elisions reveal about attitudes to gender and crime in nineteenth-century England and Wales.Peer reviewe

Toxin-Based Therapeutic Approaches

Protein toxins confer a defense against predation/grazing or a superior pathogenic competence upon the producing organism. Such toxins have been perfected through evolution in poisonous animals/plants and pathogenic bacteria. Over the past five decades, a lot of effort has been invested in studying their mechanism of action, the way they contribute to pathogenicity and in the development of antidotes that neutralize their action. In parallel, many research groups turned to explore the pharmaceutical potential of such toxins when they are used to efficiently impair essential cellular processes and/or damage the integrity of their target cells. The following review summarizes major advances in the field of toxin based therapeutics and offers a comprehensive description of the mode of action of each applied toxin

Subsets of leg proprioceptors influence leg kinematics but not interleg coordination in Drosophila melanogaster walking

Legged locomotion in terrestrial animals is often essential for mating and survival, and locomotor behavior must be robust and adaptable to be successful. This adaptability is largely provided by proprioceptors monitoring positions and movements of body parts and providing feedback to other components of locomotor networks. In insects, proprioceptive chordotonal organs span joints and encode parameters of relative movement between segments. Previous studies have used whole-organ ablation, reduced preparations or broad physiological manipulations to impair the function of the femoral chordotonal organ ( fCO), which monitors the femur-tibia joint, and have demonstrated its contribution to interleg coordination and walking behavior. The fCO in Drosophila melanogaster comprises groups of neurons that differ in their morphology and encoding properties (club, hook, claw); sub-population-level manipulations of fCO function have not been methodologically accessible. Here, we took advantage of the genetic toolkit available in D. melanogaster to identify sub-populations of fCO neurons and used transient optogenetic inhibition to investigate their roles in locomotor coordination. Our findings demonstrate that optogenetic inhibition of a subset of club and hook neurons replicates the effects of inhibiting the whole fCO; when inhibited alone, however, the individual subset types did not strongly affect spatial aspects of single-leg kinematics. Moreover, fCO subsets seem to play only a minor role in interleg temporal coordination. Thus, the fCO contains functionally distinct subgroups, and this functional classification may differ from those based on anatomy and encoding properties; this should be investigated in future studies of proprioceptors and their involvement in locomotor networks