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"Mainwaring, Benjamin"
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Sleep deprivation suppresses aggression in Drosophila
by
Mainwaring, Benjamin
,
Yue, Zhifeng
,
Sehgal, Amita
in
Aggression
,
Aggressiveness
,
Animal reproduction
2015
Sleep disturbances negatively impact numerous functions and have been linked to aggression and violence. However, a clear effect of sleep deprivation on aggressive behaviors remains unclear. We find that acute sleep deprivation profoundly suppresses aggressive behaviors in the fruit fly, while other social behaviors are unaffected. This suppression is recovered following post-deprivation sleep rebound, and occurs regardless of the approach to achieve sleep loss. Genetic and pharmacologic approaches suggest octopamine signaling transmits changes in aggression upon sleep deprivation, and reduced aggression places sleep-deprived flies at a competitive disadvantage for obtaining a reproductive partner. These findings demonstrate an interaction between two phylogenetically conserved behaviors, and suggest that previous sleep experiences strongly modulate aggression with consequences for reproductive fitness. We know from personal experience that sleepless nights can change the way we behave, sometimes making us more irritable and less adept at social interactions. However, it can be difficult to establish cause and effect: does a lack of sleep lead to altered behavior, or vice versa? The fruit fly, Drosophila melanogaster, is a popular model organism for studying questions like this because its neural circuitry is relatively well understood. To explore the effects of lack of sleep on social behaviors, and in particular on aggression, Kayser et al. disrupted the sleep of male fruit flies using various techniques, such as shaking them during the night, and then observed how they behaved. The experiments revealed that sleep-deprived flies were less aggressive than flies with undisturbed sleep. Furthermore, sleep-deprived male flies were less successful at mating with female flies when they were in direct competition with a rested male fly. Normal behavior was restored when the sleep-deprived flies were allowed to recover lost sleep for as little as six hours before the next aggression assay. To investigate how sleep loss leads to a decrease in aggressive behavior, Kayser et al. used different drugs to treat the sleep-deprived flies. A drug activating the equivalent of the noradrenergic system in flies helped them to recover normal fighting behaviors despite a lack of sleep. In mammals, noradrenaline is a chemical that affects heart rate, sleep-wake patterns, aggression and a number of other phenomena. Although aggressive behavior is often perceived as negative in humans, it can be important for survival. Human brains and behaviors are obviously more complex than those of Drosophila. However, learning more about the neuronal circuits that control sleep and social behavior in fruit flies may lead to an improved understanding of these phenomena in humans and, in the longer term, the development of drugs that can influence or modulate aggressive behaviors.
Journal Article
Identification of octopaminergic neurons that modulate sleep suppression by male sex drive
by
Kenny, Alexandra R
,
Machado, Daniel R
,
Mainwaring, Benjamin
in
Animal
,
Animal reproduction
,
Animals
2017
Molecular and circuit mechanisms for balancing competing drives are not well understood. While circadian and homeostatic mechanisms generally ensure sufficient sleep at night, other pressing needs can overcome sleep drive. Here, we demonstrate that the balance between sleep and sex drives determines whether male flies sleep or court, and identify a subset of octopaminergic neurons (MS1) that regulate sleep specifically in males. When MS1 neurons are activated, isolated males sleep less, and when MS1 neurons are silenced, the normal male sleep suppression in female presence is attenuated and mating behavior is impaired. MS1 neurons do not express the sexually dimorphic FRUITLESS (FRU) transcription factor, but form male-specific contacts with FRU-expressing neurons; calcium imaging experiments reveal bidirectional functional connectivity between MS1 and FRU neurons. We propose octopaminergic MS1 neurons interact with the FRU network to mediate sleep suppression by male sex drive. Most people sleep for around seven or eight hours at night, but if there is something important or interesting to do – for example, taking care of a baby, finishing a task before a deadline, or watching an entertaining movie – we may stay up late. In other words, sleep is regulated by motivational states. The drive to sleep accumulates during wakefulness and decreases during sleep. Thus sleep and other motivational drives compete to decide whether we sleep or engage in other important or interesting activities. The idea that sleep and sex drives might compete with each other is intuitive, but had not been studied experimentally. Machado, Afonso et al. have now studied how this competition determines the behavior of male fruit flies. The presence of a female fly usually keeps a male fly awake at night. However, a male that has recently mated several times (and has low sex drive) or one that was sleep deprived (and has high sleep drive) ignores the female and goes to sleep. Further investigation revealed a small number of previously unknown neurons (termed MS1) are required for sexual arousal to overcome the male’s desire to sleep. These neurons do not belong to a circuit that is known to be important for male sexual behavior, but they do communicate with that circuit using a neurotransmitter called octopamine. This communication suppresses sleep and promotes courtship. The next steps will be to identify the specific neurons that communicate directly with the MS1 neurons and to determine whether MS1 neurons have a direct role in regulating sex drive. Investigating these details will help us to understand more generally how competing drives influence behavioral choices.
Journal Article
Intrinsic maturation of sleep output neurons regulates sleep ontogeny in Drosophila
2021
The maturation of sleep behavior across a lifespan (sleep ontogeny) is an evolutionarily conserved phenomenon. Mammalian studies have shown that in addition to increased sleep duration, early life sleep exhibits stark differences compared to mature sleep with regard to the amount of time spent in certain sleep states. How intrinsic maturation of sleep output circuits contributes to sleep ontogeny is poorly understood. The fruit fly Drosophila melanogaster exhibits multifaceted changes to sleep from juvenile to mature adulthood. Here, we use a non-invasive probabilistic approach to investigate changes in sleep architecture in juvenile and mature flies. Increased sleep in juvenile flies is driven primarily by a decreased probability of transitioning to wake, and characterized by more time in deeper sleep states. Functional manipulations of sleep-promoting neurons in the dFB suggest these neurons differentially regulate sleep in juvenile and mature flies. Transcriptomic analysis of dFB neurons at different ages and a subsequent RNAi screen implicate genes involved in distinct molecular processes in sleep control of juvenile and mature flies. These results reveal that dynamic transcriptional states of sleep output neurons contribute to changes in sleep across the lifespan. Competing Interest Statement The authors have declared no competing interest.
Why Democracy Survives Presidential Encroachments: Argentina Since 1983
by
García Holgado, Benjamín
,
Mainwaring, Scott
in
Democracy
,
Democratic Breakdown
,
Democratic Erosion
2023
This article presents a novel argument about what enables democracies to survive when executives attempt to weaken institutional constraints. We argue that democracies erode because (1) an illiberal executive attempts to undermine democracy and (2) this executive commands a majority in the national legislature. Democracies survive if the executive is not deeply illiberal or if the opposition controls a majority of the national legislature. The empirical section presents data about executive illiberalism and the balance of power in the national legislature for thirteen Latin American presidents. We test our argument in four negative cases (episodes) in Argentina since 1983. We use primary sources including 125 original interviews to explain how two presidents who attempted to centralize power fell short of eroding democracy
Journal Article
Racial and Ethnic Disparities Among Participants in US-Based Phase 3 Randomized Cancer Clinical Trials
by
David Fuller, C
,
Jagsi, Reshma
,
Smith, Benjamin D
in
Brief Communication
,
Cancer
,
Clinical trials
2020
Although improving representation of racial and ethnic groups in United States clinical trials has been a focus of federal initiatives for nearly 3 decades, the status of racial and ethnic minority enrollment on cancer trials is largely unknown. We used a broad collection of phase 3 cancer trials derived from ClinicalTrials.gov to evaluate racial and ethnic enrollment among US cancer trials. The difference in incidence by race and ethnicity was the median absolute difference between trial and corresponding Surveillance, Epidemiology, and End Results data. All statistical tests were 2-sided. Using a cohort of 168 eligible trials, median difference in incidence by race and ethnicity was +6.8% for Whites (interquartile range [IQR] = +1.8% to +10.1%; P < .001 by Wilcoxon signed-rank test comparing median difference in incidence by race and ethnicity to a value of 0), -2.6% for Blacks (IQR = -5.1% to +1.2%; P = .004), -4.7% for Hispanics (IQR = -7.5% to -0.3%; P < .001), and -4.7% for Asians (IQR = -5.7% to -3.3%; P < .001). These data demonstrate overrepresentation of Whites, with continued underrepresentation of racial and ethnic minority subgroups.
Journal Article
Why Democracy Survives Presidential Encroachments: Argentina since 1983
2023
This article presents a novel argument about what enables democracies to survive when executives attempt to weaken institutional constraints. We argue that democracies erode because (1) an illiberal executive attempts to undermine democracy and (2) this executive commands a majority in the national legislature. Democracies survive if the executive is not deeply illiberal or if the opposition controls a majority of the national legislature. The empirical section presents data about executive illiberalism and the balance of power in the national legislature for thirteen Latin American presidents. We test our argument in four negative cases (episodes) in Argentina since 1983. We use primary sources including 125 original interviews to explain how two presidents who attempted to centralize power fell short of eroding democracy.
Journal Article
A Pilot Survey Study of Anterior Cruciate Ligament Injuries in Female University Athletes
by
Davis, Holly
,
Tooth, Georgia
,
McDonnell, Stephen
in
Arthritis
,
Connective tissue
,
Female athletes
2024
Introduction Female sports players are at increased risk of soft tissue knee injuries (STKIs) compared to their male counterparts. Injury prevention programs effectively reduce the incidence of anterior cruciate ligament (ACL) knee injuries. This pilot study, therefore, aimed to examine the prevalence, type, and management of STKIs within a population of female university sports players at the University of Cambridge. Additionally, this study aimed to examine the perceived risk of ACL injuries and knowledge of long-term complications, alongside participation and attitudes towards injury prevention programs. Methodology A survey was distributed to women's university sports teams at the University of Cambridge. Information was gathered on participant demographics and sporting history. Relevant medical history, including joint laxity, connective tissue disorders, and previous knee injuries, was also collected. Participant involvement in and attitudes towards injury prevention programs were evaluated. Results Data from eighty-five participants (n = 85) were collected, all of whom were female. Forty-two percent of participants had sustained a previous knee injury, of which the majority (44%) were ACL injuries. In the ACL-injured group, 38% (n=6) had undergone ACL reconstructive surgery, 44% (n=7) had received only physiotherapy, and 19% (n=3) had received no form of treatment. Only 44% of these participants sustaining an ACL injury reported a return to the same level of post-injury sport. Seventy-two percent of respondents felt they were at increased risk of ACL injury compared to males. Most participants (87%) did not follow an injury prevention program, but 95% expressed a willingness to enroll in one. Conclusions This pilot study indicates that most knee injuries in female university athletes in this cohort at Cambridge University are ACL injuries, with a considerable number being managed conservatively. The low rate of return to pre-injury sporting levels highlights the significant impact of ACL injuries on athletic careers. This study demonstrates results similar to previous studies on the broader population. However, due to the pilot nature of the research and limited statistical power, the results should be interpreted with caution before transposing to the wider population. Further investigation is required into why many of these ACL-injured female athletes were managed conservatively and whether this finding is mirrored in their male counterparts. Despite recognizing their higher risk than males, participants displayed low engagement in injury prevention programs, indicating a gap between awareness and action. The willingness to participate in prevention programs suggests the potential for improved engagement through targeted interventions. Future research should focus on identifying and addressing specific barriers to participation in injury prevention programs and exploring the reasons behind the preference for conservative management of ACL injuries. Additionally, expanding the sample size and including a more diverse athletic population would enhance the generalizability of the findings.
Journal Article
Measuring Compliance and Perceptions of an Anterior Cruciate Ligament (ACL) Injury Prevention Programme: Insights From Female University Athletes
by
Weeks, Georgia
,
Tooth, Georgia
,
McDonnell, Stephen
in
Compliance
,
Delphi method
,
Demographics
2025
Objectives This pilot study aimed to measure the compliance of female university athletes with a three-month \"Prevent Injury, Enhance Performance\" (PEP) warm-up, a validated anterior cruciate ligament (ACL) injury prevention programme, and to gather athletes' perceptions, including barriers to participation in the prevention programme. Methods Participants were recruited from \"The Ospreys\" (Cambridge University's elite sportswomen's club) and considered eligible if they were English-speaking female athletes competing in a high-risk sport, aged 18 to 30. Participants completed a questionnaire pre- and post-completion of three months of the PEP prevention programme. Gathered information included participant demographics, sporting history, education and awareness of ACL injury risk factors, prevention programme perceptions, and compliance. Results A total of 45 participants were recruited, with a mean age of 21.69 years (± 2.51). The most common self-perceived risk of ACL injury among participants was 3 (out of 10) on a Likert scale. A total of 62% (n = 28) claimed awareness of ACL injury risk factors. The mean compliance with the prevention programme was 1.46 times per week. The time-consuming nature of the prevention programme was the most reported barrier to compliance (94%, n = 42). Conclusion Adherence to a three-month ACL injury prevention programme was limited, and the programme's time-intensive nature was perceived as the most common obstacle to completion. Few athletes were aware of the risk factors and prevention methods for ACL injuries. To prevent the severe long-term impacts of ACL injuries, it is crucial to investigate further the barriers to adopting injury prevention programmes. More time-efficient injury prevention programmes could be developed to improve athlete engagement.
Journal Article
Is the NICE process flawed?
by
Bridgewater, John
,
Cassidy, Jim
,
Wasan, Harpreet
in
Antineoplastic Agents - therapeutic use
,
Appraisals
,
Cancer therapies
2002
Journal Article