Polyamine elevation and nitrogen stress are toxic hallmarks of chronic sleep loss in Drosophila melanogaster

AbstractChronic sleep loss profoundly impacts health in ways coupled to metabolism; however, much existing literature links sleep and metabolism only on acute timescales. To explore the impact of chronically reduced sleep, we conducted unbiased metabolomics on heads from three Drosophila short-sleeping mutants. Common features included elevated ornithine and polyamines; and lipid, acyl-carnitine, and TCA cycle changes suggesting mitochondrial dysfunction. Biochemical studies of overall, circulating, and excreted nitrogen in sleep mutants demonstrate a specific defect in eliminating nitrogen, suggesting that elevated polyamines may function as a nitrogen sink. Both supplementing polyamines and inhibiting their synthesis with RNAi regulated sleep in control flies. Finally, both polyamine-supplemented food and high-protein feeding were highly toxic to sleep mutants, suggesting their altered nitrogen metabolism is maladaptive. Together, our results suggest polyamine accumulation specifically, and nitrogen stress in general, as potential mechanisms linking chronic sleep loss to adverse health outcomes.

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Residual, differential neurobehavioral deficits linger after multiple recovery nights following chronic sleep restriction or acute total sleep deprivation

SLEEP ◽

10.1093/sleep/zsaa224 ◽

2020 ◽

Author(s):

Erika M Yamazaki ◽

Caroline A Antler ◽

Charlotte R Lasek ◽

Namni Goel

Keyword(s):

Sleep Deprivation ◽

Response Speed ◽

Sleep Loss ◽

Sleep Restriction ◽

Total Sleep Deprivation ◽

Psychomotor Vigilance Test ◽

Recovery Sleep ◽

Time In Bed ◽

Neurobehavioral Deficits ◽

Chronic Sleep

Abstract Study Objectives The amount of recovery sleep needed to fully restore well-established neurobehavioral deficits from sleep loss remains unknown, as does whether the recovery pattern differs across measures after total sleep deprivation (TSD) and chronic sleep restriction (SR). Methods In total, 83 adults received two baseline nights (10–12-hour time in bed [TIB]) followed by five 4-hour TIB SR nights or 36-hour TSD and four recovery nights (R1–R4; 12-hour TIB). Neurobehavioral tests were completed every 2 hours during wakefulness and a Maintenance of Wakefulness Test measured physiological sleepiness. Polysomnography was collected on B2, R1, and R4 nights. Results TSD and SR produced significant deficits in cognitive performance, increases in self-reported sleepiness and fatigue, decreases in vigor, and increases in physiological sleepiness. Neurobehavioral recovery from SR occurred after R1 and was maintained for all measures except Psychomotor Vigilance Test (PVT) lapses and response speed, which failed to completely recover. Neurobehavioral recovery from TSD occurred after R1 and was maintained for all cognitive and self-reported measures, except for vigor. After TSD and SR, R1 recovery sleep was longer and of higher efficiency and better quality than R4 recovery sleep. Conclusions PVT impairments from SR failed to reverse completely; by contrast, vigor did not recover after TSD; all other deficits were reversed after sleep loss. These results suggest that TSD and SR induce sustained, differential biological, physiological, and/or neural changes, which remarkably are not reversed with chronic, long-duration recovery sleep. Our findings have critical implications for the population at large and for military and health professionals.

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Effects of sodium fluoride and Ocimum sanctum extract on the lifespan and climbing ability of Drosophila melanogaster

The Journal of Basic and Applied Zoology ◽

10.1186/s41936-021-00229-8 ◽

2021 ◽

Vol 82 (1) ◽

Author(s):

Sidra Perveen ◽

Shalu Kumari ◽

Himali Raj ◽

Shahla Yasmin

Keyword(s):

Oxidative Stress ◽

Lipid Peroxidation ◽

Drosophila Melanogaster ◽

Sodium Fluoride ◽

Ocimum Sanctum ◽

Activity Assay ◽

Lipid Peroxidation Assay ◽

Climbing Ability ◽

The Impact ◽

Sublethal Concentrations

Abstract Background Fluoride may induce oxidative stress and apoptosis. It may also lead to neurobehavioural defects including neuromuscular damage. The present study aimed to explore the effects of sub lethal concentrations of sodium fluoride (NaF) on the lifespan and climbing ability of Drosophila melanogaster. In total, 0.6 mg/L and 0.8 mg/L of NaF were selected as sublethal concentrations of NaF for the study. Lifespan was measured and climbing activity assay was performed. Results The study showed significant decrease in lifespan of flies treated with fluoride. With increasing age, significant reduction in climbing activity was observed in flies treated with sodium fluoride as compared to normal (control) flies. Flies treated with tulsi (Ocimum sanctum) and NaF showed increase in lifespan and climbing activity as compared to those treated with NaF only. Lipid peroxidation assay showed significant increase in malondialdehyde (MDA) values in the flies treated with NaF as compared to control. The MDA values decreased significantly in flies treated with tulsi mixed with NaF. Conclusions The results indicate that exposure to sub lethal concentration of NaF may cause oxidative stress and affect the lifespan and climbing activity of D. melanogaster. Tulsi extract may help in reducing the impact of oxidative stress and toxicity caused by NaF.

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The impact of sleep loss on performance monitoring and error-monitoring: A systematic review and meta-analysis

Sleep Medicine Reviews ◽

10.1016/j.smrv.2021.101490 ◽

2021 ◽

pp. 101490

Author(s):

Johanna M. Boardman ◽

Kate Porcheret ◽

Jacob W. Clark ◽

Thomas Andrillon ◽

Anna W.T. Cai ◽

...

Keyword(s):

Systematic Review ◽

Performance Monitoring ◽

Meta Analysis ◽

Sleep Loss ◽

Error Monitoring ◽

The Impact

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Understanding the influence of socioeconomic status on the association between combinations of lifestyle factors and adverse health outcomes: a systematic review protocol

BMJ Open ◽

10.1136/bmjopen-2020-042212 ◽

2021 ◽

Vol 11 (5) ◽

pp. e042212

Author(s):

Hamish Foster ◽

Peter Polz ◽

Frances Mair ◽

Jason Gill ◽

Catherine A O'Donnell

Keyword(s):

Systematic Review ◽

Socioeconomic Status ◽

Health Outcomes ◽

Meta Analysis ◽

Lifestyle Factors ◽

Lifestyle Factor ◽

Unhealthy Lifestyle ◽

Adverse Health ◽

Adverse Health Outcomes ◽

The Impact

IntroductionCombinations of unhealthy lifestyle factors are strongly associated with mortality, cardiovascular disease (CVD) and cancer. It is unclear how socioeconomic status (SES) affects those associations. Lower SES groups may be disproportionately vulnerable to the effects of unhealthy lifestyle factors compared with higher SES groups via interactions with other factors associated with low SES (eg, stress) or via accelerated biological ageing. This systematic review aims to synthesise studies that examine how SES moderates the association between lifestyle factor combinations and adverse health outcomes. Greater understanding of how lifestyle risk varies across socioeconomic spectra could reduce adverse health by (1) identifying novel high-risk groups or targets for future interventions and (2) informing research, policy and interventions that aim to support healthy lifestyles in socioeconomically deprived communities.Methods and analysisThree databases will be searched (PubMed, EMBASE, CINAHL) from inception to March 2020. Reference lists, citations and grey literature will also be searched. Inclusion criteria are: (1) prospective cohort studies; (2) investigations of two key exposures: (a) lifestyle factor combinations of at least three lifestyle factors (eg, smoking, physical activity and diet) and (b) SES (eg, income, education or poverty index); (3) an assessment of the impact of SES on the association between combinations of unhealthy lifestyle factors and health outcomes; (4) at least one outcome from—mortality (all cause, CVD and cancer), CVD or cancer incidence. Two independent reviewers will screen titles, abstracts and full texts of included studies. Data extraction will focus on cohort characteristics, exposures, direction and magnitude of SES effects, methods and quality (via Newcastle-Ottawa Scale). If appropriate, a meta-analysis, pooling the effects of SES, will be performed. Alternatively, a synthesis without meta-analysis will be conducted.Ethics and disseminationEthical approval is not required. Results will be disseminated via peer-reviewed publication, professional networks, social media and conference presentations.PROSPERO registration numberCRD42020172588.

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Sleep Deprivation and Sleep-Onset Insomnia are Associated with Blunted Physiological Reactivity to Stressors

Military Medicine ◽

10.1093/milmed/usaa464 ◽

2021 ◽

Vol 186 (Supplement_1) ◽

pp. 246-252

Author(s):

Devon A Hansen ◽

Brieann C Satterfield ◽

Matthew E Layton ◽

Hans P A Van Dongen

Keyword(s):

Sleep Deprivation ◽

Laboratory Study ◽

Salivary Cortisol ◽

Sleep Onset ◽

Deprivation Condition ◽

Increased Risk ◽

Significant Difference ◽

Sleep Deficiency ◽

The Impact ◽

Chronic Sleep

ABSTRACT Introduction Military operations often involve intense exposure to stressors combined with acute sleep deprivation, while military personnel also experience high prevalence of chronic sleep deficiency from insomnia and other sleep disorders. However, the impact of acute and chronic sleep deficiency on physiologic stressor responses is poorly understood. In a controlled laboratory study with normal sleepers and individuals with chronic sleep-onset insomnia, we measured responses to an acute stressor administered in a sleep deprivation condition or a control condition. Methods Twenty-two adults (aged 22-40 years; 16 females)—11 healthy normal sleepers and 11 individuals with sleep-onset insomnia—completed a 5-day (4-night) in-laboratory study. After an adaptation day and a baseline day, subjects were assigned to a 38-hour total sleep deprivation (TSD) condition or a control condition; the study ended with a recovery day. At 8:00 PM after 36 hours awake in the sleep deprivation condition or 12 hours awake in the control condition, subjects underwent a Maastricht Acute Stress Test (MAST). Salivary cortisol was measured immediately before the MAST at 8:00 PM, every 15 minutes after the MAST from 8:15 PM until 9:15 PM, and 30 minutes later at 9:45 PM. Baseline salivary cortisol was collected in the evening of the baseline day. Additionally, before and immediately upon completion of the MAST, self-report ratings of affect and pain were collected. Results The MAST elicited a stressor response in both normal sleepers and individuals with sleep-onset insomnia, regardless of the condition, as evidenced by increases in negative affect and pain ratings. Relative to baseline, cortisol levels increased immediately following the MAST, peaked 30 minutes later, and then gradually returned to pre-MAST levels. At the cortisol peak, there was a significant difference across groups and conditions, reflecting a pronounced blunting of the cortisol response in the normal sleepers in the TSD condition and the sleep-onset insomnia group in both the TSD and control conditions. Conclusions Blunted stressor reactivity as a result of sleep deficiency, whether acute or chronic, may reflect reduced resiliency attributable to allostatic load and may put warfighters at increased risk in high-stakes, rapid response scenarios.

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Preexposure to Isavuconazole Increases the Virulence of Mucorales but Not Aspergillus fumigatus in a Drosophila melanogaster Infection Model

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.01896-18 ◽

2018 ◽

Vol 63 (2) ◽

pp. e01896-18 ◽

Cited By ~ 2

Author(s):

Sebastian Wurster ◽

Russell E. Lewis ◽

Nathaniel D. Albert ◽

Dimitrios P. Kontoyiannis

Keyword(s):

Drosophila Melanogaster ◽

Aspergillus Fumigatus ◽

Clinical Isolates ◽

Infection Model ◽

Content Type ◽

The Impact

ABSTRACT Breakthrough mucormycosis in patients receiving isavuconazole prophylaxis or therapy has been reported. We compared the impact of isavuconazole and voriconazole exposure on the virulence of clinical isolates of Aspergillus fumigatus and different Mucorales species in a Drosophila melanogaster infection model. In contrast to A. fumigatus, a hypervirulent phenotype was found in all tested Mucorales upon preexposure to either voriconazole or isavuconazole. These findings may contribute to the explanation of breakthrough mucormycosis in isavuconazole-treated patients.

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Viral route of infection determines the effect of Drosophila melanogaster gut bacteria on host resistance and tolerance to disease

10.1101/2021.02.18.431843 ◽

2021 ◽

Author(s):

Miguel Landum ◽

Marta Salvado Silva ◽

Nelson Martins ◽

Luís Teixeira

Keyword(s):

Drosophila Melanogaster ◽

Viral Infections ◽

Systemic Infection ◽

Lactobacillus Brevis ◽

Gut Bacteria ◽

Associated Bacteria ◽

Germ Free ◽

Viral Loads ◽

Route Of Infection ◽

The Impact

AbstractThe microbial community interacting with a host can modulate the outcome of pathogenic infections. For instance, Wolbachia, one of the most prevalent invertebrate endosymbionts, strongly increases resistance of Drosophila melanogaster and other insect hosts, to many RNA viruses. D. melanogaster is also in continuous association with gut bacteria, whose role in antiviral immunity is poorly characterized. Here we asked how gut-colonizing bacteria impact viral titres and host survival, and how these interact with route of infection or Wolbachia presence. We compared germ-free flies and flies associated with two gut bacteria species recently isolated from wild flies (Acetobacter thailandicus and Lactobacillus brevis). We found that Wolbachia-conferred protection to both DCV or FHV is not affected by the presence or absence of these gut bacteria. Flies carrying A. thailandicus have lower DCV loads than germ-free flies, upon systemic infection, but reduced survival, indicating that these bacteria increase resistance to virus and decrease disease tolerance. Association with L. brevis, alone or in combination with A. thailandicus, did not lead to changes in survival to systemic infection. In contrast to the effect on systemic infection, we did not observe an impact of these bacteria on survival or viral loads after oral infection. Overall, the impact of gut-associated bacteria in resistance and tolerance to viruses was mild, when compared with Wolbachia. These results indicate that the effect of gut-associated bacteria to different viral infections, and different routes of infection, is complex and understanding it requires a detailed characterization of several parameters of infection.

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Berber Factor in North Africa: Common Features and Local Peculiarities

Journal of International Analytics ◽

10.46272/2587-8476-2017-0-1-42-51 ◽

2017 ◽

pp. 42-51

Author(s):

Yu. Zinin

Keyword(s):

North Africa ◽

Arab Spring ◽

Local Conditions ◽

Common Features ◽

Political Processes ◽

The North ◽

The Arab Spring ◽

The Impact

The article considers a place and influence of Berber-speaking communities in each of five countries of the North Africa: Algeria, Morocco, Libya, Mauritania and Tunis.After gaining the independence, demands are growing in all these states to recognize cultural, regional, and sometimes political peculiarities of Berbers.The situation in every country is different due to local conditions and background of interactions of Amazigs (self-designation of Berber) with the Arab speaking majority, as well as their participation in political processes.The author investigates and discuss the impact of the Arab Spring on the rise of self-consciousness, solidarity and consolidation of Amazig minority. It is Berber, often European educated elite which usually expresses and propagates such conceptions and trends.

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Combining metabolomics and experimental evolution reveals key mechanisms underlying longevity differences in laboratory evolved Drosophila melanogaster populations

10.1101/2021.10.16.464668 ◽

2021 ◽

Author(s):

Mark Phillips ◽

Kenneth R. Arnold ◽

Zer Vue ◽

Heather Beasley ◽

Edgar Garza Lopez ◽

...

Keyword(s):

Drosophila Melanogaster ◽

Carbohydrate Metabolism ◽

Experimental Evolution ◽

Statistical Power ◽

Accelerated Aging ◽

Experimental System ◽

Tca Cycle ◽

Dna And Rna ◽

Metabolomic Data ◽

Genetic Mechanisms

Experimental evolution with Drosophila melanogaster has been used extensively for decades to study aging and longevity. In recent years, the addition of DNA and RNA sequencing to this framework has allowed researchers to leverage the statistical power inherent to experimental evolution study the genetic basis of longevity itself. Here we incorporated metabolomic data into to this framework to generate even deeper insights into the physiological and genetic mechanisms underlying longevity differences in three groups of experimentally evolved D. melanogaster populations with different aging and longevity patterns. Our metabolomic analysis found that aging alters mitochondrial metabolism through increased consumption of NAD+ and increased usage of the TCA cycle. Combining our genomic and metabolomic data produced a list of biologically relevant candidate genes. Among these candidates, we found significant enrichment for genes and pathways associated with neurological development and function, and carbohydrate metabolism. While we do not explicitly find enrichment for aging canonical genes, neurological dysregulation and carbohydrate metabolism are both known to be associated with accelerated aging and reduced longevity. Taken together, our results in total provide very plausible genetic mechanisms for what might be driving longevity differences in this experimental system. More broadly, our findings demonstrate the value of combining multiple types of omic data with experimental evolution when attempting to dissect mechanisms underlying complex and highly polygenic traits like aging.

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