scholarly journals A screen for sleep and starvation resistance identifies a wake-promoting role for the auxiliary channel unc79

2021 ◽  
Author(s):  
Kazuma Murakami ◽  
Justin Palermo ◽  
Bethany A Stanhope ◽  
Allen G Gibbs ◽  
Alex C Keene
Keyword(s):  
Sleep Duration ◽  
Mushroom Body ◽  
Metabolic Diseases ◽  
Genetic Screen ◽  
Metabolic Function ◽  
Starvation Resistance ◽  
Pacemaker Neurons ◽  
Number Of Genes ◽  
Circadian Behavior

Abstract The regulation of sleep and metabolism are highly interconnected, and dysregulation of sleep is linked to metabolic diseases that include obesity, diabetes, and heart disease. Further, both acute and long-term changes in diet potently impact sleep duration and quality. To identify novel factors that modulate interactions between sleep and metabolic state, we performed a genetic screen for their roles in regulating sleep duration, starvation resistance, and starvation-dependent modulation of sleep. This screen identified a number of genes with potential roles in regulating sleep, metabolism or both processes. One such gene encodes the auxiliary ion channel UNC79, which was implicated in both the regulation of sleep and starvation resistance. Genetic knockdown or mutation of unc79 results in flies with increased sleep duration, as well as increased starvation resistance. Previous findings have shown that unc79 is required in pacemaker for 24-hour circadian rhythms. Here, we find that unc79 functions in the mushroom body, but not pacemaker neurons, to regulate sleep duration and starvation resistance. Together, these findings reveal spatially localized separable functions of unc79 in the regulation of circadian behavior, sleep, and metabolic function.

scholarly journals A screen for sleep and starvation resistance identifies a wake-promoting role for the auxiliary channel unc79

2021 ◽  
Author(s):  
Kazuma Murakami ◽  
Justin Palermo ◽  
Bethany A. Stanhope ◽  
Alex C. Keene
Keyword(s):  
Sleep Duration ◽  
Mushroom Body ◽  
Metabolic Diseases ◽  
Genetic Screen ◽  
Metabolic Function ◽  
Starvation Resistance ◽  
Pacemaker Neurons ◽  
Number Of Genes ◽  
Circadian Behavior

AbstractThe regulation of sleep and metabolism are highly interconnected, and dysregulation of sleep is linked to metabolic diseases that include obesity, diabetes, and heart disease. Further, both acute and long-term changes in diet potently impact sleep duration and quality. To identify novel factors that modulate interactions between sleep and metabolic state, we performed a genetic screen for their roles in regulating sleep duration, starvation resistance, and starvation-dependent modulation of sleep. This screen identified a number of genes with potential roles in regulating sleep, metabolism or both processes. One such gene encodes the auxiliary ion channel UNC79, which was implicated in both the regulation of sleep and starvation resistance. Genetic knockdown or mutation of unc79 results in flies with increased sleep duration, as well as increased starvation resistance. Previous findings have shown that unc79 is required in pacemaker for 24-hour circadian rhythms. Here, we find that unc79 functions in the mushroom body, but not pacemaker neurons, to regulate sleep duration and starvation resistance. Together, these findings reveal spatially localized separable functions of unc79 in the regulation of circadian behavior, sleep, and metabolic function.

scholarly journals Transcription of a plasticity gene is activated by neuronal hyperpolarization

2019 ◽  
Author(s):  
Zhonghua Zhu ◽  
Tamara Sanchez Ortiz ◽  
Shaul Mezan ◽  
Sebastian Kadener ◽  
Justin Blau
Keyword(s):  
Transcription Factor ◽  
Synaptic Plasticity ◽  
Neuronal Activity ◽  
Mushroom Body ◽  
Transcriptional Factors ◽  
List Type ◽  
Circadian Pacemaker ◽  
Pacemaker Neurons ◽  
Rhythmic Expression

SummaryLong term synaptic plasticity requires transcription in response to changes in neuronal activity. While genes induced by neuronal activity have been extensively studied, genes induced by hyperpolarization are largely unknown. We focused on Pura, a Rho1 GEF whose rhythmic expression drives the daily retraction of the projections of Drosophila LNv circadian pacemaker neurons. We found that Pura transcription is repressed by activity and induced by hyperpolarization in LNvs – the opposite of typical activity-regulated genes. Pura is repressed by activity-regulated transcriptional factors including Mef2 and Sr (fly Egr-1) and activated by Toy, a Pax6 transcription factor. toy transcription is also induced by inactivity. Thus toy and Pura represent a class of genes induced by hyperpolarization.HighlightsHyperpolarization activates transcription of Pura, a plasticity geneThis phenomenon occurs in circadian pacemaker neurons and mushroom body neuronsThe Pura enhancer integrates recent neuronal activity to regulate transcriptionHyperpolarization activates transcription of toy (Pax-6), which then activates Pura

Covid-19 In Man: A Very Dangerous Affair.

2021 ◽  
Vol 21 ◽  
Author(s):  
Giuseppe Lisco ◽  
Vito A. Giagulli ◽  
Giovanni De Pergola ◽  
Anna De Tullio ◽  
Edoardo Guastamacchia ◽  
...  
Keyword(s):  
Poor Prognosis ◽  
Metabolic Diseases ◽  
Systemic Disease ◽  
Public Health Issue ◽  
Immune System Dysfunction ◽  
Data Support ◽  
Systemic Spread ◽  
The Impact

Background: The novel pandemic of Coronavirus disease 2019 (COVID-19) has becoming a public health issue since March 2020 considering that more than 30 million people were found to be infected worldwide. Particularly, recent evidences suggested that men may be considered as at higher risk of poor prognosis or death once the infection occurred and concerns surfaced in regard of the risk of a possible testicular injury due to SARS-CoV-2 infection. Results: Several data support the existence of a bivalent role of testosterone (T) in driving poor prognosis in patients with COVID-19. On one hand, this is attributable to the fact that T may facilitate SARS-CoV-2 entry in human cells by means of an enhanced expression of transmembrane serine-protease 2 (TMPRSS2) and angiotensin-converting enzyme 2 (ACE2). At the same time, younger man with normal testicular function compared to women of similar age are prone to develop a blunted immune response against SARS-CoV-2, being exposed to less viral clearance and more viral shedding and systemic spread of the disease. Conversely, low levels of serum T observed in hypogonadal men predispose them to a greater background systemic inflammation, cardiovascular and metabolic diseases, and immune system dysfunction, hence driving harmful consequences once SARS-CoV-2 infection occurred. Finally, SARS-CoV-2, as a systemic disease, may also affect testicles with possible concerns for current and future testicular efficiency. Preliminary data suggested that SARS-CoV-2 genome is not normally found in gonads and gametes, therefore sex transmission could be excluded as a possible way to spread the COVID-19. Conclusion: Most data support a role of T as a bivalent risk factor for poor prognosis (high/normal in younger; lower in elderly) in COVID-19. However, the impact of medical treatment aimed to modify T homeostasis for improving the prognosis of affected patients is unknown in this clinical setting. In addition, testicular damage may be a harmful consequence of the infection even in case it occurred asymptomatically but no long-term evidences are currently available to confirm and quantify this phenomenon. Different authors excluded the presence of SARS-CoV-2 in sperm and oocytes, thus limiting worries about both a potential sexual and gamete-to-embryos transmission of COVID-19. Despite these evidence, long-term and well-designed studies are needed to clarify these issues.

scholarly journals Upregulated energy metabolism in the Drosophila mushroom body is the trigger for long-term memory

2017 ◽  
Vol 8 (1) ◽  
Author(s):  
Pierre-Yves Plaçais ◽  
Éloïse de Tredern ◽  
Lisa Scheunemann ◽  
Séverine Trannoy ◽  
Valérie Goguel ◽  
...  
Keyword(s):  
Energy Metabolism ◽  
Mushroom Body ◽  
Long Term Memory ◽  
Term Memory

scholarly journals Long-term memory requires sequential protein synthesis in three subsets of mushroom body output neurons in Drosophila

2017 ◽  
Vol 7 (1) ◽  
Author(s):  
Jie-Kai Wu ◽  
Chu-Yi Tai ◽  
Kuan-Lin Feng ◽  
Shiu-Ling Chen ◽  
Chun-Chao Chen ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Mushroom Body ◽  
Long Term Memory ◽  
Term Memory ◽  
Output Neurons

scholarly journals New Horizons in Microbiota and Metabolic Health Research

2020 ◽  
Author(s):  
Sidharth P Mishra ◽  
Shalini Jain ◽  
Subhash Taraphder ◽  
Hariom Yadav
Keyword(s):  
Gut Microbiota ◽  
Drug Response ◽  
Metabolic Diseases ◽  
Prognostic Markers ◽  
Metabolic Function ◽  
Leaky Gut ◽  
New Horizons ◽  
Disease Prognosis ◽  
Obesity And Diabetes ◽  
Metabolic Interactions

Abstract Decade-old studies have demonstrated that microbes living in our gut (microbiota) contribute to both maintaining normal metabolic function and to the pathology of metabolic diseases, such as obesity and diabetes. Emerging evidence suggests that gut microbiota influences the personalized effects of diets and drugs and impact the gut–brain axis and leaky gut inflammation to control metabolic function/diseases. Gut microbiota can be an ideal source of prognostic markers and therapies for metabolic diseases. Here we discuss the emerging concepts in the area of microbiota and metabolic interactions in personalized nutrition, drug response, and disease prognosis.

scholarly journals Fetal expression of genes related to metabolic function is impacted by supplementation of ground beef and sucrose during gestation in a swine model

2020 ◽  
Vol 98 (8) ◽  
Author(s):  
Ashley S Hoyle ◽  
Ana Clara B Menezes ◽  
Megan A Nelson ◽  
Kendall C Swanson ◽  
Kimberly A Vonnahme ◽  
...  
Keyword(s):  
Metabolic Diseases ◽  
Fetal Liver ◽  
Ground Beef ◽  
Transcript Level ◽  
Transcript Abundance ◽  
Mrna Abundance ◽  
Late Gestation ◽  
Swine Model ◽  
Metabolic Function ◽  
Longissimus Dorsi Muscle

Abstract To determine the effects of maternal supplementation on the mRNA abundance of genes associated with metabolic function in fetal muscle and liver, pregnant sows (Landrace × Yorkshire; initial body weight (BW) 221.58 ± 33.26 kg; n = 21) fed a complete gestation diet (corn–soybean meal based diet, CSM) were randomly assigned to 1 of 4 isocaloric supplementation treatments: control (CON, 378 g/d CSM, n = 5), sucrose (SUGAR, 255 g/d crystalized sugar, n = 5), cooked ground beef (BEEF, 330 g/d n = 6), or BEEF + SUGAR (B+S, 165 g/d cooked ground beef and 129 g/d crystalized sugar, n = 5), from days 40 to 110 of gestation. Sows were euthanized on day 111 of gestation. Two male and 2 female fetuses of median BW were selected from each litter, and samples of the longissimus dorsi muscle and liver were collected. Relative transcript level was quantified via qPCR with HPRT1 as the reference gene for both muscle and liver samples. The following genes were selected and analyzed in the muscle: IGF1R, IGF2, IGF2R, GYS-1, IRS-1, INSR, SREBP-1C, and LEPR; while the following were analyzed in the liver: IGF2, IGF2R, FBFase, G6PC, PC, PCK1, FGF21, and LIPC. No effect of fetal sex by maternal treatment interaction was observed in mRNA abundance of any of the genes evaluated (P > 0.11). In muscle, the maternal nutritional treatment influenced (P = 0.02) IGF2 mRNA abundance, with B+S and SUGAR fetuses having lower abundance than CON, which was not different from BEEF. Additionally, SREBP-1 mRNA abundance was greater (P < 0.01) for B+S compared with CON, BEEF, or SUGAR fetuses; and females tended (P = 0.06) to have an increased abundance of SREBP-1 than males. In fetal liver, IGF2R mRNA abundance was greater (P = 0.01) for CON and BEEF than SUGAR and B+S; while FBPase mRNA abundance was greater (P = 0.03) for B+S compared with the other groups. In addition, maternal nutritional tended (P = 0.06) to influence LIPC mRNA abundance, with increased abundance in CON compared with SUGAR and B+S. These data indicate limited changes in transcript abundance due to substitution of supplemental sugar by ground beef during mid to late gestation. However, the differential expression of FBPase and SREBP-1c in response to the simultaneous supplementation of sucrose and ground beef warrants further investigations, since these genes may play important roles in determining the offspring susceptibility to metabolic diseases.

scholarly journals Live Fast, Die Young, and Sleep Later: Life History Strategy and Human Sleep Behavior

2020 ◽  
Author(s):  
Vahe Dishakjian ◽  
Daniel M T Fessler ◽  
Adam Maxwell Sparks
Keyword(s):  
Life History ◽  
Individual Differences ◽  
Sleep Duration ◽  
Sleep Onset ◽  
Life History Strategy ◽  
The Body ◽  
Equation Modeling ◽  
Sleep Onset Latency ◽  
Sleep Behaviors

Abstract Background and objectives Life History Theory (LHT) describes trade-offs that organisms make with regard to three investment pathways: growth, maintenance, and reproduction. In light of the reparative functions of sleep, we examine sleep behaviors and corresponding attitudes as proximate manifestations of an individual’s underlying relative prioritization of short-term reproduction versus long-term maintenance. Methodology We collected survey data from 568 participants across two online studies having different participant pools. We use a mixture of segmented and hierarchical regression models, structural equation modeling, and machine learning to infer relationships between sleep duration/quality, attitudes about sleep, and biodemographic/psychometric measures of life history strategy (LHS). Results An age-mediated U- or V-shaped relationship appears when LHS is plotted against habitual sleep duration, with the fastest strategies occupying the sections of the curve with the highest mortality risk: < 6.5 hours (short sleep) and > 8.5 hours (long sleep). LH “fastness” is associated with increased sleepiness and worse overall sleep quality: delayed sleep onset latency, more wakefulness after sleep onset, higher sleep-wake instability, and greater sleep duration variability. Hedonic valuations of sleep may mediate the effects of LHS on certain sleep parameters. Conclusions and implications The costs of deprioritizing maintenance can be parameterized in the domain of sleep, where “life history fastness” corresponds with sleep patterns associated with greater senescence and mortality. Individual differences in sleep having significant health implications can thus be understood as components of lifelong trajectories likely stemming from calibration to developmental circumstances. Relatedly, hedonic valuations of sleep may constitute useful avenues for non-pharmacological management of chronic sleep disorders. LAY Summary Sleep is essential because it allows the body to repair and maintain itself. But time spent sleeping is time that cannot be spent doing other things. People differ in how much they prioritize immediate rewards, including sociosexual opportunities, versus long-term goals. In this research, we show that individual differences in sleep behaviors, and attitudes toward sleep, correspond with psychological and behavioral differences reflecting such differing priorities. Orientation toward sleep can thus be understood as part of the overall lifetime strategies that people pursue.

Overestimation of Risk and Increased Fear of Long-term Complications of Diabetes in People with Type 1 and 2 Diabetes

2019 ◽  
Vol 127 (10) ◽  
pp. 645-652 ◽  
Author(s):  
Florian Arend ◽  
Ulrich A. Müller ◽  
Andreas Schmitt ◽  
Margarete Voigt ◽  
Nadine Kuniss
Keyword(s):  
Diabetes Complications ◽  
Metabolic Diseases ◽  
Population Based ◽  
Diabetes Type ◽  
Complications Of Diabetes ◽  
Personal Risk ◽  
Disease Management Programmes

AbstrAct Objective The quality report of the disease management programmes of North Rhine Westphalia 2016 showed prevalences for long-term complications (neuropathy, nephropathy, retinopathy) of less than 30% for people with diabetes type 1 (DM1) and type 2 (DM2). The aim of this study was to assess risk expectations and fear regarding long-term complications of diabetes in people with DM1 and DM2. Methods We assessed risk expectations and fear regarding diabetes complications in people with DM1 (n=110) and DM2 (n=143 without insulin, n=249 with insulin) visiting an University outpatient department of metabolic diseases. Fear of long-term complications was measured with the “Fear of Complications Questionnaire (FCQ)” (range 0–45 points, scores ≥30 suggest elevated fear). Participants were asked to estimate general and personal risks of long-term complications 10 years after developing diabetes in %. Results Elevated fear of complications (FCQ scores ≥30) was observed in 34.5, 25.9, and 43.0% of those with DM1, DM2 without insulin and DM2 with insulin, respectively. Participants estimated a mean general risk of diabetes-related complications after 10 years amounting to 45.9±15.8% (DM1), 49.7±15.4% (DM2 without insulin), and 52.5±16.4% (DM2 with insulin) and personal risk with 52.5±24.4% (DM1), 45.8±22.7% (DM2 without insulin), and 54.1±23.4% (DM2 with insulin), respectively. Higher risk expectations were associated with higher fear of complications (p<0.001). Conclusion Risk estimations regarding long-term complications were exaggerated in people with DM1 and DM2. About one third of the participants reported elevated fear of complications. Participants’ risk expectations and fear regarding diabetes complications appear excessive compared to population-based prevalence rates.

scholarly journals Long-Term Recreational Football Training and Health in Aging

2020 ◽  
Vol 17 (6) ◽  
pp. 2087
Author(s):  
Esther Imperlini ◽  
Annamaria Mancini ◽  
Stefania Orrù ◽  
Daniela Vitucci ◽  
Valeria Di Onofrio ◽  
...  
Keyword(s):  
Quality Control ◽  
Dna Repair ◽  
Successful Aging ◽  
Protein Quality ◽  
Metabolic Diseases ◽  
Control Mechanisms ◽  
Older Subjects ◽  
Football Training ◽  
Over Time

This narrative review aims to critically analyze the effects of exercise on health in aging. Here we discuss the main clinical and biomolecular modifications induced by long-term recreational football training in older subjects. In particular, the effects induced by long-term recreational football training on cardiovascular, metabolic and musculo-skeletal fitness, together with the modifications in the muscle expression of hallmarks related to oxidative metabolism, DNA repair and senescence suppression pathways and protein quality control mechanisms will be provided. All these topics will be debated also in terms of preventing non-communicable metabolic diseases, in order to achieve successful aging over time.

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