The NFκB Dif is required for behavioral and molecular correlates of sleep homeostasis in Drosophila.

The nuclear factor binding the κ light chain in B-cells (NFκB) is involved in a wide range of cellular processes including development, growth, innate immunity, and sleep. However, genetic studies of the role of specific NFκB transcription factors in sleep have been limited. Drosophila fruit flies carry three genes encoding NFκB transcription factors, Dorsal, Dorsal Immunity Factor (Dif), and Relish.

The NFκB is required for behavioral and molecular correlates of sleep homeostasis in .

The nuclear factor binding the κ light chain in B-cells (NFκB) is involved in a wide range of cellular processes including development, growth, innate immunity, and sleep. However, efforts have been limited toward understanding how specific NFκB transcription factors function in sleep. fruit flies carry three genes encoding NFκB transcription factors, , (), and .

The microbiome stabilizes circadian rhythms in the gut.

The gut microbiome is well known to impact host physiology and health. Given widespread control of physiology by circadian clocks, we asked how the microbiome interacts with circadian rhythms in the gut. The microbiome did not cycle in flies fed ad libitum, and timed feeding (TF) drove limited cycling only in clockless flies.

Sleep and Cellular Stress.

Sleep is a universal phenomenon occurring in all species studied thus far. Sleep loss results in adverse physiological effects at both the organismal and cellular levels suggesting an adaptive role for sleep in the maintenance of overall health. This review examines the bidirectional relationship between sleep and cellular stress.

Genetic Mechanisms Underlying Sleep.

Sleep is important for cognitive ability, and perturbations of sleep are associated with a myriad of brain disorders. However, how sleep promotes health and function during wake is poorly understood. To address the cellular and molecular mechanisms underlying sleep, we use the fruit fly as a genetic model.

A sleep-inducing gene, , links sleep and immune function in .

Sleep remains a major mystery of biology. In particular, little is known about the mechanisms that account for the drive to sleep. In an unbiased screen of more than 12,000 lines, we identified a single gene, , that induces sleep.

A Conserved Circadian Function for the Neurofibromatosis 1 Gene.

Loss of the Neurofibromatosis 1 (Nf1) protein, neurofibromin, in Drosophila disrupts circadian rhythms of locomotor activity without impairing central clock function, suggesting effects downstream of the clock. However, the relevant cellular mechanisms are not known. Leveraging the discovery of output circuits for locomotor rhythms, we dissected cellular actions of neurofibromin in recently identified substrates.

Wolbachia affects sleep behavior in Drosophila melanogaster.

Wolbachia are endosymbiotic bacteria present in a wide range of insects. Although their dramatic effects on host reproductive biology have been well studied, the effects of Wolbachia on sleep behavior of insect hosts are not well documented. In this study, we report that Wolbachia infection caused an increase of total sleep time in both male and female Drosophila melanogaster.

Hypertension Treatment and Concern About Falling: Baseline Data from the Systolic Blood Pressure Intervention Trial.

Objectives: To determine the extent of concern about falling in older adults with hypertension, whether lower blood pressure (BP) and greater use of antihypertensive medications are associated with greater concern about falling, and whether lower BP has a greater effect on concern about falling in older and more functionally impaired individuals.

Design: Secondary analysis involving cross-sectional study of baseline characteristics of participants enrolled in the Systolic Blood Pressure Intervention Trial (SPRINT).

Setting: Approximately 100 outpatient sites.

Sleep Homeostasis and General Anesthesia: Are Fruit Flies Well Rested after Emergence from Propofol?

Background: Shared neurophysiologic features between sleep and anesthetic-induced hypnosis indicate a potential overlap in neuronal circuitry underlying both states. Previous studies in rodents indicate that preexisting sleep debt discharges under propofol anesthesia. The authors explored the hypothesis that propofol anesthesia also dispels sleep pressure in the fruit fly.

FMRFamide signaling promotes stress-induced sleep in Drosophila.

Enhanced sleep in response to cellular stress is a conserved adaptive behavior across multiple species, but the mechanism of this process is poorly understood. Drosophila melanogaster increases sleep following exposure to septic or aseptic injury, and Caenorhabditis elegans displays sleep-like quiescence following exposure to high temperatures that stress cells. We show here that, similar to C.

Low 25-hydroxyvitamin D concentrations predict incident depression in well-functioning older adults: the health, aging, and body composition study.

Background: Cross-sectional studies suggest that low 25-hydroxyvitamin D (25[OH]D) may be a risk factor for depression; however, there are few prospective studies. We examined the association between 25(OH)D and depressive symptoms in community-dwelling persons aged 70-79 years in the Health, Aging, and Body Composition (Health ABC) Study (n = 2598).

Methods: Depressive symptoms were assessed using the Center for Epidemiologic Studies-Depression Scale (CES-D) at baseline and 2-, 3- and 4-year follow-up.

Increased sleep promotes survival during a bacterial infection in Drosophila.

Study Objectives: The relationship between sleep and immune function is not well understood at a functional or molecular level. We therefore used a genetic approach in Drosophila to manipulate sleep and evaluated effects on the ability of flies to fight bacterial infection.

Setting: Laboratory.

Acute sleep deprivation enhances post-infection sleep and promotes survival during bacterial infection in Drosophila.

Study Objectives: Sleep is known to increase as an acute response to infection. However, the function of this behavioral response in host defense is not well understood. To address this problem, we evaluated the effect of acute sleep deprivation on post-infection sleep and immune function in Drosophila.

Optimization and qualification of a memory B-cell ELISpot for the detection of vaccine-induced memory responses in HIV vaccine trials.

Various aspects of the human immune system can be analyzed to determine the efficacy of a vaccine. We have developed a B-cell ELISpot to measure HIV-specific antibody-secreting B cells in the peripheral blood as a result of vaccination or natural infection. Our method includes stimulating peripheral blood mononuclear cells with interleukin-2 and a polyclonal activator, R848, to induce memory B cells to differentiate into antibody-secreting cells.

Quantitative measurement of the immune response and sleep in Drosophila.

A complex interaction between the immune response and host behavior has been described in a wide range of species. Excess sleep, in particular, is known to occur as a response to infection in mammals (1) and has also recently been described in Drosophila melanogaster(2). It is generally accepted that sleep is beneficial to the host during an infection and that it is important for the maintenance of a robust immune system(3,4).

Patient management after noninvasive cardiac imaging results from SPARC (Study of myocardial perfusion and coronary anatomy imaging roles in coronary artery disease).

Objectives: This study examined short-term cardiac catheterization rates and medication changes after cardiac imaging.

Background: Noninvasive cardiac imaging is widely used in coronary artery disease, but its effects on subsequent patient management are unclear.

Methods: We assessed the 90-day post-test rates of catheterization and medication changes in a prospective registry of 1,703 patients without a documented history of coronary artery disease and an intermediate to high likelihood of coronary artery disease undergoing cardiac single-photon emission computed tomography, positron emission tomography, or 64-slice coronary computed tomography angiography.

Endogenous retinoids in mammalian growth plate cartilage: analysis and roles in matrix homeostasis and turnover.

The growth plate contains resting and proliferating chondrocytes in its upper zones (UGP) and maturing and hypertrophic chondrocytes in its lower zones (LGP), but the mechanisms by which it operates to sustain skeletal growth are not fully clear. Retinoid signaling was previously found to be nearly absent in UGP, but to be much stronger in LGP coincident with hypertrophy, extracellular matrix turnover and endochondral bone formation. To determine whether such distinct signaling levels and phenotypic events reflect different endogenous retinoid levels, the upper two-thirds and lower one-third of rabbit rib growth plates were microsurgically isolated and processed for ultrasensitive retinoid LC-tandem MS quantification.

Sleep triggered by an immune response in Drosophila is regulated by the circadian clock and requires the NFkappaB Relish.

Background: Immune challenge impacts behavior in many species. In mammals, this adaptive behavior is often manifested as an increase in sleep. Sleep has therefore been proposed to benefit the host by enhancing immune function and thereby overcome the challenge.

Interhemispheric modulation induced by cortical stimulation and motor training.

Background: Interhemispheric inhibition might be a beneficial cortico-cortical interaction, but also might be maladaptive in people with neurological disorders. One recently revisited technique that has been shown to be effective in improving motor function in people with stroke using interhemispheric modulation is transcranial direct current stimulation (tDCS).

Objective: The aim of this study was to investigate the effects of tDCS combined with unilateral motor training with contralateral hand restraint on interhemispheric inhibition between the dominant and nondominant hemispheres of the brain and on motor performance in participants who were healthy.

Wnt/beta-catenin and retinoic acid receptor signaling pathways interact to regulate chondrocyte function and matrix turnover.

Activation of the Wnt/beta-catenin and retinoid signaling pathways is known to tilt cartilage matrix homeostasis toward catabolism. Here, we investigated possible interactions between these pathways. We found that all-trans-retinoic acid (RA) treatment of mouse epiphyseal chondrocytes in culture did increase Wnt/beta-catenin signaling in the absence or presence of exogenous Wnt3a, as revealed by lymphoid enhancer factor/T-cell factor/beta-catenin reporter activity and beta-catenin nuclear accumulation.

Inhibition of ectopic bone formation by a selective retinoic acid receptor alpha-agonist: a new therapy for heterotopic ossification?

Heterotopic ossification (HO) consists of formation of ectopic cartilage followed by endochondral bone and is triggered by major surgeries, large wounds, and other conditions. Current therapies, including low-dose irradiation, are not always effective and do not target the skeletogenic process directly. Because chondrogenesis requires a decrease of nuclear retinoic acid receptor alpha (RARalpha) action, we reasoned that pharmacologic activation of this receptor pathway should inhibit HO.