Daily and Seasonal Variation in the Spectral Composition of Light Exposure in Humans

Light is considered the most potent synchronizer of the human circadian system and exerts many other non-image-forming effects, including those that affect brain function. These effects are mediated in part by intrinsically photosensitive retinal ganglion cells that express the photopigment melanopsin. The spectral sensitivity of melanopsin is greatest for blue light at approximately 480 nm. At present, there is little information on how the spectral composition of light to which people are exposed varies over the 24 h period and across seasons. Twenty-two subjects, aged 22±4 yrs (mean±SD) participated during the winter months (November–February), and 12 subjects aged 25±3 yrs participated during the summer months (April–August). Subjects wore Actiwatch-RGB monitors, as well as Actiwatch-L monitors, for seven consecutive days while living in England. These monitors measured activity and light exposure in the red, green, and blue spectral regions, in addition to broad-spectrum white light, with a 2 min resolution. Light exposure during the day was analyzed for the interval between 09:00 and 21:00 h. The time course of white-light exposure differed significantly between seasons (p = 0.0022), with light exposure increasing in the morning hours and declining in the afternoon hours, and with a more prominent decline in the winter. Overall light exposure was significantly higher in summer than winter (p = 0.0002). Seasonal differences in the relative contribution of blue-light exposure to overall light exposure were also observed (p = 0.0006), in particular during the evening hours. During the summer evenings (17:00–21:00 h), the relative contribution of blue light was significantly higher (p < 0.0001) (40.2±1.1%) than during winter evenings (26.6±0.9%). The present data show that in addition to overall light exposure, the spectral composition of light exposure varies over the day and with season

Comparative analysis indicates that alternative splicing in plants has a limited role in functional expansion of the proteome

<p>Abstract</p> <p>Background</p> <p>Alternative splicing (AS) is a widespread phenomenon in higher eukaryotes but the extent to which it leads to functional protein isoforms and to proteome expansion at large is still a matter of debate. In contrast to animal species, for which AS has been studied extensively at the protein and functional level, protein-centered studies of AS in plant species are scarce. Here we investigate the functional impact of AS in dicot and monocot plant species using a comparative approach.</p> <p>Results</p> <p>Detailed comparison of AS events in alternative spliced orthologs from the dicot <it>Arabidopsis thaliana </it>and the monocot <it>Oryza sativa </it>(rice) revealed that the vast majority of AS events in both species do not result from functional conservation. Transcript isoforms that are putative targets for the nonsense-mediated decay (NMD) pathway are as likely to contain conserved AS events as isoforms that are translated into proteins. Similar results were obtained when the same comparison was performed between the two more closely related monocot species rice and <it>Zea mays </it>(maize).</p> <p>Genome-wide computational analysis of functional protein domains encoded in alternatively and constitutively spliced genes revealed that only the RNA recognition motif (RRM) is overrepresented in alternatively spliced genes in all species analyzed. In contrast, three domain types were overrepresented in constitutively spliced genes. AS events were found to be less frequent within than outside predicted protein domains and no domain type was found to be enriched with AS introns. Analysis of AS events that result in the removal of complete protein domains revealed that only a small number of domain types is spliced-out in all species analyzed. Finally, in a substantial fraction of cases where a domain is completely removed, this domain appeared to be a unit of a tandem repeat.</p> <p>Conclusion</p> <p>The results from the ortholog comparisons suggest that the ability of a gene to produce more than one functional protein through AS does not persist during evolution. Cross-species comparison of the results of the protein-domain oriented analyses indicates little correspondence between the analyzed species. Based on the premise that functional genetic features are most likely to be conserved during evolution, we conclude that AS has only a limited role in functional expansion of the proteome in plants.</p

Correlated mutations via regularized multinomial regression

Background In addition to sequence conservation, protein multiple sequence alignments contain evolutionary signal in the form of correlated variation among amino acid positions. This signal indicates positions in the sequence that influence each other, and can be applied for the prediction of intra- or intermolecular contacts. Although various approaches exist for the detection of such correlated mutations, in general these methods utilize only pairwise correlations. Hence, they tend to conflate direct and indirect dependencies. Results We propose RMRCM, a method for Regularized Multinomial Regression in order to obtain Correlated Mutations from protein multiple sequence alignments. Importantly, our method is not restricted to pairwise (column-column) comparisons only, but takes into account the network nature of relationships between protein residues in order to predict residue-residue contacts. The use of regularization ensures that the number of predicted links between columns in the multiple sequence alignment remains limited, preventing overprediction. Using simulated datasets we analyzed the performance of our approach in predicting residue-residue contacts, and studied how it is influenced by various types of noise. For various biological datasets, validation with protein structure data indicates a good performance of the proposed algorithm for the prediction of residue-residue contacts, in comparison to previous results. RMRCM can also be applied to predict interactions (in addition to only predicting interaction sites or contact sites), as demonstrated by predicting PDZ-peptide interactions. Conclusions A novel method is presented, which uses regularized multinomial regression in order to obtain correlated mutations from protein multiple sequence alignments

Nap sleep spindle correlates of intelligence

Contains fulltext : 152518.pdf (publisher's version ) (Open Access)Sleep spindles are thalamocortical oscillations in non-rapid eye movement (NREM) sleep, that play an important role in sleep-related neuroplasticity and offline information processing. Several studies with full-night sleep recordings have reported a positive association between sleep spindles and fluid intelligence scores, however more recently it has been shown that only few sleep spindle measures correlate with intelligence in females, and none in males. Sleep spindle regulation underlies a circadian rhythm, however the association between spindles and intelligence has not been investigated in daytime nap sleep so far. In a sample of 86 healthy male human subjects, we investigated the correlation between fluid intelligence and sleep spindle parameters in an afternoon nap of 100 minutes. Mean sleep spindle length, amplitude and density were computed for each subject and for each derivation for both slow and fast spindles. A positive association was found between intelligence and slow spindle duration, but not any other sleep spindle parameter. As a positive correlation between intelligence and slow sleep spindle duration in full-night polysomnography has only been reported in females but not males, our results suggest that the association between intelligence and sleep spindles is more complex than previously assumed

SEPALLATA3: the 'glue' for MADS box transcription factor complex formation

A yeast 3-hybrid screen in Arabidopsis reveals MADS box protein complexes: SEP3 is shown to mediate complex formation and floral timing

Adrenalectomy alters the sensitivity of the central nervous system melanocortin system

Removal of adrenal steroids by adrenalectomy (ADX) reduces food intake and body weight in rodents and prevents excessive weight gain in many genetic and dietary models of obesity. Thus, glucocorticoids appear to play a key role to promote positive energy balance in normal and pathological conditions. By comparison, central nervous system melanocortin signaling provides critical inhibitory tone to regulate energy balance. The present experiments sought to test whether glucocorticoids influence energy balance by altering the sensitivity to melanocortin receptor ligands. Because melanocortin-producing neurons are hypothesized to be downstream of leptin in a key weight-reducing circuit, we tested rats for their sensitivity to leptin and confirmed reports that the hypophagic response to third ventricular (i3vt) leptin is increased in ADX rats and is normalized by glucocorticoid replacement. Next we tested rats for their sensitivity to the melanocortin agonist melanotan II and found that, as for leptin, ADX enhanced the hypophagic response via a glucocorticoid-dependent mechanism. The central nervous system melanocortin system is unique in that it includes the endogenous melanocortin receptor antagonist, AgRP. The orexigenic effect of i3vt AgRP was absent in ADX rats and restored by glucocorticoid replacement. We conclude that the potent weight-reducing effects of ADX likely involve heightened responsiveness to melanocortin receptor stimulation

Voluntary exercise can strengthen the circadian system in aged mice

Consistent daily rhythms are important to healthy aging according to studies linking disrupted circadian rhythms with negative health impacts. We studied the effects of age and exercise on baseline circadian rhythms and on the circadian system's ability to respond to the perturbation induced by an 8 h advance of the light:dark (LD) cycle as a test of the system's robustness. Mice (male, mPer2luc/C57BL/6) were studied at one of two ages: 3.5 months (n = 39) and &gt;18 months (n = 72). We examined activity records of these mice under entrained and shifted conditions as well as mPER2::LUC measures ex vivo to assess circadian function in the suprachiasmatic nuclei (SCN) and important target organs. Age was associated with reduced running wheel use, fragmentation of activity, and slowed resetting in both behavioral and molecular measures. Furthermore, we observed that for aged mice, the presence of a running wheel altered the amplitude of the spontaneous firing rate rhythm in the SCN in vitro. Following a shift of the LD cycle, both young and aged mice showed a change in rhythmicity properties of the mPER2::LUC oscillation of the SCN in vitro, and aged mice exhibited longer lasting internal desynchrony. Access to a running wheel alleviated some age-related changes in the circadian system. In an additional experiment, we replicated the effect of the running wheel, comparing behavioral and in vitro results from aged mice housed with or without a running wheel (&gt;21 months, n = 8 per group, all examined 4 days after the shift). The impact of voluntary exercise on circadian rhythm properties in an aged animal is a novel finding and has implications for the health of older people living with environmentally induced circadian disruption

Amplitude Reduction and Phase Shifts of Melatonin, Cortisol and Other Circadian Rhythms after a Gradual Advance of Sleep and Light Exposure in Humans

Background: The phase and amplitude of rhythms in physiology and behavior are generated by circadian oscillators and entrained to the 24-h day by exposure to the light-dark cycle and feedback from the sleep-wake cycle. The extent to which the phase and amplitude of multiple rhythms are similarly affected during altered timing of light exposure and the sleepwake cycle has not been fully characterized. Methodology/Principal Findings: We assessed the phase and amplitude of the rhythms of melatonin, core body temperature, cortisol, alertness, performance and sleep after a perturbation of entrainment by a gradual advance of the sleep-wake schedule (10 h in 5 days) and associated light-dark cycle in 14 healthy men. The light-dark cycle consisted either of moderate intensity ‘room ’ light (,90–150 lux) or moderate light supplemented with bright light (,10,000 lux) for 5 to 8 hours following sleep. After the advance of the sleep-wake schedule in moderate light, no significant advance of the melatonin rhythm was observed whereas, after bright light supplementation the phase advance was 8.1 h (SEM 0.7 h). Individual differences in phase shifts correlated across variables. The amplitude of the melatonin rhythm assessed under constant conditions was reduced after moderate light by 54 % (17–94%) and after bright light by 52 % (range 12–84%), as compared to the amplitude at baseline in the presence of a sleep-wake cycle. Individual differences in amplitude reduction of the melatonin rhythm correlated with the amplitude of body temperature, cortisol and alertness