Predicting human nocturnal nonvisual responses to monochromatic and polychromatic light with a melanopsin photosensitivity function

The short-wavelength (blue) light sensitivity of human circadian, neurobehavioral, neuroendocrine, and neurophysiological responses is attributed to melanopsin. Whether melanopsin is the sole factor in determining the efficacy of a polychromatic light source in driving nonvisual responses, however, remains to be established. Monochromatic (λ(max) 437, 479, and 532 nm administered singly and in combination with 479 nm light) and polychromatic (color temperature: 4000 K and 17000 K) light stimuli were photon matched for their predicted ability to stimulate melanopsin, and their capacity to affect nocturnal melatonin levels, auditory reaction time, and subjective alertness and mood was assessed. Young, healthy male participants aged 18-35 yrs (23.6?±?3.6 yrs [mean?±?SD]; n=12) participated in 12 overnight sessions that included an individually timed 30-min nocturnal light stimulus on the rising limb of the melatonin profile. At regular intervals before, during, and after the light stimulus, subjective mood and alertness were verbally assessed, blood samples were taken for analysis of plasma melatonin levels, and an auditory reaction time task (psychomotor vigilance task; PVT) was performed. Proc GLM (general linear model) repeated-measures ANOVA (analysis of variance) revealed significantly lower melatonin suppression with the polychromatic light conditions (4000 and 17000 K) compared to the "melanopsin photon-matched" monochromatic light conditions (p相似文献   

Characterization of tannin acylhydrolase activity in the ruminal bacterium Selenomonas ruminantium

A strain of the anaerobe Selenomonas ruminantium subsp. ruminantium that is capable of growing on tannic acid or condensed tannin as a sole energy source has been isolated from ruminal contents of feral goats browsing tannin-rich Acacia sp. Growth on tannic acid was accompanied by release of gallic acid into the culture medium but the bacterium was incapable of using gallic acid as a sole energy source. Tannin acylhydrolase (EC 3.1.1.20) activity was measured in crude cell-free extracts of the bacterium. The enzyme has a pH optimum of 7, a temperature optimum of 30-40 degrees C and a molecular size of 59 kDa. In crude extracts, the maximal rate of gallic acid methyl ester hydrolysis was 6.3 micromol min(-1) mg(-1) of protein and the K(m) for gallic acid methyl ester was 1.6 mM. Enzyme activity was displayed in situ in polyacrylamide and isoelectric focusing gels and was demonstrated to increase 17-fold and 36-fold respectively when cells were grown in the presence of gallic acid methyl ester or tannic acid.     

Natural Light Exposure,Sleep and Depression among Day Workers and Shiftworkers at Arctic and Equatorial Latitudes

Objectives

This study aimed to investigate the relationship between individual natural light exposure, sleep need, and depression at two latitudes, one extreme with a few hours of light per day during winter, and the other with equal hours of light and darkness throughout the year.

Methods

This cross-sectional study included a sample of Brazilian workers (Equatorial, n = 488 workers) and a Swedish sample (Arctic, n = 1,273).

Results

The reported mean total natural light exposure per 4-week cycle differed significantly between the Equatorial and Arctic regions. However, shiftworkers from both sites reported similar hours of natural light exposure. Short light exposure was a predictor for insufficient sleep.

Conclusion

Reduced exposure to natural light appears to increase the perception of obtaining insufficient sleep. Arctic workers were more prone to develop depression than Equatorial workers.     

Structure-based design and SAR development of 5,6-dihydroimidazolo[1,5-f]pteridine derivatives as novel Polo-like kinase-1 inhibitors

Using structure-based drug design, we identified a novel series of 5,6-dihydroimidazolo[1,5-f]pteridine PLK1 inhibitors. Rational improvements to compounds of this class resulted in single-digit nanomolar enzyme and cellular activity against PLK1, and oral bioavailability. Compound 1 exhibits >7 fold induction of phosphorylated Histone H3 and is efficacious in an in vivo HT-29 tumor xenograft model.     

Identification of human plasma metabolites exhibiting time-of-day variation using an untargeted liquid chromatography-mass spectrometry metabolomic approach

Although daily rhythms regulate multiple aspects of human physiology, rhythmic control of the metabolome remains poorly understood. The primary objective of this proof-of-concept study was identification of metabolites in human plasma that exhibit significant 24-h variation. This was assessed via an untargeted metabolomic approach using liquid chromatography-mass spectrometry (LC-MS). Eight lean, healthy, and unmedicated men, mean age 53.6 (SD ± 6.0) yrs, maintained a fixed sleep/wake schedule and dietary regime for 1 wk at home prior to an adaptation night and followed by a 25-h experimental session in the laboratory where the light/dark cycle, sleep/wake, posture, and calorific intake were strictly controlled. Plasma samples from each individual at selected time points were prepared using liquid-phase extraction followed by reverse-phase LC coupled to quadrupole time-of-flight MS analysis in positive ionization mode. Time-of-day variation in the metabolites was screened for using orthogonal partial least square discrimination between selected time points of 10:00 vs. 22:00 h, 16:00 vs. 04:00 h, and 07:00 (d 1) vs. 16:00 h, as well as repeated-measures analysis of variance with time as an independent variable. Subsequently, cosinor analysis was performed on all the sampled time points across the 24-h day to assess for significant daily variation. In this study, analytical variability, assessed using known internal standards, was low with coefficients of variation <10%. A total of 1069 metabolite features were detected and 203 (19%) showed significant time-of-day variation. Of these, 34 metabolites were identified using a combination of accurate mass, tandem MS, and online database searches. These metabolites include corticosteroids, bilirubin, amino acids, acylcarnitines, and phospholipids; of note, the magnitude of the 24-h variation of these identified metabolites was large, with the mean ratio of oscillation range over MESOR (24-h time series mean) of 65% (95% confidence interval [CI]: 49-81%). Importantly, several of these human plasma metabolites, including specific acylcarnitines and phospholipids, were hitherto not known to be 24-h variant. These findings represent an important baseline and will be useful in guiding the design and interpretation of future metabolite-based studies.     

Effects of light on human circadian rhythms.

Blind subjects with defective retinal processing provide a good model to study the effects of light (or absence of light) on the human circadian system. The circadian rhythms (melatonin, cortisol, timing of sleep/wake) of individuals with different degrees of light perception (n = 67) have been studied. Blind subjects with some degree of light perception (LP) mainly have normally entrained circadian rhythms, whereas subjects with no conscious light perception (NPL) are more likely to exhibit disturbed circadian rhythms. All subjects who were bilaterally enucleated showed free running melatonin and cortisol rhythms. Studies assessing the light-induced suppression of melatonin show the response to be intensity and wavelength dependent. In contrast to ocular light exposure, extraocular light failed to suppress night-time melatonin. Thus, ocular light appears to be the predominant time cue and major determinant of circadian rhythm type. Optimisation of the light for entrainment (intensity, duration, wavelength, time of administration) requires further study.     

Who owns your body? Legal issues on the ownership of bodily material

Who owns your body and parts removed from it? Can you legally sell your bodily material – or information derived from it? Can you legally prevent other people gaining access to your excised bodily material, including your blood relatives who might need your tissue or genetic information for their own genetic tests? What legal remedies are there if people take or use your bodily material without your consent? And why are the answers to these questions vitally important for scientists?     

Axonal transport of actin in rabbit retinal ganglion cells

We labeled proteins in the cell bodies of rabbit retinal ganglion cells with [35S]methionine and subsequently observed the appearance of radioactive actin in tissues containing the axons and synaptic terminals of these neurons, i.e., the optic nerve (ON), optic tract (OT), lateral geniculate nucleus (LGN) and the superior colliculus (SC). The temporal sequence of appearance of labeled actin (which was identified by its specific binding to DNase I, its electrophoretic mobility, and its peptide map) in these tissues indicated that actin is an axonally transported protein with a maximum transport velocity of 3.4--4.3 mm/d. The kinetics of labeling actin were similar to the kinetics of labeling two proteins (M1 and M2) which resemble myosin; these myosin-like proteins were previously found to be included in the groups of proteins (groups III and IV) transported with the third and fourth most rapid maximum velocities. The similarity in transport between actin and myosin-like proteins supports the idea that a number of proteins in the third and fourth transport groups may be functionally related by virtue of their involvement in a force-generating mechanism and suggests the possibility that these proteins may be axonally transported as a preformed force-generating unit.     

The significance of D-amino acids in soil, fate and utilization by microbes and plants: review and identification of knowledge gaps

Background

D-amino acids are far less abundant in nature than L-amino acids. Both L- and D-amino acids enter soil from different sources including plant, animal and microbial biomass, antibiotics, faeces and synthetic insecticides. Moreover, D-amino acids appear in soil due to abiotic or biotic racemization of L-amino acids. Both L- and D-amino acids occur as bound in soil organic matter and as “free“ amino acids dissolved in soil solution or exchangeably bound to soil colloids. D-amino acids are mineralized at slower rates compared to the corresponding L-enantiomers. Plants have a capacity to directly take up “free“ D-amino acids by their roots but their ability to utilize them is low and thus D-amino acids inhibit plant growth.

Scope

The aim of this work is to review current knowledge on D-amino acids in soil and their utilization by soil microorganisms and plants, and to identify critical knowledge gaps and directions for future research.

Conclusion

Assessment of “free“ D-amino acids in soils is currently complicated due to the lack of appropriate extraction procedures. This information is necessary for consequent experimental determination of their significance for crop production and growth of plants in different types of managed and unmanaged ecosystems. Hypotheses on occurrence of “free“ D-amino acids in soil are presented in this review.     

Muc1 Limits Helicobacter felis Binding to Gastric Epithelial Cells But Does not Limit Colonization and Gastric Pathology Following Infection

Background: The mucin Muc1 is constitutively expressed by the gastric mucosa and is likely the first point of direct contact between the host stomach and the adherent pathogens. The expression of Muc1 has been shown to limit colonization of mice by Helicobacter pylori, known to adhere to the gastric epithelium, as well as associated pathology. However, the potential role of this mucin against nonadherent Helicobacter has not been previously studied. We therefore examined the importance of Muc1 on the pathogenesis of Helicobacter felis, believed not to adhere to the murine mucosa. Methods and results: Using primary cell cultures, we found that H. felis can bind gastric epithelial cells in vitro, and adherence to epithelial cells deficient in Muc1 was increased compared to controls that expressed the mucin. However, following infection of deficient mice, we found that Muc1 did not impact on H. felis colonization or pathogenesis in vivo, in contrast to previous observations with H. pylori. Conclusions: This demonstrates a variable effect of Muc1 on protection against closely related adherent and nonadherent Helicobacter species, and supports a key role for Muc1 in limiting attachment of adherent bacteria to the gastric mucosal surface.