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Author Chamorro, E.; Bonnin-Arias, C.; Perez-Carrasco, M.J.; Munoz de Luna, J.; Vazquez, D.; Sanchez-Ramos, C. url  doi
openurl 
  Title Effects of light-emitting diode radiations on human retinal pigment epithelial cells in vitro Type Journal Article
  Year 2013 Publication Photochemistry and Photobiology Abbreviated Journal Photochem Photobiol  
  Volume 89 Issue (up) 2 Pages 468-473  
  Keywords Human Health; Apoptosis/*radiation effects; Biological Markers/metabolism; Caspases/metabolism; Cell Survival/radiation effects; DNA Damage; Epithelial Cells/cytology/metabolism/*radiation effects; Histones/metabolism; Humans; Light; Membrane Potential, Mitochondrial/*radiation effects; Mitochondria/*radiation effects; Photoperiod; Primary Cell Culture; Reactive Oxygen Species/metabolism; Retinal Pigment Epithelium/cytology/metabolism/*radiation effects  
  Abstract Human visual system is exposed to high levels of natural and artificial lights of different spectra and intensities along lifetime. Light-emitting diodes (LEDs) are the basic lighting components in screens of PCs, phones and TV sets; hence it is so important to know the implications of LED radiations on the human visual system. The aim of this study was to investigate the effect of LEDs radiations on human retinal pigment epithelial cells (HRPEpiC). They were exposed to three light-darkness (12 h/12 h) cycles, using blue-468 nm, green-525 nm, red-616 nm and white light. Cellular viability of HRPEpiC was evaluated by labeling all nuclei with DAPI; Production of reactive oxygen species (ROS) was determined by H2DCFDA staining; mitochondrial membrane potential was quantified by TMRM staining; DNA damage was determined by H2AX histone activation, and apoptosis was evaluated by caspases-3,-7 activation. It is shown that LED radiations decrease 75-99% cellular viability, and increase 66-89% cellular apoptosis. They also increase ROS production and DNA damage. Fluorescence intensity of apoptosis was 3.7% in nonirradiated cells and 88.8%, 86.1%, 83.9% and 65.5% in cells exposed to white, blue, green or red light, respectively. This study indicates three light-darkness (12 h/12 h) cycles of exposure to LED lighting affect in vitro HRPEpiC.  
  Address Neuro-Computing and Neuro-Robotics Research Group, Universidad Complutense de Madrid, Madrid, Spain. eva.chamorro@opt.ucm.es  
  Corporate Author Thesis  
  Publisher Place of Publication Editor  
  Language English Summary Language Original Title  
  Series Editor Series Title Abbreviated Series Title  
  Series Volume Series Issue Edition  
  ISSN 0031-8655 ISBN Medium  
  Area Expedition Conference  
  Notes PMID:22989198 Approved no  
  Call Number LoNNe @ christopher.kyba @ Serial 511  
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Author Sporl, F.; Korge, S.; Jurchott, K.; Wunderskirchner, M.; Schellenberg, K.; Heins, S.; Specht, A.; Stoll, C.; Klemz, R.; Maier, B.; Wenck, H.; Schrader, A.; Kunz, D.; Blatt, T.; Kramer, A. url  doi
openurl 
  Title Kruppel-like factor 9 is a circadian transcription factor in human epidermis that controls proliferation of keratinocytes Type Journal Article
  Year 2012 Publication Proceedings of the National Academy of Sciences of the United States of America Abbreviated Journal Proc Natl Acad Sci U S A  
  Volume 109 Issue (up) 27 Pages 10903-10908  
  Keywords Human Health; Anti-Inflammatory Agents/pharmacology; Biological Clocks/genetics/physiology; Cell Differentiation/physiology; Cell Proliferation/drug effects; Cells, Cultured; Circadian Rhythm/genetics/*physiology; Epidermis/cytology/*physiology; Genome-Wide Association Study; Homeostasis/physiology; Humans; Hydrocortisone/pharmacology; Keratinocytes/cytology/drug effects/*physiology; Kruppel-Like Transcription Factors/*genetics/*metabolism; Luciferases/genetics; Skin Neoplasms/genetics/physiopathology  
  Abstract Circadian clocks govern a wide range of cellular and physiological functions in various organisms. Recent evidence suggests distinct functions of local clocks in peripheral mammalian tissues such as immune responses and cell cycle control. However, studying circadian action in peripheral tissues has been limited so far to mouse models, leaving the implication for human systems widely elusive. In particular, circadian rhythms in human skin, which is naturally exposed to strong daytime-dependent changes in the environment, have not been investigated to date on a molecular level. Here, we present a comprehensive analysis of circadian gene expression in human epidermis. Whole-genome microarray analysis of suction-blister epidermis obtained throughout the day revealed a functional circadian clock in epidermal keratinocytes with hundreds of transcripts regulated in a daytime-dependent manner. Among those, we identified a circadian transcription factor, Kruppel-like factor 9 (Klf9), that is substantially up-regulated in a cortisol and differentiation-state-dependent manner. Gain- and loss-of-function experiments showed strong antiproliferative effects of Klf9. Putative Klf9 target genes include proliferation/differentiation markers that also show circadian expression in vivo, suggesting that Klf9 affects keratinocyte proliferation/differentiation by controlling the expression of target genes in a daytime-dependent manner.  
  Address Research and Development, Beiersdorf AG, 20245 Hamburg, Germany  
  Corporate Author Thesis  
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  Language English Summary Language Original Title  
  Series Editor Series Title Abbreviated Series Title  
  Series Volume Series Issue Edition  
  ISSN 0027-8424 ISBN Medium  
  Area Expedition Conference  
  Notes PMID:22711835; PMCID:PMC3390879 Approved no  
  Call Number LoNNe @ kagoburian @ Serial 814  
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Author Cajochen, C.; Munch, M.; Kobialka, S.; Krauchi, K.; Steiner, R.; Oelhafen, P.; Orgul, S.; Wirz-Justice, A. url  doi
openurl 
  Title High sensitivity of human melatonin, alertness, thermoregulation, and heart rate to short wavelength light Type Journal Article
  Year 2005 Publication The Journal of Clinical Endocrinology and Metabolism Abbreviated Journal J Clin Endocrinol Metab  
  Volume 90 Issue (up) 3 Pages 1311-1316  
  Keywords Human Health; Adult; Body Temperature Regulation/physiology/*radiation effects; Circadian Rhythm/physiology/radiation effects; Color; Heart Rate/physiology/*radiation effects; Humans; *Light; Male; Melatonin/*metabolism; Retinal Cone Photoreceptor Cells/physiology; Sleep Stages/physiology/radiation effects; Wakefulness/physiology/*radiation effects  
  Abstract Light can elicit acute physiological and alerting responses in humans, the magnitude of which depends on the timing, intensity, and duration of light exposure. Here, we report that the alerting response of light as well as its effects on thermoregulation and heart rate are also wavelength dependent. Exposure to 2 h of monochromatic light at 460 nm in the late evening induced a significantly greater melatonin suppression than occurred with 550-nm monochromatic light, concomitant with a significantly greater alerting response and increased core body temperature and heart rate ( approximately 2.8 x 10(13) photons/cm(2)/sec for each light treatment). Light diminished the distal-proximal skin temperature gradient, a measure of the degree of vasoconstriction, independent of wavelength. Nonclassical ocular photoreceptors with peak sensitivity around 460 nm have been found to regulate circadian rhythm function as measured by melatonin suppression and phase shifting. Our findings-that the sensitivity of the human alerting response to light and its thermoregulatory sequelae are blue-shifted relative to the three-cone visual photopic system-indicate an additional role for these novel photoreceptors in modifying human alertness, thermophysiology, and heart rate.  
  Address Centre for Chronobiology, Psychiatric University Clinic, Wilhelm Kleinstr. 27, CH-4025 Basel, Switzerland. christian.cajochen@pukbasel.ch  
  Corporate Author Thesis  
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  Language English Summary Language Original Title  
  Series Editor Series Title Abbreviated Series Title  
  Series Volume Series Issue Edition  
  ISSN 0021-972X ISBN Medium  
  Area Expedition Conference  
  Notes PMID:15585546 Approved no  
  Call Number LoNNe @ kagoburian @ Serial 728  
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Author Gooley, J.J.; Rajaratnam, S.M.W.; Brainard, G.C.; Kronauer, R.E.; Czeisler, C.A.; Lockley, S.W. url  doi
openurl 
  Title Spectral responses of the human circadian system depend on the irradiance and duration of exposure to light Type Journal Article
  Year 2010 Publication Science Translational Medicine Abbreviated Journal Sci Transl Med  
  Volume 2 Issue (up) 31 Pages 31ra33  
  Keywords Adolescent; Adult; Circadian Rhythm/physiology/*radiation effects; Dose-Response Relationship, Radiation; Humans; Light; Melatonin/secretion; Photoperiod; Phototherapy; Retina/physiology/radiation effects; Retinal Cone Photoreceptor Cells/physiology/radiation effects; Retinal Ganglion Cells/physiology/radiation effects; Rod Opsins/physiology; Young Adult; blue light; light at night; melatonin; melanopsin; light therapy  
  Abstract In humans, modulation of circadian rhythms by light is thought to be mediated primarily by melanopsin-containing retinal ganglion cells, not rods or cones. Melanopsin cells are intrinsically blue light-sensitive but also receive input from visual photoreceptors. We therefore tested in humans whether cone photoreceptors contribute to the regulation of circadian and neuroendocrine light responses. Dose-response curves for melatonin suppression and circadian phase resetting were constructed in subjects exposed to blue (460 nm) or green (555 nm) light near the onset of nocturnal melatonin secretion. At the beginning of the intervention, 555-nm light was equally effective as 460-nm light at suppressing melatonin, suggesting a significant contribution from the three-cone visual system (lambda(max) = 555 nm). During the light exposure, however, the spectral sensitivity to 555-nm light decayed exponentially relative to 460-nm light. For phase-resetting responses, the effects of exposure to low-irradiance 555-nm light were too large relative to 460-nm light to be explained solely by the activation of melanopsin. Our findings suggest that cone photoreceptors contribute substantially to nonvisual responses at the beginning of a light exposure and at low irradiances, whereas melanopsin appears to be the primary circadian photopigment in response to long-duration light exposure and at high irradiances. These results suggest that light therapy for sleep disorders and other indications might be optimized by stimulating both photoreceptor systems.  
  Address Division of Sleep Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA  
  Corporate Author Thesis  
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  Language English Summary Language Original Title  
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  Series Volume Series Issue Edition  
  ISSN 1946-6234 ISBN Medium  
  Area Expedition Conference  
  Notes PMID:20463367 Approved no  
  Call Number IDA @ john @ Serial 294  
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Author Brainard, G.C.; Sliney, D.; Hanifin, J.P.; Glickman, G.; Byrne, B.; Greeson, J.M.; Jasser, S.; Gerner, E.; Rollag, M.D. url  doi
openurl 
  Title Sensitivity of the human circadian system to short-wavelength (420-nm) light Type Journal Article
  Year 2008 Publication Journal of Biological Rhythms Abbreviated Journal J Biol Rhythms  
  Volume 23 Issue (up) 5 Pages 379-386  
  Keywords Human Health; Adult; Circadian Rhythm/*radiation effects; Female; Humans; *Light; Male; Melatonin/metabolism; Models, Biological; Neurosecretory Systems; Photons; Pineal Gland/metabolism; Retinal Ganglion Cells/*metabolism; Vision, Ocular  
  Abstract The circadian and neurobehavioral effects of light are primarily mediated by a retinal ganglion cell photoreceptor in the mammalian eye containing the photopigment melanopsin. Nine action spectrum studies using rodents, monkeys, and humans for these responses indicate peak sensitivities in the blue region of the visible spectrum ranging from 459 to 484 nm, with some disagreement in short-wavelength sensitivity of the spectrum. The aim of this work was to quantify the sensitivity of human volunteers to monochromatic 420-nm light for plasma melatonin suppression. Adult female (n=14) and male (n=12) subjects participated in 2 studies, each employing a within-subjects design. In a fluence-response study, subjects (n=8) were tested with 8 light irradiances at 420 nm ranging over a 4-log unit photon density range of 10(10) to 10(14) photons/cm(2)/sec and 1 dark exposure control night. In the other study, subjects (n=18) completed an experiment comparing melatonin suppression with equal photon doses (1.21 x 10(13) photons/cm(2)/sec) of 420 nm and 460 nm monochromatic light and a dark exposure control night. The first study demonstrated a clear fluence-response relationship between 420-nm light and melatonin suppression (p<0.001) with a half-saturation constant of 2.74 x 10(11) photons/cm(2)/sec. The second study showed that 460-nm light is significantly stronger than 420-nm light for suppressing melatonin (p<0.04). Together, the results clarify the visible short-wavelength sensitivity of the human melatonin suppression action spectrum. This basic physiological finding may be useful for optimizing lighting for therapeutic and other applications.  
  Address Department of Neurology, Thomas Jefferson University, Philadelphia, PA 19107, USA. george.brainard@jefferson.edu  
  Corporate Author Thesis  
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  Language English Summary Language Original Title  
  Series Editor Series Title Abbreviated Series Title  
  Series Volume Series Issue Edition  
  ISSN 0748-7304 ISBN Medium  
  Area Expedition Conference  
  Notes PMID:18838601 Approved no  
  Call Number LoNNe @ kagoburian @ Serial 724  
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