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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 (down) 109 Issue 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  
  Publisher Place of Publication Editor  
  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  
Permanent link to this record
 

 
Author van der Burght, B.W.; Hansen, M.; Olsen, J.; Zhou, J.; Wu, Y.; Nissen, M.H.; Sparrow, J.R. url  doi
openurl 
  Title Early changes in gene expression induced by blue light irradiation of A2E-laden retinal pigment epithelial cells Type Journal Article
  Year 2013 Publication Acta Ophthalmologica Abbreviated Journal Acta Ophthalmol  
  Volume (down) 91 Issue 7 Pages e537-45  
  Keywords Apoptosis; Cell Line; Cell Survival; Gene Expression Regulation/*physiology; Humans; Light; Lipofuscin/genetics; Oligonucleotide Array Sequence Analysis; Principal Component Analysis; Pyridinium Compounds; RNA, Messenger/genetics; Real-Time Polymerase Chain Reaction; Retinal Pigment Epithelium/metabolism/pathology/*radiation effects; Retinoids/*genetics; Transcriptome; A2e; age-related macular degeneration; apoptosis; complement cascade; gene expression; retinal pigment epithelial cells; blue light; retinal pigment epithelial; epigenetics  
  Abstract PURPOSE: Accumulation of bisretinoids as lipofuscin in retinal pigment epithelial (RPE) cells is implicated in the pathogenesis of some blinding diseases including age-related macular degeneration (AMD). To identify genes whose expression may change under conditions of bisretinoid accumulation, we investigated the differential gene expression in RPE cells that had accumulated the lipofuscin fluorophore A2E and were exposed to blue light (430 nm). METHODS: A2E-laden RPE cells were exposed to blue light (A2E/430 nm) at various time intervals. Cell death was quantified using Dead Red staining, and RNA levels for the entire genome was determined using DNA microarrays (Affymetrix GeneChip Human Genome 2.0 Plus). Array results for selected genes were confirmed by real-time reverse-transcriptase polymerase chain reaction. RESULTS: Principal component analysis revealed that the A2E-laden RPE cells irradiated with blue light were clearly distinguishable from the control samples. We found differential regulation of genes belonging to the following functional groups: transcription factors, stress response, apoptosis and immune response. Among the last mentioned were downregulation of four genes that coded for proteins that have an inhibitory effect on the complement cascade: (complement factor H, complement factor H-related 1, complement factor I and vitronectin) and of two belonging to the classical pathway (complement component 1, s subcomponent and complement component 1, r subcomponent). CONCLUSION: This study demonstrates that blue light irradiation of A2E-laden RPE cells can alter the transcription of genes belonging to different functional pathways including stress response, apoptosis and the immune response. We suggest that these molecules may be associated to the pathogenesis of AMD and can potentially serve as future therapeutic targets.  
  Address Department of International Health, Immunology and Microbiology, Eye Research Unit, University of Copenhagen, Copenhagen, DenmarkDepartment of Cellular and Molecular Medicine, University of Copenhagen, Copenhagen, DenmarkDepartment of Ophthalmology, Columbia University, New York, New York, USA  
  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 1755-375X ISBN Medium  
  Area Expedition Conference  
  Notes PMID:23742627 Approved no  
  Call Number IDA @ john @ Serial 346  
Permanent link to this record
 

 
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 (down) 90 Issue 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  
  Publisher Place of Publication Editor  
  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 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 (down) 89 Issue 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 Meng, Y.; He, Z.; Yin, J.; Zhang, Y.; Zhang, T. url  doi
openurl 
  Title Quantitative calculation of human melatonin suppression induced by inappropriate light at night Type Journal Article
  Year 2011 Publication Medical & Biological Engineering & Computing Abbreviated Journal Med Biol Eng Comput  
  Volume (down) 49 Issue 9 Pages 1083-1088  
  Keywords Algorithms; Circadian Rhythm/physiology/*radiation effects; Humans; *Lighting; Melatonin/*secretion; *Models, Biological; Retinal Cone Photoreceptor Cells/physiology/radiation effects; Retinal Ganglion Cells/physiology/radiation effects; Retinal Rod Photoreceptor Cells/physiology/radiation effects  
  Abstract Melatonin (C(1)(3)H(1)(6)N(2)O(2)) has a wide range of functions in the body. When is inappropriately exposed to light at night, human circadian rhythm will be interfered and then melatonin secretion will become abnormal. For nearly three decades great progresses have been achieved in analytic action spectra and melatonin suppression by various light conditions. However, so far few articles focused on the quantitative calculation of melatonin suppression induced by light. In this article, an algorithm is established, in which all the contributions of rods, cones, and intrinsically photosensitive retinal ganglion cells are considered. Calculation results accords with the experimental data in references very well, which indicate the validity of this algorithm. This algorithm can also interpret the rule of melatonin suppression varying with light correlated color temperature very well.  
  Address Photonics Research Center, School of Physics, Nankai University, Tianjin 300071, China  
  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 0140-0118 ISBN Medium  
  Area Expedition Conference  
  Notes PMID:21717231 Approved no  
  Call Number IDA @ john @ Serial 236  
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