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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 Kempinger, L.; Dittmann, R.; Rieger, D.; Helfrich-Forster, C. url  doi
openurl 
  Title The nocturnal activity of fruit flies exposed to artificial moonlight is partly caused by direct light effects on the activity level that bypass the endogenous clock Type Journal Article
  Year 2009 Publication Chronobiology International Abbreviated Journal Chronobiol Int  
  Volume (down) 26 Issue 2 Pages 151-166  
  Keywords ARNTL Transcription Factors; Animals; Basic Helix-Loop-Helix Transcription Factors/genetics/metabolism; Behavior, Animal/physiology; Biological Clocks/*physiology; CLOCK Proteins; Circadian Rhythm/*physiology; Darkness; Drosophila Proteins/genetics/metabolism; Drosophila melanogaster/*physiology; *Light; *Moon; Motor Activity/*physiology; Nuclear Proteins/genetics/metabolism; Period Circadian Proteins; Photoperiod; Transcription Factors/genetics/metabolism  
  Abstract Artificial moonlight was recently shown to shift the endogenous clock of fruit flies and make them nocturnal. To test whether this nocturnal activity is partly due to masking effects of light, we exposed the clock-mutants per(01), tim(01), per(01);tim(01), cyc(01), and Clk(JRK) to light/dark and light/dim-light cycles and determined the activity level during the day and night. We found that under moonlit nights, all clock mutants shifted their activity significantly into the night, suggesting that this effect is independent of the clock. We also recorded the flies under continuous artificial moonlight and darkness to judge the effect of dim constant light on the activity level. All mutants, except Clk(JRK) flies, were significantly more active under artificial moonlight conditions than under complete darkness. Unexpectedly, we found residual rhythmicity of per(01) and especially tim(01) mutants under these conditions, suggesting that TIM and especially PER retained some activity in the absence of its respective partner. Nevertheless, as even the double mutants and the cyc(01) and Clk(JRK) mutants shifted their activity into the night, we conclude that dim light stimulates the activity of fruit flies in a clock-independent manner. Thus, nocturnal light has a twofold influence on flies: it shifts the circadian clock, and it increases nocturnal activity independently of the clock. The latter was also observed in some primates by others and might therefore be of a more general validity.  
  Address Institute of Zoology, University of Regensburg, Regensburg, 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 0742-0528 ISBN Medium  
  Area Expedition Conference  
  Notes PMID:19212834 Approved no  
  Call Number IDA @ john @ Serial 113  
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Author Cajochen, C.; Jud, C.; Munch, M.; Kobialka, S.; Wirz-Justice, A.; Albrecht, U. url  doi
openurl 
  Title Evening exposure to blue light stimulates the expression of the clock gene PER2 in humans Type Journal Article
  Year 2006 Publication The European Journal of Neuroscience Abbreviated Journal Eur J Neurosci  
  Volume (down) 23 Issue 4 Pages 1082-1086  
  Keywords Human Health; Adult; Color; Darkness; Dose-Response Relationship, Radiation; Female; Gene Expression/*radiation effects; Humans; *Light; Male; Melatonin/metabolism; Mucous Membrane/metabolism/radiation effects; Nuclear Proteins/genetics/*metabolism; Period Circadian Proteins; Transcription Factors/genetics/*metabolism  
  Abstract We developed a non-invasive method to measure and quantify human circadian PER2 gene expression in oral mucosa samples and show that this gene oscillates in a circadian (= about a day) fashion. We also have the first evidence that induction of human PER2 expression is stimulated by exposing subjects to 2 h of light in the evening. This increase in PER2 expression was statistically significant in comparison to a non-light control condition only after light at 460 nm (blue) but not after light exposure at 550 nm (green). Our results indicate that the non-image-forming visual system is involved in human circadian gene expression. The demonstration of a functional circadian machinery in human buccal samples and its response to light opens the door for investigation of human circadian rhythms at the gene level and their associated disorders.  
  Address Centre for Chronobiology, Psychiatric University Clinics, University of Basel, CH-4025 Basel, Switzerland. christian.cajochen@unibas.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 0953-816X ISBN Medium  
  Area Expedition Conference  
  Notes PMID:16519674 Approved no  
  Call Number LoNNe @ kagoburian @ Serial 727  
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Author Filipski, E.; Li, X.M.; Levi, F. url  doi
openurl 
  Title Disruption of circadian coordination and malignant growth Type Journal Article
  Year 2006 Publication Cancer Causes & Control : CCC Abbreviated Journal Cancer Causes Control  
  Volume (down) 17 Issue 4 Pages 509-514  
  Keywords Human Health; Animals; Biological Clocks; Body Temperature; Cell Cycle Proteins; Cell Line, Tumor; Chronobiology Disorders/*complications/physiopathology; Circadian Rhythm; Corticosterone/blood; DNA-Binding Proteins/metabolism; Jet Lag Syndrome/complications/physiopathology; Lymphocyte Count; Mice; Neoplasm Transplantation; Nuclear Proteins/metabolism; Nuclear Receptor Subfamily 1, Group D, Member 1; Osteosarcoma/*pathology/physiopathology; Pancreatic Neoplasms/*pathology/physiopathology; Period Circadian Proteins; Receptors, Cytoplasmic and Nuclear/metabolism; Suprachiasmatic Nucleus/physiopathology; Transcription Factors/metabolism  
  Abstract Altered circadian rhythms predicted for poor survival in patients with metastatic colorectal or breast cancer. An increased incidence of cancers has been reported in flying attendants and in women working predominantly at night. To explore the contribution of circadian structure to tumor growth we ablated the 24-h rest-activity cycle and markedly altered the rhythms in body temperature, serum corticosterone and lymphocyte count in mice by complete stereotaxic destruction of the suprachiasmatic nuclei (SCN) or by subjecting the mice to experimental chronic jet-lag. Such disruption of circadian coordination significantly accelerated malignant growth in two transplantable tumor models, Glasgow osteosarcoma and Pancreatic adenocarcinoma. The mRNA expression of clock genes per2 and reverb-alpha in controls displayed significant circadian rhythms in the liver (Cosinor, p=0.006 and p=0.003, respectively) and in the tumor (p=0.04 and p<0.001, respectively). Both rhythms were suppressed in the liver and in the tumor of jet lagged mice. This functional disturbance of molecular clock resulted in down regulation of p53 and overexpression of c-Myc, two effects which may favor cancer growth. CONCLUSIONS: These results indicate that circadian system could play an important role in malignant growth control. This should be taken into consideration in cancer prevention and therapy.  
  Address INSERM E 354 Cancer Chronotherapeutics, Hopital Paul Brousse, Villejuif, France. filipski@vjf.inserm.fr  
  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 0957-5243 ISBN Medium  
  Area Expedition Conference  
  Notes PMID:16596304 Approved no  
  Call Number LoNNe @ kagoburian @ Serial 748  
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Author Bray, M.S.; Young, M.E. url  doi
openurl 
  Title Chronobiological Effects on Obesity Type Journal Article
  Year 2012 Publication Current Obesity Reports Abbreviated Journal Curr Obes Rep  
  Volume (down) 1 Issue 1 Pages 9-15  
  Keywords Human Health; Chronobiological effects; Circadian; Gene; Molecular clock; Obesity; Rhythm; Shift work; Sleep; Transcription  
  Abstract The development of obesity is the consequence of a multitude of complex interactions between both genetic and environmental factors. It has been suggested that the dramatic increase in the prevalence of obesity over the past 30 years has been the result of environmental changes that have enabled the full realization of genetic susceptibility present in the population. Among the many environmental alterations that have occurred in our recent history is the ever-increasing dyssynchrony between natural cycles of light/dark and altered patterns of sleep/wake and eating behavior associated with our “24-hour” lifestyle. An extensive research literature has established clear links between increased risk for obesity and both sleep deprivation and shift work, and our understanding of the consequences of such dyssynchrony at the molecular level is beginning to emerge. Studies linking alterations in cellular circadian clocks to metabolic dysfunction point to the increasing importance of chronobiology in obesity etiology.  
  Address Departments of Epidemiology and Genetics, University of Alabama at Birmingham, Birmingham, AL  
  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 2162-4968 ISBN Medium  
  Area Expedition Conference  
  Notes PMID:23682347; PMCID:PMC3653336 Approved no  
  Call Number LoNNe @ christopher.kyba @ Serial 510  
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