1,720,986 research outputs found

    Circadian Clock and OxInflammation: Functional Crosstalk in Cutaneous Homeostasis

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    Circadian rhythms are biological oscillations that occur with an approximately 24 h period and optimize cellular homeostasis and responses to environmental stimuli. A growing collection of data suggests that chronic circadian disruption caused by novel lifestyle risk factors such as shift work, travel across time zones, or irregular sleep-wake cycles has long-term consequences for human health. Among the multiplicity of physiological systems hypothesized to have a role in the onset of pathologies in case of circadian disruption, there are redox-sensitive defensive pathways and inflammatory machinery. Due to its location and barrier physiological role, the skin is a prototypical tissue to study the influence of environmental insults induced OxInflammation disturbance and circadian system alteration. To better investigate the link among outdoor stressors, OxInflammation, and circadian system, we tested the differential responses of keratinocytes clock synchronized or desynchronized, in an in vitro inflammatory model exposed to O3. Being both NRF2 and NF-κB two key redox-sensitive transcription factors involved in cellular redox homeostasis and inflammation, we analyzed their activation and expression in challenged keratinocytes by O3. Our results suggest that a synchronized circadian clock not only facilitates the protective role of NRF2 in terms of a faster and more efficient defensive response against environmental insults but also moderates the cellular damage resulting from a condition of chronic inflammation. Our results bring new insights on the role of circadian clock in regulating the redox-inflammatory crosstalk influenced by O3 and possibly can be extrapolated to other pollutants able to affect the oxinflammatory cellular processes

    Metabotropic glutamate receptors 1 and 5 differentially regulate bulbar dopaminergic cell function

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    Effects of activation of metabotropic glutamatergic receptors (mGluR) were investigated in mouse dopaminergic olfactory bulb neurons. After blockage of ionotropic receptors, focal application of glutamate or of group I/II mGluR agonist t-ACPD resulted in a depolarization, paralleled by an inward current in voltage-clamp conditions. The Group I agonist DHPG induced a depolarization, which could be largely blocked by mGluR1 antagonists. The DHPG action i) was prevented by buffering intracellular Ca2+ with BAPTA and by a phospholipase C inhibitor; ii) was not affected by the block of Ca2+ entry, and iii) was blocked by inhibitors of the Na+/Ca2+ exchanger. These observations were interpreted as a mGluR1-mediated intracellular Ca2+ release, followed by the activation of an electrogenic Na+/Ca2+ exchanger. The mGluR5 agonist CHPG induced a hyperpolarization of membrane potential, resulting in a decrease of the spontaneous firing frequency. CHPG induced i) a decrease in membrane resistance; ii) an increase in the action potential repolarization rate, and iii) an increase in the amplitude of the afterhyperpolarization. This was interpreted as a mGluR5-mediated opening of a K+ conductance. These data suggest that mGluR1 and mGluR5 play different and non-overlapping roles in the regulation of the excitability of bulbar dopaminergic neurons. © 2010 Elsevier B.V. All rights reserved

    Influence of temperature on the liver circadian clock in the ruin lizard Podarcis sicula

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    Reptiles represent an interesting animal model to investigate the influence of temperature on molecular circadian clocks. The ruin lizard Podarcis sicula lives in a continental climate and it is subjected to wide range of environmental temperatures during the course of the year. As consequence, ruin lizard daily activity pattern includes either the hibernation or periods of inactivity determined by hypothermia. Here we showed the rhythmic expression of two clock genes, lPer2 and lClock, in the liver of active lizards exposed to summer photo-thermoperiodic conditions. Interestingly, the exposition of lizards to hypothermic conditions, typical of winter season, induced a strong dampening of clock genes mRNA rhythmicity with a coincident decrease of levels. We also examined the qualitative and quantitative distribution of lPER2 and lCLOCK protein in different cellular compartments during the 24-h cycle. In the liver of active lizards both proteins showed a rhythmic expression profile in all cellular compartments. After 3 days at 6°C, some temporal fluctuations of the lCLOCK and lPER2 are still detectable, although, with some marked modifications in respect to the values detected in the liver of active lizards. Besides demonstrating the influence of low temperature on the lizard liver circadian oscillators, present results could provide new essential information for comparative studies on the influence of temperature on the circadian system across vertebrate classes. © 2007 Wiley-Liss, Inc

    Going Beyond Counting First Authors in Author Co-citation Analysis

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    The present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed

    Circadian clock and oxidative Stress: functional cross-talk in skin homeostasis

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    Ozone is among the most toxic environmental stressors to which we are continuously exposed. Due to its critical location, skin is one of the most susceptible tissues to oxidative stress damaging effect of ozone. An increasing collection of data suggests a significant role of circadian system in regulation of cellular response to oxidative stress. However, the molecular mechanism linking circadian clock and antioxidant pathway it is not completely understood. Here we investigated a possible protective role of entrained circadian clock to ozone induced damage in keratinocytes, the main cellular component of human epidermis. Our results showed that, clock-synchronized keratinocytes compared to arrhythmic ones exhibited a more efficient antioxidant response, attested by a faster activation of the master antioxidant regulatory factor NRF2. Moreover, analysis of clock gene expression profiles reveals a more rapid induction of the cardinal clock gene Bmal1 in entrained cells. Based on these findings, we suppose that an adequate coordination of circadian system and antioxidant pathway might be essential to maintain homeostasis in the skin. Alteration of metabolic pathways occurred in neurological diseases or in irregular schedule of life activity could negatively influence tissue gene expression programs and associated organ physiology via its effect on the circadian system

    Variations on the Author

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    “Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship

    Appropriate Similarity Measures for Author Cocitation Analysis

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    We provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis

    Individual differences and knockout in zebrafish reveal similar cognitive effects of BDNF between teleosts and mammals

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    The remarkable similarities in cognitive performance between teleosts and mammals suggest that the underlying cognitive mechanisms might also be similar in these two groups. We tested this hypothesis by assessing the effects of the brain-derived neurotrophic factor (BDNF), which is critical for mammalian cognitive functioning, on fish's cognitive abilities. We found that individual differences in zebrafish's learning abilities were positively correlated with bdnf expression. Moreover, a CRISPR/Cas9 mutant zebrafish line that lacks the BDNF gene (bdnf(-/-)) showed remarkable learning deficits. Half of the mutants failed a colour discrimination task, whereas the remaining mutants learned the task slowly, taking three times longer than control bdnf(+/+) zebrafish. The mutants also took twice as long to acquire a T-maze task compared to control zebrafish and showed difficulties exerting inhibitory control. An analysis of habituation learning revealed that cognitive impairment in mutants emerges early during development, but could be rescued with a synthetic BDNF agonist. Overall, our study indicates that BDNF has a similar activational effect on cognitive performance in zebrafish and in mammals, supporting the idea that its function is conserved in vertebrates

    Expression of glucocorticoid-receptor covaries with individual differences in visual lateralisation in zebrafish

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    Cerebral lateralisation, the differential cognitive processing in the two brain hemispheres, is variable among individuals in most vertebrates. Part of this variance has been attributed to plasticity in response to environmental stressors experienced by individuals and might be therefore mediated by the action of glucocorticoids (GCs). Accordingly, we tested the hypothesis that the GC pathway related to stress, which involved its cognate receptor GR, affects individuals' lateralisation. First, we characterised the behavioural lateralisation phenotype of outbred wild-type zebrafish using three different tests: a motor test, a test involving a visual social stimulus (subject's mirror image), and a test with a visual stimulus of negative valence (predator). Subsequently, we quantified the expression of the gr gene in the brain of the subjects, specifically in the telencephalon and mesencephalon of each hemisphere. Our zebrafish population exhibited individual variation but no population-level bias in behavioural lateralisation and gr expression across the two hemispheres. When we correlated the lateralisation patterns in the behavioural tests with gr expression, we observed that individuals with higher mesencephalic expression of gr in the right hemisphere were more inclined to process their mirror image using the right hemisphere. Additionally, individuals with higher gr expression in the telencephalon, showed reduced lateralisation in processing the predator stimulus. This study supports the hypothesis that GCs might affect some aspects of lateralisation, in particular those related to visual stimuli, thought the GC-Gr pathway and suggests that intraspecific variance in lateralisation could result from individual differences in gr expression
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