1,720,959 research outputs found
Understanding the role of hepatic Neuronal PAS Domain Protein 2 (NPAS2) in circadian rhythmicity and cognition
Get PDFCircadian rhythms are highly conserved, endogenous biological oscillations with a periodicity of approximately 24 hours. These cycles have significant impacts on the sleep wake cycle, metabolism, mood, and cognition. A defining characteristic of these rhythms is their ability to be entrained by external stimuli, such as light and temperature, known as zeitgebers. Such rhythms are generated by a hierarchy of biological clocks which are centrally controlled by the suprachiasmatic nucleus (SCN) within the anterior hypothalamus. The SCN orchestrates phase synchronisation of clocks in peripheral tissues to allow for rhythmic regulation of endogenous processes throughout the day. Further understanding of circadian rhythms is important, since disruption of the clock and modern day non-circadian light schedules have been associated with cancers, metabolic diseases, and ageing.
One gene central to the rhythmic control of physiological processes is neuronal PAS domain protein 2 (NPAS2). NPAS2 is a bHLH-PAS domain containing protein which is the lesser-known paralog of CLOCK. Both CLOCK and NPAS2 are transcription factors that can form heterodimeric complexes with BMAL1 in the positive limb of the core circadian transcription-translation feedback loop to initiate the transcription of clock-controlled genes. The presence of one of the two, NPAS2 or CLOCK, is vital to maintain rhythmicity, but in the absence of one, the other will compensate in circadian functionality. In addition to circadian roles, NPAS2 has been implicated in cognition and emotional long-term memory. Knockdown of NPAS2 has also been seen to cause anxiolytic effects in behavioural paradigms, and striatal NPAS2 levels increase following acute and chronic stress, showing an additional role for the circadian gene in stress responses. Here, we utilised conditional peripheral knockouts of NPAS2 in mouse models to elucidate the role of hepatic NPAS2 in global circadian rhythmicity, locomotor activity, recognition memory and anxiety. These experiments were originally performed as a peripheral control for brain specific knockout mice.
To investigate peripheral NPAS2 roles in circadian period, phase and locomotor activity, pre- and post-natal hepatic NPAS2 knockout mice were employed in cycling and constant lighting conditions. These mouse models displayed no effect of loss of liver NPAS2 on entrainment or adaptation to constant lighting conditions, however, significant female-specific weight loss following social isolation was observed that was absent in C57BL/6J wild type controls. Most notably, significant sexual dimorphism in circadian parameters following extended time in constant light were revealed in control mice, indicating female superiority in light condition adaptation. This effect was lost in hepatic NPAS2 deleted models. Furthermore, novel object recognition tests uncovered significant differences in cognitive performance in constant light, in favour of post-natal hepatic NPAS2 knockout mice. Recognition tests also showed male superiority in the cognitive performance of control mice that was abolished in liver deleted NPAS2 mice. These results suggest a sex-specific mechanism by which hepatic NPAS2 may influence recognition memory.
A proposed method by which cognition is altered following hepatic NPAS2 loss is through aberrant circadian gene expression within the brain. Downstream investigations into circadian gene expression in the frontal lobe revealed altered expression and phase of core clock genes Bmal1, Clock and Rev-erbß in animals with hepatic NPAS2 loss. Additionally, loss of sexually dimorphic central circadian gene expression was also noted in post-natal NPAS2 liver knockouts. Taken together, these results suggest, first, that hepatic loss of NPAS2 may influence centrally mediated behaviours such as cognition, and second, suggest this may represent a sex-specific mechanism. To complement the findings of this work, brain specific NPAS2 knockout mice could be employed to investigate the impact of direct NPAS2 loss in the brain on cognition and circadian gene expression
Understanding the role of hepatic Neuronal PAS Domain Protein 2 (NPAS2) in circadian rhythmicity and cognition
Get PDFCircadian rhythms are highly conserved, endogenous biological oscillations with a periodicity of approximately 24 hours. These cycles have significant impacts on the sleep wake cycle, metabolism, mood, and cognition. A defining characteristic of these rhythms is their ability to be entrained by external stimuli, such as light and temperature, known as zeitgebers. Such rhythms are generated by a hierarchy of biological clocks which are centrally controlled by the suprachiasmatic nucleus (SCN) within the anterior hypothalamus. The SCN orchestrates phase synchronisation of clocks in peripheral tissues to allow for rhythmic regulation of endogenous processes throughout the day. Further understanding of circadian rhythms is important, since disruption of the clock and modern day non-circadian light schedules have been associated with cancers, metabolic diseases, and ageing.
One gene central to the rhythmic control of physiological processes is neuronal PAS domain protein 2 (NPAS2). NPAS2 is a bHLH-PAS domain containing protein which is the lesser-known paralog of CLOCK. Both CLOCK and NPAS2 are transcription factors that can form heterodimeric complexes with BMAL1 in the positive limb of the core circadian transcription-translation feedback loop to initiate the transcription of clock-controlled genes. The presence of one of the two, NPAS2 or CLOCK, is vital to maintain rhythmicity, but in the absence of one, the other will compensate in circadian functionality. In addition to circadian roles, NPAS2 has been implicated in cognition and emotional long-term memory. Knockdown of NPAS2 has also been seen to cause anxiolytic effects in behavioural paradigms, and striatal NPAS2 levels increase following acute and chronic stress, showing an additional role for the circadian gene in stress responses. Here, we utilised conditional peripheral knockouts of NPAS2 in mouse models to elucidate the role of hepatic NPAS2 in global circadian rhythmicity, locomotor activity, recognition memory and anxiety. These experiments were originally performed as a peripheral control for brain specific knockout mice.
To investigate peripheral NPAS2 roles in circadian period, phase and locomotor activity, pre- and post-natal hepatic NPAS2 knockout mice were employed in cycling and constant lighting conditions. These mouse models displayed no effect of loss of liver NPAS2 on entrainment or adaptation to constant lighting conditions, however, significant female-specific weight loss following social isolation was observed that was absent in C57BL/6J wild type controls. Most notably, significant sexual dimorphism in circadian parameters following extended time in constant light were revealed in control mice, indicating female superiority in light condition adaptation. This effect was lost in hepatic NPAS2 deleted models. Furthermore, novel object recognition tests uncovered significant differences in cognitive performance in constant light, in favour of post-natal hepatic NPAS2 knockout mice. Recognition tests also showed male superiority in the cognitive performance of control mice that was abolished in liver deleted NPAS2 mice. These results suggest a sex-specific mechanism by which hepatic NPAS2 may influence recognition memory.
A proposed method by which cognition is altered following hepatic NPAS2 loss is through aberrant circadian gene expression within the brain. Downstream investigations into circadian gene expression in the frontal lobe revealed altered expression and phase of core clock genes Bmal1, Clock and Rev-erbß in animals with hepatic NPAS2 loss. Additionally, loss of sexually dimorphic central circadian gene expression was also noted in post-natal NPAS2 liver knockouts. Taken together, these results suggest, first, that hepatic loss of NPAS2 may influence centrally mediated behaviours such as cognition, and second, suggest this may represent a sex-specific mechanism. To complement the findings of this work, brain specific NPAS2 knockout mice could be employed to investigate the impact of direct NPAS2 loss in the brain on cognition and circadian gene expression
Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe 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
Variations on the Author
Get PDF“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
Get PDFWe 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
Dispelling the Myths Behind First-author Citation Counts
Get PDFWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
koamabayili/VECTRON-author-checklist: VECTRON author checklist
No full textWe have done our best to complete the author checklist relating to the use of animals in the hut study. Note that the objective for the hut study was to evaluate the IRS treatment applications for residual efficacy against Anopheles mosquitoes, including the local An. coluzzii mosquito population. Cows were only used to attract mosquitoes into the huts and no tests were carried out directly on the cows. The author checklist is intended for use with studies where experiments are carried out on animals, which is why we have had such difficulty in completing this for the hut study, as many of the questions do not relate to how the cows were used
Author-wise bibliometric analysis based on entropy.
No full textAuthor-wise bibliometric analysis based on entropy.</p
- …
