Identification of a lipid-rich depot in the orbital cavity of the thirteen-lined ground squirrel

We discovered a previously undescribed orbital lipid depot in the thirteen-lined ground squirrel during the first ever magnetic resonance image (MRI) of this common experimental model of mammalian hibernation. In animals housed at constant ambient temperatures (5°C or 25°C, 12 h:12 h light:dark photoperiod), the volume of this depot increased in the autumn and decreased in the spring, suggesting an endogenous circannual pattern. Water-fat MRI revealed that throughout the year this depot is composed of ∼40% lipid, similar to brown adipose tissue (BAT). During arousal from torpor, thermal images showed higher surface temperatures near this depot before the rest of the head warmed, suggesting a thermoregulatory function. This depot, however, does not contain uncoupling protein 1, a BAT biomarker, or uncoupling protein 3. Histology shows blood vessels in close proximity to each other, suggesting it may serve as a vascular rete, perhaps to preferentially warm the eye and brain during arousals

Population pharmacokinetics-based recommendations for a single delayed or missed dose of nusinersen

Nusinersen is an antisense oligonucleotide approved for the treatment of spinal muscular atrophy. The drug is given intrathecally at 12 mg, beginning with 3 loading doses at 2-week intervals, a fourth loading dose 30 days thereafter, and maintenance doses at 4-month intervals. This population pharmacokinetic model was developed to clarify how to maintain targeted nusinersen exposure after an unforeseen one-time delay or missed dose. Simulations demonstrated that the impact of a one-time delay in dosing or a missed dose on median cerebrospinal fluid exposures depended on duration of interruption and the regimen phase in which it occurred. Delays in loading doses delayed reaching the peak trough concentration by approximately the duration of the interruption. Resumption of the regimen as soon as possible resulted in achieving steady state trough concentration upon completion of the loading phase. A short delay (30-90 days) during the maintenance phase led to prolonged lower median cerebrospinal fluid concentration if all subsequent doses were shifted by the same 4-month interval. However, administration of the delayed dose, followed by the subsequent dose as originally scheduled, rapidly restored trough concentration. If a dose must be delayed, patients should return to the original dosing schedule as soon as possible

Citizens without nations

To broach the question of whether citizenship could exist without (or beyond) community, this paper discusses genealogies of citizenship as membership that binds an individual to the community of birth (of the self or a parent). It is birthright as fraternity that blurs the boundary between citizenship and nationality. After briefly discussing recent critical studies on birthright citizenship (whether it is civic or ethnic or blood or soil) by Ayelet Shachar and Jacqueline Stevens, the paper discusses three critical genealogies of the relationship between birthright and citizenship by Max Weber, Hannah Arendt, and Michel Foucault. Although each provides a critical perspective into the question, Weber reduces citizenship to fraternity with nation and Arendt reduces citizenship to fraternity with the state. It is Foucault who illustrates racialization of fraternity as the connection between citizenship and nationality. Yet, since Foucault limits his genealogical investigations to the 18th and 19th centuries, a genealogy of fraternity of what he calls an immense biblical and Greek tradition remains for Derrida to articulate as a question of citizenship

Identification of a lipid-rich depot in the orbital cavity of the 13-lined ground squirrel

We discovered a previously undescribed orbital lipid depot in the 13-lined ground squirrel during the first ever magnetic resonance image (MRI) of this common experimental model of mammalian hibernation. In animals housed at constant ambient temperatures (5ºC or 25ºC, 12h L:12h D photoperiod) the volume of this depot increased in the autumn and decreased in the spring, suggesting an endogenous circannual pattern. Water-fat MRI revealed that throughout the year this depot is composed of ~40% lipid, similar to brown adipose tissue (BAT). During arousal from torpor, thermal images showed higher surface temperatures near this depot before the rest of the head warmed, suggesting a thermoregulatory function. This depot, however, does not contain uncoupling protein 1, a BAT biomarker, or uncoupling protein 3. Histology shows blood vessels in close proximity to each other, suggesting it may serve as a vascular rete, perhaps to preferentially warm the eye and brain during arousals

"Oh! What a tangled web we weave": Englishness, communicative leisure, identity work and the cultural web of the English folk morris dance scene

In this paper, we consider the relationship between Englishness and the English folk morris dance scene, considering how the latter draws from and reinforces the former. Englishness is considered within the context of the cultural web; a tool more often applied to business management but linked to a sociological viewpoint here. By doing so, we draw the connections between this structured business model and the cultural identity of Englishness. Then, we use the framework of the cultural web and theories of leisure, culture and identity to understand how morris dancers see their role as dancers and ‘communicative leisure’ agents in consciously defending Englishness, English traditions and inventions, the practices and traditions of folk and morris, and the various symbolic communities they inhabit. We argue that most morris dancers in our research become and maintain their leisured identities as dancers because they are attracted to the idea of tradition – even if that tradition is invented and open to change

Tourism and transformation: negotiating metaphors, experiencing change

WOS:000338007000001 (Nº de Acesso Web of Science)The article introduces this special issue on tourism and transformation. After offering a brief review of the place and significance of ‘transformation’ in social sciences studies of tourism – from ‘impact studies’ to ethnographies of tourists and, more recently, ‘tourist media studies’ – we propose to take one step further and focus our attention on the performativity and reflexivity of ‘transformation’. Our main argument is that much may be gained analytically by considering how notions and experiences of transformation are addressed, negotiated and purposefully deployed in tourism contexts. We conclude with an outline of each of the contributions to this special issue, stressing that the collection re-opens the issue of transformation in tourism and provides new insights into how experiences-turned metaphors and metaphors-turnedexperiences influence both the travel experience and the development of theory

Cultural experience tourist motives dimensionality : a cross-cultural study

This empirical research of tourists&rsquo; cultural experiences aims to advance theory by developing a measurement model of tourists&rsquo; motives towards attending cultural experiences for samples of Western and Asian tourists visiting Melbourne, Australia. Drawing upon Iso-Ahola&rsquo;s (1989) seeking/avoiding dichotomy theory for tourist motivation dimensions, the hypothesized dimensions primarily included escape and seeking-related dimensions, and some hedonic dimensions because of their relevance to aesthetic products (Hirschman &amp; Holbrook, 1982; Holbrook &amp; Hirschman, 1982), which are the context for this study. Exploratory factor analysis (EFA) and confirmatory factor analysis (CFA) were used to crossvalidate the underlying dimensionality structure of cultural experience motives. A four-factor model was extracted from the EFA consistent with some theoretical formulations and was retained in the CFA. Specific cultural language group differences for the motive dimensions were also hypothesized between Western and Asian tourist samples, and within the Chinese- and Japanese-speaking Asian tourist samples, but not within the different cultural groups of English-speaking Western tourists. These cross-cultural hypotheses were tested for the motive dimension measurement model using invariance testing in CFA. The findings for the motive dimensions differing by cultural group were not as expected. Significant cultural differences between Western and Asian tourists were not found, but a new finding of this study was significant differences between English-speaking tourists in their motives for attending cultural experiences. Marketing implications of these findings are also presented.<br /

The production and consumption activities relating to the celebrity artist

This paper considers the impact of the celebrity artist on the associated production and consumption activities. It also considers the role which entrepreneurial marketing plays in helping to create the celebrity artist aura. The artist Thomas Kinkade is used to illustrate how this occurs in practice. Here, authenticity and nostalgia dimensions are also influential factors. Underpinning these relationships are the roles played out by the media, including communication of celebrity artist identity, and the catalysing of its commodification within the celebrity artist brandscape. An enduring celebrity brand results due to the market creation activities of the celebrity artist. A conceptual model is developed which synthesises the factors behind the production and consumption of the celebrity artist which can stimulate further research. This paper provides innovative insight into the world of the celebrity artist by interrogating the market making and shaping devices behind successful production and consumption practices

Variations in TcdB Activity and the Hypervirulence of Emerging Strains of Clostridium difficile

Hypervirulent strains of Clostridium difficile have emerged over the past decade, increasing the morbidity and mortality of patients infected by this opportunistic pathogen. Recent work suggested the major C. difficile virulence factor, TcdB, from hypervirulent strains (TcdBHV) was more cytotoxic in vitro than TcdB from historical strains (TcdBHIST). The current study investigated the in vivo impact of altered TcdB tropism, and the underlying mechanism responsible for the differences in activity between the two forms of this toxin. A combination of protein sequence analyses, in vivo studies using a Danio rerio model system, and cell entry combined with fluorescence assays were used to define the critical differences between TcdBHV and TcdBHIST. Sequence analysis found that TcdB was the most variable protein expressed from the pathogenicity locus of C. difficile. In line with these sequence differences, the in vivo effects of TcdBHV were found to be substantially broader and more pronounced than those caused by TcdBHIST. The increased toxicity of TcdBHV was related to the toxin's ability to enter cells more rapidly and at an earlier stage in endocytosis than TcdBHIST. The underlying biochemical mechanism for more rapid cell entry was identified in experiments demonstrating that TcdBHV undergoes acid-induced conformational changes at a pH much higher than that of TcdBHIST. Such pH-related conformational changes are known to be the inciting step in membrane insertion and translocation for TcdB. These data provide insight into a critical change in TcdB activity that contributes to the emerging hypervirulence of C. difficile