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Collects eighteen stories featuring Anna, Elsa, and the other characters from the movie \"Frozen.\"

Early preimplantation embryos are extremely sensitive to dysregulation of cell volume, which can lead to developmental arrest. It was previously shown that mouse embryos at the two-cell stage respond to a cell volume decrease by quickly activating Na+/H+ exchange via a signaling mechanism that involves the tyrosine kinase Janus kinase 2 (JAK2). However, it was not known whether this mechanism is active at the one-cell stage, when embryos are most sensitive to perturbed cell volume. Na+/H+ exchanger activity elicited by an induced cell volume decrease was significantly lower at the mid one-cell stage than at the late one-cell stage or during the two-cell stage. This activity could be completely blocked by the broad specificity tyrosine kinase inhibitor genistein at either stage, but only at the two-cell stagewas there a substantial component of activity that was sensitive to low concentrations of the JAK2-selective inhibitors TG101348 or ruxolitinib. Western blots to detect active JAK2 phosphorylated on tyrosine Y1007/8 revealed that JAK2 became substantially phosphorylated in response to a cell volume decrease at the mid two-cell, but not mid one-cell stage. Such cell volume decrease-induced JAK2 phosphorylation appeared by the late one-cell stage. At least in part this appears to be due to an increase in total JAK2 protein at the late one-cell stage. Furthermore, TG101348 impaired maintenance of cell volume at the two-cell, but not mid one-cell, stages. Thus, cell volume homeostasis requiring Na+/H+ exchange signaled by JAK2 first becomes prominent during mouse embryonic development at the late one-cell stage. Summary Sentence The major mechanism of acute recovery from decreased cell volume in somatic cells, activation of sodium hydrogen exchanger NHE1 (SLC9A1) by the tyrosine kinase Janus kinase 2 (JAK2), first develops at the late one-cell stage of mouse embryo.

Aims and ObjectivesCollective competence of a healthcare team is key to patient safety and quality in healthcare. This presentation reports part of a UK-Japan interdisciplinary research project on emergency care team interactions, focusing on gaze behaviour. The study investigates how healthcare professionals achieve joint attention for joint action. To describe the complex practice, we are developing a programme to automatically annotate multiple gaze data. Method and DesignFor a pilot study, a small-scale simulation session was filmed in a large teaching hospital in the UK with two pairs of eye-tracking glasses (Tobii Pro Glasses 2) worn by an ED consultant and an ED nurse. The scenario was a collapse in a ward, which involved two simulated patients, one acting as a female patient aged 72 and the other as her sister. Video images of the first three minutes of the recording were extracted from two eye-trackers, and the moments when a doctor and a nurse shared a field of view were automatically annotated by utilizing the feature point detection technology. Results and ConclusionThree forms of joint gaze behaviours were recognised: joint attention (two people look at the same part of an object), narrow joint field view (two people look at different parts of an object, see figure 1), and broad joint field view (two people share a view field but look at different objects). Although it is still preliminary, the technology enables researchers to analyse shared field view, in addition to joint attention, between team members. This has great potential for further research on health team interactions and its application to medical education.Abstract 2238 Figure 1Still image: annotated images of a narrow joint field view between the doctor and the nurse.

The Greatwall kinase inhibits PP2A-B55 phosphatase activity during mitosis to stabilise critical Cdk1-driven mitotic phosphorylation. Although Greatwall represents a potential oncogene and prospective therapeutic target, our understanding of the cellular and molecular consequences of chemical Greatwall inactivation remains limited. To address this, we introduce C-604, a highly selective Greatwall inhibitor, and characterise both immediate and long-term cellular responses to the chemical attenuation of Greatwall activity. We demonstrate that Greatwall inhibition causes systemic destabilisation of the mitotic phosphoproteome, premature mitotic exit and pleiotropic cellular pathologies. Importantly, we show that the cellular and molecular abnormalities associated with reduced Greatwall activity are specifically dependent on the B55α isoform, rather than other B55 variants, underscoring PP2A-B55α phosphatases as key mediators of the cytotoxic effects of Greatwall-targeting agents in human cells. Additionally, we establish that sensitivity to Greatwall inhibition varies in different cell line models and that dependency on Greatwall activity reflects the balance between Greatwall and B55α expression levels. Our findings highlight Greatwall dependency as a cell-specific vulnerability and propose the B55α-to-Greatwall expression ratio as a predictive biomarker of cellular responses to Greatwall-targeted therapeutics. The authors develop and characterise a selective Greatwall inhibitor, C-604, and show that its cytotoxicity stems from PP2A-B55α hyperactivation. They identify B55α and Greatwall levels as biomarkers of responses to Greatwall-targeted therapy.

The enzyme 5,10-methylenetetrahydrofolate reductase (MTHFR) links the folate cycle that produces one-carbon units with the methionine cycle that converts these into S -adenosylmethionine (SAM), the universal methyl donor for almost all methyltransferases. Previously, MTHFR has been shown to be regulated by phosphorylation, which suppresses its activity. SAM levels have been shown to increase substantially soon after initiation of meiotic maturation of the mouse germinal vesicle (GV) stage oocyte and then decrease back to their original low level in mature second meiotic metaphase (MII) eggs. As MTHFR controls the entry of one-carbon units into the methionine cycle, it is a candidate regulator of the SAM levels in oocytes and eggs. Mthfr transcripts are expressed in mouse oocytes and preimplantation embryos and MTHFR protein is present at each stage. In mature MII eggs, the apparent molecular weight of MTHFR was increased compared with GV oocytes, which we hypothesized was due to increased phosphorylation. The increase in apparent molecular weight was reversed by treatment with lambda protein phosphatase (LPP), indicating that MTHFR is phosphorylated in MII eggs. In contrast, LPP had no effect on MTHFR from GV oocytes, 2-cell embryos, or blastocysts. MTHFR was progressively phosphorylated after initiation of meiotic maturation, reaching maximal levels in MII eggs before decreasing again after egg activation. As phosphorylation suppresses MTHFR activity, it is predicted that MTHFR becomes inactive during meiotic maturation and is minimally active in MII eggs, which is consistent with the reported changes in SAM levels during mouse oocyte maturation.

The cultural sensation known as the movida madrileña has been a subject of fascination since its origins in Madrid throughout the late 1970s and 1980s. This dissertation examines one of its most famous products, the journal La Luna de Madrid (1983-1988). This dissertation explores examples of illustration and photography throughout the journal's first seven issues, from November 1983-May 1984. Concentrating on the use of strategies from tourism promotion, this framework reveals how visual elements work with text to encourage readers to become tourists of modern Madrid. Chapter One provides a background of how tourism images and messages have shaped perceptions of Spanish cultural identity from dictatorship to democracy, from the 1950s to the 1980s. Within this context, it is possible to understand the efficacy of tourism promotional tropes in portraying an attractive vision of Madrid in the journal's pages. Chapter Two emphasizes how the movida represented the positive changes developing in Post-Franco Madrid, leading local and regional political leaders to employ this phenomenon in programs focused upon cultural revitalization and civic participation. This chapter argues that the movida not only appears as the main cultural tendency of interest within La Luna de Madrid , but that its treatment within the journal allows it to be viewed as an attractive tourism destination. Chapter Three and Chapter Four provide close readings and in-depth visual analysis of certain repeated illustrated and photographic segments within La Luna de Madrid from November 1983-May 1984. By narrowing the research scope to these first seven months of publication, we can examine how patterns of viewing are established that encourage readers to contemplate selective historical and contemporary cultural trends in Madrid from the perspective of a tourist. The combination of text and imagery at work in La Luna de Madrid reinforces the efforts of the various creative practices of the movida while giving readers opportunities to participate in this cultural scene. This dissertation argues that experiments with the visual and rhetorical tropes of tourism in La Luna de Madrid attempt to foster favorable impressions of the Spanish capital's past and present.

The Greatwall kinase inhibits PP2A-B55 phosphatase activity during mitosis to stabilise critical Cdk1-driven mitotic phosphorylation. Although Greatwall represents a potential oncogene and prospective therapeutic target, our understanding of cellular and molecular consequences of chemical Greatwall inactivation remains limited. To address this, we introduce C-604, a highly selective Greatwall inhibitor, and characterise both immediate and long-term cellular responses to the chemical attenuation of Greatwall activity. We demonstrate that Greatwall inhibition causes systemic destabilisation of the mitotic phosphoproteome, premature mitotic exit and pleiotropic cellular pathologies. Importantly, we demonstrate that the cellular and molecular abnormalities linked to reduced Greatwall activity are specifically dependent on the B55α isoform rather than other B55 variants, underscoring PP2A-B55α phosphatases as key mediators of cytotoxic effects of Greatwall-targeting agents in human cells. Additionally, we show that sensitivity to Greatwall inhibition varies in different cell line models and that dependency on Greatwall activity reflects the balance between Greatwall and B55α expression levels. Our findings highlight Greatwall dependency as a cell-specific vulnerability and propose the B55α-to-Greatwall expression ratio as a predictive biomarker of cellular responses to Greatwall-targeted therapeutics.

A Day in the Life of the Digital Humanities (Day of DH) is a community documentation project that brings together digital humanists from around the world to document what they do on one day, typically March 18. The goal of the project, which has been run three times since 2009, is to bring together participants to reflect on the question, “Just what do computing humanists really do?” To do this, participants document their day through photographs and commentary using one of the Day of DH blogs set up for them. The collection of these journals (with links, tags, and comments) is, after editing, made available online. This paper discusses the design of this social project, from the ethical issues raised to the final web of journals and shares some of the lessons we have learned. One of the major challenges of social media is getting participation. We made participating easy by personally inviting a seed group, choosing an accessible technology, maintaining a light but constant level of communication prior to the event, and asking only for a single day of commitment. In addition, we tried to make participation at least rewarding in formal academic terms by structuring the Day of DH as a collaborative publication. In terms of improvements, we have over the iterations changed the handling ethics clearances for images and connected to other social media like Twitter.