Defining authorship in user-generated content : copyright struggles in The Game of Thrones

The notion of authorship is a core element in antipiracy campaigns accompanying an emerging copyright regime, worldwide. These campaigns are built on discourses that aim to ‘problematize’ the issues of ‘legality’ of content downloading practices, ‘protection’ for content creators and the alleged damage caused to creators’ livelihood by piracy. Under these tensions, fandom both subverts such discourses, through sharing and production practices, and legitimizes industry’s mythology of an ‘original’ author. However, how is the notion of authorship constructed in the cooperative spaces of fandom? The article explores the most popular fandom sites of A Song of Ice and Fire, the book series that inspires the TV-show Game of Thrones and argues that the notion of authorship is not one-dimensional, but rather consists of attributes that develop across three processes: community building, the creative and the industrial/production process. Here, fandom constructs a figure of the ‘author’ which, although more complex than the one presented by the industry in its copyright/anti-piracy campaigns, maintains the status quo of regulatory frameworks based on the idea of a ‘primary’ creator

Comprehensive behavioral testing in the R6/2 mouse model of Huntington's disease shows no benefit from CoQ10 or minocycline

Previous studies of the effects of coenzyme Q10 and minocycline on mouse models of Huntington's disease have produced conflicting results regarding their efficacy in behavioral tests. Using our recently published best practices for husbandry and testing for mouse models of Huntington's disease, we report that neither coenzyme Q10 nor minocycline had significant beneficial effects on measures of motor function, general health (open field, rotarod, grip strength, rearing-climbing, body weight and survival) in the R6/2 mouse model. The higher doses of minocycline, on the contrary, reduced survival. We were thus unable to confirm the previously reported benefits for these two drugs, and we discuss potential reasons for these discrepancies, such as the effects of husbandry and nutrition

Similarity, precedent and argument from analogy

In this paper, it is shown (1) that there are two schemes for argument from analogy that seem to be competitors but are not, (2) how one of them is based on a distinctive type of similarity premise, (3) how to analyze the notion of similarity using story schemes illustrated by some cases, (4) how arguments from precedent are based on arguments from analogy, and in many instances arguments from classification, and (5) that when similarity is defined by means of episode schemes, we can get a clearer idea of how it integrates with the use of argument from classification and argument from precedent in case-based reasoning by using a dialogue structure

Decreased Neutrophil Apoptosis in Quiescent ANCA-Associated Systemic Vasculitis

Background: ANCA-Associated Systemic Vasculitis (AASV) is characterized by leukocytoclasis, accumulation of unscavenged apoptotic and necrotic neutrophils in perivascular tissues. Dysregulation of neutrophil cell death may contribute directly to the pathogenesis of AASV. less thanbrgreater than less thanbrgreater thanMethods: Neutrophils from Healthy Blood Donors (HBD), patients with AASV most in complete remission, Polycythemia Vera (PV), Systemic Lupus Erythematosus (SLE), Rheumatoid Arthritis (RA) and renal transplant recipients (TP) were incubated in vitro, and the rate of spontaneous apoptosis was measured by FACS. Plasma levels of cytokines and sFAS were measured with cytometric bead array and ELISA. Expression of pro/anti-apoptotic factors, transcription factors C/EBP-alpha, C/EBP-beta and PU.1 and inhibitors of survival/JAK2-pathway were measured by real-time-PCR. less thanbrgreater than less thanbrgreater thanResults: AASV, PV and RA neutrophils had a significantly lower rate of apoptosis compared to HBD neutrophils (AASV 50 +/- 14% vs. HBD 64 +/- 11%, p andlt; 0.0001). In RA but not in AASV and PV, low apoptosis rate correlated with increased plasma levels of GM-CSF and high mRNA levels of anti-apoptotic factors Bcl-2A1 and Mcl-1. AASV patients had normal levels of G-CSF, GM-CSF and IL-3. Both C/EBP-alpha, C/EBP-beta were significantly higher in neutrophils from AASV patients than HBD. Levels of sFAS were significantly higher in AASV compared to HBD. less thanbrgreater than less thanbrgreater thanConclusion: Neutrophil apoptosis rates in vitro are decreased in AASV, RA and PV but mechanisms seem to differ. Increased mRNA levels of granulopoiesis-associated transcription factors and increased levels of sFAS in plasma were observed in AASV. Additional studies are required to define the mechanisms behind the decreased apoptosis rates, and possible connections with accumulation of dying neutrophils in regions of vascular lesions in AASV patients.Funding Agencies|Swedish Research Council|71X-15152|Crafoord Foundation||</p

Variation in Size and Growth of the Great Scallop Pecten maximus along a Latitudinal Gradient

Understanding the relationship between growth and temperature will aid in the evaluation of thermal stress and threats to ectotherms in the context of anticipated climate changes. Most Pecten maximus scallops living at high latitudes in the northern hemisphere have a larger maximum body size than individuals further south, a common pattern among many ectotherms. We investigated differences in daily shell growth among scallop populations along the Northeast Atlantic coast from Spain to Norway. This study design allowed us to address precisely whether the asymptotic size observed along a latitudinal gradient, mainly defined by a temperature gradient, results from differences in annual or daily growth rates, or a difference in the length of the growing season. We found that low annual growth rates in northern populations are not due to low daily growth values, but to the smaller number of days available each year to achieve growth compared to the south. We documented a decrease in the annual number of growth days with age regardless of latitude. However, despite initially lower annual growth performances in terms of growing season length and growth rate, differences in asymptotic size as a function of latitude resulted from persistent annual growth performances in the north and sharp declines in the south. Our measurements of daily growth rates throughout life in a long-lived ectothermic species provide new insight into spatio-temporal variations in growth dynamics and growing season length that cannot be accounted for by classical growth models that only address asymptotic size and annual growth rate

Activation of Akt Is Essential for the Propagation of Mitochondrial Respiratory Stress Signaling and Activation of the Transcriptional Coactivator Heterogeneous Ribonucleoprotein A2

This article shows that mitochondrial respiratory dysfunction activates a stress signaling that induces Akt1 activation. Akt1 activation occurs through calcineurin-mediated IGF1R/PI3-K pathway. Akt1-mediated phosphorylation of hnRNPA2 is a key requirement for the propagation of stress signaling and activation of nuclear target genes

Heat shock protein-90-alpha, a prolactin-STAT5 target gene identified in breast cancer cells, is involved in apoptosis regulation

Introduction The prolactin-Janus-kinase-2-signal transducer and activator of transcription-5 (JAK2-STAT5) pathway is essential for the development and functional differentiation of the mammary gland. The pathway also has important roles in mammary tumourigenesis. Prolactin regulated target genes are not yet well defined in tumour cells, and we undertook, to the best of our knowledge, the first large genetic screen of breast cancer cells treated with or without exogenous prolactin. We hypothesise that the identification of these genes should yield insights into the mechanisms by which prolactin participates in cancer formation or progression, and possibly how it regulates normal mammary gland development. Methods We used subtractive hybridisation to identify a number of prolactin-regulated genes in the human mammary carcinoma cell line SKBR3. Northern blotting analysis and luciferase assays identified the gene encoding heat shock protein 90-alpha (HSP90A) as a prolactin-JAK2-STAT5 target gene, whose function was characterised using apoptosis assays. Results We identified a number of new prolactin-regulated genes in breast cancer cells. Focusing on HSP90A, we determined that prolactin increased HSP90A mRNA in cancerous human breast SKBR3 cells and that STAT5B preferentially activated the HSP90A promoter in reporter gene assays. Both prolactin and its downstream protein effector, HSP90&#945;, promote survival, as shown by apoptosis assays and by the addition of the HSP90 inhibitor, 17-allylamino-17-demethoxygeldanamycin (17-AAG), in both untransformed HC11 mammary epithelial cells and SKBR3 breast cancer cells. The constitutive expression of HSP90A, however, sensitised differentiated HC11 cells to starvation-induced wild-type p53-independent apoptosis. Interestingly, in SKBR3 breast cancer cells, HSP90&#945; promoted survival in the presence of serum but appeared to have little effect during starvation. Conclusions In addition to identifying new prolactin-regulated genes in breast cancer cells, we found that prolactin-JAK2-STAT5 induces expression of the HSP90A gene, which encodes the master chaperone of cancer. This identifies one mechanism by which prolactin contributes to breast cancer. Increased expression of HSP90A in breast cancer is correlated with increased cell survival and poor prognosis and HSP90&#945; inhibitors are being tested in clinical trials as a breast cancer treatment. Our results also indicate that HSP90&#945; promotes survival depending on the cellular conditions and state of cellular transformation

Disturbed Expression of Splicing Factors in Renal Cancer Affects Alternative Splicing of Apoptosis Regulators, Oncogenes, and Tumor Suppressors

BACKGROUND: Clear cell renal cell carcinoma (ccRCC) is the most common type of renal cancer. One of the processes disturbed in this cancer type is alternative splicing, although phenomena underlying these disturbances remain unknown. Alternative splicing consists of selective removal of introns and joining of residual exons of the primary transcript, to produce mRNA molecules of different sequence. Splicing aberrations may lead to tumoral transformation due to synthesis of impaired splice variants with oncogenic potential. In this paper we hypothesized that disturbed alternative splicing in ccRCC may result from improper expression of splicing factors, mediators of splicing reactions. METHODOLOGY/PRINCIPAL FINDINGS: Using real-time PCR and Western-blot analysis we analyzed expression of seven splicing factors belonging to SR proteins family (SF2/ASF, SC35, SRp20, SRp75, SRp40, SRp55 and 9G8), and one non-SR factor, hnRNP A1 (heterogeneous nuclear ribonucleoprotein A1) in 38 pairs of tumor-control ccRCC samples. Moreover, we analyzed splicing patterns of five genes involved in carcinogenesis and partially regulated by analyzed splicing factors: RON, CEACAM1, Rac1, Caspase-9, and GLI1. CONCLUSIONS/SIGNIFICANCE: We found that the mRNA expression of splicing factors was disturbed in tumors when compared to paired controls, similarly as levels of SF2/ASF and hnRNP A1 proteins. The correlation coefficients between expression levels of specific splicing factors were increased in tumor samples. Moreover, alternative splicing of five analyzed genes was also disturbed in ccRCC samples and splicing pattern of two of them, Caspase-9 and CEACAM1 correlated with expression of SF2/ASF in tumors. We conclude that disturbed expression of splicing factors in ccRCC may possibly lead to impaired alternative splicing of genes regulating tumor growth and this way contribute to the process of carcinogenesis