Karen Finley's Performance and Judith Butler's Performative: Subverting the Binary Logic of Theatrical Functions

This paper argues that the feminist performance art of Karen Finley challenges the terms Judith Butler sets between performance and performativity and concludes that Finley's art engages in a social, cultural and political critique whereby she determines a new set of codes for her performances. Résumé Cet article soutient que les arts du spectacle féministe de Karen Finley défient les termes que Judith Butler établit entre la représentation et la performativité et conclut que l'art de Finley engage dans une critique sociale culturelle et politique par laquelle elle détermine un nouvel ensemble de codes pour ses représentations

The effects of bag style on muscle activity of the trapezius, erector spinae and latissimus dorsi during walking in female university students

© by The Author(s). This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License. (CC BY-NC-ND 3.0)Back pain is common in adolescents which has been associated with carrying a bag. However, there is little research examining the effects of bag style in female adolescents. The aim of the study was to investigate the effects of different bag conditions on muscle activity of the trapezius, erector spinae and latissimus dorsi muscles in female university students during walking. Twelve female university students walked on a treadmill for 5 minutes at 1.1 m/s during five conditions; control, 1 strapped rucksack, 2 strapped rucksack, ipsilateral shoulder strap and contralateral shoulder strap, each containing 10% bodyweight. Electromyography for the trapezius, erector spinae and latissimus dorsi was recorded for the last 30 s of each condition. Two-way ANOVA and paired t-tests were used to identify differences between right and left muscles and between bag conditions. Results showed that muscle activity of the left trapezius was significantly higher than the right trapezius during the 1 strap rucksack condition. For the left trapezius, the 2 strapped rucksack and the control condition had significantly lower muscle activity compared to the 1 strapped rucksack and the ipsilateral shoulder strap. For the left erector spinae muscle, there was significantly greater muscle activity when wearing the contralateral shoulder strap compared to the control. For the right erector spinae, significantly lower muscle activity was observed when wearing the 2 strapped rucksack compared to the ipsilateral shoulder strap and contralateral shoulder strap. There were no significant differences in muscle activity of the latissimus dorsi muscles between any of the bag conditions. These findings suggest that a two strapped rucksack should be used when carrying loads to reduce spinal muscle activity which may, in turn, reduce reports of back pain in female adolescentPeer reviewedFinal Published versio

The Na+/Glucose Cotransporter Inhibitor Canagliflozin Activates AMPK by Inhibiting Mitochondrial Function and Increasing Cellular AMP Levels

Canagliflozin, dapagliflozin and empagliflozin, all recently approved for treatment of Type 2 diabetes, were derived from the natural product phlorizin. They reduce hyperglycemia by inhibiting glucose re-uptake by SGLT2 in the kidney, without affecting intestinal glucose uptake by SGLT1. We now report that canagliflozin also activates AMP-activated protein kinase (AMPK), an effect also seen with phloretin (the aglycone breakdown product of phlorizin), but not to any significant extent with dapagliflozin, empagliflozin or phlorizin. AMPK activation occurred at canagliflozin concentrations measured in human plasma in clinical trials, and was caused by inhibition of Complex I of the respiratory chain, leading to increases in cellular AMP or ADP. Although canagliflozin also inhibited cellular glucose uptake independently of SGLT2, this did not account for AMPK activation. Canagliflozin also inhibited lipid synthesis, an effect that was absent in AMPK knockout cells and that required phosphorylation of ACC1 and/or ACC2 at the AMPK sites. Oral administration of canagliflozin activated AMPK in mouse liver, although not in muscle, adipose tissue or spleen. As phosphorylation of acetyl-CoA carboxylase by AMPK is known to lower liver lipid content, these data suggest a potential additional benefit of canagliflozin therapy compared to other SGLT2 inhibitors

WNT10B/β-catenin signalling induces HMGA2 and proliferation in metastatic triple-negative breast cancer

Wnt/β-catenin signalling has been suggested to be active in basal-like breast cancer. However, in highly aggressive metastatic triple-negative breast cancers (TNBC) the role of β-catenin and the underlying mechanism(s) for the aggressiveness of TNBC remain unknown. We illustrate that WNT10B induces transcriptionally active β-catenin in human TNBC and predicts survival-outcome of patients with both TNBC and basal-like tumours. We provide evidence that transgenic murine Wnt10b-driven tumours are devoid of ERα, PR and HER2 expression and can model human TNBC. Importantly, HMGA2 is specifically expressed during early stages of embryonic mammogenesis and absent when WNT10B expression is lost, suggesting a developmentally conserved mode of action. Mechanistically, ChIP analysis uncovered that WNT10B activates canonical β-catenin signalling leading to up-regulation of HMGA2. Treatment of mouse and human triple-negative tumour cells with two Wnt/β-catenin pathway modulators or siRNA to HMGA2 decreases HMGA2 levels and proliferation. We demonstrate that WNT10B has epistatic activity on HMGA2, which is necessary and sufficient for proliferation of TNBC cells. Furthermore, HMGA2 expression predicts relapse-free-survival and metastasis in TNBC patients

MiRNA-Related SNPs and Risk of Esophageal Adenocarcinoma and Barrett's Esophagus: Post Genome-Wide Association Analysis in the BEACON Consortium.

Incidence of esophageal adenocarcinoma (EA) has increased substantially in recent decades. Multiple risk factors have been identified for EA and its precursor, Barrett's esophagus (BE), such as reflux, European ancestry, male sex, obesity, and tobacco smoking, and several germline genetic variants were recently associated with disease risk. Using data from the Barrett's and Esophageal Adenocarcinoma Consortium (BEACON) genome-wide association study (GWAS) of 2,515 EA cases, 3,295 BE cases, and 3,207 controls, we examined single nucleotide polymorphisms (SNPs) that potentially affect the biogenesis or biological activity of microRNAs (miRNAs), small non-coding RNAs implicated in post-transcriptional gene regulation, and deregulated in many cancers, including EA. Polymorphisms in three classes of genes were examined for association with risk of EA or BE: miRNA biogenesis genes (157 SNPs, 21 genes); miRNA gene loci (234 SNPs, 210 genes); and miRNA-targeted mRNAs (177 SNPs, 158 genes). Nominal associations (P0.50), and we did not find evidence for interactions between variants analyzed and two risk factors for EA/BE (smoking and obesity). This analysis provides the most extensive assessment to date of miRNA-related SNPs in relation to risk of EA and BE. While common genetic variants within components of the miRNA biogenesis core pathway appear unlikely to modulate susceptibility to EA or BE, further studies may be warranted to examine potential associations between unassessed variants in miRNA genes and targets with disease risk.This work was supported by the National Institutes of Health [R01CA136725 to T.L.V. and D.C.W, T32CA009168 to T.L.V, and K05CA124911 to T.L.V.]. Additional funding sources for individual studies included in the BEACON GWAS, and for BEACON investigators, have been acknowledged previously (16).This is the final version of the article. It first appeared from PLOS via http://dx.doi.org/10.1371/journal.pone.012861

Polymorphisms in Genes of Relevance for Oestrogen and Oxytocin Pathways and Risk of Barrett's Oesophagus and Oesophageal Adenocarcinoma: A Pooled Analysis from the BEACON Consortium.

BACKGROUND: The strong male predominance in oesophageal adenocarcinoma (OAC) and Barrett's oesophagus (BO) continues to puzzle. Hormonal influence, e.g. oestrogen or oxytocin, might contribute. METHODS: This genetic-epidemiological study pooled 14 studies from three continents, Australia, Europe, and North America. Polymorphisms in 3 key genes coding for the oestrogen pathway (receptor alpha (ESR1), receptor beta (ESR2), and aromatase (CYP19A1)), and 3 key genes of the oxytocin pathway (the oxytocin receptor (OXTR), oxytocin protein (OXT), and cyclic ADP ribose hydrolase glycoprotein (CD38)), were analysed using a gene-based approach, versatile gene-based test association study (VEGAS). RESULTS: Among 1508 OAC patients, 2383 BO patients, and 2170 controls, genetic variants within ESR1 were associated with BO in males (p = 0.0058) and an increased risk of OAC and BO combined in males (p = 0.0023). Genetic variants within OXTR were associated with an increased risk of BO in both sexes combined (p = 0.0035) and in males (p = 0.0012). We followed up these suggestive findings in a further smaller data set, but found no replication. There were no significant associations between the other 4 genes studied and risk of OAC, BO, separately on in combination, in males and females combined or in males only. CONCLUSION: Genetic variants in the oestrogen receptor alpha and the oxytocin receptor may be associated with an increased risk of BO or OAC, but replication in other large samples are needed

Germline variation in inflammation-related pathways and risk of Barrett's oesophagus and oesophageal adenocarcinoma

Esophageal adenocarcinoma (EA) incidence has risen sharply in Western countries over recent decades. Local and systemic inflammation, operating downstream of disease-associated exposures, is considered an important contributor to EA pathogenesis. Several risk factors have been identified for EA and its precursor, Barrett’s esophagus (BE), including symptomatic reflux, obesity, and smoking. The role of inherited genetic susceptibility remains an area of active investigation. To explore whether germline variation related to inflammatory processes influences susceptibility to BE/EA, we used data from a genome-wide association study (GWAS) of 2,515 EA cases, 3,295 BE cases, and 3,207 controls. Our analysis included 7,863 single nucleotide polymorphisms (SNPs) in 449 genes assigned to five pathways: cyclooxygenase (COX), cytokine signaling, oxidative stress, human leukocyte antigen, and NFκB. A principal components-based analytic framework was employed to evaluate pathway-level and gene-level associations with disease risk. We identified a significant signal for the COX pathway in relation to BE risk (P=0.0059, FDR q=0.03), and in gene-level analyses found an association with MGST1 (microsomal glutathione-S-transferase 1; P=0.0005, q=0.005). Assessment of 36 MGST1 SNPs identified 14 variants associated with elevated BE risk (q<0.05). Of these, four were subsequently confirmed (P<5.5 × 10−5) in a meta-analysis encompassing an independent set of 1,851 BE cases and 3,496 controls. Three of these SNPs (rs3852575, rs73112090, rs4149204) were associated with similar elevations in EA risk. This study provides the most comprehensive evaluation of inflammation-related germline variation in relation to risk of BE/EA, and suggests that variants in MGST1 influence disease susceptibility

Interactions Between Genetic Variants and Environmental Factors Affect Risk of Esophageal Adenocarcinoma and Barrett's Esophagus.

BACKGROUND & AIMS: Genome-wide association studies (GWAS) have identified more than 20 susceptibility loci for esophageal adenocarcinoma (EA) and Barrett's esophagus (BE). However, variants in these loci account for a small fraction of cases of EA and BE. Genetic factors might interact with environmental factors to affect risk of EA and BE. We aimed to identify single nucleotide polymorphisms (SNPs) that may modify the associations of body mass index (BMI), smoking, and gastroesophageal reflux disease (GERD), with risks of EA and BE. METHODS: We collected data on single BMI measurements, smoking status, and symptoms of GERD from 2284 patients with EA, 3104 patients with BE, and 2182 healthy individuals (controls) participating in the Barrett's and Esophageal Adenocarcinoma Consortium GWAS, the UK Barrett's Esophagus Gene Study, and the UK Stomach and Oesophageal Cancer Study. We analyzed 993,501 SNPs in DNA samples of all study subjects. We used standard case-control logistic regression to test for gene-environment interactions. RESULTS: For EA, rs13429103 at chromosome 2p25.1, near the RNF144A-LOC339788 gene, showed a borderline significant interaction with smoking status (P = 2.18×10-7). Ever smoking was associated with an almost 12-fold increase in risk of EA among individuals with rs13429103-AA genotype (odds ratio=11.82; 95% CI, 4.03-34.67). Three SNPs (rs12465911, rs2341926, rs13396805) at chromosome 2q23.3, near the RND3-RBM43 gene, interacted with GERD symptoms (P = 1.70×10-7, P = 1.83×10-7, and P = 3.58×10-7, respectively) to affect risk of EA. For BE, rs491603 at chromosome 1p34.3, near the EIF2C3 gene, and rs11631094 at chromosome 15q14, at the SLC12A6 gene, interacted with BMI (P = 4.44×10-7) and pack-years of smoking history (P = 2.82×10-7), respectively. CONCLUSION: The associations of BMI, smoking, and GERD symptoms with risks of EA and BE appear to vary with SNPs at chromosomes 1, 2, and 15. Validation of these suggestive interactions is warranted.UK funding from MRC and Cancer Research U

Mitochondria-localized AMPK responds to local energetics and contributes to exercise and energetic stress-induced mitophagy

Mitochondria form a complex, interconnected reticulum that is maintained through coordination among biogenesis, dynamic fission, and fusion and mitophagy, which are initiated in response to various cues to maintain energetic homeostasis. These cellular events, which make up mitochondrial quality control, act with remarkable spatial precision, but what governs such spatial specificity is poorly understood. Herein, we demonstrate that specific isoforms of the cellular bioenergetic sensor, 5′ AMP-activated protein kinase (AMPKα1/α2/β2/γ1), are localized on the outer mitochondrial membrane, referred to as mitoAMPK, in various tissues in mice and humans. Activation of mitoAMPK varies across the reticulum in response to energetic stress, and inhibition of mitoAMPK activity attenuates exercise-induced mitophagy in skeletal muscle in vivo. Discovery of a mitochondrial pool of AMPK and its local importance for mitochondrial quality control underscores the complexity of sensing cellular energetics in vivo that has implications for targeting mitochondrial energetics for disease treatment

Climate emergency summit III:nature-based solutions report

An RSGS &amp; SNH report from the Climate Summit held in April 2020"The Climate Emergency is the result of burning fossils fuels and changes in the way we use the land that short-circuit global carbon and nitrogen cycles. To remain within safe climate limits (1.5-2°C), the remaining carbon budget for all people, and for all time, is now so small that stopping fossil fuel use, while essential, will not by itself address the problem. Changing the way we use the land and sea is now essential. Nature-based solutions are vital to creating a safe operating space for humanity. "Extract from the foreword by Dr Clive Mitchell, Outcome Manager: People and Nature, Scottish Natural Heritage. The report has 45 contributors for a variety of institutions