Sp1 acetylation is associated with loss of DNA binding at promoters associated with cell cycle arrest and cell death in a colon cell line

Butyrate, a known histone deacetylase inhibitor (HDACi) and product of fibre fermentation, is postulated to mediate the protective effect of dietary fibre against colon cancer. The transcription factor Sp1 is a target of acetylation and is known to be associated with class I HDACs, including HDAC1. Sp1 is a ubiquitous transcription factor and Sp1-regulated genes include those involved in cell cycle regulation, apoptosis and lipogenesis: all major pathways in cancer development. The only known acetylated residue of Sp1 is lysine703 which resides in the DNA binding domain. Here we show that acetylated Sp1 loses p21- and bak-promoter -binding function in vitro. Furthermore treatment with a panel of HDAC inhibitors showed clustering of activities for a subset of inhibitors, causing G2 cell cycle arrest, Sp1 acetylation, p21 and Bak over-expression, all with very similar EC50 concentrations. These HDACi activities were not distributed according to the molecular class of compound. In order to mimic loss of binding, an siRNA strategy was used to reduce Sp1 expression. This resulted in altered expression of multiple elements of the p53/p21 pathway. Taken together our data suggest a mechanistic model for the chemopreventive actions of butyrate in colon epithelial cells, and provide new insight into the differential activities some classes of HDAC inhibitors

'When I click "ok" I become Sassy – I become a girl.' Young people and gender identity: Subverting the ‘body’ in massively multi-player online role-playing games

This article is available open access through the publisher’s website through the link below. Copyright @ 2012 Taylor & Francis.This article explores young people's practices in the virtual spaces of online gaming communities. Based on a five-year ethnographic study of virtual worlds, it considers how young people construct and maintain identities within virtual social systems. In particular, the article discusses digital gender practices and considers the potential that these games offer for their young users to engage in alternate gender identities. We argue that these digital spaces offer spaces for the imagination and can enhance agency and, potentially, resistance. However, digital identity is simultaneously no ‘liberated space’ and it incorporates norms and practices that often mirror those of the material world. We argue that this ‘porosity’ is an important tool through which young people come to understand gender identity

Quantum Locality

It is argued that while quantum mechanics contains nonlocal or entangled states, the instantaneous or nonlocal influences sometimes thought to be present due to violations of Bell inequalities in fact arise from mistaken attempts to apply classical concepts and introduce probabilities in a manner inconsistent with the Hilbert space structure of standard quantum mechanics. Instead, Einstein locality is a valid quantum principle: objective properties of individual quantum systems do not change when something is done to another noninteracting system. There is no reason to suspect any conflict between quantum theory and special relativity.Comment: Introduction has been revised, references added, minor corrections elsewhere. To appear in Foundations of Physic

First Measurements with NeXtRAD, a Polarimetric X/L Band Radar Network

NeXtRAD is a fully polarimetric, X/L Band radar network. It is a development of the older NetRAD system and builds on the experience gained with extensive deployments of NetRAD for sea clutter and target measurements. In this paper we will report on the first measurements with NeXtRAD, looking primarily at sea clutter and some targets, as well as early attempts at calibration using corner reflectors, and an assessment of the polarimetric response of the system. We also highlight innovations allowing for efficient data manipulation post measurement campaigns, as well as the plans for the coming years with this system

VIP enhances TRH-stimulated prolactin secretion of pituitary tumours Studies with 31P NMR

AbstractIntravenous thyrotrophin releasing hormone (TRH) caused a 6.5-fold increase in plasma prolactin (PRL) in rats carrying implanted pituitary tumours. Vasoactive intestinal polypeptide (VIP) had no effect, but TRH given after VIP raised TRH stimulated secretion 13-fold above basal. 31P NMR spectroscopy showed that VIP caused a decrease in high energy metabolites (depleted phosphocreatine, elevated inorganic phosphate and lowered intracellular pH). TRH alone caused a similar but smaller effect; given after VIP, it caused no detectable depletion. We suggest that the changes in high energy metabolite cencentrations reflect increased cellular energy consumption consistent with a priming process (stage 1) in PRL secretion, followed by hormone release (stage 2). VIP induces stage 1 whereas RTH induced both stages

Typicality vs. probability in trajectory-based formulations of quantum mechanics

Bohmian mechanics represents the universe as a set of paths with a probability measure defined on it. The way in which a mathematical model of this kind can explain the observed phenomena of the universe is examined in general. It is shown that the explanation does not make use of the full probability measure, but rather of a suitable set function deriving from it, which defines relative typicality between single-time cylinder sets. Such a set function can also be derived directly from the standard quantum formalism, without the need of an underlying probability measure. The key concept for this derivation is the {\it quantum typicality rule}, which can be considered as a generalization of the Born rule. The result is a new formulation of quantum mechanics, in which particles follow definite trajectories, but which is only based on the standard formalism of quantum mechanics.Comment: 24 pages, no figures. To appear in Foundation of Physic

Bell inequalities as constraints on unmeasurable correlations

The interpretation of the violation of Bell-Clauser-Horne inequalities is revisited, in relation with the notion of extension of QM predictions to unmeasurable correlations. Such extensions are compatible with QM predictions in many cases, in particular for observables with compatibility relations described by tree graphs. This implies classical representability of any set of correlations , , , and the equivalence of the Bell-Clauser-Horne inequalities to a non void intersection between the ranges of values for the unmeasurable correlation associated to different choices for B. The same analysis applies to the Hardy model and to the "perfect correlations" discussed by Greenberger, Horne, Shimony and Zeilinger. In all the cases, the dependence of an unmeasurable correlation on a set of variables allowing for a classical representation is the only basis for arguments about violations of locality and causality.Comment: Some modifications have been done in order to improve clarity of presentation and comparison with other approache

Specific pathway abundances in the neonatal calf faecal microbiome are associated with susceptibility to Cryptosporidium parvum infection: a metagenomic analysis.

Cryptosporidium parvum is the main cause of calf scour worldwide. With limited therapeutic options and research compared to other Apicomplexa, it is important to understand the parasites' biology and interactions with the host and microbiome in order to develop novel strategies against this infection. The age-dependent nature of symptomatic cryptosporidiosis suggests a link to the undeveloped immune response, the immature intestinal epithelium, and its associated microbiota. This led us to hypothesise that specific features of the early life microbiome could predict calf susceptibility to C. parvum infection. In this study, a single faecal swab sample was collected from each calf within the first week of life in a cohort of 346 animals. All 346 calves were subsequently monitored for clinical signs of cryptosporidiosis, and calves that developed diarrhoea were tested for Rotavirus, Coronavirus, E. coli F5 (K99) and C. parvum by lateral flow test (LFT). A retrospective case–control approach was taken whereby a subset of healthy calves (Control group; n = 33) and calves that went on to develop clinical signs of infectious diarrhoea and test positive for C. parvum infection via LFT (Cryptosporidium-positive group; n = 32) were selected from this cohort, five of which were excluded due to low DNA quality. A metagenomic analysis was conducted on the faecal microbiomes of the control group (n = 30) and the Cryptosporidium-positive group (n = 30) prior to infection, to determine features predictive of cryptosporidiosis. Taxonomic analysis showed no significant differences in alpha diversity, beta diversity, and taxa relative abundance between controls and Cryptosporidium-positive groups. Analysis of functional potential showed pathways related to isoprenoid precursor, haem and purine biosynthesis were significantly higher in abundance in calves that later tested positive for C. parvum (q ≤ 0.25). These pathways are either absent or streamlined in the C. parvum parasites. Though the de novo production of isoprenoid precursors, haem and purines are absent, C. parvum has been shown to encode enzymes that catalyse the downstream reactions of these pathway metabolites, indicating that C. parvum may scavenge those products from an external source. The host has previously been put forward as the source of essential metabolites, but our study suggests that C. parvum may also be able to harness specific metabolic pathways of the microbiota in order to survive and replicate. This finding is important as components of these microbial pathways could be exploited as potential therapeutic targets for the prevention or mitigation of cryptosporidiosis in bovine neonates

More losers than winners in a century of future Southern Ocean seafloor warming

The waters of the Southern Ocean are projected to warm over the coming century, with potential adverse consequences for native cold-adapted organisms. Warming waters have caused temperate marine species to shift their ranges poleward. The seafloor animals of the Southern Ocean shelf have long been isolated by the deep ocean surrounding Antarctica and the Antarctic Circumpolar Current, with little scope for southward migration. How these largely endemic species will react to future projected warming is unknown. By considering 963 invertebrate species, we show that within the current century, warming temperatures alone are unlikely to result in wholesale extinction or invasion affecting Antarctic seafloor life. However, 79% of Antarctica’s endemic species do face a significant reduction in suitable temperature habitat (an average 12% reduction). Our findings highlight the species and regions most likely to respond significantly (negatively and positively) to warming and have important implications for future management of the region

Real World Interpretations of Quantum Theory

I propose a new class of interpretations, {\it real world interpretations}, of the quantum theory of closed systems. These interpretations postulate a preferred factorization of Hilbert space and preferred projective measurements on one factor. They give a mathematical characterisation of the different possible worlds arising in an evolving closed quantum system, in which each possible world corresponds to a (generally mixed) evolving quantum state. In a realistic model, the states corresponding to different worlds should be expected to tend towards orthogonality as different possible quasiclassical structures emerge or as measurement-like interactions produce different classical outcomes. However, as the worlds have a precise mathematical definition, real world interpretations need no definition of quasiclassicality, measurement, or other concepts whose imprecision is problematic in other interpretational approaches. It is natural to postulate that precisely one world is chosen randomly, using the natural probability distribution, as the world realised in Nature, and that this world's mathematical characterisation is a complete description of reality.Comment: Minor revisions. To appear in Foundations of Physic