Stanniocalcin-1 Regulates Extracellular ATP-Induced Calcium Waves in Human Epithelial Cancer Cells by Stimulating ATP Release from Bystander Cells

Background: The epithelial cell response to stress involves the transmission of signals between contiguous cells that can be visualized as a calcium wave. In some cell types, this wave is dependent on the release of extracellular trinucleotides from injured cells. In particular, extracellular ATP has been reported to be critical for the epithelial cell response to stress and has recently been shown to be upregulated in tumors in vivo. Methodology/Principal Findings: Here, we identify stanniocalcin-1 (STC1), a secreted pleiotrophic protein, as a critical mediator of calcium wave propagation in monolayers of pulmonary (A549) and prostate (PC3) epithelial cells. Addition of STC1 enhanced and blocking STC1 decreased the distance traveled by an extracellular ATP-dependent calcium wave. The same effects were observed when calcium was stimulated by the addition of exogenous ATP. We uncover a positive feedback loop in which STC1 promotes the release of ATP from cells in vitro and in vivo. Conclusions/Significance: The results indicated that STC1 plays an important role in the early response to mechanical injury by epithelial cells by modulating signaling of extracellular ATP. This is the first report to describe STC1 as a modulator o

Validation of a consumer-grade activity monitor for continuous daily activity monitoring in individuals with multiple sclerosis.

Background:Technological advancements of remote-monitoring used in clinical-care and research require validation of model updates. Objectives:To compare the output of a newer consumer-grade accelerometer to a previous model in people with multiple sclerosis (MS) and to the ActiGraph, a waist-worn device widely used in MS research. Methods:Thirty-one individuals with MS participated in a 7-day validation by the Fitbit Flex (Flex), Fitbit Flex-2 (Flex2) and ActiGraph GT3X. Primary outcome was step count. Valid epochs of 5-min block increments, where there was overlap of ≥1 step/min for both devices were compared and summed to give a daily total for analysis. Results:Bland-Altman plots showed no systematic difference between the Flex and Flex2; mean step-count difference of 25 more steps-per-day more recorded by Flex2 (95% confidence intervals (CI) = 2, 48; p = 0.04),interclass correlation coefficient (ICC) = 1.00. Compared to the ActiGraph, Flex2 (and Flex) tended to record more steps (808 steps-per-day more than the ActiGraph (95% CI= -2380, 765; p < 0.01), although the ICC was high (0.98) indicating that the devices were likely measuring the same kind of activity. Conclusions:Steps from Flex and Flex2 can be used interchangeably. Differences in total step count between ActiGraph and Flex devices can make cross-device comparisons of numerical step-counts challenging particularly for faster walkers

Epstein - Barr virus latent membrane protein 1 suppresses reporter activity through modulation of promyelocytic leukemia protein-nuclear bodies

The Epstein-Barr virus (EBV) encoded Latent Membrane Protein 1 (LMP1) has been shown to increase the expression of promyelocytic leukemia protein (PML) and the immunofluorescent intensity of promyelocytic leukemia nuclear bodies (PML NBs). PML NBs have been implicated in the modulation of transcription and the association of reporter plasmids with PML NBs has been implicated in repression of reporter activity. Additionally, repression of various reporters in the presence of LMP1 has been noted. This study demonstrates that LMP1 suppresses expression of reporter activity in a dose responsive manner and corresponds with the LMP1 induced increase in PML NB intensity. Disruption of PML NBs with arsenic trioxide or a PML siRNA restores reporter activity. These data offer an explanation for previously conflicting data on LMP1 signaling and calls attention to the possibility of false-positives and false-negatives when using reporter assays as a research tool in cells expressing LMP1

Ambiguous figures and the content of experience

Representationalism is the position that the phenomenal character of an experience is either identical with, or supervenes on, the content of that experience. Many representationalists hold that the relevant content of experience is nonconceptual. I propose a counterexample to this form of representationalism that arises from the phenomenon of Gestalt switching, which occurs when viewing ambiguous figures. First, I argue that one does not need to appeal to the conceptual content of experience or to judgements to account for Gestalt switching. I then argue that experiences of certain ambiguous figures are problematic because they have different phenomenal characters but that no difference in the nonconceptual content of these experiences can be identified. I consider three solutions to this problem that have been proposed by both philosophers and psychologists and conclude that none can account for all the ambiguous figures that pose the problem. I conclude that the onus is on representationalists to specify the relevant difference in content or to abandon their position

The host galaxies of luminous quasars

We present results of a deep HST/WFPC2 imaging study of 17 quasars at z~0.4, designed to determine the properties of their host galaxies. The sample consists of quasars with absolute magnitudes in the range -24>M_V>-28, allowing us to investigate host galaxy properties across a decade in quasar luminosity, but at a single redshift. We find that the hosts of all the RLQs, and all the RQQs with nuclear luminosities M_V<-24, are massive bulge-dominated galaxies, confirming and extending the trends deduced from our previous studies. From the best-fitting model host galaxies we have estimated spheroid and black-hole masses, and the efficiency (with respect to Eddington luminosity) with which each quasar is radiating. The largest inferred black-hole mass in our sample is \~3.10^9 M_sun, comparable to those at the centres of M87 and Cygnus A. We find no evidence for super-Eddington accretion in even the most luminous objects. We investigate the role of scatter in the black-hole:spheroid mass relation in determining the ratio of quasar to host-galaxy luminosity, by generating simulated populations of quasars lying in hosts with a Schechter mass function. Within the subsample of the highest luminosity quasars, the observed variation in nuclear-host luminosity ratio is consistent with being the result of the scatter in the black-hole:spheroid relation. Quasars with high nuclear-host ratios can be explained by sub-Eddington accretion onto black holes in the high-mass tail of the black-hole:spheroid relation. Our results imply that, owing to the Schechter cutoff, host mass should not continue to increase linearly with quasar luminosity, at the very highest luminosities. Any quasars more luminous than M_V=-27 should be found in massive elliptical hosts which at the present day would have M_V ~ -24.5.Comment: Accepted for publication in MNRAS. 18 pages; 7 figures and 17 greyscale images are reproduced here at low quality due to space limitations. High-resolution figures are available from ftp://ftp.roe.ac.uk/pub/djef/preprints/floyd2004

Population Connectivity of Pelagic Megafauna in the Cuba-Mexico-United States Triangle

The timing and extent of international crossings by billfishes, tunas, and sharks in the Cuba-Mexico-United States (U.S.) triangle was investigated using electronic tagging data from eight species that resulted in \u3e22,000 tracking days. Transnational movements of these highly mobile marine predators were pronounced with varying levels of bi- or tri-national population connectivity displayed by each species. Billfishes and tunas moved throughout the Gulf of Mexico and all species investigated (blue marlin, white marlin, Atlantic bluefin tuna, yellowfin tuna) frequently crossed international boundaries and entered the territorial waters of Cuba and/or Mexico. Certain sharks (tiger shark, scalloped hammerhead) displayed prolonged periods of residency in U.S. waters with more limited displacements, while whale sharks and to a lesser degree shortfin mako moved through multiple jurisdictions. The spatial extent of associated movements was generally associated with their differential use of coastal and open ocean pelagic ecosystems. Species with the majority of daily positions in oceanic waters off the continental shelf showed the greatest tendency for transnational movements and typically traveled farther from initial tagging locations. Several species converged on a common seasonal movement pattern between territorial waters of the U.S. (summer) and Mexico (winter)

Higher Food Prices May Threaten Food Security Status among American Low-Income Households with Children

Children in food-insecure households are more likely to experience poorer health function and worse academic achievement. To investigate the relation between economic environmental factors and food insecurity among children, we examined the relation between general and specific food prices (fast food, fruits and vegetables, beverages) and risk of low (LFS) and very low food security (VLFS) status among low-income American households with children. Using information for 27,900 child-year observations from the Early Childhood Longitudinal Study-Kindergarten Class of 1998 1999 linked with food prices obtained from the Cost of Living Data of the Council for Community and Economic Research, formerly known as the American Chamber of Commerce Researchers\u27 Association, fixed effects models were estimated within stratified income groups. Higher overall food prices were associated with increased risk of LFS and VLFS (coefficient = 0.617; P \u3c 0.05). Higher fast food and fruit and vegetable prices also contributed to higher risk of food insecurity (coefficient = 0.632, P \u3c 0.01 for fast food; coefficient = 0.879, P \u3c 0.01 for fruits and vegetables). However, increasing beverage prices, including the prices of soft drinks, orange juice, and coffee, had a protective effect on food security status, even when controlling for general food prices. Thus, although food price changes were strongly related to food security status among low-income American households with children, the effects were not uniform across types of food. These relations should be accounted for when implementing policies that change specific food prices

Diamonds, gold and crime displacement: Hatton Garden, and the evolution of organised crime in the UK

The 2015 Hatton Garden Heist was described as the ‘largest burglary in English legal history’. However, the global attention that this spectacular crime attracted to ‘The Garden’ tended to concentrate upon the value of the stolen goods and the vintage of the burglars. What has been ignored is how the burglary shone a spotlight into Hatton Garden itself, as an area with a unique ‘upperworld’ commercial profile and skills cluster that we identify as an incubator and facilitator for organised crime. The Garden is the UK’s foremost jewellery production and retail centre and this paper seeks to explore how Hatton Garden’s businesses integrated with a fluid criminal population to transition, through hosting lucrative (and bureaucratically complex) VAT gold frauds from 1980 to the early 1990s, to become a major base for sophisticated acquisitive criminal activities. Based on extensive interviews over a thirty year period, evidence from a personal research archive and public records, this paper details a cultural community with a unique criminal profile due to the particularities of its geographical location, ethnic composition, trading culture, skills base and international connections. The processes and structures that facilitate criminal markets are largely under-researched (Antonopoulos et al. 2015: 11), and this paper considers how elements of Hatton Garden’s ‘upperworld’ businesses integrated with project criminals, displaced by policing strategies, to effect this transition

Genetic Ablation of PLA2G6 in Mice Leads to Cerebellar Atrophy Characterized by Purkinje Cell Loss and Glial Cell Activation

Infantile neuroaxonal dystrophy (INAD) is a progressive, autosomal recessive neurodegenerative disease characterized by axonal dystrophy, abnormal iron deposition and cerebellar atrophy. This disease was recently mapped to PLA2G6, which encodes group VI Ca2+-independent phospholipase A2 (iPLA2 or iPLA2β). Here we show that genetic ablation of PLA2G6 in mice (iPLA2β-/-) leads to the development of cerebellar atrophy by the age of 13 months. Atrophied cerebella exhibited significant loss of Purkinje cells, as well as reactive astrogliosis, the activation of microglial cells, and the pronounced up-regulation of the pro-inflammatory cytokines tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β). Moreover, glial cell activation and the elevation in TNF-α and IL-1β expression occurred before apparent cerebellar atrophy. Our findings indicate that the absence of PLA2G6 causes neuroinflammation and Purkinje cell loss and ultimately leads to cerebellar atrophy. Our study suggests that iPLA2β-/- mice are a valuable model for cerebellar atrophy in INAD and that early anti-inflammatory therapy may help slow the progression of cerebellar atrophy in this deadly neurodegenerative disease

Algunes reflexions entorn de la conceptualització de la infància i adolescència en risc social a l'Estat espanyol

L'article realitza una aproximació a les interpretacions del concepte de risc social de la infancia per part de diversos autors d'àmbit estatal, tenint també en compte els marcs legals català i espanyol. Pretén aclarir quins són els criteris valoratius emprats, tant des de l'àmbit acadèmic com del professional, per interpretar les categoritzacions de la infància i l'adolescència en processos de dificultat i precarietat social. Des d'aquesta perspectiva, s'hi analitza l'estreta relació entre factors de risc, desemparament i marginació. S'hi rebutgen les interpretacions que responsabilitzen el propi menor de la desadaptació, i s'hi defensa la hipótesi de la necessitat d'una intervenció socioeducativa que treballi per una disminució dels factors de risc en el propi medi, mantenint el seu protagonisme en aquest procés.This article is an approach to the different acceptances of the concept social risk as well as the terms neglect and maladjustment, based on the reflections made by different authors and both statal and autonomous legal framework. It intends to clarify which are the criteria of values used in academic and professional ambits in order to understand the categoriesfound in the fields of childhood and adolescence in difficult and precarious conditions. The strong relation between risk factors, neglect and margination has been analysed from this point of view. In the same way the interpretations that hold the minor himself responsible for his maladjustment are rejected and the author defends the necessity of a socio-educational intervention, which reduces the risk factors in the child's environment, and the need of paying close attention to the child's main role in this process.El artículo realiza una aproximación a las interpretaciones del concepto de riesgo social de la infancia por parte de diversos autores de ámbito estatal, teniendo también en cuenta los marcos legales catalán y español. Pretende aclarar cuáles son los criterios valorativos utilizados, tanto desde el ámbito academico como profesional, para interpretar las categorizaciones de la infancia en procesos de dificultad y precariedad. Desde esta perspectiva, se analiza la estrecha relación entre factores de riesgo, desamparamiento y marginación. Se rechazan las interpretaciones que responsabilizan al propio menor de la desadaptación y se defiende la hipótesis de la necesidad de una intervención socioeducativa que trabaje para una disminución de los factores de riesgo en el propio medio, manteniendo su protagonismo en este proceso