Context Specificity in Causal Signaling Networks Revealed by Phosphoprotein Profiling.

Signaling networks downstream of receptor tyrosine kinases are among the most extensively studied biological networks, but new approaches are needed to elucidate causal relationships between network components and understand how such relationships are influenced by biological context and disease. Here, we investigate the context specificity of signaling networks within a causal conceptual framework using reverse-phase protein array time-course assays and network analysis approaches. We focus on a well-defined set of signaling proteins profiled under inhibition with five kinase inhibitors in 32 contexts: four breast cancer cell lines (MCF7, UACC812, BT20, and BT549) under eight stimulus conditions. The data, spanning multiple pathways and comprising ∼70,000 phosphoprotein and ∼260,000 protein measurements, provide a wealth of testable, context-specific hypotheses, several of which we experimentally validate. Furthermore, the data provide a unique resource for computational methods development, permitting empirical assessment of causal network learning in a complex, mammalian setting.This work was supported by the National Institutes of Health National Cancer Institute (grant U54 CA112970 to J.W.G., G.B.M., S.M., and P.T.S.). S.M.H. and S.M. were supported by the UK Medical Research Council (unit program numbers MC_UP_1302/1 and MC_UP_1302/3). S.M. was a recipient of a Royal Society Wolfson Research Merit Award. The MD Anderson Cancer Center RPPA Core Facility is funded by the National Institutes of Health National Cancer Institute (Cancer Center Core Grant CA16672)

Early recognition of coeliac disease through community pharmacies: A proof of concept study

Setting: 15 community pharmacies in the UK Objective: Proof of concept study to test the use of community pharmacies for active case finding of patients with coeliac disease. Method: Customers accessing over-the counter and prescription medicines indicated in the treatment of possible symptoms of coeliac disease over a six month period were offered a free point of care test. All patients were given advice regarding the test results and those who tested positive were advised to make an appointment with their general practitioner. Patients and pharmacists involved in service provision were asked to complete a satisfaction survey. Pharmacists were additionally invited to undertake interviews to better understand their views on the service. Main outcome measures: Feasibility of service, acceptability to stakeholders and proportion testing positive for coeliac disease. Results: Of the 551 individuals tested, 52 (9.4%) tested positive. 277 (50.3%) were tested for accessing irritable bowel syndrome treatment, 142 (25.8%) due to presenting for diarrhoea. The proportion of patients testing positive with different symptoms or for different treatments were similar. Of 43 customers who returned the satisfaction survey, all would recommend the service to others, believing the community pharmacy to be a suitable location. Community pharmacists believed that it enabled them to improve relationships with their customers and that medical practices were receptive to the service. Conclusion: This proof of concept study has shown that community pharmacies using a point of care test can effectively recognise and refer patients for confirmatory coeliac disease testing with high levels of customer and service provider satisfaction

The Sexual Use of a Social Networking Site: The Case of Pup Twitter

This article examines how Twitter has been adopted and used by a sexual subculture in distinct ways. Drawing on interviews with 26 gay and bisexual men based in the UK who identify as ‘pups’, it demonstrates how a kinky sexual subculture exists on a social networking site in new and innovative ways, adapting various elements of Twitter to form a unique subculture that I call ‘Pup Twitter’. Engaging with debates about social trends related to sexuality, as well as contemporary understandings of social networking sites, the study documents how this subcultural sexual community, while predating Twitter, has adopted online methods to enhance communication, engagement, and even visibility. The intersection of sexuality and social networking sites is an area ripe for further study, and this article develops empirical and conceptual ways to examine this issue in the future

Neuronal Shot Noise and Brownian 1/f21/f^2 Behavior in the Local Field Potential

We demonstrate that human electrophysiological recordings of the local field potential (LFP) from intracranial electrodes, acquired from a variety of cerebral regions, show a ubiquitous $1/f^2$ scaling within the power spectrum. We develop a quantitative model that treats the generation of these fields in an analogous way to that of electronic shot noise, and use this model to specifically address the cause of this $1/f^2$ Brownian noise. The model gives way to two analytically tractable solutions, both displaying Brownian noise: 1) uncorrelated cells that display sharp initial activity, whose extracellular fields slowly decay and 2) rapidly firing, temporally correlated cells that generate UP-DOWN states

Media events and cosmopolitan fandom:"Playful nationalism' in the Eurovision Song Contest

Academic literature on media events is increasingly concerned with their global dimensions and the applicability of Dayan and Katz's (1992) theoretical concept in a post-national context. This paper contributes to this debate by exploring the Eurovision Song Contest as a global media event. In particular, we employ a perspective from 'inside the media event', drawing upon empirical material collected during the 2014 Eurovision final in Copenhagen and focusing on the experiences of fans attending the contest. We argue that the ESC as a media event is experienced by its fans as a cosmopolitan space, open and diverse, whereas national belonging is expressed in a playful way tied to the overall visual aesthetics of the contest. However, the bounded and narrow character of participation render this cosmopolitan space rather limited

Smc5/6 coordinates formation and resolution of joint molecules with chromosome morphology to ensure meiotic divisions

During meiosis, Structural Maintenance of Chromosome (SMC) complexes underpin two fundamental features of meiosis: homologous recombination and chromosome segregation. While meiotic functions of the cohesin and condensin complexes have been delineated, the role of the third SMC complex, Smc5/6, remains enigmatic. Here we identify specific, essential meiotic functions for the Smc5/6 complex in homologous recombination and the regulation of cohesin. We show that Smc5/6 is enriched at centromeres and cohesin-association sites where it regulates sister-chromatid cohesion and the timely removal of cohesin from chromosomal arms, respectively. Smc5/6 also localizes to recombination hotspots, where it promotes normal formation and resolution of a subset of joint-molecule intermediates. In this regard, Smc5/6 functions independently of the major crossover pathway defined by the MutLγ complex. Furthermore, we show that Smc5/6 is required for stable chromosomal localization of the XPF-family endonuclease, Mus81-Mms4Eme1. Our data suggest that the Smc5/6 complex is required for specific recombination and chromosomal processes throughout meiosis and that in its absence, attempts at cell division with unresolved joint molecules and residual cohesin lead to severe recombination-induced meiotic catastroph

A new method for determination of varicella-zoster virus immunoglobulin G avidity in serum and cerebrospinal fluid

BACKGROUND: Avidity determination of antigen-specific immunoglobulin G (IgG) antibodies is an established serological method to differentiate acute from past infections. In order to compare the avidity of varicella-zoster virus (VZV) IgG in pairs of serum and cerebrospinal fluid (CSF) samples, we developed a new technique of avidity testing, the results of which are not influenced by the concentration of specific IgG. METHODS: The modifications introduced for the new VZV IgG avidity method included the use of urea hydrogen peroxide as denaturing reagent, the adaptation of the assay parameters in order to increase the sensitivity for the detection of low-level VZV IgG in CSF, and the use of a new calculation method for avidity results. The calculation method is based on the observation that the relationship between the absorbance values of the enzyme immunoassays with and without denaturing washing step is linear. From this relationship, a virtual absorbance ratio can be calculated. To evaluate the new method, a panel of serum samples from patients with acute and past VZV infection was tested as well as pairs of serum and CSF. RESULTS: For the serum panel, avidity determination with the modified assay gave results comparable to standard avidity methods. Based on the coefficient of variation, the new calculation method was superior to established methods of avidity calculation. CONCLUSIONS: The new avidity method permits a meaningful comparison of VZV IgG avidity in serum and CSF and should be of general applicability for easy determination of avidity results, which are not affected by the concentration of specific IgG

Case report: Malignant teratoma of the uterine corpus

<p>Abstract</p> <p>Background</p> <p>Teratomas are the commonest germ cell tumours and are most frequently found in the testes and ovary. Extragonadal teratomas are rare and mainly occur in midline structures. Uterine teratomas are extremely rare with only a few previous case reports, usually involving mature teratomas of the uterine cervix.</p> <p>Case Presentation</p> <p>We report an 82-year-old lady presenting with post-menopausal bleeding. Initial investigations revealed a benign teratoma of the uterus which was removed. Her symptoms persisted and a recurrent, now malignant, teratoma of the uterine corpus was resected at hysterectomy. Six months after surgery she relapsed with para-aortic lymphadenopathy and was treated with a taxane, etoposide and cisplatin-containing chemotherapy regimen followed by retroperitoneal lymph node dissection.</p> <p>Conclusion</p> <p>In this report we discuss the aetiology, diagnosis and management of uterine teratomas, and review previous case studies.</p

Causal relationships between frequency bands of extracellular signals in visual cortex revealed by an information theoretic analysis

Characterizing how different cortical rhythms interact and how their interaction changes with sensory stimulation is important to gather insights into how these rhythms are generated and what sensory function they may play. Concepts from information theory, such as Transfer Entropy (TE), offer principled ways to quantify the amount of causation between different frequency bands of the signal recorded from extracellular electrodes; yet these techniques are hard to apply to real data. To address the above issues, in this study we develop a method to compute fast and reliably the amount of TE from experimental time series of extracellular potentials. The method consisted in adapting efficiently the calculation of TE to analog signals and in providing appropriate sampling bias corrections. We then used this method to quantify the strength and significance of causal interaction between frequency bands of field potentials and spikes recorded from primary visual cortex of anaesthetized macaques, both during spontaneous activity and during binocular presentation of naturalistic color movies. Causal interactions between different frequency bands were prominent when considering the signals at a fine (ms) temporal resolution, and happened with a very short (ms-scale) delay. The interactions were much less prominent and significant at coarser temporal resolutions. At high temporal resolution, we found strong bidirectional causal interactions between gamma-band (40–100 Hz) and slower field potentials when considering signals recorded within a distance of 2 mm. The interactions involving gamma bands signals were stronger during movie presentation than in absence of stimuli, suggesting a strong role of the gamma cycle in processing naturalistic stimuli. Moreover, the phase of gamma oscillations was playing a stronger role than their amplitude in increasing causations with slower field potentials and spikes during stimulation. The dominant direction of causality was mainly found in the direction from MUA or gamma frequency band signals to lower frequency signals, suggesting that hierarchical correlations between lower and higher frequency cortical rhythms are originated by the faster rhythms

Knowledge, attitudes and practices related to avian influenza among poultry workers in Nepal: a cross sectional study

<p>Abstract</p> <p>Background</p> <p>Avian influenza is a considerable threat to global public health. Prevention and control depend on awareness and protective behaviours of the general population as well as high risk-groups. This study aims to explore the knowledge, attitudes and practices related to avian influenza among poultry workers in Nepal.</p> <p>Methods</p> <p>The study was based on a cross-sectional study design, using a structured questionnaire administered in face-to-face interviews with 96 poultry workers age 15 and above from the Rupandehi district in Nepal.</p> <p>Results</p> <p>The majority of respondents were male (80%), mean age was 35 (SD = 11.6). Nearly everybody was aware that AI cases had been detected in Nepal and that poultry workers were at risk for infection. The major sources of AI information were radio, TV and newspapers. Knowledge about preventive measures was high with regard to some behaviours (hand washing), but medium to low with regard to others (using cleaning and disinfecting procedures or protective clothing). Poultry workers who got their information from TV and newspapers and those who were more afraid of contracting AI had higher knowledge than those who did not. Being employed as compared to being an owner of a poultry farm as well as having a high level of knowledge was associated with practising more preventive behaviours. While on one hand many specific government control measures found a high degree of acceptance, a majority of study participants also thought that government control and compensation measures as a whole were insufficient.</p> <p>Conclusions</p> <p>The study provides information about knowledge and practices regarding avian influenza among poultry workers in Nepal. It highlights the importance of targeting lack of knowledge as well as structural-material barriers to successfully build preparedness for a major outbreak situation.</p