Information Transfer in Gonadotropin-releasing Hormone (GnRH) Signaling: extracellular signal-regulated kinase (ERK)-mediated feedback loops control hormone sensing

The computation model used in the study of GnRH signalling which was used to generate the data appearing in this paper is in ORE at http://hdl.handle.net/10871/27844Cell signaling pathways are noisy communication channels, and statistical measures derived from information theory can be used to quantify the information they transfer. Here we use single cell signaling measures to calculate mutual information as a measure of information transfer via gonadotropin-releasing hormone (GnRH) receptors (GnRHR) to extracellular signal-regulated kinase (ERK) or nuclear factor of activated T-cells (NFAT). This revealed mutual information values <1 bit, implying that individual GnRH-responsive cells cannot unambiguously differentiate even two equally probable input concentrations. Addressing possible mechanisms for mitigation of information loss, we focused on the ERK pathway and developed a stochastic activation model incorporating negative feedback and constitutive activity. Model simulations revealed interplay between fast (min) and slow (min-h) negative feedback loops with maximal information transfer at intermediate feedback levels. Consistent with this, experiments revealed that reducing negative feedback (by expressing catalytically inactive ERK2) and increasing negative feedback (by Egr1-driven expression of dual-specificity phosphatase 5 (DUSP5)) both reduced information transfer from GnRHR to ERK. It was also reduced by blocking protein synthesis (to prevent GnRH from increasing DUSP expression) but did not differ for different GnRHRs that do or do not undergo rapid homologous desensitization. Thus, the first statistical measures of information transfer via these receptors reveals that individual cells are unreliable sensors of GnRH concentration and that this reliability is maximal at intermediate levels of ERK-mediated negative feedback but is not influenced by receptor desensitization.This work was supported by a Biochemical and Biophysical Science Research Council award (BBSRC BB/J014699/1; to C. A. M. and K. T.-A.)

Interferometric 890 mu m images of high-redshift submillimeter galaxies

We present high-resolution 890 μm images of two 20 mJy submillimeter galaxies, SMM J123711+622212 and MIPS J142824.0+352619, obtained using the Submillimeter Array (SMA). Using submillimeter interferometric observations with an angular resolution of 25, the coordinates of these high-redshift sources are determined with an accuracy of 02. The new SMA data on SMM J123711+622212 reveal an unresolved submillimeter source offset to the east by 08 from an optical galaxy found in deep HST images, suggesting either a large galaxy with a dusty central region or an interacting galaxy system. The SMA image of hyperluminous (LFIR = 3.2 × 1013 L) source MIPS J142824.0+352619 provides a firm upper limit to the source size of 12. This constraint provides evidence that the foreground lens is only weakly affecting the observed high far-infrared luminosity

El Nino and Health Risks from Landscape Fire Emissions in Southeast Asia

Emissions from landscape fires affect both climate and air quality. Here, we combine satellite-derived fire estimates and atmospheric modelling to quantify health effects from fire emissions in southeast Asia from 1997 to 2006. This region has large interannual variability in fire activity owing to coupling between El Nino-induced droughts and anthropogenic land-use change. We show that during strong El Nino years, fires contribute up to 200 micrograms per cubic meter and 50 ppb in annual average fine particulate matter (PM2.5) and ozone surface concentrations near fire sources, respectively. This corresponds to a fire contribution of 200 additional days per year that exceed the World Health Organization 50 micrograms per cubic metre 24-hr PM(sub 2.5) interim target and an estimated 10,800 (6,800-14,300)-person (approximately 2 percent) annual increase in regional adult cardiovascular mortality. Our results indicate that reducing regional deforestation and degradation fires would improve public health along with widely established benefits from reducing carbon emissions, preserving biodiversity and maintaining ecosystem services

Diagnostic and cost utility of whole exome sequencing in peripheral neuropathy.

OBJECTIVE: To explore the diagnostic utility and cost effectiveness of whole exome sequencing (WES) in a cohort of individuals with peripheral neuropathy. METHODS: Singleton WES was performed in individuals recruited though one pediatric and one adult tertiary center between February 2014 and December 2015. Initial analysis was restricted to a virtual panel of 55 genes associated with peripheral neuropathies. Patients with uninformative results underwent expanded analysis of the WES data. Data on the cost of prior investigations and assessments performed for diagnostic purposes in each patient was collected. RESULTS: Fifty patients with a peripheral neuropathy were recruited (median age 18 years; range 2-68 years). The median time from initial presentation to study enrollment was 6 years 9 months (range 2 months-62 years), and the average cost of prior investigations and assessments for diagnostic purposes AU$4013 per patient. Eleven individuals received a diagnosis from the virtual panel. Eight individuals received a diagnosis following expanded analysis of the WES data, increasing the overall diagnostic yield to 38%. Two additional individuals were diagnosed with pathogenic copy number variants through SNP microarray. CONCLUSIONS: This study provides evidence that WES has a high diagnostic utility and is cost effective in patients with a peripheral neuropathy. Expanded analysis of WES data significantly improves the diagnostic yield in patients in whom a diagnosis is not found on the initial targeted analysis. This is primarily due to diagnosis of conditions caused by newly discovered genes and the resolution of complex and atypical phenotypes

Complementary and conventional medicine: a concept map

BACKGROUND: Despite the substantive literature from survey research that has accumulated on complementary and alternative medicine (CAM) in the United States and elsewhere, very little research has been done to assess conceptual domains that CAM and conventional providers would emphasize in CAM survey studies. The objective of this study is to describe and interpret the results of concept mapping with conventional and CAM practitioners from a variety of backgrounds on the topic of CAM. METHODS: Concept mapping, including free sorts, ratings, and multidimensional scaling was used to organize conceptual domains relevant to CAM into a visual "cluster map." The panel consisted of CAM providers, conventional providers, and university faculty, and was convened to help formulate conceptual domains to guide the development of a CAM survey for use with United States military veterans. RESULTS: Eight conceptual clusters were identified: 1) Self-assessment, Self-care, and Quality of Life; 2) Health Status, Health Behaviors; 3) Self-assessment of Health; 4) Practical/Economic/ Environmental Concerns; 5) Needs Assessment; 6) CAM vs. Conventional Medicine; 7) Knowledge of CAM; and 8) Experience with CAM. The clusters suggest panelists saw interactions between CAM and conventional medicine as a critical component of the current medical landscape. CONCLUSIONS: Concept mapping provided insight into how CAM and conventional providers view the domain of health care, and was shown to be a useful tool in the formulation of CAM-related conceptual domains

Limits on WWZ and WW\gamma couplings from p\bar{p}\to e\nu jj X events at \sqrt{s} = 1.8 TeV

We present limits on anomalous WWZ and WW-gamma couplings from a search for WW and WZ production in p-bar p collisions at sqrt(s)=1.8 TeV. We use p-bar p -> e-nu jjX events recorded with the D0 detector at the Fermilab Tevatron Collider during the 1992-1995 run. The data sample corresponds to an integrated luminosity of 96.0+-5.1 pb^(-1). Assuming identical WWZ and WW-gamma coupling parameters, the 95% CL limits on the CP-conserving couplings are -0.33<lambda<0.36 (Delta-kappa=0) and -0.43<Delta-kappa<0.59 (lambda=0), for a form factor scale Lambda = 2.0 TeV. Limits based on other assumptions are also presented.Comment: 11 pages, 2 figures, 2 table

Search For Heavy Pointlike Dirac Monopoles

We have searched for central production of a pair of photons with high transverse energies in $p\bar p$ collisions at $\sqrt{s} = 1.8$ TeV using $70 pb^{-1}$ of data collected with the D\O detector at the Fermilab Tevatron in 1994--1996. If they exist, virtual heavy pointlike Dirac monopoles could rescatter pairs of nearly real photons into this final state via a box diagram. We observe no excess of events above background, and set lower 95% C.L. limits of $610, 870, or 1580 GeV/c^2$ on the mass of a spin 0, 1/2, or 1 Dirac monopole.Comment: 12 pages, 4 figure

Search for New Physics in e mu X Data at D0 Using Sleuth: A Quasi-Model-Independent Search Strategy for New Physics

We present a quasi-model-independent search for the physics responsible for electroweak symmetry breaking. We define final states to be studied, and construct a rule that identifies a set of relevant variables for any particular final state. A new algorithm ("Sleuth") searches for regions of excess in those variables and quantifies the significance of any detected excess. After demonstrating the sensitivity of the method, we apply it to the semi-inclusive channel e mu X collected in 108 pb^-1 of ppbar collisions at sqrt(s) = 1.8 TeV at the D0 experiment during 1992-1996 at the Fermilab Tevatron. We find no evidence of new high p_T physics in this sample.Comment: 23 pages, 12 figures. Submitted to Physical Review

The Dijet Mass Spectrum and a Search for Quark Compositeness in bar{p}p Collisions at sqrt{s} = 1.8 TeV

Using the DZero detector at the 1.8 TeV pbarp Fermilab Tevatron collider, we have measured the inclusive dijet mass spectrum in the central pseudorapidity region |eta_jet| < 1.0 for dijet masses greater than 200 Gev/c^2. We have also measured the ratio of spectra sigma(|eta_jet| < 0.5)/sigma(0.5 < |eta_jet| < 1.0). The order alpha_s^3 QCD predictions are in good agreement with the data and we rule out models of quark compositeness with a contact interaction scale < 2.4 TeV at the 95% confidence level.Comment: 11 pages, 4 figures, 2 tables, submitted to Phys. Rev. Let