Human prostaglandin EP3 receptor isoforms show different agonist-induced internalization patterns

AbstractThe human prostaglandin EP3 receptor comprises eight isoforms that differ in carboxyl-tail. We show here that the isoforms are trafficked differently. When expressed in HEK293 cells, the isoforms located to the cell surface, although a fraction of some remained in the cell. Upon prostaglandin E2 stimulation, EP3.I internalized almost completely, EP3.II, EP3.V, EP3.VI and EP3.f internalized to a lesser extent and EP3.III and EP3.IV did not internalize. Both EP3.I and EP3.f internalized with β-arrestin and internalization were blocked by a dominant negative form of Eps15, a clathrin-associated protein. Although EP3.II internalized, β-arrestin did not translocate with the receptor and internalization was not blocked by mutant Eps15. EP3.V and EP3.VI internalized to discrete areas of the cell with β-arrestin

Toward Defining Literacy

Literacy is a topic much on the public\u27s mind these days. It is one of those subjects on which all laypersons think they are experts. When it comes time, however, to establish measures of illiteracy rates or to set policies, it becomes apparent that we know less than we thought we did. It is small comfort to know that specialists also have their differences

GEM/POPs: a global 3-D dynamic model for semi-volatile persistent organic pollutants ? Part 2: Global transports and budgets of PCBs

International audienceGlobal transports and budgets of three PCBs were investigated with a 3-D dynamic model for semi-volatile persistent organic pollutants ? GEM/POPs. Dominant pathways were identified for PCB transports in the atmosphere with a transport flux peaking below 8 km for gaseous and 14 km for particulate PCB28, and peaking below 4 km for gaseous and 6 km for particulate PCB180. The inter-continental transports of PCBs in the Northern Hemisphere (NH) are dominated in the zonal direction with their route changes regulated seasonally by the variation of westerly jet. The transport pathways from Europe and North Atlantic contributed the most PCBs to the Arctic. Inter-hemispheric transports of PCBs originated from the regions of Europe, Asia and North America in three different flow-paths, accompanying with easterly jet, Asian monsoon winds and trade winds. PCBs from the Southern Hemisphere (SH) could also be exported into the NH. According to the PCB emissions of year 2000, Europe, North America and Asia are the three largest sources of the three PCBs, contributing to the global background concentrations in the atmosphere, soil and water. Globally, PCB28 in soil and water has become a comparable source to the anthropogenic emissions while heavier PCBs such as PCB153 and 180 are still transporting into soil and water. For all three congeners, particulate PCBs are concentrated in the higher levels than gaseous PCBs. More than half of the particulate PCB28 could reach up to the stratosphere, while most of the heavier counter-parts (PCB153 and PCB180) are stored in the troposphere including boundary layer with more than 99% gaseous PCB180 below 6 km

An in vivo analysis of safe laparoscopic grasping thresholds for colorectal surgery

Background Analysis of safe laparoscopic grasping thresholds for the colon has not been performed. This study aimed to analyse tissue damage thresholds when the colon is grasped laparoscopically, correlating histological changes to mechanical compressive forces. Methods An instrumented laparoscopic grasper was used to measure the forces applied to porcine colon, with data captured and plotted as a force–time (f–t) curve. Haematoxylin and eosin histochemistry of tissue subjected to 10, 20, 40, 50 and 70 N for 5, 30 and 60 s was performed, and the area of colonic circular and longitudinal muscle was compared in grasped and un-grasped regions. The area under the f–t curve was calculated as a measure of the accumulated force applied, known as the force–time product (FTP). Results FTP ranged from 55.7 to 3793 N.s. Significant differences were observed between the muscle area of the grasped and un-grasped regions in both longitudinal and circular muscle at 50 N and above for all grasping times. For the longitudinal muscle, significant differences were observed between grasped and un-grasped areas at 20 N force for 30 s (mean difference = 59 mm2, 95% CI 41–77 mm2, P = 0.04), 20 N force for 60 s (mean difference = 31 mm2, 95% CI 21.5–40.5 mm2, P = 0.006) and 40 N force for 30 s (mean difference 37 mm2, 95% CI 27–47 mm2, P = 0.006). Changes in histology correlated with mechanical forces applied to the longitudinal muscle at a FTP over 300 N s. Conclusions This study characterizes the grasping forces that result in histological changes to the colon and correlates these with a mechanical measurement of the applied force. The findings will contribute to the development of smart laparoscopic graspers with active constraints to prevent excessive grasping and tissue injury

Modeling sea-salt aerosols in the atmosphere: 2. Atmospheric concentrations and fluxes

Atmospheric sea-salt aerosol concentrations are studied using both long-term observations and model simulations of Na+ at seven stations around the globe. Good agreement is achieved between observations and model predictions in the northern hemisphere. A stronger seasonal variation occurs in the high-latitude North Atlantic than in regions close to the equator and in high-latitude southern hemisphere. Generally, concentrations are higher for both boreal and austral winters. With the model, the production flux and removal flux at the atmosphere-ocean interface was calculated and used to estimate the global sea-salt budget. The flux also shows seasonal variation similar to that of sea-salt concentration. Depending on the geographic location, the model predicts that dry deposition accounts for 60–70% of the total sea-salt removed from the atmosphere while in-cloud and below-cloud precipitation scavenging accounts for about 1% and 28–39% of the remainder, respectively. The total amount of sea-salt aerosols emitted from the world oceans to the atmosphere is estimated to be in the vicinity of 1.17×1016 g yr−1. Approximately 99% of the sea-salt aerosol mass generated by wind falls back to the sea with about 1–2% remaining in the atmosphere to be exported from the original grid square (300×300 km). Only a small portion of that exported (∼4%) is associated with submicron particles that are likely to undergo long-range transport

GEM/POPs: a global 3-D dynamic model for semi-volatile persistent organic pollutants ? Part 1: Model description and evaluations of air concentrations

International audienceGEM/POPs was developed to simulate the transport, deposition and partitioning of semi-volatile persistent organic pollutants (POPs) in the atmosphere within the framework of Canadian weather forecasting model GEM. In addition to the general processes such as anthropogenic emissions, atmosphere/water and atmosphere/soil exchanges, GEM/POPs incorporates a dynamic aerosol module to provide the aerosol surface areas for the semi-volatile POPs to partition between gaseous and particle phases and a mechanism for particle-bound POPs to be removed. Simulation results of three PCBs (28, 153 and 180) for the year 2000 indicate that the model captured the main features of global atmospheric PCBs when compared with observations from EMEP, IADN and Alert stations. The annual averaged concentrations and the fractionation of the three PCBs as a function of latitudes agreed reasonably well with observations. The impacts of atmospheric aerosols on the transports and partitioning of the three PCBs are reasonably simulated. The ratio of particulate to gaseous PCBs in the atmospheric column ranges from less than 0.1 for PCB28 to as high as 100 for PCB180, increasing from the warm lower latitudes to the cold high latitudes. Application of GEM/POPs in a study of the global transports and budgets of various PCBs accompanies this paper

Randomised controlled feasibility trial of a web-based weight management intervention with nurse support for obese patients in primary care

<b>Background</b><p></p> There is a need for cost-effective weight management interventions that primary care can deliver to reduce the morbidity caused by obesity. Automated web-based interventions might provide a solution, but evidence suggests that they may be ineffective without additional human support. The main aim of this study was to carry out a feasibility trial of a web-based weight management intervention in primary care, comparing different levels of nurse support, to determine the optimal combination of web-based and personal support to be tested in a full trial.<p></p> <b>Methods</b><p></p> This was an individually randomised four arm parallel non-blinded trial, recruiting obese patients in primary care. Following online registration, patients were randomly allocated by the automated intervention to either usual care, the web-based intervention only, or the web-based intervention with either basic nurse support (3 sessions in 3 months) or regular nurse support (7 sessions in 6 months). The main outcome measure (intended as the primary outcome for the main trial) was weight loss in kg at 12 months. As this was a feasibility trial no statistical analyses were carried out, but we present means, confidence intervals and effect sizes for weight loss in each group, uptake and retention, and completion of intervention components and outcome measures.<p></p> <b>Results</b><p></p> All randomised patients were included in the weight loss analyses (using Last Observation Carried Forward). At 12 months mean weight loss was: usual care group (n = 43) 2.44 kg; web-based only group (n = 45) 2.30 kg; basic nurse support group (n = 44) 4.31 kg; regular nurse support group (n = 47) 2.50 kg. Intervention effect sizes compared with usual care were: d = 0.01 web-based; d = 0.34 basic nurse support; d = 0.02 regular nurse support. Two practices deviated from protocol by providing considerable weight management support to their usual care patients.<p></p> <b>Conclusions</b><p></p> This study demonstrated the feasibility of delivering a web-based weight management intervention supported by practice nurses in primary care, and suggests that the combination of the web-based intervention with basic nurse support could provide an effective solution to weight management support in a primary care context

South African women’s perspectives on self-sampling for cervical cancer screening: A mixed-methods study

Background. Self-sampling as a method of screening for cervical cancer and its precursors is an attractive option for low-resource settings. However, to allow successful integration of self-sampling into national screening programmes, it is necessary to understand women’s perceptions and beliefs surrounding this method of sampling the cervix.Objectives. To explore women’s attitudes to self-collection of samples for cervical screening in a low-resource setting in South Africa (SA).Methods. Mixed methods were used to meet the study objectives. We recruited women aged 30 - 65 years into a study in Cape Town, SA, to participate in a cross-sectional survey. All women collected a vaginal self-sample, and underwent visual inspection with acetic acid, colposcopy, and collection of cervical samples and appropriate histology specimens by a doctor. Women had a quantitative questionnairebased exit interview. A subset of these women participated in focus group discussions (FGDs).Results. A total of 822 women answered the exit survey questionnaire and 41 women participated in the FGDs. Most women from the survey had a positive perception of self-sampling, with 93.6% of the women reporting not feeling embarrassed and 89.4% reporting experiencing no discomfort at all when taking a self-sample. This was  corroborated by the FGD participants, who found self-sampling easier, more comfortable and less embarrassing than clinician sampling. However, many women (64.7%) felt more confident when the sample was taken by a clinician, despite having a positive attitude towards self-sampling. In most cases this was because they thought that the clinician would take a better sample, as explained by the FGD  participants. Although 93.9% of the women were  willing to collect a selfsample, the women in the FGDs expressed a preference for doing so at the health facility  rather than at home. There were many reasons for this, including the cost of returning to the clinic with the sample.Conclusions. Attitudes regarding self-sample collection were positive in this study population. Participants were willing to perform selfsampling, but expressed concerns regarding the quality of the specimen and the financial implications of returning to the clinic with it. Pilot implementation studies will be useful before this method of sampling is adopted and integrated into screening programmes

Fast Plasma Investigation for MMS: Simulation of the Burst Triggering System

The Magnetospheric Multiscale (MMS) mission will study small-scale reconnection structures and their rapid motions from closely spaced platforms using instruments capable of high angular, energy, and time resolution measurements. To meet these requirements, the Fast Plasma Instrument (FPI) consists of eight (8) identical half top-hat electron sensors and eight (8) identical ion sensors and an Instrument Data Processing Unit (IDPU). The sensors (electron or ion) are grouped into pairs whose 6 degree x 180 degree fields-of-view (FOV) are set 90 degrees apart. Each sensor is equipped with electrostatic aperture steering to allow the sensor to scan a 45 degree x 180 degree fan about the its nominal viewing (0 deflection) direction. Each pair of sensors, known as the Dual Electron Spectrometer (DES) and the Dual Ion Spectrometer (DIS), occupies a quadrant on the MMS spacecraft and the combination of the eight electron/ion sensors, employing aperture steering, image the full-sky every 30-ms (electrons) and 150-ms (ions), respectively. To probe the diffusion regions of reconnection, the highest temporal/spatial resolution mode of FPI results in the DES complement of a given spacecraft generating 6.5-Mb (raised dot) per second of electron data while the DIS generates 1.1-Mb (raised dot) per second of ion data yielding an FPI total data rate of 6.6-Mb (raised dot) per second. The FPI electron/ion data is collected by the IDPU then transmitted to the Central Data Instrument Processor (CIDP) on the spacecraft for science interest ranking. Only data sequences that contain the greatest amount of temporal/spatial structure will be intelligently down-linked by the spacecraft. This requires a data ranking process known as the burst trigger system. The burst trigger system uses pseudo physical quantities to approximate the local plasma environments. As each pseudo quantity will have a different value, a set of two scaling factors is employed for each pseudo term. These pseudo quantities are then combined at the instrument, spacecraft, and observatory level leading to a final ranking of data based on expected scientific interest. Here, we present simulations of the fixed point burst trigger system for the FPI. A variety of data sets based on previous mission data as well as analytical formulations are tested. Comparisons of floating point calculations versus the fixed point hardware simulation are shown. Analysis of the potential sources of error from overflows, quantization, etc. are examined and mitigation methods are presented. Finally a series of calibration curves are presented, showing the expected error in pseudo quantities based solely on the scale parameters chosen and the expected data range. We conclude with a presentation of the current base-lined FPI burst trigger approach