Fibroblast-derived HGF drives acinar lung cancer cell polarization through integrin-dependent RhoA-ROCK1 inhibition

The formation of lumens in epithelial tissues requires apical-basal polarization of cells, and the co-ordination of this individual polarity collectively around a contiguous lumen. Signals from the Extracellular Matrix (ECM) instruct epithelia as to the orientation of where basal, and thus consequently apical, surfaces should be formed. We report that this pathway is normally absent in Calu-3 human lung adenocarcinoma cells in 3-Dimensional culture, but that paracrine signals from MRC5 lung fibroblasts can induce correct orientation of polarity and acinar morphogenesis. We identify HGF, acting through the c-Met receptor, as the key polarity-inducing morphogen, which acts to activate β1-integrin-dependent adhesion. HGF and ECM-derived integrin signals co-operate via a c-Src-dependent inhibition of the RhoA-ROCK1 signalling pathway via p190A RhoGAP. This occurred via controlling localization of these signalling pathways to the ECM-abutting surface of cells in 3-Dimensional culture. Thus, stromal derived signals can influence morphogenesis in epithelial cells by controlling activation and localization of cell polarity pathways

Microwave Dielectric Heating of Drops in Microfluidic Devices

We present a technique to locally and rapidly heat water drops in microfluidic devices with microwave dielectric heating. Water absorbs microwave power more efficiently than polymers, glass, and oils due to its permanent molecular dipole moment that has a large dielectric loss at GHz frequencies. The relevant heat capacity of the system is a single thermally isolated picoliter drop of water and this enables very fast thermal cycling. We demonstrate microwave dielectric heating in a microfluidic device that integrates a flow-focusing drop maker, drop splitters, and metal electrodes to locally deliver microwave power from an inexpensive, commercially available 3.0 GHz source and amplifier. The temperature of the drops is measured by observing the temperature dependent fluorescence intensity of cadmium selenide nanocrystals suspended in the water drops. We demonstrate characteristic heating times as short as 15 ms to steady-state temperatures as large as 30 degrees C above the base temperature of the microfluidic device. Many common biological and chemical applications require rapid and local control of temperature, such as PCR amplification of DNA, and can benefit from this new technique.Comment: 6 pages, 4 figure

Role of a plausible nuisance contributor in the declining obesity-mortality risks over time.

CONTEXT: Recent analyses of epidemiological data including the National Health and Nutrition Examination Survey (NHANES) have suggested that the harmful effects of obesity may have decreased over calendar time. The shifting BMI distribution over time coupled with the application of fixed broad BMI categories in these analyses could be a plausible nuisance contributor to this observed change in the obesity-associated mortality over calendar time. OBJECTIVE: To evaluate the extent to which observed temporal changes in the obesity-mortality association may be due to a shifting population distribution for body mass index (BMI), coupled with analyses based on static, broad BMI categories. DESIGN, SETTING, AND PARTICIPANTS: Simulations were conducted using data from NHANES I and III linked with mortality data. Data from NHANES I were used to fit a true model treating BMI as a continuous variable. Coefficients estimated from this model were used to simulate mortality for participants in NHANES III. Hence, the population-level association between BMI and mortality in NHANES III was fixed to be identical to the association estimated in NHANES I. Hazard ratios (HRs) for obesity categories based on BMI for NHANES III with simulated mortality data were compared to the corresponding estimated HRs from NHANES I. MAIN OUTCOME MEASURES: Change in hazard ratios for simulated data in NHANES III compared to observed estimates from NHANES I. RESULTS: On average, hazard ratios for NHANES III based on simulated mortality data were 29.3% lower than the estimates from NHANES I using observed mortality follow-up. This reduction accounted for roughly three-fourths of the apparent decrease in the obesity-mortality association observed in a previous analysis of these data. CONCLUSIONS: Some of the apparent diminution of the association between obesity and mortality may be an artifact of treating BMI as a categorical variable

Mechanotransduction and nuclear function

Many signaling pathways converge on the nucleus to regulate critical nuclear events such as transcription, DNA replication and cell cycle progression. While the vast majority of research in this area has focused on signals generated in response to hormones or other soluble factors, the nucleus also responds to mechanical forces. During the past decade or so, much has been learned about how mechanical force can affect transcription, as well as the growth and differentiation of cells. Much has also been learned about how force is transmitted via the cytoskeleton to the nucleus and then across the nuclear envelope to the nuclear lamina and chromatin. In this brief review, we focus on some of the key proteins that transmit mechanical signals across the nuclear envelope

Defining the complementarities between antibodies and haptens to refine our understanding and aid the prediction of a successful binding interaction

Acknowledgments The authors would like to thank the Scottish Universities Life Sciences Alliance (SULSA) for their support.Peer reviewedPublisher PD

Influence of tides on melting and freezing beneath Filchner-Ronne Ice Shelf, Antarctica

An isopycnic coordinate ocean circulation model is applied to the ocean cavity beneath Filchner-Ronne Ice Shelf, investigating the role of tides on sub-ice shelf circulation and ice shelf basal mass balance. Including tidal forcing causes a significant intensification in the sub-ice shelf circulation, with an increase in melting (3-fold) and refreezing (6-fold); the net melt rate and seawater flux through the cavity approximately doubles. With tidal forcing, the spatial pattern and magnitude of basal melting and freezing generally match observations. The 0.22 m a(-1) net melt rate is close to satellite-derived estimates and at the lower end of oceanographic values. The Ice Shelf Water outflow mixes with shelf waters, forming a cold (<-1.9 degrees C), dense overflow (0.83 Sv) that spills down the continental slope. These results demonstrate that tidal forcing is fundamental to both ice shelf-ocean interactions and deep-water formation in the southern Weddell Sea. Citation: Makinson, K., P. R. Holland, A. Jenkins, K. W. Nicholls, and D. M. Holland (2011), Influence of tides on melting and freezing beneath Filchner-Ronne Ice Shelf, Antarctica, Geophys. Res. Lett., 38, L06601, doi: 10.1029/2010GL046462

Public understanding of solar radiation management

We report the results of the first large-scale international survey of public perception of geoengineering and solar radiation management (SRM). Our sample of 3105 individuals in the United States, Canada and the United Kingdom was recruited by survey firms that administer internet surveys to nationally representative population samples. Measured familiarity was higher than expected, with 8% and 45% of the population correctly defining the terms geoengineering and climate engineering respectively. There was strong support for allowing the study of SRM. Support decreased and uncertainty rose as subjects were asked about their support for using SRM immediately, or to stop a climate emergency. Support for SRM is associated with optimism about scientific research, a valuing of SRM's benefits and a stronger belief that SRM is natural, while opposition is associated with an attitude that nature should not be manipulated in this way. The potential risks of SRM are important drivers of public perception with the most salient being damage to the ozone layer and unknown risks. SRM is a new technology and public opinions are just forming; thus all reported results are sensitive to changes in framing, future information on risks and benefits, and changes to context.Physic

Simulation of phosphorus implantation into silicon with a single-parameter electronic stopping power model

We simulate dopant profiles for phosphorus implantation into silicon using a new model for electronic stopping power. In this model, the electronic stopping power is factorized into a globally averaged effective charge Z1*, and a local charge density dependent electronic stopping power for a proton. There is only a single adjustable parameter in the model, namely the one electron radius rs0 which controls Z1*. By fine tuning this parameter, we obtain excellent agreement between simulated dopant profiles and the SIMS data over a wide range of energies for the channeling case. Our work provides a further example of implant species, in addition to boron and arsenic, to verify the validity of the electronic stopping power model and to illustrate its generality for studies of physical processes involving electronic stopping.Comment: 11 pages, 7 figures. See http://bifrost.lanl.gov/~reed