Inhibition of focal adhesion kinase (FAK) signaling in focal adhesions decreases cell motility and proliferation.

It has been proposed that the focal adhesion kinase (FAK) mediates focal adhesion formation through tyrosine phosphorylation during cell adhesion. We investigated the role of FAK in focal adhesion structure and function. Loading cells with a glutathione-S-transferase fusion protein (GST-Cterm) containing the FAK focal adhesion targeting sequence, but not the kinase domain, decreased the association of endogenous FAK with focal adhesions. This displacement of endogenous FAK in both BALB/c 3T3 cells and human umbilical vein endothelial cells loaded with GST-Cterm decreased focal adhesion phosphotyrosine content. Neither cell type, however, exhibited a reduction in focal adhesions after GST-Cterm loading. These results indicate that FAK mediates adhesion-associated tyrosine phosphorylation, but not the formation of focal adhesions. We then examined the effect of inhibiting FAK function on other adhesion-dependent cell behavior. Cells microinjected with GST-Cterm exhibited decreased migration. In addition, cells injected with GST-Cterm had decreased DNA synthesis compared with control-injected or noninjected cells. These findings suggest that FAK functions in the regulation of cell migration and cell proliferation

Respiratory Failure Secondary to Human Metapneumovirus Requiring Extracorporeal Membrane Oxygenation in a 32-Month-Old Child

Human metapneumovirus (HMPV) is a common virus that can cause respiratory problems ranging from mild upper respiratory tract disease to respiratory failure requiring mechanical support. Here, we report a case of a 32-month-old male with a previous history of asthma, who developed respiratory failure two weeks after onset of cough and rhinorrhea and required extracorporeal membrane oxygenation (ECMO) for 9 days after failing high-frequency oscillatory ventilation (HFOV). To our knowledge, this is the oldest reported pediatric patient with respiratory failure secondary to human metapneumovirus that did not respond to mechanical ventilation. This case highlights three critical points: the potentially fatal causative role of HMPV in respiratory failure in an older pediatric age group of immunocompetent hosts, the importance of early recognition of impending respiratory failure, and the timely utilization of ECMO

An inhibitory role for FAK in regulating proliferation: a link between limited adhesion and RhoA-ROCK signaling

Focal adhesion kinase (FAK) transduces cell adhesion to the extracellular matrix into proliferative signals. We show that FAK overexpression induced proliferation in endothelial cells, which are normally growth arrested by limited adhesion. Interestingly, displacement of FAK from adhesions by using a FAK−/− cell line or by expressing the C-terminal fragment FRNK also caused an escape of adhesion-regulated growth arrest, suggesting dual positive and negative roles for FAK in growth regulation. Expressing kinase-dead FAK-Y397F in FAK−/− cells prevented uncontrolled growth, demonstrating the antiproliferative function of inactive FAK. Unlike FAK overexpression–induced growth, loss of growth control in FAK−/− or FRNK-expressing cells increased RhoA activity, cytoskeletal tension, and focal adhesion formation. ROCK inhibition rescued adhesion-dependent growth control in these cells, and expression of constitutively active RhoA or ROCK dysregulated growth. These findings demonstrate the ability of FAK to suppress and promote growth, and underscore the importance of multiple mechanisms, even from one molecule, to control cell proliferation

Integrin-mediated survival signals regulate the apoptotic function of Bax through its conformation and subcellular localization

Most normal cells require adhesion to extracellular matrix for survival, but the molecular mechanisms that link cell surface adhesion events to the intracellular apoptotic machinery are not understood. Bcl-2 family proteins regulate apoptosis induced by a variety of cellular insults through acting on internal membranes. A pro-apoptotic Bcl-2 family protein, Bax, is largely present in the cytosol of many cells, but redistributes to mitochondria after treatment with apoptosis-inducing drugs. Using mammary epithelial cells as a model for adhesion-regulated survival, we show that detachment from extracellular matrix induced a rapid translocation of Bax to mitochondria concurrent with a conformational change resulting in the exposure of its BH3 domain. Bax translocation and BH3 epitope exposure were reversible and occurred before caspase activation and apoptosis. Pp125FAK regulated the conformation of the Bax BH3 epitope, and PI 3-kinase and pp60src prevented apoptosis induced by defective pp125FAK signaling. Our results provide a mechanistic connection between integrin-mediated adhesion and apoptosis, through the kinase-regulated subcellular distribution of Bax

Impact of baryons on the cluster mass function and cosmological parameter determination

Recent results by the Planck collaboration have shown that cosmological parameters derived from the cosmic microwave background anisotropies and cluster number counts are in tension, with the latter preferring lower values of the matter density parameter, $\Omega_\mathrm{m}$, and power spectrum amplitude, $\sigma_8$. Motivated by this, we investigate the extent to which the tension may be ameliorated once the effect of baryonic depletion on the cluster mass function is taken into account. We use the large-volume Millennium Gas simulations in our study, including one where the gas is pre-heated at high redshift and one where the gas is heated by stars and active galactic nuclei (in the latter, the self-gravity of the baryons and radiative cooling are omitted). In both cases, the cluster baryon fractions are in reasonably good agreement with the data at low redshift, showing significant depletion of baryons with respect to the cosmic mean. As a result, it is found that the cluster abundance in these simulations is around 15 per cent lower than the commonly-adopted fit to dark matter simulations by Tinker et al (2008) for the mass range $10^{14}-10^{14.5}h^{-1} \mathrm{M}_\odot$. Ignoring this effect produces a significant artificial shift in cosmological parameters which can be expressed as $\Delta[\sigma_8(\Omega_\mathrm{m}/0.27)^{0.38}]\simeq -0.03$ at $z=0.17$ (the median redshift of the $\mathit{Planck}$ cluster sample) for the feedback model. While this shift is not sufficient to fully explain the $\mathit{Planck}$ discrepancy, it is clear that such an effect cannot be ignored in future precision measurements of cosmological parameters with clusters. Finally, we outline a simple, model-independent procedure that attempts to correct for the effect of baryonic depletion and show that it works if the baryon-dark matter back-reaction is negligible.Comment: 10 pages, 5 figures, Accepted by MNRA

The Grizzly, February 4, 1983

Trouble at Cutillo\u27s: Frats Earn Reputation as Animals • Drinking Concerns Richter • Economics Council Sponsors Entrepreneur-Related Forum • President\u27s Corner • Wismer Tries Again • Pfacelift at Pfahler • Bear Blades Burnished Beat Wilmington Twice • Serendipity Celebration Features Films • Writing Center Welcomes Students • Who\u27s Who in Who\u27s Who? • Commentary: Speak Up for Coed Housing • Didja Ever Wonder • Wrestlers Earn Split • Lewis on Wall Street • Disruptive Fans Cause Flare-up at Widener • Top Individual Efforts Mark Gymnastics Team • Interview: Chupein Named to All-League Team • Lady Hoops Still Struggling • Men\u27s Basketball Find Road a Bit Bumpy • Swimmers Maul Terrors of Western Marylandhttps://digitalcommons.ursinus.edu/grizzlynews/1092/thumbnail.jp

The XMM Cluster Survey: Forecasting cosmological and cluster scaling-relation parameter constraints

We forecast the constraints on the values of sigma_8, Omega_m, and cluster scaling relation parameters which we expect to obtain from the XMM Cluster Survey (XCS). We assume a flat Lambda-CDM Universe and perform a Monte Carlo Markov Chain analysis of the evolution of the number density of galaxy clusters that takes into account a detailed simulated selection function. Comparing our current observed number of clusters shows good agreement with predictions. We determine the expected degradation of the constraints as a result of self-calibrating the luminosity-temperature relation (with scatter), including temperature measurement errors, and relying on photometric methods for the estimation of galaxy cluster redshifts. We examine the effects of systematic errors in scaling relation and measurement error assumptions. Using only (T,z) self-calibration, we expect to measure Omega_m to +-0.03 (and Omega_Lambda to the same accuracy assuming flatness), and sigma_8 to +-0.05, also constraining the normalization and slope of the luminosity-temperature relation to +-6 and +-13 per cent (at 1sigma) respectively in the process. Self-calibration fails to jointly constrain the scatter and redshift evolution of the luminosity-temperature relation significantly. Additional archival and/or follow-up data will improve on this. We do not expect measurement errors or imperfect knowledge of their distribution to degrade constraints significantly. Scaling-relation systematics can easily lead to cosmological constraints 2sigma or more away from the fiducial model. Our treatment is the first exact treatment to this level of detail, and introduces a new `smoothed ML' estimate of expected constraints.Comment: 28 pages, 17 figures. Revised version, as accepted for publication in MNRAS. High-resolution figures available at http://xcs-home.org (under "Publications"

The Grizzly, September 24, 1982

Crime Comes to Collegeville: Attempted Assault on Main Street • New Advising System for Freshmen Students • Union Program Board Projects VCR Movies • McNamara to Speak at Ursinus Gym • What? More New Faculty? • Speech Exemption Exam Set • Writing Center Opens • Time for Action • Name That Tune! • In the Limelight • USGA Notes • Forum Review • Kohler Exhibits at Myrin • Brown Sets X-country Record • Volleyball Team Keeps Their Winning Ways • Field Hockey Tops Gettysburg in O.T. • U.C. Soccer Wins Their First • Grizzlies Look Tough in 6-6 Tiehttps://digitalcommons.ursinus.edu/grizzlynews/1082/thumbnail.jp

Production Complexity, Adaptability and Economic Growth

This paper analyzes the impact of production complexity and its adaptability on the level of output and on its rate of growth. We develop an endogenous growth model where increased complexity raises the rate of economic growth but has an ambiguous effect on the level of output. Our empirical measure of production adaptability captures the proximity of production sectors within the product space, which we modify to reflect intra-industry trade and the international fragmentation of production. We test the model against a sample of 89 countries over the two decades to 2009 and find that its main predictions are validated

The Grizzly, October 22, 1982

Ferry Named Ursinus Queen • Unique Course Offered • U.C. Choir Presents Bach • Night School Enrollment Up • 1983 Spring Registration • Letters to the Editor • President\u27s Corner • Lewis on Wall Street • Half a Great Show • Watching the Boob Tube • Homecoming \u2782 • And to Prove My Point • New Bus Schedule • Washington Semester: Get Out of Here • Bear Pack Falls to Stiff Competition • Soccer Conquers Albright and Alumni • Grapplers Take to the Mats • Grizzlies Suffer Homecoming Setback • Delaware tops Lady Bearshttps://digitalcommons.ursinus.edu/grizzlynews/1085/thumbnail.jp