The limits of filopodium stability

Filopodia are long, finger-like membrane tubes supported by cytoskeletal filaments. Their shape is determined by the stiffness of the actin filament bundles found inside them and by the interplay between the surface tension and bending rigidity of the membrane. Although one might expect the Euler buckling instability to limit the length of filopodia, we show through simple energetic considerations that this is in general not the case. By further analyzing the statics of filaments inside membrane tubes, and through computer simulations that capture membrane and filament fluctuations, we show under which conditions filopodia of arbitrary lengths are stable. We discuss several in vitro experiments where this kind of stability has already been observed. Furthermore, we predict that the filaments in long, stable filopodia adopt a helical shape

Long-term tillage effects on the distribution of P fractions of German loess soils

Different tillage systems may effect P dynamics in soils due to differently distributed plant residues, different aggregate dynamics and erosion losses. Objectives were to investigate the effect of tillage in a long-term field trial, initiated from 1990 to 1997 on the availability of P at four research sites. The treatments were no-till (NT) without cultivation and conventional tillage (mouldboard ploughing down to 25-30 cm, CT) on loess soils. Soil P was divided into pools of different availabilities by a sequential extraction. The Pt content (792 mg kg-1 soil) in the topsoil of NT was 15% higher compared to CT, while with increasing depth the Pt concentration decreased more under NT than under CT. Oxalate extractable iron and organic carbon were well related to the labile Pi fractions, while there was a high correlation of the stable fractions with the clay contents and pH. The higher P concentrations in the topsoil of NT resulted presumably from the shallower incorporation of root and harvest residues and erosion compared to CT

Transport through (Ga,Mn)As nanoislands: Coulomb-blockade and temperature dependence of the conductance

We report on magnetotransport measurements of nanoconstricted (Ga,Mn)As devices showing very large resistance changes that can be controlled by both an electric and a magnetic field. Based on the bias voltage and temperature dependent measurements down to the millikelvin range we compare the models currently used to describe transport through (Ga,Mn)As nanoconstrictions. We provide an explanation for the observed spin-valve like behavior during a magnetic field sweep by means of the magnetization configurations in the device. Furthermore, we prove that Coulomb-blockade plays a decisive role for the transport mechanism and show that modeling the constriction as a granular metal describes the temperature and bias dependence of the conductance correctly and allows to estimate the number of participating islands located in the constriction.Comment: 5 pages, 3 figures, completed affiliations and corrected typo

Large-scale Structural Rearrangement of a Serine Hydrolase from Francisella Tularensis Facilitates Catalysis

Tularemia is a deadly, febrile disease caused by infection by the gram-negative bacterium, Francisella tularensis. Members of the ubiquitous serine hydrolase protein family are among current targets to treat diverse bacterial infections. Herein we present a structural and functional study of a novel bacterial carboxylesterase (FTT258) from F. tularensis, a homologue of human acyl protein thioesterase (hAPT1). The structure of FTT258 has been determined in multiple forms, and unexpectedly large conformational changes of a peripheral flexible loop occur in the presence of a mechanistic cyclobutanone ligand. The concomitant changes in this hydrophobic loop and the newly exposed hydrophobic substrate binding pocket suggest that the observed structural changes are essential to the biological function and catalytic activity of FTT258. Using diverse substrate libraries, site-directed mutagenesis, and liposome binding assays, we determined the importance of these structural changes to the catalytic activity and membrane binding activity of FTT258. Residues within the newly exposed hydrophobic binding pocket and within the peripheral flexible loop proved essential to the hydrolytic activity of FTT258, indicating that structural rearrangement is required for catalytic activity. Both FTT258 and hAPT1 also showed significant association with liposomes designed to mimic bacterial or human membranes, respectively, even though similar structural rearrangements for hAPT1 have not been reported. The necessity for acyl protein thioesterases to have maximal catalytic activity near the membrane surface suggests that these conformational changes in the protein may dually regulate catalytic activity and membrane association in bacterial and human homologues

IL-23 stimulates epidermal hyperplasia via TNF and IL-20R2–dependent mechanisms with implications for psoriasis pathogenesis

Aberrant cytokine expression has been proposed as an underlying cause of psoriasis, although it is unclear which cytokines play critical roles. Interleukin (IL)-23 is expressed in human psoriasis and may be a master regulator cytokine. Direct intradermal administration of IL-23 in mouse skin, but not IL-12, initiates a tumor necrosis factor–dependent, but IL-17A–independent, cascade of events resulting in erythema, mixed dermal infiltrate, and epidermal hyperplasia associated with parakeratosis. IL-23 induced IL-19 and IL-24 expression in mouse skin, and both genes were also elevated in human psoriasis. IL-23–dependent epidermal hyperplasia was observed in IL-19−/− and IL-24−/− mice, but was inhibited in IL-20R2−/− mice. These data implicate IL-23 in the pathogenesis of psoriasis and support IL-20R2 as a novel therapeutic target

Mapping annual forest cover in sub-humid and semi-arid Regions through analysis of Landsat and PALSAR imagery

Accurately mapping the spatial distribution of forests in sub-humid to semi-arid regions over time is important for forest management but a challenging task. Relatively large uncertainties still exist in the spatial distribution of forests and forest changes in the sub-humid and semi-arid regions. Numerous publications have used either optical or synthetic aperture radar (SAR) remote sensing imagery, but the resultant forest cover maps often have large errors. In this study, we propose a pixel- and rule-based algorithm to identify and map annual forests from 2007 to 2010 in Oklahoma, USA, a transitional region with various climates and landscapes, using the integration of the L-band Advanced Land Observation Satellite (ALOS) PALSAR Fine Beam Dual Polarization (FBD) mosaic dataset and Landsat images. The overall accuracy and Kappa coefficient of the PALSAR/Landsat forest map were about 88.2% and 0.75 in 2010, with the user and producer accuracy about 93.4% and 75.7%, based on the 3270 random ground plots collected in 2012 and 2013. Compared with the forest products from Japan Aerospace Exploration Agency (JAXA), National Land Cover Database (NLCD), Oklahoma Ecological Systems Map (OKESM) and Oklahoma Forest Resource Assessment (OKFRA), the PALSAR/Landsat forest map showed great improvement. The area of the PALSAR/Landsat forest was about 40,149 km2 in 2010, which was close to the area from OKFRA (40,468 km2), but much larger than those from JAXA (32,403 km2) and NLCD (37,628 km2). We analyzed annual forest cover dynamics, and the results show extensive forest cover loss (2761 km2, 6.9% of the total forest area in 2010) and gain (3630 km2, 9.0%) in southeast and central Oklahoma, and the total area of forests increased by 684 km2 from 2007 to 2010. This study clearly demonstrates the potential of data fusion between PALSAR and Landsat images for mapping annual forest cover dynamics in sub-humid to semi-arid regions, and the resultant forest maps would be helpful to forest management.This study was supported in part by research grants from the National Institute of Food and Agriculture, U.S. Department of Agriculture (2013-69002), the National Science Foundation (NSF) EPSCoR program (OIA-1301789), and the Department of the Interior, United States Geological Survey to AmericaView (G14AP00002).Ye

Resource Use Trajectories for Aged Medicare Beneficiaries with Complex Coronary Conditions

To use coronary revascularization choice to illustrate the application of a method simulating a treatment's effect on subsequent resource use

Activation of PI3K/mTOR pathway occurs in most adult low-grade gliomas and predicts patient survival

Recent evidence suggests the Akt-mTOR pathway may play a role in development of low-grade gliomas (LGG). We sought to evaluate whether activation of this pathway correlates with survival in LGG by examining expression patterns of proteins within this pathway. Forty-five LGG tumor specimens from newly diagnosed patients were analyzed for methylation of the putative 5′-promoter region of PTEN using methylation-specific PCR as well as phosphorylation of S6 and PRAS40 and expression of PTEN protein using immunohistochemistry. Relationships between molecular markers and overall survival (OS) were assessed using Kaplan-Meier methods and exact log-rank test. Correlation between molecular markers was determined using the Mann-Whitney U and Spearman Rank Correlation tests. Eight of the 26 patients with methylated PTEN died, as compared to 1 of 19 without methylation. There was a trend towards statistical significance, with PTEN methylated patients having decreased survival (P = 0.128). Eight of 29 patients that expressed phospho-S6 died, whereas all 9 patients lacking p-S6 expression were alive at last follow-up. There was an inverse relationship between expression of phospho-S6 and survival (P = 0.029). There was a trend towards decreased survival in patients expressing phospho-PRAS40 (P = 0.077). Analyses of relationships between molecular markers demonstrated a statistically significant positive correlation between expression of p-S6(235) and p-PRAS40 (P = 0.04); expression of p-S6(240) correlated positively with PTEN methylation (P = 0.04) and negatively with PTEN expression (P = 0.03). Survival of LGG patients correlates with phosphorylation of S6 protein. This relationship supports the use of selective mTOR inhibitors in the treatment of low grade glioma