A Triad of Lys12, Lys41, Arg78 Spatial Domain, a Novel Identified Heparin Binding Site on Tat Protein, Facilitates Tat-Driven Cell Adhesion

Tat protein, released by HIV-infected cells, has a battery of important biological effects leading to distinct AIDS-associated pathologies. Cell surface heparan sulfate protoglycans (HSPGs) have been accepted as endogenous Tat receptors, and the Tat basic domain has been identified as the heparin binding site. However, findings that deletion or substitution of the basic domain inhibits but does not completely eliminate Tat–heparin interactions suggest that the basic domain is not the sole Tat heparin binding site. In the current study, an approach integrating computational modeling, mutagenesis, biophysical and cell-based assays was used to elucidate a novel, high affinity heparin-binding site: a Lys12, Lys41, Arg78 (KKR) spatial domain. This domain was also found to facilitate Tat-driven β1 integrin activation, producing subsequent SLK cell adhesion in an HSPG-dependent manner, but was not involved in Tat internalization. The identification of this new heparin binding site may foster further insight into the nature of Tat-heparin interactions and subsequent biological functions, facilitating the rational design of new therapeutics against Tat-mediated pathological events

A novel method to improve temperature simulations of general circulation models based on ensemble empirical mode decomposition and its application to multi-model ensembles

A novel method based on the ensemble empirical mode decomposition (EEMD) method was developed to improve model performance. This method was evaluated by applying it to global surface air temperatures, which were simulated by eight general circulation models from the Coupled Model Intercomparison Project Phase 5 (CMIP5). The temperature simulations of the eight models were separated into their different components by EEMD. The model's performance improved after the first high-frequency component was removed from the original simulations by EEMD for each model, on both the global and continental scale. Moreover, EEMD was more effective in improving the model's performance compared to the wavelet transform method. The multi-model ensembles (MMEs) were calculated based on the EEMD-improved model simulations using the Average Ensemble Mean, Multiple Linear Regression, Singular Value Decomposition and Bayesian Model Averaging methods. The results showed that the MME forecasts performed better when the calculations were based on the EEMD-improved simulations as opposed to the original simulations on both the global and continental scale. Therefore, the results of the MME were further improved by using the EEMD-improved model simulations. This new method provides a simple way to improve model performance and can be easily applied to further improve MME simulations

Molecular Mechanisms of Fiber Differential Development between G. barbadense and G. hirsutum Revealed by Genetical Genomics

Cotton fiber qualities including length, strength and fineness are known to be controlled by genes affecting cell elongation and secondary cell wall (SCW) biosynthesis, but the molecular mechanisms that govern development of fiber traits are largely unknown. Here, we evaluated an interspecific backcrossed population from G. barbadense cv. Hai7124 and G. hirsutum acc. TM-1 for fiber characteristics in four-year environments under field conditions, and detected 12 quantitative trait loci (QTL) and QTL-by-environment interactions by multi-QTL joint analysis. Further analysis of fiber growth and gene expression between TM-1 and Hai7124 showed greater differences at 10 and 25 days post-anthesis (DPA). In this two period important for fiber performances, we integrated genome-wide expression profiling with linkage analysis using the same genetic materials and identified in total 916 expression QTL (eQTL) significantly (P<0.05) affecting the expression of 394 differential genes. Many positional cis-/trans-acting eQTL and eQTL hotspots were detected across the genome. By comparative mapping of eQTL and fiber QTL, a dataset of candidate genes affecting fiber qualities was generated. Real-time quantitative RT-PCR (qRT-PCR) analysis confirmed the major differential genes regulating fiber cell elongation or SCW synthesis. These data collectively support molecular mechanism for G. hirsutum and G. barbadense through differential gene regulation causing difference of fiber qualities. The down-regulated expression of abscisic acid (ABA) and ethylene signaling pathway genes and high-level and long-term expression of positive regulators including auxin and cell wall enzyme genes for fiber cell elongation at the fiber developmental transition stage may account for superior fiber qualities

Fast catheter tracking in echocardiographic sequences for cardiac catheterization interventions

For most cardiac catheterization interventions, X-ray imaging is currently used as a standard imaging technique. However, lack of 3D soft tissue information and harmful radiation mean that X-ray imaging is not an ideal modality. In contrast, 3D echocardiography can overcome these disadvantages. In this paper, we propose a fast catheter tracking strategy for 3D ultrasound sequences. The main advantage of our strategy is low use of X-ray imaging, which significantly decreases the radiation exposure. In addition, 3D soft tissue imaging can be introduced by using ultrasound. To enable the tracking procedure, initialization is carried out on the first ultrasound frame. Given the location of the catheter in the previous frame, which is in the form of a set of ordered landmarks, 3D Speeded-Up Robust Feature (SURF) responses are calculated for candidate voxels in the surrounding region of each landmark on the next frame. One candidate is selected among all voxels for each landmark based on Fast Primal-Dual optimization (Fast-PD). As a result, a new set of ordered landmarks is extracted, corresponding to the potential location of the catheter on the next frame. In order to adapt the tracking to the changing length of the catheter in the view, landmarks which may not be located on the catheter are ruled out. Then a catheter growing strategy is performed to extend the tracked part of the catheter to the untracked part. Based on 10 ultrasound phantom sequences and two clinical sequences, comprising more than 1300 frames, our experimental results show that the tracking system can track catheters with an error of less than 2.5mm and a speed of more than 3 fps

Radiation-transfer modeling of snow-pack photochemical processes during ALERT 2000

The delta-Eddington radiation transfer model is used to calculate actinic fluxes and photolysis rates within the snow pack during the ALERT 2000 field campaign. Actinic fluxes are enhanced within the snow pack due to the high albedo of snow and conversion of direct light to diffuse light. The conversion of direct to diffuse light is highly dependent on the solar zenith angle, as demonstrated by model calculations. The optical properties of Alert snow are modeled as 100μm radius ice spheres with impurity added to increase the absorption coefficient over that of pure water ice. Using these optical properties, the model achieves good agreement with observations of irradiance within the snow pack. The model is used to calculate the total actinic flux as a function of solar zenith angle and depth for either clear sky or cloudy conditions. The actinic flux is then used to calculate photochemical production of nitrogen oxides from nitrate photolysis assuming that nitrate in snow has the same absorption cross section and quantum yield in snow as in aqueous solution. Assuming all photo-produced nitrogen oxides are released to the gas phase, we derive a maximal flux of nitrogen oxides (NOx+HONO and possibly other products) from the snow pack. The value of this maximal flux depends critically on the assumed quantum yield for production of NO2, which is unknown in ice. Depending on the assumed quantum yield, the calculated maximal flux varies between values four times smaller than the observed NOx+HONO flux to five times larger than the NOx+HONO flux. Therefore, it appears that the calculated flux is in approximate agreement with the observations with a great need for improved understanding of nitrogen photochemistry in snow. © 2002 Elsevier Science Ltd. All rights reserved