Sildenafil-Induced Revascularization of Rat Hindlimb Involves Arteriogenesis through PI3K/AKT and eNOS Activation

Hypoxia and inflammation play a major role in revascularization following ischemia. Sildenafil inhibits phosphodiesterase-5, increases intracellular cGMP and induces revascularization through a pathway which remains incompletely understood. Thus, we investigated the effect of sildenafil on post-ischemic revascularization. The left femoral artery was ligated in control and sildenafil-treated (25 mg/kg per day) rats. Vascular density was evaluated and expressed as the left/right leg (L/R) ratio. In control rats, L/R ratio was 33 ± 2% and 54 ± 9%, at 7- and 21-days post-ligation, respectively, and was significantly increased in sildenafil-treated rats to 47 ± 4% and 128 ± 11%, respectively. A neutralizing anti-VEGF antibody significantly decreased vascular density (by 0.48-fold) in control without effect in sildenafil-treated animals. Blood flow and arteriolar density followed the same pattern. In the ischemic leg, HIF-1α and VEGF expression levels increased in control, but not in sildenafil–treated rats, suggesting that sildenafil did not induce angiogenesis. PI3-kinase, Akt and eNOS increased after 7 days, with down-regulation after 21 days. Sildenafil induced outward remodeling or arteriogenesis in mesenteric resistance arteries in association with eNOS protein activation. We conclude that sildenafil treatment increased tissue blood flow and arteriogenesis independently of VEGF, but in association with PI3-kinase, Akt and eNOS activation.     

Intestinal Radiation Protection and Mitigation by Second-Generation Probiotic Lactobacillus-reuteri Engineered to Deliver Interleukin-22

(1) Background: The systemic administration of therapeutic agents to the intestine including cytokines, such as Interleukin-22 (IL-22), is compromised by damage to the microvasculature 24 hrs after total body irradiation (TBI). At that time, there is significant death of intestinal microvascular endothelial cells and destruction of the lamina propria, which limits drug delivery through the circulation, thus reducing the capacity of therapeutics to stabilize the numbers of Lgr5+ intestinal crypt stem cells and their progeny, and improve survival. By its direct action on intestinal stem cells and their villus regeneration capacity, IL-22 is both an ionizing irradiation protector and mitigator. (2) Methods: To improve delivery of IL-22 to the irradiated intestine, we gavaged Lactobacillus-reuteri as a platform for the second-generation probiotic Lactobacillus-reuteri-Interleukin-22 (LR-IL-22). (3) Results: There was effective radiation mitigation by gavage of LR-IL-22 at 24 h after intestinal irradiation. Multiple biomarkers of radiation damage to the intestine, immune system and bone marrow were improved by LR-IL-22 compared to the gavage of control LR or intraperitoneal injection of IL-22 protein. (4) Conclusions: Oral administration of LR-IL-22 is an effective protector and mitigator of intestinal irradiation damage.     

Modulation of Immune Cells as a Therapy for Cutaneous Lupus Erythematosus

Cutaneous lupus erythematosus (CLE) is an autoimmune disorder like systemic lupus erythematosus (SLE). Both SLE and CLE characterize autoantibody secretion and immune cell recruitment. In particular, CLE can be divided into three more frequent types, varying in the severity of the skin lesions they present. The role of type I IFN was shown to be one of the leading causes of the development of this pathology in the skin. Different treatments have been developed and tested against these different variants of CLE to decrease the increasing levels of CLE in humans. In this article, a literature revision discussing the similarities between SLE and CLE is carried out. In addition, new advances in understanding the development of CLE and the leading treatments being evaluated in animal models and clinical trials are reviewed.     

Recent PELE Developments and Applications in Drug Discovery Campaigns

Computer simulation techniques are gaining a central role in molecular pharmacology. Due to several factors, including the significant improvements of traditional molecular modelling, the irruption of machine learning methods, the massive data generation, or the unlimited computational resources through cloud computing, the future of pharmacology seems to go hand in hand with in silico predictions. In this review, we summarize our recent efforts in such a direction, centered on the unconventional Monte Carlo PELE software and on its coupling with machine learning techniques. We also provide new data on combining two recent new techniques, aquaPELE capable of exhaustive water sampling and fragPELE, for fragment growing.     

Bacterial swimming motility enhances cell deposition and surface coverage

The influence of bacterial motility on cell transport and deposition was investigated in a well-characterized radial stagnation point flow (RSPF) chamber. Deposition experiments were conducted with nonmotile (PA01 deltafliC deltapilA) and motile (PA01 deltapilA) strains of Pseudomonas aeruginosa, and oppositely (positively) charged modified quartz surfaces. Deposition dynamics ofthe two bacterial strains were determined over a wide range of solution ionic strengths and at two flow velocities. The observed deposition dynamics were modeled using a modified expression of the random sequential adsorption (RSA) blocking function accounting for the impacts of hydrodynamic and electrostatic interactions on cell deposition. Results for the nonmotile bacteria indicated that the changes in blocking rate and surface coverage with ionic strength and flow rate were similar to those expected for nonbiological, "soft" particles, for which the coupling of hydrodynamic interactions and electrostatic repulsion governs the deposition dynamics. In contrast deposition dynamics of the motile bacterial cells reduced blocking rates and enhanced maximum coverages, approaching the jamming limit predicted for "hard" ellipsoids of 0.583. We hypothesized that cell motility allows the upstream swimming of bacteria and subsequent cell deposition on regions which are otherwise inaccessible to nonmotile cell deposition due to the "shadow effect".     

Plant identification: man vs. machine

This paper reports a large-scale experiment aimed at evaluating how state-of-art computer vision systems perform in identifying plants compared to human expertise. A subset of the evaluation dataset used within LifeCLEF 2014 plant identification challenge was therefore shared with volunteers of diverse expertise, ranging from the leading experts of the targeted flora to inexperienced test subjects. In total, 16 human runs were collected and evaluated comparatively to the 27 machine-based runs of LifeCLEF challenge. One of the main outcomes of the experiment is that machines are still far from outperforming the best expert botanists at the image-based plant identification competition. On the other side, the best machine runs are competing with experienced botanists and clearly outperform beginners and inexperienced test subjects. This shows that the performances of automated plant identification systems are very promising and may open the door to a new generation of ecological surveillance systems.     

Structure–function relationships of fullerene esters in polymer solar cells: unexpected structural effects on lifetime and efficiency

We report both transport measurements and spectroscopic data of polymer/fullerene blend photovoltaics using a small library of fullerene esters to correlate device properties with a range of functionality and structural diversity of the ester substituent. We observe that minor structural changes can lead to significant and surprising differences in device efficiency and lifetime. For example we have found that isomeric R‐groups in the fullerene ester‐based devices we have studied have dramatically different efficiencies. The characteristic lifetimes derived from both transport and spectroscopic measurements are generally comparable; however, some more rapid effects in specific fullerene esters are not observed spectroscopically. It is apparent from our results that each fullerene derivative requires re‐optimization to reveal the best device performance. Furthermore we conclude that a library approach is essential for evaluating the effects of structural differences in the constituent molecules and serves as important device optimization method that is not being currently employed in photovoltaic investigations. Copyright © 2015 John Wiley & Sons, Ltd.     

Studies on the mechanism of ZSM-5 formation

The nucleation of (Al-free) zeolite precursor gels was studied using X-ray diffraction,²⁹Si FT-NMR, and ion exchange. Results suggest that in ZSM-5 nucleation, the channel intersections are first formed. These clathrate-like units, each containing essentially one TPA⁺ cation, are initially randomly connected, but progressively anneal with rearrangement under the influence of OH^– ions to form the ZSM-5 framework.