The Photophysics of Polythiophene Nanoparticles for Biological Applications

In this work the photophysics of poly(3-hexylthiophene) nanoparticles (NPs) is investigated in the context of their biological applications. The NPs, made as colloidal suspensions in aqueous buffers, present a distinct absorption band in the low-energy region. On the basis of systematic analysis of absorption and transient absorption (TA) spectra taken under different pH conditions, this band is associated with charge-transfer states generated by the polarization of loosely bound polymer chains and originating from complexes formed with electron-withdrawing species. Importantly, the ground-state depletion of these states upon photoexcitation is active even on microsecond timescales, thus suggesting that they act as precursor states for long-living polarons; this could be beneficial for cellular stimulation. Preliminary transient absorption microscopy results for NPs internalized within the cells reveal the presence of long-living species, further substantiating their relevance in biointerfaces.     

Therapeutic Acellular Scaffolds for Limiting Left Ventricular Remodelling-Current Status and Future Directions

Myocardial infarction (MI) is one of the leading causes of heart-related deaths worldwide. Following MI, the hypoxic microenvironment triggers apoptosis, disrupts the extracellular matrix and forms a non-functional scar that leads towards adverse left ventricular (LV) remodelling. If left untreated this eventually leads to heart failure. Besides extensive advancement in medical therapy, complete functional recovery is never accomplished, as the heart possesses limited regenerative ability. In recent decades, the focus has shifted towards tissue engineering and regenerative strategies that provide an attractive option to improve cardiac regeneration, limit adverse LV remodelling and restore function in an infarcted heart. Acellular scaffolds possess attractive features that have made them a promising therapeutic candidate. Their application in infarcted areas has been shown to improve LV remodelling and enhance functional recovery in post-MI hearts. This review will summarise the updates on acellular scaffolds developed and tested in pre-clinical and clinical scenarios in the past five years with a focus on their ability to overcome damage caused by MI. It will also describe how acellular scaffolds alone or in combination with biomolecules have been employed for MI treatment. A better understanding of acellular scaffolds potentialities may guide the development of customised and optimised therapeutic strategies for MI treatment.     

Erythrocytes as a Model for Heavy Metal-Related Vascular Dysfunction: The Protective Effect of Dietary Components

Heavy metals are toxic environmental pollutants associated with severe ecological and human health risks. Among them is mercury (Hg), widespread in air, soil, and water, due to its peculiar geo-biochemical cycle. The clinical consequences of Hg exposure include neurotoxicity and nephrotoxicity. Furthermore, increased risk for cardiovascular diseases is also reported due to a direct effect on cardiovascular tissues, including endothelial cells, recently identified as important targets for the harmful action of heavy metals. In this review, we will discuss the rationale for the potential use of erythrocytes as a surrogate model to study Hg-related toxicity on the cardiovascular system. The toxic effects of Hg on erythrocytes have been amply investigated in the last few years. Among the observed alterations, phosphatidylserine exposure has been proposed as an underlying mechanism responsible for Hg-induced increased proatherogenic and prothrombotic activity of these cells. Furthermore, following Hg-exposure, a decrease in NOS activity has also been reported, with consequent lowering of NO bioavailability, thus impairing endothelial function. An additional mechanism that may induce a decrease in NO availability is the generation of an oxidative microenvironment. Finally, considering that chronic Hg exposure mainly occurs through contaminated foods, the protective effect of dietary components is also discussed.     

TRPM2 Oxidation Activates Two Distinct Potassium Channels in Melanoma Cells through Intracellular Calcium Increase

Tumor microenvironments are often characterized by an increase in oxidative stress levels. We studied the response to oxidative stimulation in human primary (IGR39) or metastatic (IGR37) cell lines obtained from the same patient, performing patch-clamp recordings, intracellular calcium ([Ca²⁺]_i) imaging, and RT-qPCR gene expression analysis. In IGR39 cells, chloramine-T (Chl-T) activated large K⁺ currents (KROS) that were partially sensitive to tetraethylammonium (TEA). A large fraction of KROS was inhibited by paxilline—a specific inhibitor of large-conductance Ca²⁺-activated BK channels. The TEA-insensitive component was inhibited by senicapoc—a specific inhibitor of the Ca²⁺-activated KCa3.1 channel. Both BK and KCa3.1 activation were mediated by an increase in [Ca²⁺]_i induced by Chl-T. Both KROS and [Ca²⁺]_i increase were inhibited by ACA and clotrimazole—two different inhibitors of the calcium-permeable TRPM2 channel. Surprisingly, IGR37 cells did not exhibit current increase upon the application of Chl-T. Expression analysis confirmed that the genes encoding BK, KCa3.1, and TRPM2 are much more expressed in IGR39 than in IGR37. The potassium currents and [Ca²⁺]_i increase observed in response to the oxidizing agent strongly suggest that these three molecular entities play a major role in the progression of melanoma. Pharmacological targeting of either of these ion channels could be a new strategy to reduce the metastatic potential of melanoma cells, and could complement classical radio- or chemotherapeutic treatments.     

Antagonizing S1P3 Receptor with Cell-Penetrating Pepducins in Skeletal Muscle Fibrosis

S1P is the final product of sphingolipid metabolism, which interacts with five widely expressed GPCRs (S1P_1-5). Increasing numbers of studies have indicated the importance of S1P₃ in various pathophysiological processes. Recently, we have identified a pepducin (compound KRX-725-II) acting as an S1P₃ receptor antagonist. Here, aiming to optimize the activity and selectivity profile of the described compound, we have synthesized a series of derivatives in which Tyr, in position 4, has been substituted with several natural aromatic and unnatural aromatic and non-aromatic amino acids. All the compounds were evaluated for their ability to inhibit vascular relaxation induced by KRX-725 (as S1P₃ selective pepducin agonist) and KRX-722 (an S1P₁-selective pepducin agonist). Those selective towards S1P₃ (compounds V and VII) were also evaluated for their ability to inhibit skeletal muscle fibrosis. Finally, molecular dynamics simulations were performed to derive information on the preferred conformations of selective and unselective antagonists.     

Downward comparison in everyday life: Reconciling self-enhancement models with the mood–cognition priming model.

Two models concerning downward comparison are motivational; they predict that when people are unhappy, they make downward comparisons to self-enhance (e.g., Wills, 1981). In contrast, the affect-cognition priming model (Wheeler & Miyake, 1992) predicts that unhappy people make upward comparisons because negative affect makes mood-congruent comparisons more accessible. The authors propose that both motivational and accessibility factors influence social comparisons. A study of undergraduates' self-recorded everyday comparisons supported this view. In addition, results (a) pointed to motivational influences other than self-enhancement and an accessibility influence other than mood-congruent priming, (b) suggested that motivated and unintended comparisons may differ somewhat in their susceptibility to motivational and accessibility influences, and (c) identified challenges to both self-enhancement and priming models. (PsycINFO Database Record (c) 2011 APA, all rights reserved)     

Predicting categorical forest variables using an improved k-Nearest Neighbour estimator and Landsat imagery

The k-Nearest Neighbour (k-NN) estimation and prediction technique is widely used to produce pixel-level predictions and areal estimates of continuous forest variables such as area and volume, often by sub-categories such as species. An advantage of k-NN is that the same parameters (e.g., k-value, distance metric, weight vector for the feature space variables) can be used for all variables, whether continuous or categorical. An obvious question is the degree to which accuracy can be improved if the k-NN estimation parameters are tailored for specific variable groups such as volumes by tree species or categorical variables. We investigated prediction of categorical forest attribute variables from satellite image spectral data using k-NN with optimisation of the weight vector for the ancillary variables obtained using a genetic algorithm. We tested several genetic algorithm fitness functions, all derived from well-known accuracy measures. For a Finnish test site, the categorical forest attribute variables were site fertility and tree species dominance, and for an Italian test site, the variables were forest type and conifer/broad-leaved dominance. The results for both test sites were validated using independent data sets. Our results indicate that use of the genetic algorithm to optimize the weight vector for prediction of a single forest attribute variable had a slight positive effect on the prediction accuracies for other variables. Errors can be further decreased if the optimisation is done by variable groups.     

On graph-based characteristics of optimal overlay topologies

In this paper, we address the challenge of overlay topology design by considering which overlay topology best minimizes cost function, taking into account overlay link creation cost and routing cost. First, we formulate the problem as Integer Linear Programming (ILP) given a traffic matrix and assuming cooperative behavior of nodes. Then, we propose some heuristics to find near-optimal overlay topologies with a reduced complexity. The solutions to the ILP problem on real network topologies have been analyzed, showing that the traffic demands between the nodes affect the decision to create new overlay links. Next, the obtained optimal and near-optimal overlay topologies are thoroughly analyzed and the heuristics are compared through extensive numerical evaluations. Finally guidelines for the selection of the best heuristic as a function of the cost parameters are also provided.     

困难会激发我们的创造力——Flickr创始人之一卡泰丽娜·费克访谈

2002年夏天,卡泰丽娜·费克(Caterina Fake)、斯图尔特·巴特菲尔德(StewartButterfield)和杰森·克拉森(Jason Classon)创办了网络软件公司Ludicorp。Ludicorp公司的第一款产品是永不结束的游戏(Game Neverending),这是一种大型的多人在线角色扮演游戏。在2004年,他们为原来的游戏增加了一个新功能,就是即时交换照片功能的多人聊天室,正是这项新的功能,使得这款游戏迅速火爆起来,新加功能的受欢迎程度甚至超过了游戏本身。此时,整个开发团队意识到了其间的价值,于是他们决定抓住永不结束的游戏这个机会,在其基础上开发一款新的照片交换社区网站,网站的名字就叫做Flickr。果然,Flickr迅速崛起,成为最著名的Web2.0公司之一。尽管它在2005年3月被雅虎公司所收购,但卡泰丽娜·费克的创业激情永远不会停止。