Cytoskeleton Elements Contribute to Prion Peptide-Induced Endothelial Barrier Breakdown in a Blood–Brain Barrier In Vitro System

The mechanisms involved in the interaction of PrP 106-126, a peptide corresponding to the prion protein amyloidogenic region, with the blood–brain barrier (BBB) were studied. PrP 106-126 treatment that was previously shown to impair BBB function, reduced cAMP levels in cultured brain endothelial cells, increased nitric oxide (NO) levels, and changed the activation mode of the small GTPases Rac1 (inactivation) and RhoA (activation). The latter are well established regulators of endothelial barrier properties that act via cytoskeletal elements. Indeed, liquid chromatography-mass spectrometry (LC-MS)-based proteomic profiling study revealed extensive changes in expression of cytoskeleton-related proteins. These results shed light on the nature of the interaction between the prion peptide PrP 106-126 and the BBB and emphasize the importance of the cytoskeleton in endothelium response to prion- induced stress.     

A TD-DFT-Based Study on the Attack of the OH· Radical on a Guanine Nucleotide

Heavy charged particles induce severe damage in DNA, which is a radiobiological advantage when treating radioresistant tumors. However, these particles can also induce cancer in humans exposed to them, such as astronauts in space missions. This damage can be directly induced by the radiation or indirectly by the attack of free radicals mainly produced by water radiolysis. We previously studied the impact of a proton on a DNA base pair, using the Time Dependent-Density Functional Theory (TD-DFT). In this work, we go a step further and study the attack of the OH· radical on the Guanine nucleotide to unveil how this molecule subsequently dissociates. The OH· attack on the H1′, H2′, H3′, and H5′ atoms in the guanine was investigated using the Ehrenfest dynamics within the TD-DFT framework. In all cases, the hydrogen abstraction succeeded, and the subsequent base pair dissociation was observed. The DNA dissociates in three major fragments: the phosphate group, the deoxyribose sugar, and the nitrogenous base, with slight differences, no matter which hydrogen atom was attacked. Hydrogen abstraction occurs at about 6 fs, and the nucleotide dissociation at about 100 fs, which agrees with our previous result for the direct proton impact on the DNA. These calculations may be a reference for adjusting reactive force fields so that more complex DNA structures can be studied using classical molecular dynamics, including both direct and indirect DNA damage.     

Beyond the fascination of online-games: Probing addictive behavior and depression in the world of online-gaming

This study examined problematic gaming behavior and depressive tendencies among people who play different types of online-games. Other game-related variables were investigated to determine if other differences between three game types could be established. Participants in the current research (n = 468) can be classified into three independent groups. Subjected users either solely played massive multiplayer online role-playing games (MMORPGs) or they preferred online-ego-shooters (OES) or real-time-strategy games (RTS). Results indicate that MMORPG users show more often problematic gaming behavior, depressive tendencies and lower self-esteem compared to users playing other online-games. MMORPG users reported to playing significantly more often in order to escape from real-life problems, which might be a valuable coping strategy but might also lead to problematic gaming behavior.     

Role of MicroRNA-7 (MiR-7) in Cancer Physiopathology

miRNAs are non-coding RNA sequences of approximately 22 nucleotides that interact with genes by inhibiting their translation through binding to their 3′ or 5′ UTR regions. Following their discovery, the role they play in the development of various pathologies, particularly cancer, has been studied. In this context, miR-7 is described as an important factor in the development of cancer because of its role as a tumor suppressor, regulating a large number of genes involved in the development and progression of cancer. Recent data support the function of miR-7 as a prognostic biomarker in cancer, and miR-7 has been proposed as a strategy in cancer therapy. In this work, the role of miR-7 in various types of cancer is reviewed, illustrating its regulation, direct targets, and effects, as well as its possible relationship to the clinical outcome of cancer patients.     

Coherent interaction of atoms with a beam of light confined in a light cage

Controlling coherent interaction between optical fields and quantum systems in scalable, integrated platforms is essential for quantum technologies. Miniaturise...     

Diverse nearest neighbors queries using linear skylines

k-nearest neighbor (k-NN) queries are well-known and widely used in a plethora of applications. However, in the original definition of k-NN queries there is no concern regarding diversity of the answer set with respect to the user’s interests. For instance, travelers may be looking for touristic sites that are close to where they are, but that would also lead them to see different parts of the city. Likewise, if one is looking for restaurants close by, it may be more interesting to learn about restaurants of different categories or ethnicities which are nonetheless relatively close. The interesting novel aspect of this type of query is that there are two competing criteria to be optimized: closeness and diversity. We propose two approaches that leverage the notion of linear skyline queries in order to find the k diverse nearest neighbors within a radius r from a given query point, or (k, r)-DNNs for short. Our proposed approaches return a relatively small set containing all optimal solutions for any linear combination of the weights a user could give to the two competing criteria, and we consider three different notions of diversity: spatial, categorical and angular. Our experiments, varying a number of parameters and exploring synthetic and real datasets, in both Euclidean space and road networks, respectively, show that our approaches are several orders of magnitude faster than a straightforward approach.     

IL-33 and IL-37: A Possible Axis in Skin and Allergic Diseases

Interleukin (IL)-37 and IL-33 are among the latest cytokines identified, playing a role in several inflammatory conditions, spanning from systemic conditions to tumors to localized diseases. As newly discovered interleukins, their role is still scarcely understood, but their potential role as therapeutic targets or disease activity markers suggests the need to reorganize the current data for a better interpretation. The aim of this review is to collect and organize data produced by several studies to create a complete picture. The research was conducted on the PubMed database, and the resulting articles were sorted by title, abstract, English language, and content. Several studies have been assessed, mostly related to atopic dermatitis and immunologic pathways. Collective data demonstrates a pro-inflammatory role of IL-33 and an anti-inflammatory one for IL-37, possibly related to each other in an IL-33/IL-37 axis. Although further studies are needed to assess the safety and plausibility of targeting these two interleukins for patients affected by skin conditions, the early results indicate that both IL-33 and IL-37 represent markers of disease activity.