In Silico Analysis of the Molecular-Level Impact of SMPD1 Variants on Niemann-Pick Disease Severity

Sphingomyelin phosphodiesterase (SMPD1) is a key enzyme in the sphingolipid metabolism. Genetic SMPD1 variants have been related to the Niemann-Pick lysosomal storage disorder, which has different degrees of phenotypic severity ranging from severe symptomatology involving the central nervous system (type A) to milder ones (type B). They have also been linked to neurodegenerative disorders such as Parkinson and Alzheimer. In this paper, we leveraged structural, evolutionary and stability information on SMPD1 to predict and analyze the impact of variants at the molecular level. We developed the SMPD1-ZooM algorithm, which is able to predict with good accuracy whether variants cause Niemann-Pick disease and its phenotypic severity; the predictor is freely available for download. We performed a large-scale analysis of all possible SMPD1 variants, which led us to identify protein regions that are either robust or fragile with respect to amino acid variations, and show the importance of aromatic-involving interactions in SMPD1 function and stability. Our study also revealed a good correlation between SMPD1-ZooM scores and in vitro loss of SMPD1 activity. The understanding of the molecular effects of SMPD1 variants is of crucial importance to improve genetic screening of SMPD1-related disorders and to develop personalized treatments that restore SMPD1 functionality.     

The use of epilithic Antarctic lichens (Usnea aurantiacoatra and U. antartica) to determine deposition patterns of heavy metals in the Shetland Islands, Antarctica

Trace-metal contents were recorded for the epilithic antarctic lichens Usnea aurantiacoatra and U. antartica, sampled close to the Argentine scientific station 'Jubany' on '25 de Mayo' (King George) Island, in the Southern Shetland Archipelago (Antarctica). The corresponding heavy-metal levels have been measured through atomic absorption spectrophotometry, following internationally accepted analytical methods. The results obtained support the hypothesis that an atmospheric circulation of trace metals exists on the assessed area, and the activities developed at the different scientific stations located on this island would be a potential source of heavy metals to the evaluated environment. The geographical distribution of trace metals atmospherically transported in the area close to 'Jubany Station' was studied through the corresponding metal contents of the assessed lichens. Finally, the suitability of both analyzed lichen species, Usnea aurantiacoatra and U. antartica, as biological indicators for quantitative monitoring of airborne metals for this antarctic environment was recognized.     

Savoring Versus Dampening: Self-Esteem Differences in Regulating Positive Affect.

Five studies examined the hypotheses that when people experience positive affect, those low in self-esteem are especially likely to dampen that affect, whereas those high in self-esteem are especially likely to savor it. Undergraduate participants' memories for a positive event (Study 1) and their reported reactions to a success (Study 2) supported the dampening prediction. Results also suggest that dampening was associated with worse mood the day after a success (Study 2), that positive and negative affect regulation are distinct, that self-esteem is associated with affect regulation even when Neuroticism and Extraversion are controlled (Studies 3 and 4), and that self-esteem may be especially important for certain types of positive events and positive affect regulation (Study 5). (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Alder ene functionalization of polyisobutene oligomer and styrene-butadiene-styrene triblock copolymer

The Alder ene functionalization reaction of double bonds containing macromolecules such as polyisobutene oligomer (PIB) and a styrene-butadiene-styrene triblock copolymer (SBS) samples with maleic anhydride (MAH) or diethyl maleate (DEM) as enophiles is described. The analysis of the products by means of different techniques assesses the addition of the polar molecules to the reactive vinylidene units of the polymer with functional degrees (FD) depending on the type of enophile and polymer reactivity. The role of the reaction conditions and the use as Lewis acids as catalysts are discussed in terms of their influence on the addition reaction extent and on the polymer molecular weight.     

Mangrove forests as a nature-based solution for coastal flood protection: Biophysical and ecological considerations

Nature-based coastal protection is increasingly recognised as a potentially sustainable and cost-effective solution to reduce coastal flood risk. It uses coastal ecosystems such as mangrove forests to create resilient designs for coastal flood protection. However, to use mangroves effectively as a nature-based measure for flood risk reduction, we must understand the biophysical processes that govern risk reduction capacity through mangrove ecosystem size and structure. In this perspective, we evaluate the current state of knowledge on local physical drivers and ecological processes that determine mangrove functioning as part of a nature-based flood defence. We show that the forest properties that comprise coastal flood protection are well-known, but models cannot yet pinpoint how spatial heterogeneity of the forest structure affects the capacity for wave or surge attenuation. Overall, there is relatively good understanding of the ecological processes that drive forest structure and size, but there is a lack of knowledge on how daily bed-level dynamics link to long-term biogeomorphic forest dynamics, and on the role of combined stressors influencing forest retreat. Integrating simulation models of forest structure under changing physical (e.g. due to sea-level change) and ecological drivers with hydrodynamic attenuation models will allow for better projections of long-term natural coastal protection.     

Virtual reality for collaborative e-learning

In the past, the term e-learning referred to any method of learning that used electronic delivery methods. With the advent of the Internet however, e-learning has evolved and the term is now most commonly used to refer to online courses. A multitude of systems are now available to manage and deliver learning content online. While these have proved popular, they are often single-user learning environments which provide little in the way of interaction or stimulation for the student. As the concept of lifelong learning now becomes a reality and thus more and more people are partaking in online courses, researchers are constantly exploring innovative techniques to motivate online students and enhance the e-learning experience. This article presents our research in this area and the resulting development of CLEV-R, a Collaborative Learning Environment with Virtual Reality. This web-based system uses Virtual Reality (VR) and multimedia and provides communication tools to support collaboration among students. In this article, we describe the features of CLEV-R, its adaptation for mobile devices and present the findings from an initial evaluation.     

Multimedia ontology population through semantic analysis and hierarchical deep features extraction techniques

Knowledge and Information Systems - The rapid increase of available data in different complex contexts needs automatic tasks to manage and process contents. Semantic Web technologies represent the...     

Semantics-driven annotation of patient-specific 3D data: a step to assist diagnosis and treatment of rheumatoid arthritis

In the digital era, patient-specific 3D models (3D-PSMs) are becoming increasingly relevant in computer-assisted diagnosis, surgery training on digital models, or implant design. While advanced imaging and reconstruction techniques can create accurate and detailed 3D models of patients’ anatomy, software tools that are able to fully exploit the potential of 3D-PSMs are still far from being satisfactory. In particular, there is still a lack of integrated approaches for extracting, coding, sharing and retrieving medically relevant information from 3D-PSMs and use it concretely as a support to diagnosis and treatment. In this article, we propose the SemAnatomy3D framework, which demonstrates how the ontology-driven annotation of 3D-PSMs and of their anatomically relevant features (parts of relevance) can assist clinicians to document more effectively pathologies and their evolution. We exemplify the idea in the context of the diagnosis of rheumatoid arthritis of the hand district, and show how feature extraction tools and semantic 3D annotation can provide a rich characterization of anatomical landmarks (e.g., articular facets, prominent features, ligament attachments) and pathological markers (erosions, bone loss). The core contributions are an ontology-driven part-based annotation method for the 3D-PSMs and a novel automatic localization of erosion and quantification of the OMERACT RAMRIS erosion score. Finally, our results have been compared against a medical ground truth.