Mass spectrometry-based methods for identifying oxidized proteins in disease:advances and challenges

Many inflammatory diseases have an oxidative aetiology, which leads to oxidative damage to biomolecules, including proteins. It is now increasingly recognized that oxidative post-translational modifications (oxPTMs) of proteins affect cell signalling and behaviour, and can contribute to pathology. Moreover, oxidized proteins have potential as biomarkers for inflammatory diseases. Although many assays for generic protein oxidation and breakdown products of protein oxidation are available, only advanced tandem mass spectrometry approaches have the power to localize specific oxPTMs in identified proteins. While much work has been carried out using untargeted or discovery mass spectrometry approaches, identification of oxPTMs in disease has benefitted from the development of sophisticated targeted or semi-targeted scanning routines, combined with chemical labeling and enrichment approaches. Nevertheless, many potential pitfalls exist which can result in incorrect identifications. This review explains the limitations, advantages and challenges of all of these approaches to detecting oxidatively modified proteins, and provides an update on recent literature in which they have been used to detect and quantify protein oxidation in disease.

Multiscale modelling:approaches and challenges

Multiscale systems that are characterized by a great range of spatial–temporal scales arise widely in many scientific domains. These range from the study of protein conformational dynamics to multiphase processes in, for example, granular media or haemodynamics, and from nuclear reactor physics to astrophysics. Despite the diversity in subject areas and terminology, there are many common challenges in multiscale modelling, including validation and design of tools for programming and executing multiscale simulations. This Theme Issue seeks to establish common frameworks for theoretical modelling, computing and validation, and to help practical applications to benefit from the modelling results. This Theme Issue has been inspired by discussions held during two recent workshops in 2013: ‘Multiscale modelling and simulation’ at the Lorentz Center, Leiden (http://www.lorentzcenter.nl/lc/web/2013/569/info.php3?wsid=569&venue=Snellius), and ‘Multiscale systems: linking quantum chemistry, molecular dynamics and microfluidic hydrodynamics’ at the Royal Society Kavli Centre. The objective of both meetings was to identify common approaches for dealing with multiscale problems across different applications in fluid and soft matter systems. This was achieved by bringing together experts from several diverse communities.

Insulin therapy in people with type 2 diabetes:opportunities and challenges?

Given the continued interest in defining the optimal management of individuals with type 2 diabetes, the Editor of Diabetes Care convened a working party of diabetes specialists to examine this topic in the context of insulin therapy. This was prompted by recent new evidence on the use of insulin in such people. The group was aware of evidence that the benefits of insulin therapy are still usually offered late, and thus the aim of the discussion was how to define the optimal timing and basis for decisions regarding insulin and to apply these concepts in practice. It was noted that recent evidence had built upon that of the previous decades, together confirming the benefits and safety of insulin therapy, albeit with concerns about the potential for hypoglycemia and gain in body weight. Insulin offers a unique ability to control hyperglycemia, being used from the time of diagnosis in some circumstances, when metabolic control is disturbed by medical illness, procedures, or therapy, as well as in the longer term in ambulatory care. For those previously starting insulin, various other forms of therapy can be added later, which offer complementary effects appropriate to individual needs. Here we review current evidence and circumstances in which insulin can be used, consider individualized choices of alternatives and combination regimens, and offer some guidance on personalized targets and tactics for glycemic control in type 2 diabetes. © 2014 by the American Diabetes Association.

Protein lipoxidation:detection strategies and challenges

Enzymatic and non-enzymatic lipid metabolism can give rise to reactive species that may covalently modify cellular or plasma proteins through a process known as lipoxidation. Under basal conditions, protein lipoxidation can contribute to normal cell homeostasis and participate in signaling or adaptive mechanisms, as exemplified by lipoxidation of Ras proteins or of the cytoskeletal protein vimentin, both of which behave as sensors of electrophilic species. Nevertheless, increased lipoxidation under pathological conditions may lead to deleterious effects on protein structure or aggregation. This can result in impaired degradation and accumulation of abnormally folded proteins contributing to pathophysiology, as may occur in neurodegenerative diseases. Identification of the protein targets of lipoxidation and its functional consequences under pathophysiological situations can unveil the modification patterns associated with the various outcomes, as well as preventive strategies or potential therapeutic targets. Given the wide structural variability of lipid moieties involved in lipoxidation, highly sensitive and specific methods for its detection are required. Derivatization of reactive carbonyl species is instrumental in the detection of adducts retaining carbonyl groups. In addition, use of tagged derivatives of electrophilic lipids enables enrichment of lipoxidized proteins or peptides. Ultimate confirmation of lipoxidation requires high resolution mass spectrometry approaches to unequivocally identify the adduct and the targeted residue. Moreover, rigorous validation of the targets identified and assessment of the functional consequences of these modifications are essential. Here we present an update on methods to approach the complex field of lipoxidation along with validation strategies and functional assays illustrated with well-studied lipoxidation targets.

Joint colloquium on plurilingualism and language education:opportunities and challenges, (AAAL/TESOL)

This colloquium was organised by Ryuko Kubota (University of British Columbia, Canada) and Sue Garton (Aston University, UK) as part of the collaboration between the American Association for Applied Linguistics (AAAL) and TESOL International Association.

SentiCircles for contextual and conceptual semantic sentiment analysis of Twitter

Lexicon-based approaches to Twitter sentiment analysis are gaining much popularity due to their simplicity, domain independence, and relatively good performance. These approaches rely on sentiment lexicons, where a collection of words are marked with fixed sentiment polarities. However, words' sentiment orientation (positive, neural, negative) and/or sentiment strengths could change depending on context and targeted entities. In this paper we present SentiCircle; a novel lexicon-based approach that takes into account the contextual and conceptual semantics of words when calculating their sentiment orientation and strength in Twitter. We evaluate our approach on three Twitter datasets using three different sentiment lexicons. Results show that our approach significantly outperforms two lexicon baselines. Results are competitive but inconclusive when comparing to state-of-art SentiStrength, and vary from one dataset to another. SentiCircle outperforms SentiStrength in accuracy on average, but falls marginally behind in F-measure. © 2014 Springer International Publishing.

Functionalised particles using dry powder coating in pharmaceutical drug delivery:promises and challenges

Introduction: Production of functionalised particles using dry powder coating is a one-step, environmentally friendly process that paves the way for the development of particles with targeted properties and diverse functionalities. Areas covered: Applying the first principles in physical science for powders, fine guest particles can be homogeneously dispersed over the surface of larger host particles to develop functionalised particles. Multiple functionalities can be modified including: flowability, dispersibility, fluidisation, homogeneity, content uniformity and dissolution profile. The current publication seeks to understand the fundamental underpinning principles and science governing dry coating process, evaluate key technologies developed to produce functionalised particles along with outlining their advantages, limitations and applications and discusses in detail the resultant functionalities and their applications. Expert opinion: Dry particle coating is a promising solvent-free manufacturing technology to produce particles with targeted functionalities. Progress within this area requires the development of continuous processing devices that can overcome challenges encountered with current technologies such as heat generation and particle attrition. Growth within this field requires extensive research to further understand the impact of process design and material properties on resultant functionalities.

Digitization of Literary Heritage in the Bulgarian Libraries: Facing Problems and Challenges

Paper deals with the current issues and challenges before digitization of literary heritage in the Bulgarian libraries. Main problems are outlined. Socialization of digitized heritage is commented.

Big Data – Opportunities and Challenges for Education

Report published in the Proceedings of the National Conference on "Education and Research in the Information Society", Plovdiv, May, 2015

Theorising noncitizenship:concepts, debates and challenges

Existing political theory, particularly which deals with justice and/or rights, has long assumed citizenship as a core concept. Noncitizenship, if it is considered at all, is generally defined merely as the negation or deprivation of citizenship. As such, it is difficult to examine successfully the status of noncitizens, obligations towards them, and the nature of their role in political systems. This article addresses this critical gap by defining the theoretical problem that noncitizenship presents and demonstrating why it is an urgent concern. It surveys the contributions to the special issue for which the article is an introduction, drawing on cross-cutting themes and debates to highlight the importance of theorising noncitizenship due to both the problematic gap that exists in the theoretical literature, and the real world problems created as a result of noncitizenship which are not currently successfully addressed. Finally, the article discusses key future directions for the theorisation of noncitizenship.

Social change in Central and Eastern Europe: General trends and national patterns

The paper addresses five issue areas. First it describes the plurality of trajectories in central and eastern European transformations, offering a broad typology. Then it addresses the drift between acceptance of democracy and the market, owing to growing inequalities. Third, problems of poverty and exclusion are addressed. Fourth, it is addressed if any known model of redistribution emerged in the post-transition economies. Fifth, consequences of the populist turn in European policies are being analyzed. Influences of the EU practices will be dealt with and some preliminary conclusions drawn. These suggest a strong intertwining between social and economic performance that limit theoretically conceivable – neoliberal, social democratic, postmodern or conservative - policy choices.