Revisiting remyelination: Towards a consensus on the regeneration of CNS myelin.

The biology of CNS remyelination has attracted considerable interest in recent years because of its translational potential to yield regenerative therapies for the treatment of chronic and progressive demyelinating diseases such as multiple sclerosis (MS). Critical to devising myelin regenerative therapies is a detailed understanding of how remyelination occurs. The accepted dogma, based on animal studies, has been that the myelin sheaths of remyelination are made by oligodendrocytes newly generated from adult oligodendrocyte progenitor cells in a classical regenerative process of progenitor migration, proliferation and differentiation. However, recent human and a growing number of animal studies have revealed a second mode of remyelination in which mature oligodendrocytes surviving within an area of demyelination are able to regenerate new myelin sheaths. This discovery, while opening up new opportunities for therapeutic remyelination, has also raised the question of whether there are fundamental differences in myelin regeneration between humans and some of the species in which experimental remyelination studies are conducted. Here we review how this second mode of remyelination can be integrated into a wider and revised framework for understanding remyelination in which apparent species differences can be reconciled but that also raises important questions for future research.We thank Sarah Neely, University of Edinburgh, for generating the schematic figure. Work in the Franklin lab is supported by UK Multiple Sclerosis Society, the Adelson Medical ResearchFoundation, and a core support grant from the Wellcome and MRC to the Wellcome-MedicalResearch Council Cambridge Stem Cell Institute. , in the Frisen lab by Swedish Research Council, the Swedish Cancer Society, the Swedish Foundation for Strategic Research, Knutoch Alice Wallenbergs Stiftelse and the ERC, and in the Lyons lab by the Wellcome Trust, the UK Multiple Sclerosis Society, the MRC, and Biogen

Echocardiographic assessment and percutaneous closure of multiple atrial septal defects

Atrial septal defect closure is now routinely performed using a percutaneous approach under echocardiographic guidance. Centrally located, secundum defects are ideal for device closure but there is considerable morphological variation in size and location of the defects. A small proportion of atrial septal defects may have multiple fenestrations and these are often considered unsuitable for device closure. We report three cases of multiple atrial septal defects successfully closed with two Amplatzer septal occluders

Digital Transformation in Service Management

The digital transformation of single companies and of entire service businesses is an omnipresent topic – not only in the academic discourse but also in the current public debate. The topic is often approached phenomenologically. We invited a group of well-renown scholars from different academic fields to share with us personal observations and interpretations of the digital transformation in service management in the form of individual commentaries that go beyond. The commentaries we received are based on different theoretical perspectives. They include motivations of why digital transformation makes service management research (smr) more relevant, they depict implications for service companies, and they outline research needs. This article conflates the submitted commentaries, and it is the first SMR special research paper – a paper type that will be continued in future issues to explore topics in a similar fashion that are likely to have a significant influence on the development of smr.</p

Agency, qualia and life: connecting mind and body biologically

Many believe that a suitably programmed computer could act for its own goals and experience feelings. I challenge this view and argue that agency, mental causation and qualia are all founded in the unique, homeostatic nature of living matter. The theory was formulated for coherence with the concept of an agent, neuroscientific data and laws of physics. By this method, I infer that a successful action is homeostatic for its agent and can be caused by a feeling - which does not motivate as a force, but as a control signal. From brain research and the locality principle of physics, I surmise that qualia are a fundamental, biological form of energy generated in specialized neurons. Subjectivity is explained as thermodynamically necessary on the supposition that, by converting action potentials to feelings, the neural cells avert damage from the electrochemical pulses. In exchange for this entropic benefit, phenomenal energy is spent as and where it is produced - which precludes the objective observation of qualia

Survey context and question wording affects self reported annoyance due to road traffic noise: a comparison between two cross-sectional studies

<p>Abstract</p> <p>Background</p> <p>Surveys are a common way to measure annoyance due to road traffic noise, but the method has some draw-backs. Survey context, question wording and answer alternatives could affect participation and answers and could have implications when comparing studies and/or performing pooled analyses. The aim of this study was to investigate the difference in annoyance reporting due to road traffic noise in two types of surveys of which one was introduced broadly and the other with the clearly stated aim of investigating noise and health.</p> <p>Methods</p> <p>Data was collected from two surveys carried out in the municipality of Malmö, southern Sweden in 2007 and 2008 (n = 2612 and n = 3810). The first survey stated an aim of investigating residential environmental exposure, especially noise and health. The second survey was a broad public health survey stating a broader aim. The two surveys had comparable questions regarding noise annoyance, although one used a 5-point scale and the other a 4-point scale. We used geographic information systems (GIS) to assess the average road and railway noise (L_Aeq,24h) at the participants' residential address. Logistic regression was used to calculate odds ratios for annoyance in relation to noise exposure.</p> <p>Results</p> <p>Annoyance at least once a week due to road traffic noise was significantly more prevalent in the survey investigating environment and health compared to the public health survey at levels > 45 dB(A), but not at lower exposure levels. However no differences in annoyance were found when comparing the extreme alternatives "never" and "every day". In the study investigating environment and health, "Noise sensitive" persons were more likely to readily respond to the survey and were more annoyed by road traffic noise compared to the other participants in that survey.</p> <p>Conclusions</p> <p>The differences in annoyance reporting between the two surveys were mainly due to different scales, suggesting that extreme alternatives are to prefer before dichotomization when comparing results between the two. Although some findings suggested that noise-sensitive individuals were more likely to respond to the survey investigating noise and health, we could not find convincing evidence that contextual differences affected either answers or participation.</p

SUSY parameter determination at the LHC using cross sections and kinematic edges

We study the determination of supersymmetric parameters at the LHC from a global fit including cross sections and edges of kinematic distributions. For illustration, we focus on a minimal supergravity scenario and discuss how well it can be constrained at the LHC operating at 7 and 14 TeV collision energy, respectively. We find that the inclusion of cross sections greatly improves the accuracy of the SUSY parameter determination, and allows to reliably extract model parameters even in the initial phase of LHC data taking with 7 TeV collision energy and 1/fb integrated luminosity. Moreover, cross section information may be essential to study more general scenarios, such as those with non-universal gaugino masses, and distinguish them from minimal, universal, models.Comment: 22 pages, 8 figure

Long-term tracking of neurological complications of encephalopathy and myopathy in a patient with nephropathic cystinosis: a case report and review of the literature

<p>Abstract</p> <p>Introduction</p> <p>Cystinosis is a hereditary storage disease resulting in intracellular accumulation of cystine and crystal formation that causes deterioration of the function of many organs. The major clinical symptom is renal failure, which progresses and necessitates renal transplantation at the beginning of the second decade of life. Encephalopathy and distal myopathy are important neurological long-term complications with a major impact on the quality of life of these patients. Application of cysteamine is the only specific therapy available; it decreases the intracellular cystine level and delays or may even prevent the failure of organ functions.</p> <p>Case presentation</p> <p>We present the case of a 38-year-old woman with cystinosis and the long-term tracking of her neurological symptoms under cysteamine treatment.</p> <p>Conclusion</p> <p>This case report describes a long observation period of neurological complications in a person with cystinosis who had strikingly different courses of encephalopathy and myopathy while on cysteamine treatment. Although encephalopathy was initially suspected, this did not develop, but distal myopathy progressed continuously despite specific therapy.</p

Kinetic modelling of competition and depletion of shared miRNAs by competing endogenous RNAs

Non-conding RNAs play a key role in the post-transcriptional regulation of mRNA translation and turnover in eukaryotes. miRNAs, in particular, interact with their target RNAs through protein-mediated, sequence-specific binding, giving rise to extended and highly heterogeneous miRNA-RNA interaction networks. Within such networks, competition to bind miRNAs can generate an effective positive coupling between their targets. Competing endogenous RNAs (ceRNAs) can in turn regulate each other through miRNA-mediated crosstalk. Albeit potentially weak, ceRNA interactions can occur both dynamically, affecting e.g. the regulatory clock, and at stationarity, in which case ceRNA networks as a whole can be implicated in the composition of the cell's proteome. Many features of ceRNA interactions, including the conditions under which they become significant, can be unraveled by mathematical and in silico models. We review the understanding of the ceRNA effect obtained within such frameworks, focusing on the methods employed to quantify it, its role in the processing of gene expression noise, and how network topology can determine its reach.Comment: review article, 29 pages, 7 figure