The 2017 Magnetism Roadmap

Building upon the success and relevance of the 2014 Magnetism Roadmap, this 2017 Magnetism Roadmap edition follows a similar general layout, even if its focus is naturally shifted, and a different group of experts and, thus, viewpoints are being collected and presented. More importantly, key developments have changed the research landscape in very relevant ways, so that a novel view onto some of the most crucial developments is warranted, and thus, this 2017 Magnetism Roadmap article is a timely endeavour. The change in landscape is hereby not exclusively scientific, but also reflects the magnetism related industrial application portfolio. Specifically, Hard Disk Drive technology, which still dominates digital storage and will continue to do so for many years, if not decades, has now limited its footprint in the scientific and research community, whereas significantly growing interest in magnetism and magnetic materials in relation to energy applications is noticeable, and other technological fields are emerging as well. Also, more and more work is occurring in which complex topologies of magnetically ordered states are being explored, hereby aiming at a technological utilization of the very theoretical concepts that were recognised by the 2016 Nobel Prize in Physics. Given this somewhat shifted scenario, it seemed appropriate to select topics for this Roadmap article that represent the three core pillars of magnetism, namely magnetic materials, magnetic phenomena and associated characterization techniques, as well as applications of magnetism. While many of the contributions in this Roadmap have clearly overlapping relevance in all three fields, their relative focus is mostly associated to one of the three pillars. In this way, the interconnecting roles of having suitable magnetic materials, understanding (and being able to characterize) the underlying physics of their behaviour and utilizing them for applications and devices is well illustrated, thus giving an accurate snapshot of the world of magnetism in 2017. The article consists of 14 sections, each written by an expert in the field and addressing a specific subject on two pages. Evidently, the depth at which each contribution can describe the subject matter is limited and a full review of their statuses, advances, challenges and perspectives cannot be fully accomplished. Also, magnetism, as a vibrant research field, is too diverse, so that a number of areas will not be adequately represented here, leaving space for further Roadmap editions in the future. However, this 2017 Magnetism Roadmap article can provide a frame that will enable the reader to judge where each subject and magnetism research field stands overall today and which directions it might take in the foreseeable future. The first material focused pillar of the 2017 Magnetism Roadmap contains five articles, which address the questions of atomic scale confinement, 2D, curved and topological magnetic materials, as well as materials exhibiting unconventional magnetic phase transitions. The second pillar also has five contributions, which are devoted to advances in magnetic characterization, magneto-optics and magneto-plasmonics, ultrafast magnetization dynamics and magnonic transport. The final and application focused pillar has four contributions, which present non-volatile memory technology, antiferromagnetic spintronics, as well as magnet technology for energy and bio-related applications. As a whole, the 2017 Magnetism Roadmap article, just as with its 2014 predecessor, is intended to act as a reference point and guideline for emerging research directions in modern magnetism

Comparative effect of N-substituted dehydroamino acids and alpha-tocopherol on rat liver lipid peroxidation activities

Free radical damage has been associated with a growing number of diseases and conditions, such as autoimmune diseases, neurodegenerative disorders and multiple types of cancer. Some dehydroamino acids and corresponding peptides can function as radical scavengers. In this study the in vitro effects on rat liver lipid peroxidation levels of fourteen N-substituted dehydroamino acid derivatives and alpha-tocopherol were investigated. alpha-Tocopherol is a powerful antioxidant that is beneficial in the treatment of many free radical related diseases. The results indicated that all the compounds showed very good inhibitory effect on the lipid peroxidation compound with alpha-tocopherol at 1 mM concentrations and the inhibition rate was in the range of 70-79 % with the exception of compound 5. At 0.1 mM concentrations compounds 1, 2 and 9 were found more active than alpha-tocopherol. The results confirmed that molecules such as dehydroamino acids which have reactive double bonds can act as a guard in vitro against oxidants.- (undefined

Human Resource and Funding Constraints for Essential Surgery in District Hospitals in Africa: A Retrospective Cross-Sectional Survey

In the second of two papers investigating surgical provision in eight district hospitals in Saharan African countries, Margaret Kruk and colleagues describe the range of providers of surgical care and anesthesia and estimate the related costs

Reactive Oxygen Species Production by Forward and Reverse Electron Fluxes in the Mitochondrial Respiratory Chain

Reactive oxygen species (ROS) produced in the mitochondrial respiratory chain (RC) are primary signals that modulate cellular adaptation to environment, and are also destructive factors that damage cells under the conditions of hypoxia/reoxygenation relevant for various systemic diseases or transplantation. The important role of ROS in cell survival requires detailed investigation of mechanism and determinants of ROS production. To perform such an investigation we extended our rule-based model of complex III in order to account for electron transport in the whole RC coupled to proton translocation, transmembrane electrochemical potential generation, TCA cycle reactions, and substrate transport to mitochondria. It fits respiratory electron fluxes measured in rat brain mitochondria fueled by succinate or pyruvate and malate, and the dynamics of NAD+ reduction by reverse electron transport from succinate through complex I. The fitting of measured characteristics gave an insight into the mechanism of underlying processes governing the formation of free radicals that can transfer an unpaired electron to oxygen-producing superoxide and thus can initiate the generation of ROS. Our analysis revealed an association of ROS production with levels of specific radicals of individual electron transporters and their combinations in species of complexes I and III. It was found that the phenomenon of bistability, revealed previously as a property of complex III, remains valid for the whole RC. The conditions for switching to a state with a high content of free radicals in complex III were predicted based on theoretical analysis and were confirmed experimentally. These findings provide a new insight into the mechanisms of ROS production in RC

Iterative sorting reveals CD133+ and CD133- melanoma cells as phenotypically distinct populations

Background: The heterogeneity and tumourigenicity of metastatic melanoma is attributed to a cancer stem cell model, with CD133 considered to be a cancer stem cell marker in melanoma as well as other tumours, but its role has remained controversial. Methods: We iteratively sorted CD133+ and CD133- cells from 3 metastatic melanoma cell lines, and observed tumourigenicity and phenotypic characteristics over 7 generations of serial xeno-transplantation in NOD/SCID mice. Results: We demonstrate that iterative sorting is required to make highly pure populations of CD133+ and CD133- cells from metastatic melanoma, and that these two populations have distinct characteristics not related to the cancer stem cell phenotype. In vitro, gene set enrichment analysis indicated CD133+ cells were related to a proliferative phenotype, whereas CD133- cells were of an invasive phenotype. However, in vivo, serial transplantation of CD133+ and CD133- tumours over 7 generations showed that both populations were equally able to initiate and propagate tumours. Despite this, both populations remained phenotypically distinct, with CD133- cells only able to express CD133 in vivo and not in vitro. Loss of CD133 from the surface of a CD133+ cell was observed in vitro and in vivo, however CD133- cells derived from CD133+ retained the CD133+ phenotype, even in the presence of signals from the tumour microenvironment. Conclusion: We show for the first time the necessity of iterative sorting to isolate pure marker-positive and marker-negative populations for comparative studies, and present evidence that despite CD133+ and CD133- cells being equally tumourigenic, they display distinct phenotypic differences, suggesting CD133 may define a distinct lineage in melanoma

Inferring Condition-Specific Modulation of Transcription Factor Activity in Yeast through Regulon-Based Analysis of Genomewide Expression

Background: A key goal of systems biology is to understand how genomewide mRNA expression levels are controlled by transcription factors (TFs) in a condition-specific fashion. TF activity is frequently modulated at the post-translational level through ligand binding, covalent modification, or changes in sub-cellular localization. In this paper, we demonstrate how prior information about regulatory network connectivity can be exploited to infer condition-specific TF activity as a hidden variable from the genomewide mRNA expression pattern in the yeast Saccharomyces cerevisiae. Methodology/Principal Findings: We first validate experimentally that by scoring differential expression at the level of gene sets or "regulons" comprised of the putative targets of a TF, we can accurately predict modulation of TF activity at the post-translational level. Next, we create an interactive database of inferred activities for a large number of TFs across a large number of experimental conditions in S. cerevisiae. This allows us to perform TF-centric analysis of the yeast regulatory network. Conclusions/Significance: We analyze the degree to which the mRNA expression level of each TF is predictive of its regulatory activity. We also organize TFs into "co-modulation networks" based on their inferred activity profile across conditions, and find that this reveals functional and mechanistic relationships. Finally, we present evidence that the PAC and rRPE motifs antagonize TBP-dependent regulation, and function as core promoter elements governed by the transcription regulator NC2. Regulon-based monitoring of TF activity modulation is a powerful tool for analyzing regulatory network function that should be applicable in other organisms. Tools and results are available online at http://bussemakerlab.org/RegulonProfiler/

Post-operative atrial fibrillation: a maze of mechanisms

Post-operative atrial fibrillation (POAF) is one of the most frequent complications of cardiac surgery and an important predictor of patient morbidity as well as of prolonged hospitalization. It significantly increases costs for hospitalization. Insights into the pathophysiological factors causing POAF have been provided by both experimental and clinical investigations and show that POAF is ‘multi-factorial’. Facilitating factors in the mechanism of the arrhythmia can be classified as acute factors caused by the surgical intervention and chronic factors related to structural heart disease and ageing of the heart. Furthermore, some proarrhythmic mechanisms specifically occur in the setting of POAF. For example, inflammation and beta-adrenergic activation have been shown to play a prominent role in POAF, while these mechanisms are less important in non-surgical AF. More recently, it has been shown that atrial fibrosis and the presence of an electrophysiological substrate capable of maintaining AF also promote the arrhythmia, indicating that POAF has some proarrhythmic mechanisms in common with other forms of AF. The clinical setting of POAF offers numerous opportunities to study its mechanisms. During cardiac surgery, biopsies can be taken and detailed electrophysiological measurements can be performed. Furthermore, the specific time course of POAF, with the delayed onset and the transient character of the arrhythmia, also provides important insight into its mechanisms

The State Socialist Mortality Syndrome

Death rates for working-age men in European state socialist countries deviated from general improvements in survival observed in the rest of Europe during the 20th century. The magnitude of structural labor force changes across countries correlates with lagged increases in death rates for men in the working ages. This pattern is consistent with a hypothesis that hyper-development of heavy industry and stagnation (even contraction) of the service sector created anomic conditions leading to unhealthy lifestyles and self-destructive behavior among men moving from primary-sector to secondary-sector occupations. Occupational contrasts within countries similarly show concentration of rising male death rates among blue collar workers. Collapse of state socialist systems produced rapid corrections in labor force structure after 1990, again correlated with a fading of the state socialist mortality syndrome in following decades

The Yin and Yang of Yeast Transcription: Elements of a Global Feedback System between Metabolism and Chromatin

When grown in continuous culture, budding yeast cells tend to synchronize their respiratory activity to form a stable oscillation that percolates throughout cellular physiology and involves the majority of the protein-coding transcriptome. Oscillations in batch culture and at single cell level support the idea that these dynamics constitute a general growth principle. The precise molecular mechanisms and biological functions of the oscillation remain elusive. Fourier analysis of transcriptome time series datasets from two different oscillation periods (0.7 h and 5 h) reveals seven distinct co-expression clusters common to both systems (34% of all yeast ORF), which consolidate into two superclusters when correlated with a compilation of 1,327 unrelated transcriptome datasets. These superclusters encode for cell growth and anabolism during the phase of high, and mitochondrial growth, catabolism and stress response during the phase of low oxygen uptake. The promoters of each cluster are characterized by different nucleotide contents, promoter nucleosome configurations, and dependence on ATP-dependent nucleosome remodeling complexes. We show that the ATP:ADP ratio oscillates, compatible with alternating metabolic activity of the two superclusters and differential feedback on their transcription via activating (RSC) and repressive (Isw2) types of promoter structure remodeling. We propose a novel feedback mechanism, where the energetic state of the cell, reflected in the ATP:ADP ratio, gates the transcription of large, but functionally coherent groups of genes via differential effects of ATP-dependent nucleosome remodeling machineries. Besides providing a mechanistic hypothesis for the delayed negative feedback that results in the oscillatory phenotype, this mechanism may underpin the continuous adaptation of growth to environmental conditions