Magnetically controlled ferromagnetic swimmers

This is the final version of the article. Available from Springer Nature via the DOI in this record.Microscopic swimming devices hold promise for radically new applications in lab-on-a-chip and microfluidic technology, diagnostics and drug delivery etc. In this paper, we demonstrate the experimental verification of a new class of autonomous ferromagnetic swimming devices, actuated and controlled solely by an oscillating magnetic field. These devices are based on a pair of interacting ferromagnetic particles of different size and different anisotropic properties joined by an elastic link and actuated by an external time-dependent magnetic field. The net motion is generated through a combination of dipolar interparticle gradient forces, time-dependent torque and hydrodynamic coupling. We investigate the dynamic performance of a prototype (3.6 mm) of the ferromagnetic swimmer in fluids of different viscosity as a function of the external field parameters (frequency and amplitude) and demonstrate stable propulsion over a wide range of Reynolds numbers. We show that the direction of swimming has a dependence on both the frequency and amplitude of the applied external magnetic field, resulting in robust control over the speed and direction of propulsion. This paves the way to fabricating microscale devices for a variety of technological applications requiring reliable actuation and high degree of control.This project has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No. 665440. We also acknowledge support via the EPSRC Centre for Doctoral Training in Metamaterials (Grant No. EP/L015331/1)

Integrating transposable elements in the 3D genome

Chromosome organisation is increasingly recognised as an essential component of genome regulation, cell fate and cell health. Within the realm of transposable elements (TEs) however, the spatial information of how genomes are folded is still only rarely integrated in experimental studies or accounted for in modelling. Whilst polymer physics is recognised as an important tool to understand the mechanisms of genome folding, in this commentary we discuss its potential applicability to aspects of TE biology. Based on recent works on the relationship between genome organisation and TE integration, we argue that existing polymer models may be extended to create a predictive framework for the study of TE integration patterns. We suggest that these models may offer orthogonal and generic insights into the integration profiles (or "topography") of TEs across organisms. In addition, we provide simple polymer physics arguments and preliminary molecular dynamics simulations of TEs inserting into heterogeneously flexible polymers. By considering this simple model, we show how polymer folding and local flexibility may generically affect TE integration patterns. The preliminary discussion reported in this commentary is aimed to lay the foundations for a large-scale analysis of TE integration dynamics and topography as a function of the three-dimensional host genome

A qualitative study of the understanding and use of ‘compassion focused coping strategies’ in people who suffer from serious weight difficulties.

Abstract Background The physical and psychological health problems associated with obesity are now well documented, as is the urgency for addressing them. In addition, associations between quality of life, depression, self-esteem, self-criticism, and obesity are now established indicating a need for a better understanding of the links between self-evaluation, affect-regulation and eating behaviours. Methods Compassion has now been identified as a major source of resilience, helpful self-relating and affect regulation. Thus this study used semi-structured interviews to explore the understanding and experiences of compassion in 2 overweight men and 10 women seeking help for weight problems. The interviews examined people's understandings of compassion, their recall of experiences of compassion in childhood, their current experiences of receiving compassion from others, being compassionate to others, being self-compassionate, and whether they would be compassionate or self-critical for relapses in overeating. Interviews were transcribed and analysed using thematic analysis (Qual Res Psychol, 3: 77-101, 2006). Results Participants saw compassion as related to ‘caring’ and being ‘listened to’. However, their recall of earlier experiences of compassion was of primarily practical help rather than emotional engagement. Typically their response to their own relapse and setbacks were self-criticism, self-disgust and even self-hatred rather than self-caring or understanding. Self-critical/hating responses tend to be associated with poor weight regulation. Conclusions When people with weight problems relapse, or struggle to control their eating, they can become quite self-critical, even self-hating, which may increase difficulties with emotionally coping and maintaining healthy lifestyles and eating habits. Although turning to others for support and compassion, and becoming self-compassionate are antidotes to self-criticism, and are associated with better coping and mental health, many participants did not utilise compassionate strategies – often the opposite. It is possible that interventions that include mindfulness and compassion training could be helpful for these difficulties.N/

Clinical Implication of Targeting of Cancer Stem Cells

The existence of cancer stem cells (CSCs) is receiving increasing interest particularly due to its potential ability to enter clinical routine. Rapid advances in the CSC field have provided evidence for the development of more reliable anticancer therapies in the future. CSCs typically only constitute a small fraction of the total tumor burden; however, they harbor self-renewal capacity and appear to be relatively resistant to conventional therapies. Recent therapeutic approaches aim to eliminate or differentiate CSCs or to disrupt the niches in which they reside. Better understanding of the biological characteristics of CSCs as well as improved preclinical and clinical trials targeting CSCs may revolutionize the treatment of many cancers. Copyright (c) 2012 S. Karger AG, Base

Defending the genome from the enemy within:mechanisms of retrotransposon suppression in the mouse germline

The viability of any species requires that the genome is kept stable as it is transmitted from generation to generation by the germ cells. One of the challenges to transgenerational genome stability is the potential mutagenic activity of transposable genetic elements, particularly retrotransposons. There are many different types of retrotransposon in mammalian genomes, and these target different points in germline development to amplify and integrate into new genomic locations. Germ cells, and their pluripotent developmental precursors, have evolved a variety of genome defence mechanisms that suppress retrotransposon activity and maintain genome stability across the generations. Here, we review recent advances in understanding how retrotransposon activity is suppressed in the mammalian germline, how genes involved in germline genome defence mechanisms are regulated, and the consequences of mutating these genome defence genes for the developing germline

Measurement of the inclusive and dijet cross-sections of b-jets in pp collisions at sqrt(s) = 7 TeV with the ATLAS detector

The inclusive and dijet production cross-sections have been measured for jets containing b-hadrons (b-jets) in proton-proton collisions at a centre-of-mass energy of sqrt(s) = 7 TeV, using the ATLAS detector at the LHC. The measurements use data corresponding to an integrated luminosity of 34 pb^-1. The b-jets are identified using either a lifetime-based method, where secondary decay vertices of b-hadrons in jets are reconstructed using information from the tracking detectors, or a muon-based method where the presence of a muon is used to identify semileptonic decays of b-hadrons inside jets. The inclusive b-jet cross-section is measured as a function of transverse momentum in the range 20 < pT < 400 GeV and rapidity in the range |y| < 2.1. The bbbar-dijet cross-section is measured as a function of the dijet invariant mass in the range 110 < m_jj < 760 GeV, the azimuthal angle difference between the two jets and the angular variable chi in two dijet mass regions. The results are compared with next-to-leading-order QCD predictions. Good agreement is observed between the measured cross-sections and the predictions obtained using POWHEG + Pythia. MC@NLO + Herwig shows good agreement with the measured bbbar-dijet cross-section. However, it does not reproduce the measured inclusive cross-section well, particularly for central b-jets with large transverse momenta.Comment: 10 pages plus author list (21 pages total), 8 figures, 1 table, final version published in European Physical Journal

Landscape structure affects the prevalence and distribution of a tick-borne zoonotic pathogen

Background Landscape structure can affect pathogen prevalence and persistence with consequences for human and animal health. Few studies have examined how reservoir host species traits may interact with landscape structure to alter pathogen communities and dynamics. Using a landscape of islands and mainland sites we investigated how natural landscape fragmentation affects the prevalence and persistence of the zoonotic tick-borne pathogen complex Borrelia burgdorferi(sensu lato), which causes Lyme borreliosis. We hypothesized that the prevalence of B. burgdorferi (s.l.) would be lower on islands compared to the mainland and B. afzelii, a small mammal specialist genospecies, would be more affected by isolation than bird-associated B. garinii and B. valaisiana and the generalist B. burgdorferi (sensu stricto). Methods Questing (host-seeking) nymphal I. Ricinus ticks (n = 6567) were collected from 12 island and 6 mainland sites in 2011, 2013 and 2015 and tested for B. burgdorferi(s.l.). Deer abundance was estimated using dung transects. Results The prevalence of B. burgdorferi (s.l.) was significantly higher on the mainland (2.5%, 47/1891) compared to island sites (0.9%, 44/4673) (P &lt; 0.01). While all four genospecies of B. burgdorferi (s.l.) were detected on the mainland, bird-associated species B. garinii and B. valaisiana and the generalist genospecies B. burgdorferi(s.s.) predominated on islands. Conclusion We found that landscape structure influenced the prevalence of a zoonotic pathogen, with a lower prevalence detected among island sites compared to the mainland. This was mainly due to the significantly lower prevalence of small mammal-associated B. afzelii. Deer abundance was not related to pathogen prevalence, suggesting that the structure and dynamics of the reservoir host community underpins the observed prevalence patterns, with the higher mobility of bird hosts compared to small mammal hosts leading to a relative predominance of the bird-associated genospecies B. garinii and generalist genospecies B. burgdorferi (s.s.) on islands. In contrast, the lower prevalence of B. afzelii on islands may be due to small mammal populations there exhibiting lower densities, less immigration and stronger population fluctuations. This study suggests that landscape fragmentation can influence the prevalence of a zoonotic pathogen, dependent on the biology of the reservoir host

Divergence of Mammalian Higher Order Chromatin Structure Is Associated with Developmental Loci

Several recent studies have examined different aspects of mammalian higher order chromatin structure - replication timing, lamina association and Hi-C inter-locus interactions - and have suggested that most of these features of genome organisation are conserved over evolution. However, the extent of evolutionary divergence in higher order structure has not been rigorously measured across the mammalian genome, and until now little has been known about the characteristics of any divergent loci present. Here, we generate a dataset combining multiple measurements of chromatin structure and organisation over many embryonic cell types for both human and mouse that, for the first time, allows a comprehensive assessment of the extent of structural divergence between mammalian genomes. Comparison of orthologous regions confirms that all measurable facets of higher order structure are conserved between human and mouse, across the vast majority of the detectably orthologous genome. This broad similarity is observed in spite of many loci possessing cell type specific structures. However, we also identify hundreds of regions (from 100 Kb to 2.7 Mb in size) showing consistent evidence of divergence between these species, constituting at least 10% of the orthologous mammalian genome and encompassing many hundreds of human and mouse genes. These regions show unusual shifts in human GC content, are unevenly distributed across both genomes, and are enriched in human subtelomeric regions. Divergent regions are also relatively enriched for genes showing divergent expression patterns between human and mouse ES cells, implying these regions cause divergent regulation. Particular divergent loci are strikingly enriched in genes implicated in vertebrate development, suggesting important roles for structural divergence in the evolution of mammalian developmental programmes. These data suggest that, though relatively rare in the mammalian genome, divergence in higher order chromatin structure has played important roles during evolution

The Impact of Shame, Self-Criticism and Social Rank on Eating Behaviours in Overweight and Obese Women Participating in a Weight Management Programme

Recent research has suggested that obesity is a stigmatised condition. Concerns with personal inferiority (social rank), shame and self-criticism may impact on weight management behaviours. The current study examined associations between social comparison (shame, self-criticism), negative affect and eating behaviours in women attending a community based weight management programme focused on behaviour change. 2,236 participants of the programme completed an online survey using measures of shame, self-criticism, social comparison, and weight-related affect, which were adapted to specifically address eating behaviour, weight and body shape perceptions. Correlation analyses showed that shame, self-criticism and social comparison were associated with negative affect. All of these variables were related to eating regulation and weight control (p < 0.001). Path analysis revealed that the association of shame, hated-self, and low self-reassurance on disinhibition and susceptibility to hunger was fully mediated by weight-related negative affect, even when controlling for the effect of depressive symptoms (p < 0.050 to p < 0.010). In addition, feelings of inadequacy and unfavourable social comparisons were associated with higher disinhibition and susceptibility to hunger, partially mediated through weight-related negative affect (p = 0.001). These variables were negatively associated with extent of weight loss during programme attendance prior to the survey, while self-reassurance and positive social comparisons were positively associated with the extent of weight loss prior to the survey (p < .050). Shame, self-criticism, and perceptions of inferiority may play a significant role in self-regulation of eating behaviour in overweight people trying to manage their weight

Genome-scale CRISPR-Cas9 knockout and transcriptional activation screening

Forward genetic screens are powerful tools for the unbiased discovery and functional characterization of specific genetic elements associated with a phenotype of interest. Recently, the RNA-guided endonuclease Cas9 from the microbial CRISPR (clustered regularly interspaced short palindromic repeats) immune system has been adapted for genome-scale screening by combining Cas9 with pooled guide RNA libraries. Here we describe a protocol for genome-scale knockout and transcriptional activation screening using the CRISPR-Cas9 system. Custom- or ready-made guide RNA libraries are constructed and packaged into lentiviral vectors for delivery into cells for screening. As each screen is unique, we provide guidelines for determining screening parameters and maintaining sufficient coverage. To validate candidate genes identified by the screen, we further describe strategies for confirming the screening phenotype, as well as genetic perturbation, through analysis of indel rate and transcriptional activation. Beginning with library design, a genome-scale screen can be completed in 9-15 weeks, followed by 4-5 weeks of validation.Paul & Daisy Soros Fellowships for New Americans (New York, N.Y.)McGovern Institute for Brain Research at MIT (Friends of McGovern Institute Fellowship)Massachusetts Institute of Technology. Poitras Center for Affective Disorders ResearchUnited States. Department of Energy (Computational Science Graduate Fellowship)National Institute of Mental Health (U.S.) (5DP1-MH100706)National Institute of Mental Health (U.S.) (1R01-MH110049)New York Stem Cell FoundationPoitras FoundationSimons FoundationPaul G. Allen Family FoundationVallee FoundationTom HarrimanB. Metcalf