Spatially Resolved Expression of Transposable Elements in Disease and Somatic Tissue with SpatialTE

Spatial transcriptomics (ST) is transforming the way we can study gene expression and its regulation through position-specific resolution within tissues. However, as in bulk RNA-Seq, transposable elements (TEs) are not being studied due to their highly repetitive nature. In recent years, TEs have been recognized as important regulators of gene expression, and thus, TE expression analysis in a spatially resolved manner could further help to understand their role in gene regulation within tissues. We present SpatialTE, a tool to analyze TE expression from ST datasets and show its application in somatic and diseased tissues. The results indicate that TEs have spatially regulated expression patterns and that their expression profiles are spatially altered in ALS disease, indicating that TEs might perform differential regulatory functions within tissue organs. We have made SpatialTE publicly available as open-source software under an MIT license.

Analysis of pir gene expression across the Plasmodium life cycle

Background Plasmodium interspersed repeat (pir) is the largest multigene family in the genomes of most Plasmodium species. A variety of functions for the PIR proteins which they encode have been proposed, including antigenic variation, immune evasion, sequestration and rosetting. However, direct evidence for these is lacking. The repetitive nature of the family has made it difficult to determine function experimentally. However, there has been some success in using gene expression studies to suggest roles for some members in virulence and chronic infection. Methods Here pir gene expression was examined across the life cycle of Plasmodium berghei using publicly available RNAseq data-sets, and at high resolution in the intraerythrocytic development cycle using new data from Plasmodium chabaudi. Results Expression of pir genes is greatest in stages of the parasite which invade and reside in red blood cells. The marked exception is that liver merozoites and male gametocytes produce a very large number of pir gene transcripts, notably compared to female gametocytes, which produce relatively few. Within the asexual blood stages different subfamilies peak at different times, suggesting further functional distinctions. Representing a subfamily of its own, the highly conserved ancestral pir gene warrants further investigation due to its potential tractability for functional investigation. It is highly transcribed in multiple life cycle stages and across most studied Plasmodium species and thus is likely to play an important role in parasite biology. Conclusions The identification of distinct expression patterns for different pir genes and subfamilies is likely to provide a basis for the design of future experiments to uncover their function.

The Implementation of Action Observation Therapy in Virtual Worlds

<p>Upper limb rehabilitation after stroke is vital to the recovery of a patient’s range of motion, dexterity and strength (Jauch et al, 2010, p. 824). Rehabilitative practises are diverse and met with varying levels of success (Brewer et al, 2012, p. 11). This research is concerned with action observation therapy and its potential for neural reorganization through consistent repetition of prescribed physiotherapy exercises. Action observation utilizes mirror neurons to stimulate neural strengthening and recovery (Ertelt et al, 2007, p. 172). The observation of an expert completion of an action by either the patient, a representation of the patient or someone else fires the corresponding mirror neuron (Fogassi et al, 2005, p. 662). Mirror neurons’ ability to be fired under multiple conditions allow a patient who is unable to complete an action, in this case a physiotherapy exercise, to still receive the neural benefit just by observing the action (Ertelt et al, 2007, p. 165). In collaboration with sensory devices in a virtual medium, action observation will be used to create a dynamic and engaging simulation with the intent of providing a physiotherapy experience that progresses in difficulty. Incremental difficulty will ensure patients are being pushed to their limits in a controlled and monitored environment (IJsselsteijn, 2007, p. 27). Neural reorganization requires a large number of repetitions of exercises over extended periods of time creating rehabilitative experiences that have traditionally been tedious and mundane (Merians et al, 2002, p. 898; O’Dell, Lin & Harrison, 2009, p. 55). Gamification of traditional methods can engage the patient over an extended period of time By masking the repetitive nature of the exercises with a fun experience, patients can receive the full benefit of the treatment while performing enjoyable tasks (Muzzaffa et al, 2013, p. 69).</p>

The Implementation of Action Observation Therapy in Virtual Worlds

<p>Upper limb rehabilitation after stroke is vital to the recovery of a patient’s range of motion, dexterity and strength (Jauch et al, 2010, p. 824). Rehabilitative practises are diverse and met with varying levels of success (Brewer et al, 2012, p. 11). This research is concerned with action observation therapy and its potential for neural reorganization through consistent repetition of prescribed physiotherapy exercises. Action observation utilizes mirror neurons to stimulate neural strengthening and recovery (Ertelt et al, 2007, p. 172). The observation of an expert completion of an action by either the patient, a representation of the patient or someone else fires the corresponding mirror neuron (Fogassi et al, 2005, p. 662). Mirror neurons’ ability to be fired under multiple conditions allow a patient who is unable to complete an action, in this case a physiotherapy exercise, to still receive the neural benefit just by observing the action (Ertelt et al, 2007, p. 165). In collaboration with sensory devices in a virtual medium, action observation will be used to create a dynamic and engaging simulation with the intent of providing a physiotherapy experience that progresses in difficulty. Incremental difficulty will ensure patients are being pushed to their limits in a controlled and monitored environment (IJsselsteijn, 2007, p. 27). Neural reorganization requires a large number of repetitions of exercises over extended periods of time creating rehabilitative experiences that have traditionally been tedious and mundane (Merians et al, 2002, p. 898; O’Dell, Lin & Harrison, 2009, p. 55). Gamification of traditional methods can engage the patient over an extended period of time By masking the repetitive nature of the exercises with a fun experience, patients can receive the full benefit of the treatment while performing enjoyable tasks (Muzzaffa et al, 2013, p. 69).</p>

MUC4 is not expressed in cell lines used for live cell imaging

Background: The ability to visualise specific mammalian gene loci in living cells is important for understanding the dynamic processes linked to transcription. However, some of the tools used to target mammalian genes for live cell imaging, such as dCas9, have been reported to themselves impede processes linked to transcription. The MUC4 gene is a popular target for live cell imaging studies due to the repetitive nature of sequences within some exons of this gene. Methods: We set out to compare the impact of dCas9 and TALE-based imaging tools on MUC4 expression, including in human cell lines previously reported as expressing MUC4. Results: We were unable to detect MUC4 mRNA in these cell lines. Moreover, analysis of publicly available data for histone modifications associated with transcription, and data for transcription itself, indicate that neither MUC4, nor any of the mucin gene family are significantly expressed in the cell lines where dCas9 targeting has been reported to repress MUC4 and MUC1 expression, or in the cell lines where dCas13 has been used to report MUC4 RNA detection in live cells. Conclusions: Methods for visualising specific gene loci and gene transcripts in live human cells are very challenging. Our data suggest that care should be given to the choice of the most appropriate cell lines for these analyses and that orthogonal methods of assaying gene expression be carefully compared.

Communication performance inherent in the repetitive attributes of projects: the case of mass housing projects

PurposeThe perception that the repetitive nature and attributes of mass housing projects (MHPs) induce significant influence on communication among projects teams have persistently been acknowledged without an empirical accentuation. This seemingly untested knowledge tends to limit the predictive accuracy of success and effectiveness of adopted communication style, strategies and models in mass housing particularly due to the incidence of the repetitive attributes. The purpose of this study is to delineate the influence of the repetitive attributes of mass housing projects on communication performance among the project team.Design/methodology/approachThrough the use of questionnaire survey and structural equation modelling analysis, a hypothesized model tested evaluated the effects of the repetitive attributes of mass housing on information flow and information composition communication performance.FindingsIn the case of influence on information flow, it was seen to be substantial whereas that of the information composition was moderate.Originality/valueThe findings offer empirical credence to the existing perception and indeed affirm that the repetitive features of MHPs significantly contribute to communication performance related to information flow and information composition among the project team. The implication of these findings is that, practitioners and stakeholders on mass housing are urged to explore bespoke communication methods, medium, strategies and management approaches that fit the MHP attributes and environment to engender managerial and communication efficiencies in the delivery.

Understanding prolific self-harm in her majesty’s women’s estate prisons, in England

Purpose The purpose of this paper is to outline qualitative research into what influences, maintains and reduces prolific self-harm within women’s prisons across England. Design/methodology/approach Semi-structured interviews were conducted with participants who were identified as engaging in prolific self-harm. Thematic analysis was applied to two data sets, and analyses were combined to generate final themes. Findings Six overarching themes were identified which served to explain what influences the repetitive nature of prolific self-harm and also what helps to reduce it. The themes were reasons for self-harm, trauma, being in prison, support, other support and interventions: management and rehabilitative. Research limitations/implications Owing to the sensitive nature of the research a stringent exclusion criteria was applied which limited the data sample from the original pool. Variance in detail was observed from the interviewer transcripts. The data sample was not large enough to examine the influence of protected characteristics. Practical implications Responsivity in the support offered by staff is critical to a reduction in repetitive harm. A re-focus on staff training, plus support mechanisms for staff supporting people in women’s prisons who self-harm prolifically has been recommended. Originality/value This paper has focussed specifically on prolific self-harm within women’s prisons. This has not been an area that has been investigated separately to the general self-harm literature in prisons. This paper provides insight into factors which influence, maintain and reduce prolific-self harm in women residing in prison.

MUC4 is not expressed in cell lines used for live cell imaging

Background: The ability to visualise specific mammalian gene loci in living cells is important for understanding the dynamic processes linked to transcription. However, some of the tools used to target mammalian genes for live cell imaging, such as dCas9, have been reported to themselves impede processes linked to transcription. The MUC4 gene is a popular target for live cell imaging studies due to the repetitive nature of sequences within some exons of this gene. Methods: We set out to compare the impact of dCas9 and TALE-based imaging tools on MUC4 expression, including in human cell lines previously reported as expressing MUC4. Results: We were unable to detect MUC4 mRNA in these cell lines. Moreover, analysis of publicly available data for histone modifications associated with transcription, and data for transcription itself, indicate that neither MUC4, nor any of the mucin gene family are significantly expressed in the cell lines where dCas9 targeting has been reported to repress MUC4 and MUC1 expression, or in the cell lines where dCas13 has been used to report MUC4 RNA detection in live cells. Conclusions: Methods for visualising specific gene loci and gene transcripts in live human cells are very challenging. Our data suggest that care should be given to the choice of the most appropriate cell lines for these analyses and that orthogonal methods of assaying gene expression be carefully compared.

Subtelomeric Chromatin in the Fission Yeast S. pombe

Telomeres play important roles in safeguarding the genome. The specialized repressive chromatin that assembles at telomeres and subtelomeric domains is key to this protective role. However, in many organisms, the repetitive nature of telomeric and subtelomeric sequences has hindered research efforts. The fission yeast S. pombe has provided an important model system for dissection of chromatin biology due to the relative ease of genetic manipulation and strong conservation of important regulatory proteins with higher eukaryotes. Telomeres and the telomere-binding shelterin complex are highly conserved with mammals, as is the assembly of constitutive heterochromatin at subtelomeres. In this review, we seek to summarize recent work detailing the assembly of distinct chromatin structures within subtelomeric domains in fission yeast. These include the heterochromatic SH subtelomeric domains, the telomere-associated sequences (TAS), and ST chromatin domains that assemble highly condensed chromatin clusters called knobs. Specifically, we review new insights into the sequence of subtelomeric domains, the distinct types of chromatin that assemble on these sequences and how histone H3 K36 modifications influence these chromatin structures. We address the interplay between the subdomains of chromatin structure and how subtelomeric chromatin is influenced by both the telomere-bound shelterin complexes and by euchromatic chromatin regulators internal to the subtelomeric domain. Finally, we demonstrate that telomere clustering, which is mediated via the condensed ST chromatin knob domains, does not depend on knob assembly within these domains but on Set2, which mediates H3K36 methylation.

Cross-frequency coupling explains the preference for simple ratios in rhythmic behaviour and the relative stability across non-synchronous patterns

Rhythms are important for understanding coordinated behaviours in ecological systems. The repetitive nature of rhythms affords prediction, planning of movements and coordination of processes within and between individuals. A major challenge is to understand complex forms of coordination when they differ from complete synchronization. By expressing phase as ratio of a cycle, we adapted levels of the Farey tree as a metric of complexity mapped to the range between in-phase and anti-phase synchronization. In a bimanual tapping task, this revealed an increase of variability with ratio complexity, a range of hidden and unstable yet measurable modes, and a rank-frequency scaling law across these modes. We use the phase-attractive circle map to propose an interpretation of these findings in terms of hierarchical cross-frequency coupling (CFC). We also consider the tendency for small-integer attractors in the single-hand repeated tapping of three-interval rhythms reported in the literature. The phase-attractive circle map has wider basins of attractions for such ratios. This work motivates the question whether CFC intrinsic to neural dynamics implements low-level priors for timing and coordination and thus becomes involved in phenomena as diverse as attractor states in bimanual coordination and the cross-cultural tendency for musical rhythms to have simple interval ratios. This article is part of the theme issue ‘Synchrony and rhythm interaction: from the brain to behavioural ecology’.