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This is a prospective, longitudinal study designed to examine mental health, well-being and performance in youth netball players across a season.

A balance of excitatory and inhibitory signalling within key cortical regions in the motor network regulates overall network activity and connectivity in humans. This balance can be non-invasively assessed by quantifying glutamate and GABA across cortical regions using magnetic resonance spectroscopic imaging (MRSI). We present planned analyses of a large dataset comprising healthy adults across a range of ages, and patients with amyotrophic lateral sclerosis (ALS) - a neurodegenerative disorder of the motor system in which altered cortical excitability is consistently observed. Using a novel MRSI protocol, GABA and glutamate are mapped in high spatial resolution across a region of interest encompassing both primary motor cortices. We will use the free software FSL-MRS toolkit to pre-process the MRSI data, fit spectra and quantify metabolite concentration. This dataset will allow the spatial distribution of neurochemical concentrations to be characterised in healthy individuals and disease, and the effect of age to be addressed. Furthermore, by combining MRS and functional MRI data, the role of neurochemicals in determining motor network function can be investigated and biomarkers of future therapeutic response to be developed. Identifying physiological processes underlying motor function and plasticity may yield targets for modulation to improve function or treat disease.

We will complete two studies, for which we will recruit a representative sample. In study 1 we examine the extent to which emotion beliefs and emotion regulation influence PTG and symptoms of psychopathology (anxiety, and depression) and physical pathology (sleep, colds, stomach problems, and headaches). In study 2 we move beyond cross-sectional associations, and longitudinally examine the extent to which cause-effect relationships exist between the variables examined in study 1.

This is a psychometric development and validation project for a new measure of cognitive-mediation beliefs.

This is a prospective, longitudinal study designed to examine the interplay between well-being and performance in a netball club across a season.

This is a prospective, longitudinal study designed to examine the interplay between well-being and performance in a netball club across a season.

The maturation of immature B cells and the survival of mature B cells is stringently controlled to maintain a diverse repertoire of antibody specificities while avoiding self-reactivity. At the molecular level this is regulated by signaling from membrane Ig and the BAFF-receptor that sustain a pro-survival program of gene expression. Whether and how posttranscriptional mechanisms contribute to B cell maturation and survival remains poorly understood. Here, we show that the polypyrimidine tract binding proteins (PTBP) PTBP1 and PTBP3 bind to a large and overlapping set of transcripts in B cells. Both PTBP1 and PTBP3 bind to introns and exons where they are predicted to regulate alternative splicing. Moreover, they also show high-density of binding to 3' untranslated regions suggesting they influence the transcriptome in diverse ways. We show that PTBP1 and PTBP3 are required in B cells beyond the immature cell stage to sustain transitional B cells and the B1, marginal zone and follicular B cell lineages. Therefore, PTBP1 and PTBP3 promote the maturation of quiescent B cells by regulating gene expression at the posttranscriptional level.

Post-mortem MRI provides the opportunity to acquire high-resolution datasets to investigate neuroanatomy, and validate the origins of image contrast through microscopy comparisons. We introduce the Digital Brain Bank (open.win.ox.ac.uk/DigitalBrainBank), a data release platform providing open access to curated, multimodal post-mortem neuroimaging datasets. Datasets span three themes-Digital Neuroanatomist: datasets for detailed neuroanatomical investigations; Digital Brain Zoo: datasets for comparative neuroanatomy; Digital Pathologist: datasets for neuropathology investigations. The first Digital Brain Bank release includes twenty one distinctive whole-brain diffusion MRI datasets for structural connectivity investigations, alongside microscopy and complementary MRI modalities. This includes one of the highest-resolution whole-brain human diffusion MRI datasets ever acquired, whole-brain diffusion MRI in fourteen non-human primate species, and one of the largest post-mortem whole-brain cohort imaging studies in neurodegeneration. The Digital Brain Bank is the culmination of our lab’s investment into post-mortem MRI methodology and MRI-microscopy analysis techniques. This manuscript provides a detailed overview of our work with post-mortem imaging to date, including the development of diffusion MRI methods to image large post-mortem samples, including whole, human brains. Taken together, the Digital Brain Bank provides cross-scale, cross-species datasets facilitating the incorporation of post-mortem data into neuroimaging studies.

Subdivision is a method for generating a limit surface from a coarse mesh by recursively dividing its faces into several smaller faces. This process leads to smooth surfaces, but often suffers from shading artifacts near extraordinary points due to the lower quality of the normal field there. The idea of subdivision shading is to apply the same subdivision rules that are used to subdivide geometry to also subdivide the normals associated with mesh vertices. This leads to smoother normal fields, which in turn removes the shading artifacts. However, the original subdivision shading method does not support sharp and semi-sharp creases, which are important ingredients in subdivision surface modelling. We present two approaches to extending subdivision shading to work also on models with (semi-)sharp creases.

Cell migration relies on coordinated activity of chemotactic and guidance receptors. Here, we report a specific role for the RNA-binding protein ZFP36L1 in limiting the abundance of molecules involved in the homing of antibody-secreting cells (ASCs) to the bone marrow (BM). In the absence of ZFP36L1, ASCs build up in the spleen and the liver and show diminished accumulation in the BM. ZFP36L1 facilitates migration by directly regulating G protein-coupled receptor kinase 2 (GRK2) and the integrin chains α4 and β1 in splenic ASCs. Expression of CXCR4 and of the integrins α4 and β1 is differentially regulated on ASCs produced at the early and late stages of the immune response. Consequently, deletion of the Zfp36l1 gene has a stronger effect on BM accumulation of high-affinity ASCs formed late in the response. Thus, ZFP36L1 is an integral part of the regulatory network controlling gene expression during ASC homing.

Explorations of visualisation of computed tomography (CT) volumes involve multiple types of observations and interactions at various viewing positions. This short paper presents a case study using a new framework that leverages having multiple DOF for computer graphics visualisations of X-Ray CT 3D reconstructed volumes for hydrocarbon exploration within Drishti, an industrial visualisation software package., Computer Graphics and Visual Computing (CGVC), Data and Visualisation, 11, 14, Mario Sandoval, Martin Turner, and Tim Morris, CCS Concepts: Human-centered computing --> Interaction techniques; Scientific visualization; Interaction devices

The pathological hallmark of amyotrophic lateral sclerosis (ALS) is the presence of cytoplasmic inclusions, containing C‐terminal fragments of the protein TDP‐43. Here, we tested the hypothesis that highly sensitive mass spectrometry with parallel reaction monitoring (MS‐PRM) can generate a high‐resolution map of pathological TDP‐43 peptide ratios to form the basis for quantitation of abnormal C‐terminal TDP‐43 fragment enrichment.Human cortex and spinal cord, microscopically staged for the presence of phosphoTDP‐43, p‐tau, alpha‐synuclein and beta‐amyloid pathology, were biochemically fractionated and analysed by immunoblot and MS for detection of full‐length and truncated (disease‐specific) TDP‐43 peptides. This informed synthesis of heavy isotope‐labelled peptides for absolute quantification of TDP‐43 by MS‐PRM across 16 ALS, 8 Parkinson’s and 8 Alzheimer’s disease and 8 aged control cases.We confirmed by immunoblot the previously described enrichment of pathological C‐terminal fragments in ALS‐TDP urea fractions. Subsequent MS analysis resolved specific TDP‐43 N‐ and C‐terminal peptides, including a novel N‐terminal truncation site‐specific peptide. Absolute quantification of peptides by MS‐PRM showed an increased C:N‐terminal TDP‐43 peptide ratio in ALS‐TDP brain compared to normal and disease controls. A C:N‐terminal ratio >1.5 discriminated ALS from controls with a sensitivity of 100% (CI 79.6‐100) and specificity of 100% (CI 68‐100), and from Parkinson’s and Alzheimer’s disease with a sensitivity of 93% (CI 70‐100) and specificity of 100% (CI 68‐100). N‐terminal truncation site‐specific peptides were increased in ALS in line with C‐terminal fragment enrichment, but were also found in a proportion of Alzheimer cases with normal C:N‐terminal ratio but coexistent TDP‐43 pathology.In conclusion this is a novel, sensitive and specific method to quantify the enrichment of pathological TDP‐43 fragments in human brain, which could form the basis for an antibody‐free assay. Our methodology has the potential to help clarify if specific pathological TDP‐43 peptide signatures are associated with primary or secondary TDP‐43 proteinopathies.

Sports officials are often under stress and pressure when they are officiating. In this novel study of Australian tennis officials, the aim was to investigate challenge and threat appraisals, self-efficacy, sources of self-efficacy and psychological resilience in a cross-section of 140 Australian tennis officials. There were 95 males and 45 females with a mean age of 49.9 years (SD = 16.15) involved in the study. Participants completed the Connor-Davidson Resilience Scale-10 (CD-RISC10); the Challenge Appraisal Scale (CAS); a modified version of the Referee Self-Efficacy Scale (REFS); and the Sports Officials Self-Rating Scale. Two hierarchical regression analyses were used to examine the extent to which self-efficacy and challenge and threat appraisals were related to psychological resilience, and to examine which sources of self-efficacy predicted self-efficacy. Age, gender, years officiating, officiating role and number of tournaments officiated within the previous 12 months, were controlled for in both analyses. The results revealed that a challenge appraisal and higher self-efficacy significantly predicted psychological resilience. While higher self-efficacy was significantly predicted by number of tournaments officiated and greater perceptions of physical and mental preparation. To develop official’s self-efficacy, challenge appraisals and psychological resilience, practical strategies and skills (e.g., reappraisal, imagery, quite eye training) could be taught to officials when they undertake their initial training or any subsequent courses or workshops.

It has been theorized that a follower can draw upon support from individuals they identify with when approaching competitive situations to improve psychophysiological challenge states, and performance potential. As such, we examine how perceptions of identity leadership influence resource appraisals, cardiovascular reactivity, and performance in a pressurised motor task across two laboratory experiments. In Study 1, 80 participants took part in a within-subjects double-blind design with two conditions: identity leadership (IL) vs no identity leadership (no IL). Results indicated that when instructions align with identity leadership principles (vs. not), followers reported greater resource appraisals to, challenge cardiovascular reactivity to, and motor performance within a motivated performance situation. In Study 2, 120 participants completed a 2 (identity leadership: IL vs. no IL) X 2 (appraisal: challenge vs. threat) between-subjects double-blind design. It was found that when instructions aligned to identity leadership (vs. not), followers reported greater resource appraisals and motor performance. When leaders used challenge (vs. threat) instructions this led to challenge cardiovascular reactivity on approach to competition. Advancing leadership and stress theory, we provide evidence that perceived identity leadership is salient for followers’ resource appraisals, cardiovascular reactivity, and motor performance.

These proceedings contain the presented papers at the 16th International Meeting on Fully Three-Dimensional Image Reconstruction in Radiology and Nuclear Medicine 2021, which was to be held in Leuven, Belgium, but had to be transformed in a virtual meeting because of the covid-19 pandemic. Fully3D is one of the major forums for presentation of new results in the field of 3D image reconstruction, primarily with applications in x-ray computer tomography, PET and SPECT. Over the life-time of the meeting the focus has shifted to reflect recent developments in the field. Many of the major developments in fully 3D PET and SPECT imaging were first presented at Fully3D, as were the key results for analytic reconstruction methods in cone beam x-ray CT. Similarly, in the 2021 meeting a broad range of topics has been presented. As expected, deep learning methods are being used increasingly: they are used as post-processing tools or incorporated in the reconstruction, often aiming at improved noise and/or artifact suppression.

Purpose: The present study investigated the cognitions and emotions of swimmers,and explored thepsychological techniques they use to manage these internal processesprior to and during their best and worst performances. Method: Seven Paralympic and five Olympic male Brazilian swimmers took part in this qualitative study. A semi-structured interview with open-ended questions was conducted to explore how swimmers interpreted and experienced specific competitive events and what they did to manage their internal processes, prior to and during what they considered to be their best and worst performances. The process of data analysis included inductiveand deductive approaches. Cognitive therapy theory wasused to establish some of the themes and sub-themes, also to contribute to the data analysis.Results: Functional cognitions and pleasant emotions were more commonly reported by swimmers associated to their best performances, whilst dysfunctional cognitions and unpleasant emotions were more common in their worst performances, both influenced by their beliefs about the preparation during the season.Swimmers used imagery, breathing, music, self-talk, and cognitive restructuring to manage their cognitions and emotions, mainly in the day of their best performances. Although swimmers believed that cognitions and emotions could influence their performances, they reporteddifficulty identifying, evaluating, and modifyingtheir dysfunctional thinking. Conclusion:Our findings suggest that different patterns of cognitions and emotions were related to swimmers’ best and worst performances, which were influenced by their beliefs about the preparation during the season.These results support the use of individualized and task-specific mental preparation programsto help athletes identify and manage dysfunctionalcognitions and emotions, and elicitadaptivebehaviors

Research in the area of body image suggests that muscularity dissatisfaction is a prominent concern among men and women. At its apex, this concern manifests into a convoluted and debilitating body image disorder termed muscle dysmorphia (MD), characterised by a marked preoccupation with ones (subjective) muscularity and leanness inadequacy. Prevention of MD is critical, however, empirical evidence informing intervention protocols are profoundly scarce. The principal aim of this study was to examine the effectiveness of a one-to-one Rational Emotive Behaviour Therapy (REBT) intervention, comprising five, 60-minute one-to-one sessions, in decreasing MD symptomatology, irrational beliefs and increasing unconditional self-acceptance in a mixed-sex cohort of four exercisers at-risk of MD. A single-case, staggered multiple-baseline across participant A-B design was adopted to examine the effects of REBT. Visual and statistical analyses, and social validation data, indicated reductions in MD, irrational beliefs, and increases in unconditional self-acceptance across all participants from pre-post intervention phases, with reductions upheld at a 6-month follow-up. This study highlights the potential role of rational and irrational beliefs in the onset and maintenance of MD. This study is the first to report the application of a CBT approach to MD symptomology, and has demonstrated the use of REBT as a potential preventative approach for individuals at risk of MD. Practitioners working with individuals at risk of MD should take a benefit-focussed approach to support individuals in developing unconditional self-acceptance beliefs, as well as a problem-focussed approach to support individuals in reducing irrational beliefs.

Collaboration is a process in which two or more agents work together to achieve shared goals. However, many existing platforms cannot generate a collaborative environment to engage multiple users with multiple controllers in a seamless manner. To address this need, this poster and work in progress article will describe LISU (Library for Interactive Settings and User-modes) an input management computing framework that enables collaboration across multiple input controllers as its default. Within the system team members cohabit any real-time simulation environments simultaneously and are then able to jointly control visualisation software across multiple controllers while being continually monitored and evaluated at a low level, allowing research questions to be answered.

The uses of unmanned aerial vehicles (UAV) are rapidly increasing across diverse applications including surveillance, policing and search and rescue. To perform domain-specific functions, software systems incorporating 2D and 3D image processing libraries are being developed to work on the recorded and streamed video. But how agile are these systems? Can their operation be modified by users? How easy is it to add or replace UAVs or their preferred imaging module or improved compute resources? In this work-in-progress paper, we present an encyclopaedia-based framework (EbF) that can answer positively to these questions. Our novel EbF specifies the use of drop-in modules to enable speedy implementation and modification of systems by the operator and, as it incorporates knowledge of the input image-capture devices and presentation preferences, the system includes automated parameter selection. Central to the framework is an encyclopaedia which is used to store all information pertaining to the current system operation and can be used by imaging modules to ensure that they can adapt to changes within the system or its environment. Results are shown over three use-case implementations that are easy to control and set-up by novice operators utilising simple computational wrapper scripts., Computer Graphics and Visual Computing (CGVC), Visualisation and Machine Learning, 27, 31, Terence Morley, Tim Morris, and Martin Turner, CCS Concepts: Computing methodologies --> Image manipulation; Shape modeling; Software and its engineering --> Software creation and management; Human-centered computing --> Human computer interaction (HCI)

The Theory of Challenge and Threat States in Athletes (TCTSA) provides a psychophysiological framework for how athletes anticipate motivated performance situations. The purpose of this review is to discuss how research has addressed the 15 predictions made by the TCTSA, to evaluate the mechanisms underpinning the TCTSA in light of the research that has emerged in the last ten years, and to inform a revised TCTSA (TCTSA-R). There was support for many of the 15 predictions in the TCTSA, with two main areas for reflection identified; to understand the physiology of challenge and to re-evaluate the concept of resource appraisals. This re-evaluation informs the TCTSA-R which elucidates the physiological changes, predispositions, and cognitive appraisals that mark challenge and threat states. First, the relative strength of the sympathetic nervous system response is outlined as a determinant of challenge and threat patterns of reactivity and we suggest that oxytocin and neuropeptide Y are also key indicators of an adaptive approach to motivated performance situations and can facilitate a challenge state. Second, although predispositions were acknowledged within the TCTSA, how these may influence challenge and threat states was not specified. In the TCTSA-R it is proposed that one’s propensity to appraise stressors as a challenge that most strongly dictates acute cognitive appraisals. Third, in the TCTSA-R a more parsimonious integration of Lazarusian ideas of cognitive appraisal and challenge and threat is proposed. Given that an athlete can make both challenge and threat primary appraisals and can have both high or low resources compared to perceived demands, a 2x2 bifurcation theory of challenge and threat is proposed. This reflects polychotomy of four parts; high challenge, low challenge, low threat, and high threat. For example, in low threat, an athlete can evince a threat state but still perform well so long as they perceive high resources. Consequently, we propose suggestions for research concerning measurement tools and a reconsideration of resources to include social support. Finally, applied recommendations are made based on adjusting demands and enhancing resources.

Purpose: The present study investigated the cognitions and emotions of swimmers,and explored the psychological techniques they use to manage these internal processes prior to and during their best and worst performances. Method: Seven Paralympic and five Olympic male Brazilian swimmers took part in this qualitative study. A semi-structured interview with open-ended questions was conducted to explore how swimmers interpreted and experienced specific competitive events and what they did to manage their internal processes, prior to and during what they considered to be their best and worst performances. The process of data analysis included inductive and deductive approaches. Cognitive therapy theory was used to establish some of the themes and sub-themes, also to contribute to the data analysis.Results: Functional cognitions and pleasant emotions were more commonly reported by swimmers associated to their best performances, whilst dysfunctional cognitions and unpleasant emotions were more common in their worst performances, both influenced by their beliefs about the preparation during the season.Swimmers used imagery, breathing, music, self-talk, and cognitive restructuring to manage their cognitions and emotions, mainly in the day of their best performances. Although swimmers believed that cognitions and emotions could influence their performances, they reported difficulty identifying, evaluating, and modifying their dysfunctional thinking. Conclusion:Our findings suggest that different patterns of cognitions and emotions were related to swimmers’ best and worst performances, which were influenced by their beliefs about the preparation during the season.These results support the use of individualized and task-specific mental preparation programs to help athletes identify and manage dysfunctional cognitions and emotions, and elicit adaptive behaviors peerReviewed

Collaboration is a process in which two or more agents work together to achieve shared goals. However, many existing platforms cannot generate a collaborative environment to engage multiple users with multiple controllers in a seamless manner. To address this need, this poster and work in progress article will describe LISU (Library for Interactive Settings and User-modes) an input management computing framework that enables collaboration across multiple input controllers as its default. Within the system team members cohabit any real-time simulation environments simultaneously and are then able to jointly control visualisation software across multiple controllers while being continually monitored and evaluated at a low level, allowing research questions to be answered., Computer Graphics and Visual Computing (CGVC), AR and VR, 79, 81, Mario Sandoval, Tim Morris, and Martin Turner, CCS Concepts: Computing methodologies --> Virtual reality; Graphics input devices; Human-centered computing --> Collaborative and social computing theory, concepts and paradigms

LISU (Library for Interactive Settings and User-modes) is an input management computing framework which enables groups of researchers to cohabit real-time simulation environments simultaneously and to visualise and manipulate virtual objects within multiple computer-assisted visualisation applications. The key novelty of LISU is an automated layered approach (physicaldriver- transport-upper layers) with importantly a built-in HCI ontology and strictly defined set of sub-APIs between the layers. All of this allows multiple input devices with multiple degrees of freedom to interact simultaneously, allowing for more intuitive and natural behaviour. Evaluation combines both linear and non-linear user modes, with a comparison system provided by Unity3D. By combining human spatial reasoning and computer graphics theory, technologies like LISU have the potential to improve our ability to understand, test and evaluate, reengineer, and then communicate better virtual dataset behaviour., Computer Graphics and Visual Computing (CGVC), AR and VR, 93, 100, Mario Sandoval, Tim Morris, and Martin Turner, CCS Concepts: Human-centered computing --> Interaction devices; Computing methodologies --> Virtual reality; Concurrent algorithms; Graphics input devices

Additional file 1 Supp Fig. 1: Additional staining of pathology in the motor cortex and spinal cord. Staining for OPTN was highly positive in all neurons in controls (A), but absent in an OPTN mutation case (D), reflecting the truncation of the protein upstream of the antibody epitope. Asterisks in (B) mark the presence of Betz cells. Arrows in (E) mark mislocalized and aggregated FUS inclusions. Arrows in (F) mark the presence of aggregated SOD1 protein in a case with the SOD1 D101G mutation (case 31). As discussed in the text, antibody SOD1 SPC-206 did highlight solid compact and skein aggregates but had strong background staining (C), making it unsuitable for quantitative automated image analysis. P62 was used instead as a marker for compact SOD-1 associated protein aggregates; granular aggregation of misfolded wild-type SOD1, which has been suggested to be present in all genotypes of ALS, was not revealed by p62 immunohistochemistry [22]. Scale bar applicable to all panels = 50 μm. Supp Fig. 2: Significant variation in the extent of pTDP-43 pathology between TARDBP and OPTN ALS mutation cases. pTDP-43 pathology in the TARDBP case was sparse, and consisted almost exclusively of compact NCI (a,b, red arrows highlight pathology). In contrast, pathology was severe and widespread in the homozygous ALS-OPTN case (c,d), with NCI, oligo inclusions and dystrophic neurites in all layers, including the subcortical white matter (e). Supp Fig. 3: CD68 staining between the primary motor cortex (a) and lumbar spinal cord (b) white and grey matter is positively correlated in all the genotypes tested; Pearson r, results as on figure. Best fit lines are manually added for illustrative purposes. Supp Fig. 4: Assessment of anterior horn neuron size. Anterior horn degeneration and shrinkage was most prominent in FUS (b) and SOD1 cases, and noticeably less severe in the single ALS-OPTN case (c), however there was significant intraindividual differences within genotypes (d). pTDP-43 aggregation in the anterior horn did not correlate with anterior horn neuron shrinkage/loss in either sporadic (blue dots) or C9ORF72 disease (red squares) (e). Supp Fig. 5: Calculated predominance ratios for single-IHC cohort using CD68 as a surrogate marker of neurodegeneration. Ratios were calculated by dividing the log expression of motor cortex CD68/mm2 by the log expression of anterior horn CD68/mm2. Lower ratios therefore represent a higher LMN burden of activated microglia. Supp Fig. 6: Betz cells occasionally display pTDP-43 aggregation but also occasionally nodular microgliosis and neuronophagia. MxIF analysis did not reveal significant evidence of pTDP-43 within Betz cells (a,b, green lined arrows indicate unaffected Betz cells), but it can occasionally be seen in some cases (c,d). However we did also find evidence of nodular microgliosis surrounding large layer V neurons in some cases (e). UL = upper layers, DL = deeper layers. Scale bars where not indicated (μm): a = 40, b,e = 50. Supp Table 3: Numerical results for Olig and TPPP/p25 quantification.

In this paper, the two major components of a new multi-layer framework ideal for two-handed interaction in desktop virtual environments called Library for Interactive Settings of User-Mode (LISU) are explained. In addition, we evaluate LISU performance with a group of participants and we report some of our initial results by giving an analysis of user experiences, and interaction speed., Computer Graphics and Visual Computing (CGVC), Posters, 97, 101, Mario Sandoval, Tim Morris, and Martin Turner, CCS Concepts: Human-centered computing --> HCI design and evaluation methods; Virtual reality; Interaction devices; Computing methodologies --> Graphics systems and interfaces; Hardware --> Signal processing systems

We were pleased that our paper “Applying the REBT cognitive disputation technique to the binary theory of emotional distress” (Turner, Jones, & Wood, 2018) sparked interest and debate within the REBT community. Our original paper was conceived to draw out the opinions of those who read it, and when we approached the three commentators, Philip Hyland, Demetris Katsikis, and Chrysoula Kostogiannis, we anticipated an insightful and engaging discussion. Our expectations were exceeded, as three different types of responses were developed by the three learned commentators. Hyland’s paper offers a rather categorical rebuttal of the binary theory of emotional distress (BTED), Katsikis’ offers a balanced and critical perspective, whilst Kostogiannis’s paper offers support for the BTED. All three approach the issue in different ways, and all three commentators draw on their own values and experiences to guide their points. It is impossible to do every element of each commentary sufficient justice, so we will focus on key points made by the commentators in our response here. In the spirit of scientific debate, we invite Hyland, Katsikis, and Kostogiannis to respond to the current paper with their further rebuttals and comments.

Polypyrimidine tract binding protein (PTBP1) is a widely expressed RNA binding protein that acts as a regulator of alternative splicing and of cytoplasmic mRNA functions. Vertebrates contain two closely-related paralogs with >75% amino acid sequence identity. Early replacement of PTBP1 by PTBP2 during neuronal differentiation causes a concerted set of splicing changes. By comparison, very little is known about the molecular functions or physiological roles of PTBP3, although its expression and conservation throughout the vertebrates suggest a role in haematopoietic cells. To begin to understand its functions we have characterized the mRNA and protein isoform repertoire of PTBP3. Combinatorial alternative splicing events at the 5' end of the gene allow for the generation of eight mRNA and three major protein isoforms. Individual mRNAs generate up to three protein isoforms via alternative translation initiation by re-initiation and leaky scanning using downstream AUG codons. The N-terminally truncated PTBP3 isoforms lack nuclear localization signals and/or most of the RRM1 domain and vary in their RNA binding properties and nuclear/cytoplasmic distribution, suggesting that PTBP3 may have major post-transcriptional cytoplasmic roles. Our findings set the stage for understanding the non-redundant physiological roles of PTBP3.

Objectives Researchers have examined how leaders' representation of shared identity content allows them to mobilize group members towards success in competitive tasks. However, research is yet to determine the psychological and physiological implications of shared identity content with a leader when approaching competitive tasks. The present research addresses this gap within a two-phase experimental study, examining the effect of shared identity content on follower intentional mobilization, self-efficacy, perceived control, approach and avoidance goals, cardiovascular challenge and threat and motor performance within a competitive task. Design A 2 × 2 between-participants two-phase experimental design, with two shared and two non-shared conditions. Method Within phase one, 220 sport and exercise undergraduate students imagined themselves in one of four scenarios and responded to measures of mobilization (e.g., willingness to invest time on a task). Then, a pre-screening questionnaire was used to evidence the students' authentic identity content when competing in sport, which informed condition within phase two. Of those who consented to phase two, a laboratory experiment with 120 undergraduate sport and exercise students was used. Within this experiment, the sharedness of identity content between leader and follower was manipulated through the students' authentic pre-screening questionnaire responses. Within phase two, competition related self-efficacy, perceived control, approach and avoidance goals, cardiovascular challenge and threat and motor performance was assessed. Results Phase one results indicated that when identity content is shared (vs. non-shared) between leader and follower, group members' willingness to invest time on a task is increased within a hypothetical scenario. In phase two, it was evidenced that when identity content is shared (vs. non-shared) between leader and follower, followers reported greater intentional mobilization, self-efficacy and perceived control when approaching a competitive task. Shared identity content with a leader did not predict cardiovascular challenge states nor greater motor performance (relative to non-shared identity content). Conclusion The present research provides evidence that a leaders' capacity to mobilize effort of group members and enhance psychological appraisal of competitive events is dependent on their ability to build shared identity content.

Extant research suggests that irrational and rational beliefs may play an important role in both substance and behavioural addictions. However, the influence of irrational and rational beliefs pertaining exercise addiction has yet to be investigated. Rational emotive behaviour therapy (REBT) is a cognitive-behavioural approach that provides a theoretical framework to identify and change irrational beliefs through cognitive restructuring and endorsing rational beliefs. The principal aim of the current study is to examine the effectiveness of a one-to-one REBT programme in decreasing irrational beliefs and exercise addiction symptoms, and increasing unconditional self-acceptance, in three male exercisers. The exercisers present high symptoms of exercise addiction, and high irrational beliefs. A single-case, staggered multiple-baseline across participant A-B design is used in the current study to examine the effects of a six-week REBT program comprising six 45-minute one-to-one counselling sessions and 5 homework assignments. Visual and statistical analyses, and social validation data indicate strong reductions in low-frustration tolerance, composite irrational beliefs, and exercise addiction from pre- to intervention phase. In addition, all participants report increased unconditional self-acceptance. This is the first study to report the effects of REBT in an exercise population, and the first to demonstrate that exercise addiction symptoms can be attenuated using REBT. This study supports literature suggesting that irrational and rational beliefs are an important mechanism in exercise addiction and provides important implications for the development of its treatment.

The aim of this research is to present a new multimodal interaction mapping framework for 3D object manipulation within the virtual reality (VR) realm, by leveraging the advantages of having multiple DoF (Degree of Freedom). In this new software engineering designed framework, interaction devices such as the keyboard, mouse, joystick, and specialist devices for 3D interactions; the Wing [5] [4] and the 3D connexion spacenavigator, can all be combined to provide a more intuitive and natural interaction command system. This can be applied to many different specific systems including industrial applications within the petroleum, geology and materials sciences.

This poster describes the use and launch of TomoPhantom; a software based phantom generation toolkit. Within CT imaging many novel reconstruction techniques are routinely tested using simplistic numerical phantoms. This package has been needed for a long time across user groups; and it now allows users to have quick access to an external library to create advanced modular analytical 2D/3D phantoms with temporal extensions. Code has just been released and available at https://github.com/dkazanc/TomoPhantom as well as published in a use case paper in SoftwareX.&nbsp

Showcase talk for CCPi (CIL Core Imaging Library) andKitware Inc (tomviz) collaboration via the EPSRC USA-UK Travel award. This presentation is an ongoing collaboration and links on the website: https://www.ccpi.ac.uk&nbsp

Background Amyotrophic lateral sclerosis (ALS) is a clinically and histopathologically heterogeneous neurodegenerative disorder, in which therapy is hindered by the rapid progression of disease and lack of biomarkers. Magnetic resonance imaging (MRI) has demonstrated its potential for detecting the pathological signature and tracking disease progression in ALS. However, the microstructural and molecular pathological substrate is poorly understood and generally defined histologically. One route to understanding and validating the pathophysiological correlates of MRI signal changes in ALS is to directly compare MRI to histology in post mortem human brains. Results The article delineates a universal whole brain sampling strategy of pathologically relevant grey matter (cortical and subcortical) and white matter tracts of interest suitable for histological evaluation and direct correlation with MRI. A standardised systematic sampling strategy that was compatible with co-registration of images across modalities was established for regions representing phosphorylated 43-kDa TAR DNA-binding protein (pTDP-43) patterns that were topographically recognisable with defined neuroanatomical landmarks. Moreover, tractography-guided sampling facilitated accurate delineation of white matter tracts of interest. A digital photography pipeline at various stages of sampling and histological processing was established to account for structural deformations that might impact alignment and registration of histological images to MRI volumes. Combined with quantitative digital histology image analysis, the proposed sampling strategy is suitable for routine implementation in a high-throughput manner for acquisition of large-scale histology datasets. Proof of concept was determined in the spinal cord of an ALS patient where multiple MRI modalities (T1, T2, FA and MD) demonstrated sensitivity to axonal degeneration and associated heightened inflammatory changes in the lateral corticospinal tract. Furthermore, qualitative comparison of R2* and susceptibility maps in the motor cortex of 2 ALS patients demonstrated varying degrees of hyperintense signal changes compared to a control. Upon histological evaluation of the same region, intensity of signal changes in both modalities appeared to correspond primarily to the degree of microglial activation. Conclusion The proposed post mortem whole brain sampling methodology enables the accurate intraindividual study of pathological propagation and comparison with quantitative MRI data, to more fully understand the relationship of imaging signal changes with underlying pathophysiology in ALS. Electronic supplementary material The online version of this article (10.1186/s12868-018-0416-1) contains supplementary material, which is available to authorized users.

Objective Diffusion tensor imaging (DTI) is sensitive to white matter tract pathology. A core signature involving the corticospinal tracts (CSTs) has been identified in amyotrophic lateral sclerosis (ALS). Raised neurofilament light chain protein (NfL) in cerebrospinal fluid (CSF) is thought to reflect axonal damage in a range of neurological disorders. The relationship between these two measures was explored. Methods CSF and serum NfL concentrations and DTI acquired at 3 Tesla on the same day were obtained from ALS patients (n = 25 CSF, 40 serum) and healthy, age-similar controls (n = 17 CSF, 25 serum). Within-group correlations between NfL and DTI measures of microstructural integrity in major white matter tracts (CSTs, superior longitudinal fasciculi [SLF], and corpus callosum) were performed using tract-based spatial statistics. Results NfL levels were higher in patients compared to controls. CSF levels correlated with clinical upper motor neuron burden and rate of disease progression. Higher NfL levels were significantly associated with lower DTI fractional anisotropy and increased radial diffusivity in the CSTs of ALS patients, but not in controls. Interpretation Elevated CSF and serum NfL is, in part, a result of CST degeneration in ALS. This highlights the wider potential for combining neurochemical and neuroimaging-based biomarkers in neurological disease.

Progression through the stages of lymphocyte development requires coordination of the cell cycle. Such coordination ensures genomic integrity while cells somatically rearrange their antigen receptor genes [in a process called variable-diversity-joining (VDJ) recombination] and, upon successful rearrangement, expands the pools of progenitor lymphocytes. Here we show that in developing B lymphocytes, the RNA-binding proteins (RBPs) ZFP36L1 and ZFP36L2 are critical for maintaining quiescence before precursor B cell receptor (pre-BCR) expression and for reestablishing quiescence after pre-BCR-induced expansion. These RBPs suppress an evolutionarily conserved posttranscriptional regulon consisting of messenger RNAs whose protein products cooperatively promote transition into the S phase of the cell cycle. This mechanism promotes VDJ recombination and effective selection of cells expressing immunoglobulin-μ at the pre-BCR checkpoint.

Neutron imaging has been employed in life sciences in recent years and has proven to be a viable technique for studying internal features without compromising integrity and internal structure of samples in addition to being complementary to other methods such as X‐ray or magnetic resonance imaging. Within the last decade, a neutron imaging beamline, IMAT, was designed and built at the ISIS Neutron and Muon Source, UK, to meet the increasing demand for neutron imaging applications in various fields spanning from materials engineering to biology. In this paper, we present the first neutron imaging experiments on different biological samples during the scientific commissioning of the IMAT beamline mainly intended to explore the beamline's capabilities and its potential as a noninvasive investigation tool in fields such as agriculture (soil‐plants systems), palaeontology and dentistry.

Additional file 1. Spinal cord MRI protocol parameters.

Additional file 3. Quantitative histological data for the primary motor cortex grey matter at the hand knob.

Objective: To test blood and CSF neurofilament light chain (NfL) levels in relation to disease progression and survival in amyotrophic lateral sclerosis (ALS). Methods: Using an electrochemiluminescence immunoassay, NfL levels were measured in samples from 2 cohorts of patients with sporadic ALS and healthy controls, recruited in London (ALS/control, plasma: n = 103/42) and Oxford (ALS/control, serum: n = 64/36; paired CSF: n = 38/20). NfL levels in patients were measured at regular intervals for up to 3 years. Change in ALS Functional Rating Scale–Revised score was used to assess disease progression. Survival was evaluated using Cox regression and Kaplan–Meier analysis. Results: CSF, serum, and plasma NfL discriminated patients with ALS from healthy controls with high sensitivity (97%, 89%, 90%, respectively) and specificity (95%, 75%, 71%, respectively). CSF NfL was highly correlated with serum levels (r = 0.78, p < 0.0001). Blood NfL levels were approximately 4 times as high in patients with ALS compared with controls in both cohorts, and maintained a relatively constant expression during follow-up. Blood NfL levels at recruitment were strong, independent predictors of survival. The highest tertile of blood NfL at baseline had a mortality hazard ratio of 3.91 (95% confidence interval 1.98–7.94, p < 0.001). Conclusion: Blood-derived NfL level is an easily accessible biomarker with prognostic value in ALS. The individually relatively stable levels longitudinally offer potential for NfL as a pharmacodynamic biomarker in future therapeutic trials. Classification of evidence: This report provides Class III evidence that the NfL electrochemiluminescence immunoassay accurately distinguishes patients with sporadic ALS from healthy controls.

Mitochondria play a key role in common neurodegenerative diseases and contain their own genome: mtDNA. Common inherited polymorphic variants of mtDNA have been associated with several neurodegenerative diseases, and somatic deletions of mtDNA have been found in affected brain regions. However, there are conflicting reports describing the role of rare inherited variants and somatic point mutations in neurodegenerative disorders, and recent evidence also implicates mtDNA levels. To address these issues we studied 1363 post mortem human brains with a histopathological diagnosis of Parkinson’s disease (PD), Alzheimer’s disease (AD), Frontotemporal dementia – Amyotrophic Lateral Sclerosis (FTD-ALS), Creutzfeldt Jacob disease (CJD), and healthy controls. We obtained high-depth whole mitochondrial genome sequences using off target reads from whole exome sequencing to determine the association of mtDNA variation with the development and progression of disease, and to better understand the development of mtDNA mutations and copy number in the aging brain. With this approach, we found a surprisingly high frequency of heteroplasmic mtDNA variants in 32.3% of subjects. However, we found no evidence of an association between rare inherited variants of mtDNA or mtDNA heteroplasmy and disease. In contrast, we observed a reduction in the amount of mtDNA copy in both AD and CJD. Based on these findings, single nucleotide variants of mtDNA are unlikely to play a major role in the pathogenesis of these neurodegenerative diseases, but mtDNA levels merit further investigation. Electronic supplementary material The online version of this article (doi:10.1186/s40478-016-0404-6) contains supplementary material, which is available to authorized users.