Comparative genomics and concerted evolution of β-tubulin paralogs in Leishmania spp

BACKGROUND: Tubulin isotypes and expression patterns are highly regulated in diverse organisms. The genome sequence of the protozoan parasite Leishmania major contains three distinct β-tubulin loci. To investigate the diversity of β-tubulin genes, we have compared the published genome sequence to draft genome sequences of two further species L. infantum and L. braziliensis. Untranscribed regions and coding sequences for each isoform were compared within and between species in relation to the known diversity of β-tubulin transcripts in Leishmania spp. RESULTS: All three β-tubulin loci were present in L. infantum and L. braziliensis, showing conserved synteny with the L. major sequence, hence confirming that these loci are paralogous. Flanking regions suggested that the chromosome 21 locus is an amastigote-specific isoform and more closely related (either structurally or functionally) to the chromosome 33 'array' locus than the chromosome 8 locus. A phylogenetic network of all isoforms indicated that paralogs from L. braziliensis and L. mexicana were monophyletic, rather than clustering by locus. CONCLUSION: L. braziliensis and L. mexicana sequences appeared more similar to each other than each did to its closest relative in another species; this indicates that these sequences have evolved convergently in each species, perhaps through ectopic gene conversion; a process not yet evident among the more recently derived L. major and L. infantum isoforms. The distinctive non-coding regions of each β-tubulin locus showed that it is the regulatory regions of these loci that have evolved most during the diversification of these genes in Leishmania, while the coding regions have been conserved and concerted. The various loci in Leishmania satisfy a need for innovative expression of β-tubulin, rather than elaboration of its structural role

Evolution of Tubulin Gene Arrays in Trypanosomatid parasites: genomic restructuring in Leishmania

BACKGROUND: α- and β-tubulin are fundamental components of the eukaryotic cytoskeleton and cell division machinery. While overall tubulin expression is carefully controlled, most eukaryotes express multiple tubulin genes in specific regulatory or developmental contexts. The genomes of the human parasites Trypanosoma brucei and Leishmania major reveal that these unicellular kinetoplastids possess arrays of tandem-duplicated tubulin genes, but with differences in organisation. While L. major possesses monotypic α and β arrays in trans, an array of alternating α- and β tubulin genes occurs in T. brucei. Polycistronic transcription in these organisms makes the chromosomal arrangement of tubulin genes important with respect to gene expression. RESULTS: We investigated the genomic architecture of tubulin tandem arrays among these parasites, establishing which character state is derived, and the timing of character transition. Tubulin loci in T. brucei and L. major were compared to examine the relationship between the two character states. Intergenic regions between tubulin genes were sequenced from several trypanosomatids and related, non-parasitic bodonids to identify the ancestral state. Evidence of alternating arrays was found among non-parasitic kinetoplastids and all Trypanosoma spp.; monotypic arrays were confirmed in all Leishmania spp. and close relatives. CONCLUSION: Alternating and monotypic tubulin arrays were found to be mutually exclusive through comparison of genome sequences. The presence of alternating gene arrays in non-parasitic kinetoplastids confirmed that separate, monotypic arrays are the derived state and evolved through genomic restructuring in the lineage leading to Leishmania. This fundamental reorganisation accounted for the dissimilar genomic architectures of T. brucei and L. major tubulin repertoires

Investigating white matter fibre density and morphology using fixel-based analysis

Voxel-based analysis of diffusion MRI data is increasingly popular. However, most white matter voxels contain contributions from multiple fibre populations (often referred to as crossing fibres), and therefore voxel-averaged quantitative measures (e.g. fractional anisotropy) are not fibre-specific and have poor interpretability. Using higher-order diffusion models, parameters related to fibre density can be extracted for individual fibre populations within each voxel (‘fixels’), and recent advances in statistics enable the multi-subject analysis of such data. However, investigating within-voxel microscopic fibre density alone does not account for macroscopic differences in the white matter morphology (e.g. the calibre of a fibre bundle). In this work, we introduce a novel method to investigate the latter, which we call fixel-based morphometry (FBM). To obtain a more complete measure related to the total number of white matter axons, information from both within-voxel microscopic fibre density and macroscopic morphology must be combined. We therefore present the FBM method as an integral piece within a comprehensive fixel-based analysis framework to investigate measures of fibre density, fibre-bundle morphology (cross-section), and a combined measure of fibre density and cross-section. We performed simulations to demonstrate the proposed measures using various transformations of a numerical fibre bundle phantom. Finally, we provide an example of such an analysis by comparing a clinical patient group to a healthy control group, which demonstrates that all three measures provide distinct and complementary information. By capturing information from both sources, the combined fibre density and cross-section measure is likely to be more sensitive to certain pathologies and more directly interpretable

Discovering lived experiences through descriptive phenomenology

• Purpose This article explores the reasons why descriptive phenomenology can provide an improved understanding of hospitality, tourism and event experiences. This is achieved through two objectives: firstly, by revealing the complexities and philosophical depths of descriptive phenomenology; secondly, by providing a practical, stepped, method that offers rigour and transparency. • Design/methodology/approach This article is based upon a study that explored the lived experience of the popular music festival-goer. It generally discusses the phenomenological philosophies of Husserl (1965 [1911]) and the descriptive phenomenological method in psychology of Giorgi (2009). It identifies some of the challenges and criticisms of descriptive phenomenology but also the strengths of using a scientific approach to phenomenological research. • Findings The philosophical strengths underlying descriptive phenomenology affords a deeper understanding of the phenomenon being studied. The lived experience music festival study illustrates that the method of data collection and analysis highlights the intricacy of the philosophical debate and research findings. Although the bracketing, or epoché, method of descriptive phenomenology has been criticised, the actual application is far more complex than trying to blank out prior knowledge. The aim is to ensure that it is the participants’ experiences that are used to identify the structure that is the phenomenon rather than the personal interpretation of the researcher. • Originality/value It is recognised that researching the life-world affords a greater depth of understanding of experiences in people’s lives. One of the disappointments has been that one branch of phenomenological research, descriptive phenomenology, has been under-utilised and at times misunderstood in hospitality, tourism and event research. This article aims to demonstrate and illustrate why and how descriptive phenomenology should be considered in the future research of such experiences

Permutations whose reverse shares the same recording tableau in the RSK correspondence

The RSK correspondence is a bijection between permutations and pairs of standard Young tableaux with identical shape, where the tableaux are commonly denoted $P$ (insertion) and $Q$ (recording). It has been an open problem to demonstrate $$|\{w \in \mathfrak{S}_n | \, Q(w) = Q(w^r)\}| = \begin{cases} \displaystyle 2^{\frac{n-1}{2}}{n-1 \choose \frac{n-1}{2}} & n \text{ odd} \newline \displaystyle 0 & n \text{ even} \end{cases},$$ where $w^r$ is the reverse permutation of $w$. First we show that for each $w$ where $Q(w) = Q(w^r)$ the recording tableau $Q(w)$ has a symmetric hook shape and satisfies a certain simple property. From these two results, we succeed in proving the desired identity.Comment: 14 pages, 4 figure

Local lung hypoxia determines epithelial fate decisions during alveolar regeneration.

After influenza infection, lineage-negative epithelial progenitors (LNEPs) exhibit a binary response to reconstitute epithelial barriers: activating a Notch-dependent ΔNp63/cytokeratin 5 (Krt5) remodelling program or differentiating into alveolar type II cells (AEC2s). Here we show that local lung hypoxia, through hypoxia-inducible factor (HIF1α), drives Notch signalling and Krt5pos basal-like cell expansion. Single-cell transcriptional profiling of human AEC2s from fibrotic lungs revealed a hypoxic subpopulation with activated Notch, suppressed surfactant protein C (SPC), and transdifferentiation toward a Krt5pos basal-like state. Activated murine Krt5pos LNEPs and diseased human AEC2s upregulate strikingly similar core pathways underlying migration and squamous metaplasia. While robust, HIF1α-driven metaplasia is ultimately inferior to AEC2 reconstitution in restoring normal lung function. HIF1α deletion or enhanced Wnt/β-catenin activity in Sox2pos LNEPs blocks Notch and Krt5 activation, instead promoting rapid AEC2 differentiation and migration and improving the quality of alveolar repair

Prevalence of macropod progressive periodontal disease ("lumpy jaw") in wild western grey kangaroos (Macropus fuliginosus)

Macropod Progressive Periodontal Disease (MPPD), colloquially referred to as “lumpy jaw”, is a commonly observed disease in captive macropods. However, the prevalence of this disease in the wild is largely unknown. A systematic study of MPPD in wild macropods would provide an indication of the endemic presence of this disease in wild populations, and could assist those managing disease in captive populations, by highlighting potential risk factors for disease development. Utilising kangaroos culled as part of a population management program, this study used visual observation and computer tomography (CT) of skulls to investigate the prevalence of MPPD in wild western grey kangaroos (Macropus fuliginosus) from the Perth metropolitan region, Western Australia. The sample suitable for visual and CT analysis comprised 121 specimens, 71 (58.7%) male and 50 (41.3%) female, with the mean age for all 121 specimens being 4.5 years (±2.63 SD). No evidence of MPPD was detected in any of the specimens examined. Overabundance may not be associated with the development of MPPD, as previously considered, and age-related factors should not be eliminated. This results may reflect low susceptibility to MPPD in western grey kangaroos, given low prevalence is reported in this species in captive populations. Further investigation into species-specificity is recommended, and should include samples with soft tissue to improve sensitivity of disease detection. Surveillance of MPPD in wild populations of macropods helps to improve our understanding of the biological significance, development and potential spread of this disease. Notably, this information may assist in the management of MPPD in captive populations, and may have a positive impact on both the welfare and conservation of macropods in captivity

Reflection-impulsivity in athletes: A cross-sectional and longitudinal investigation

Reflection-impulsivity is a dimension of cognitive or decision-making style. We conducted two quasi-experimental studies to examine reflection-impulsivity in athletes using an information sampling task. In Study 1 (n = 108; Mage = 22.7 ± SDage = 1.42; 50% female), we used a cross-sectional design to compare performance across athletic expertise (super-elite, elite, amateur, novice or non-athlete) and sport type (external-paced or self-paced). In Study 2 (Time 1 n = 106; Mage = 21.32 ± SDage = 5.77; 53% female and Time 2 n = 64; Mage = 21.19 ± SDage = 5.12; 44% female), we examined changes in reflection-impulsivity across a 16-week playing season. Study 1 showed more accurate and more efficient performance as athletic expertise increased. Study 2 revealed better effectiveness and efficiency following sport participation, a 16-week playing season, most notably in elite-level performers. No sport-type differences were noted. Taken together, the studies demonstrate an association between reflection-impulsivity and athletic expertise, while also providing evidence that competitive sports participation leads to efficient decisions based on reflection, without sacrificing accuracy, which is often a consequence of impulsive decision-making

A survey-based cross-sectional study of doctors’ expectations and experiences of non-technical skills for out of hours work

Objectives: The skill set required for junior doctors to work efficiently and safely Out of Hours (OoH) in hospitals has not been established. This is despite the OoH period representing 75% of the year and it being the time of highest mortality. We set out to explore the expectations of medical students and experiences of junior doctors of the non-technical skills needed to work OoH. Design: Survey-based cross-sectional study informed by focus groups. Setting: Online survey with participants from five large teaching hospitals across the UK. Participants: 300 Medical Students and Doctors. Outcome measure: Participants ranked the importance of non-technical skills, as identified by literature review and focus groups, needed for OoH care. Results: The focus groups revealed a total of eight non-technical skills deemed to be important. In the survey ‘Task Prioritisation’ (mean rank 1.617) was consistently identified as the most important non-technical skill. Stage of training affected the ranking of skills, with significant differences for ‘Communication with Senior Doctors’, ‘Dealing with Clinical Isolation’, ‘Task Prioritisation’ and ‘Communication with Patients’. Importantly, there was a significant discrepancy between the medical student expectations and experiences of doctors undertaking work. Conclusions: Our findings suggest that medical staff particularly value task prioritisation skills; however, these are not routinely taught in medical schools. The discrepancy between expectations of students and experience of doctors reinforces the idea that there is a gap in training. Doctors of different grades place different importance on specific non-technical skills with implications for postgraduate training. There is a pressing need for medical schools and deaneries to review non-technical training to include more than communication skills