bluuebunny/crossref_metadata_2025_split huggingface dataset:
Indigenous research methodologies: decolonizing the Australian sports sciences
Authors: Esgin Tuguy , Hersh Deborah , Rowley Kevin , Gilroy John , Newton Robert U 
Published: September 2018

AbstractTo design a questionnaire that would determine an Indigenous individual’s perceptions of the barriers and motivators to aerobic and anabolic exercise with a series of questions designed to elicit the factors that impact uptake and retention of regular physical activity. For this purpose, a questionnaire was designed to capture information relating to motivators and barriers, traditional physical activities, preferred exercise environments, exercise goals and levels of commitment to physical activity. This article does not report the results of the questionnaire itself but the preparation that was required in order to develop it. Indigenous standpoint theory. Participatory Action Research. A series of consultation meetings were arranged between the first author, a Noongar Aboriginal researcher, with a range of people from the same Noongar community as the author to discuss priorities and develop questions. The drafted questionnaire was shaped with continuous Noongar community feedback to ensure the language, length and appropriateness of questions. Questionnaire reliability was assessed using interclass correlation. Most questions had excellent internal consistency. A consensus was reached on the utility of the questionnaire. The personal contacts of the first author and nature of community involvement in the development of this questionnaire were helpful in assuring that it would be an acceptable tool for the Noongar community. The piloting of the questionnaire was also important in confirming its community acceptability. This article provides a model and suggestions for researching physical activity and exercise in a culturally safe manner.
Understanding the Effects of Personalization as a Privacy Calculus: Analyzing Self-Disclosure Across Health, News, and Commerce Contexts
Authors: Bol Nadine , Dienlin Tobias , Kruikemeier Sanne , Sax Marijn , Boerman Sophie C , Strycharz Joanna , Helberger Natali , de Vreese Claes H 
Published: September 2018

Abstract
The privacy calculus suggests that online self-disclosure is based on a cost–benefit trade-off. However, although companies progressively collect information to offer tailored services, the effect of both personalization and context-dependency on self-disclosure has remained understudied. Building on the privacy calculus, we hypothesized that benefits, privacy costs, and trust would predict online self-disclosure. Moreover, we analyzed the impact of personalization, investigating whether effects would differ for health, news, and commercial websites. Results from an online experiment using a representative Dutch sample (N = 1,131) supported the privacy calculus, revealing that it was stable across contexts. Personalization decreased trust slightly and benefits marginally. Interestingly, these effects were context-dependent: While personalization affected outcomes in news and commerce contexts, no effects emerged in the health context.
Impact of the 2012 Medicaid Health Care–Acquired Conditions Policy on Catheter-Associated Urinary Tract Infection and Vascular Catheter–Associated Infection Billing Rates
Authors: Rhee Chanu , Wang Rui , Jentzsch Maximilian S , Hsu Heather , Kawai Alison Tse , Jin Robert , Horan Kelly , Broadwell Carly , Lee Grace M 
Published: September 2018

Abstract
In July 2012, the Centers for Medicare & Medicaid Services ceased hospital Medicaid reimbursements for certain health care–acquired conditions. Using billing data from 2008–2014, we found no impact of this policy on rates of 2 targeted conditions, vascular catheter–associated infections and catheter-associated urinary tract infections, among Medicaid or non-Medicaid patients.
Is gambling an emerging public health issue for Wales, UK?
Authors: Atherton F , Beynon C 
Published: September 2018

Abstract

Background
Not all gambling exposes people to the same level of harm. Harm from gambling is found at the individual, social (family and friends) and community levels. This includes financial hardship, psychological distress and interpersonal conflict or relationship breakdown. The harm from gambling to wider society includes fraud, theft, loss of productivity in the workforce and the cost of treating this addiction. The annual estimated excess cost of gambling for Wales is between £40 and £70 million.

Methods
This study reviews the existing data sources and literature to ascertain if gambling is an emerging public health issue in Wales.

Results
In Wales 61% of adults had gambled in the last year (1.5 million people). And 1.1% of the population (30 000 people) self-report as having a problem with gambling using either the Problem Gambling Severity Index or the Diagnostic and Statistical Manual of American Psychiatric Association tools. The ‘ripple effect’ of gambling harm can mean friends and family are highly impacted.

Conclusion
The existing data and literature together with the rapidly evolving developments in infrastructure demonstrate that gambling is an emerging public health issue in Wales. The impact on families and society warrants population level interventions to tackle this public health issue.
Reverse genetic screen reveals that Il34 facilitates yolk sac macrophage distribution and seeding of the brain
Authors: Kuil Laura E. , Oosterhof Nynke , Geurts Samuël N. , der Linde Herma C. van , Meijering Erik , van Ham Tjakko J. 
Published: September 2018

ABSTRACTMicroglia are brain resident macrophages, which have specialized functions important in brain development and in disease. They colonize the brain in early embryonic stages, but few factors that drive the migration of yolk sac macrophages into the embryonic brain, or regulate their acquisition of specialized properties are currently known.Here, we present a CRISPR/Cas9-based in vivo reverse genetic screening pipeline to identify new regulators important for microglia development using zebrafish. Zebrafish larvae are particularly suitable due to their external development, transparency, high fecundity and conserved microglia features. We targeted putative microglia regulators, including signature genes and non-cell autonomous factors, by Cas9/gRNA-complex injections, followed by neutral red-based visualization of microglia. Microglia were quantified automatically in 3-day-old larvae using a software tool we called SpotNGlia. We identified that loss of function of the zebrafish homolog of the colony stimulating factor 1 receptor (CSF1R) ligand IL34, caused strongly reduced microglia numbers in early development. Previous studies on the role of the IL34 on microglia development in vivo were ambiguous. Our data, and a concurrent paper, show that in zebrafish,il34is required during the earliest seeding of the brain by microglia progenitors. Our data also indicate that Il34 is required for distribution to other organs.Previously, we showed thatcsf1raandcsf1rbdouble mutant zebrafish have no microglia. As there is a moderate effect ofil34on microglia development, relative to the effectcsf1r, additional Csf1r-dependent signalling may be needed for establishment of the microglia network. In all, we identifiedil34as a modifier of microglia colonization, by affecting distribution of yolk sac macrophages to target organs, validating our reverse genetic screening pipeline in zebrafish which can be used for the identification of additional regulators of microglia development.
Local structural connectivity directs seizure spread in focal epilepsy
Authors: Shah Preya , Ashourvan Arian , Mikhail Fadi , Pines Adam , Kini Lohith , Shinohara Russell T. , Bassett Danielle S. , Litt Brian , Davis Kathryn A. 
Published: September 2018

AbstractHow does the human brain’s structural scaffold give rise to its intricate functional dynamics? This is a central challenge in translational neuroscience, particularly in epilepsy, a disorder that affects over 50 million people worldwide. Treatment for medication-resistant focal epilepsy is often structural – through surgery, devices or focal laser ablation – but structural targets, particularly in patients without clear lesions, are largely based on functional mapping via intracranial EEG (iEEG). Unfortunately, the relationship between structural and functional connectivity in the seizing brain is poorly understood. In this study, we quantify structure-function coupling, specifically between white matter connections and iEEG, across preictal and ictal periods in 45 seizures from 9 patients with unilateral drug-resistant focal epilepsy. We use High Angular Resolution Diffusion Imaging (HARDI) tractography to construct structural connectivity networks and correlate these networks with time-varying broadband and frequency-specific functional networks derived from coregistered iEEG. Across all frequency bands, we find significant increases in structure-function coupling from preictal to ictal periods. We demonstrate that short-range structural connections are primarily responsible for this increase in coupling. Finally, we find that spatiotemporal patterns of structure-function coupling are stereotyped, and a function of each patient’s individual anatomy. These results suggest that seizures harness the underlying structural connectome as they propagate. Our findings suggest that the relationship between structural and functional connectivity in epilepsy may inform current and new therapies to map and alter seizure spread, and pave the way for better-targeted, patient-specific interventions.
Meta-population structure and the evolutionary transition to multicellularity
Authors: Rose Caroline J. , Hammerschmidt Katrin , Pichugin Yuiry , Rainey Paul B 
Published: September 2018

AbstractThe evolutionary transition to multicellularity has occurred on numerous occasions, but transitions to complex life forms are rare. While the reasons are unclear, relevant factors include the intensity of within-versus between-group selection that are likely to have shaped the course of life cycle evolution. A highly structured environment eliminates the possibility of mixing between evolving lineages, thus ensuring strong competition between groups. Less structure intensifies competition within groups, decreasing opportunity for group-level evolution. Here, using populations of the bacteriumPseudomonas fluorescens,we report the results of experiments that explore the effect of lineage mixing on the evolution of nascent multicellular groups. Groups were propagated under regimes requiring reproduction via a life cycle replete with developmental and dispersal (propagule) phases, but in one treatment lineages never mixed, whereas in a second treatment, cells from different lineages experienced intense competition during the dispersal phase. The latter treatment favoured traits promoting cell growth at the expense of traits underlying group fitness – a finding that is supported by results from a mathematical model. Together our results show that the transition to multicellularity benefits from ecological conditions that maintain discreteness not just of the group (soma) phase, but also of the dispersal (germline) phase.
snakePipes enable flexible, scalable and integrative epigenomic analysis
Authors: Bhardwaj Vivek , Heyne Steffen , Sikora Katarzyna , Rabbani Leily , Rauer Michael , Kilpert Fabian , Richter Andreas S , Ryan Devon P , Manke Thomas 
Published: September 2018

AbstractThe scale and diversity of epigenomics data has been rapidly increasing and ever more studies now present analyses of data from multiple epigenomic techniques. Performing such integrative analysis is time-consuming, especially for exploratory research, since there are currently no pipelines available that allow fast processing of datasets from multiple epigenomic assays while also allow for flexibility in running or upgrading the workflows. Here we present a solution to this problem: snakePipes, which can process and perform downstream analysis of data from all common epigenomic techniques (ChIP-seq, RNA-seq, Bisulfite-seq, ATAC-seq, Hi-C and single-cell RNA-seq) in a single package. We demonstrate how snakePipes can simplify integrative analysis by reproducing and extending the results from a recently published large-scale epigenomics study with a few simple commands. snakePipes are available under an open-source license at https://github.com/maxplanck-ie/snakepipes.
The human default consciousness and its disruption: insights from an EEG study of Buddhist jhāna meditation
Authors: Dennison Paul 
Published: September 2018

The “neural correlates of consciousness” (NCC) is a familiar topic in neuroscience, overlapping with research on the brain’s “default mode network”. Task-based studies of NCC by their nature recruit one part of the cortical network to study another, and are therefore both limited and compromised in what they can reveal about consciousness itself. The form of consciousness explored in such research, we term the human default consciousness (DCs), our everyday waking consciousness. In contrast, studies of anaesthesia, coma, deep sleep, or some extreme pathological states such as epilepsy, reveal very different cortical activity; all of which states are essentially involuntary, and generally regarded as “unconscious”. An exception to involuntary disruption of consciousness is Buddhist jhāna meditation, whose implicit aim is to intentionally withdraw from the default consciousness, to an inward-directed state of stillness referred to as jhāna consciousness, as a basis to develop insight. The default consciousness is sensorily-based, where information about, and our experience of, the outer world is evaluated against personal and organic needs and forms the basis of our ongoing self-experience. This view conforms both to Buddhist models, and to the emerging work on active inference and minimisation of free energy in determining the network balance of the human default consciousness.This paper is a preliminary report on the first detailed EEG study of jhāna meditation, with findings radically different to studies of more familiar, less focused forms of meditation. While remaining highly alert and “present” in their subjective experience, a high proportion of subjects display “spindle” activity in their EEG, superficially similar to sleep spindles of stage 2 nREM sleep, while more-experienced subjects display high voltage slow-waves reminiscent, but significantly different, to the slow waves of deeper stage 4 nREM sleep, or even high-voltage delta coma. Some others show brief posterior spike-wave bursts, again similar, but with significant differences, to absence epilepsy. Some subjects also develop the ability to consciously evoke clonic seizure-like activity at will, under full control. We suggest that the remarkable nature of these observations reflects a profound disruption of the human DCs when the personal element is progressively withdrawn.
Charting DENR-dependent translation reinitiation uncovers predictive uORF features and links to circadian timekeeping via Clock
Authors: Castelo-Szekely Violeta , De Matos Mara , Tusup Marina , Pascolo Steve , Ule Jernej , Gatfield David 
Published: September 2018

ABSTRACTThe non-canonical initiation factor DENR promotes translation reinitiation on mRNAs harbouring upstream open reading frames (uORFs). Moreover, DENR depletion shortens circadian period in mouse fibroblasts, suggesting involvement of uORF usage and reinitiation in clock regulation. To identify DENR-regulated translation events transcriptome-wide and, in particular, specific core clock transcripts affected by this mechanism, we have used ribosome profiling in DENR-deficient NIH3T3 cells. We uncovered 240 transcripts with altered translation rate, and used linear regression analysis to extract 5’ UTR features predictive of DENR dependence. Among core clock genes, we identified Clock as a DENR target. Using Clock 5’ UTR mutants, we mapped the specific uORF through which DENR acts to regulate CLOCK protein biosynthesis. Notably, these experiments revealed an alternative downstream start codon, likely representing the bona fide CLOCK N-terminus. Our findings provide insights into uORF-mediated translational regulation that can regulate the mammalian circadian clock and gene expression at large.
Accurate Determination of Human CPR Conformational Equilibrium by smFRET using Dual Orthogonal Non-Canonical Amino Acid Labeling
Authors: Quast Robert B. , Fatemi Fataneh , Kranendonk Michel , Margeat Emmanuel , Truan Gilles 
Published: September 2018

ABSTRACTConjugation of fluorescent dyes to proteins - a prerequisite for the study of conformational dynamics by single molecule Förster resonance energy transfer (smFRET) - can lead to substantial changes of the dye’s photophysical properties, ultimately biasing the quantitative determination of inter-dye distances. In particular the popular cyanine dyes and their derivatives, which are by far the most used dyes in smFRET experiments, exhibit such behavior. To overcome this, a general strategy to site-specifically equip proteins with FRET pairs by chemo-selective reactions using two distinct non-canonical amino acids simultaneously incorporated through genetic code expansion inEscherichia coliwas developed. Applied to human NADPH- cytochrome P450 reductase (CPR), the importance of homogenously labeled samples for accurate determination of FRET efficiencies was demonstrated. Furthermore, the effect of NADP+ on the ionic strength dependent modulation of the conformational equilibrium of CPR was unveiled. Given its generality and accuracy, the presented methodology establishes a new benchmark to decipher complex molecular dynamics on single molecules.
Temperature-responsive competitive inhibition of CRISPR-Cas9
Authors: Jiang Fuguo , Liu Jun-Jie , Osuna Beatriz A. , Xu Michael , Berry Joel D. , Rauch Benjamin J. , Nogales Eva , Bondy-Denomy Joseph , Doudna Jennifer A. 
Published: September 2018

SUMMARYCRISPR–Cas immune systems utilize RNA-guided nucleases to protect bacteria from bacteriophage infection. Bacteriophages have in turn evolved inhibitory ‘anti-CRISPR’ (Acr) proteins, including six inhibitors (AcrIIA1-6) that can block DNA cutting and genome editing by type II-A CRISPR-Cas9 enzymes. We show here that AcrIIA2 and its homologue, AcrIIA2b, prevent Cas9 binding to DNA by occluding protein residues required for DNA binding. Cryo-EM-determined structures of AcrIIA2 or AcrIIA2b bound to S. pyogenes Cas9 reveal a mode of competitive inhibition of DNA binding that is distinct from other known Acrs. Differences in the temperature dependence of Cas9 inhibition by AcrIIA2 and AcrIIA2b arise from differences in both inhibitor structure and the local inhibitor-binding environment on Cas9. These findings expand the natural toolbox for regulating CRISPR-Cas9 genome editing temporally, spatially and conditionally.
Tree-sequence recording in SLiM opens new horizons for forward-time simulation of whole genomes
Authors: Haller Benjamin C. , Galloway Jared , Kelleher Jerome , Messer Philipp W. , Ralph Peter L. 
Published: September 2018

AbstractThere is an increasing demand for evolutionary models to incorporate relatively realistic dynamics, ranging from selection at many genomic sites to complex demography, population structure, and ecological interactions. Such models can generally be implemented as individual-based forward simulations, but the large computational overhead of these models often makes simulation of whole chromosome sequences in large populations infeasible. This situation presents an important obstacle to the field that requires conceptual advances to overcome. The recently developed tree-sequence recording method (Kelleher et al., 2018), which stores the genealogical history of all genomes in the simulated population, could provide such an advance. This method has several benefits: (1) it allows neutral mutations to be omitted entirely from forward-time simulations and added later, thereby dramatically improving computational efficiency; (2) it allows neutral burn-in to be constructed extremely efficiently after the fact, using “recapitation”; (3) it allows direct examination and analysis of the genealogical trees along the genome; and (4) it provides a compact representation of a population’s genealogy that can be analyzed in Python using the msprime package. We have implemented the tree-sequence recording method in SLiM 3 (a free, open-source evolutionary simulation software package) and extended it to allow the recording of non-neutral mutations, greatly broadening the utility of this method. To demonstrate the versatility and performance of this approach, we showcase several practical applications that would have been beyond the reach of previously existing methods, opening up new horizons for the modeling and exploration of evolutionary processes.
Strain maps characterize the symmetry of convergence and extension patterns during Zebrafish gastrulation
Authors: Bhattacharya Dipanjan , Zhong Jun , Tavakoli Sahar , Kabla Alexandre , Matsudaira Paul 
Published: September 2018

AbstractDuring gastrulation of the zebrafish embryo, the cap of blastoderm cells organizes into the axial body plan of the embryo with left-right symmetry and head-tail, dorsal-ventral polarities. Our labs have been interested in the mechanics of early development and have investigated whether these large-scale cells movements can be described as tissue-level mechanical strain by a tectonics-based approach. The first step is to image the positions of all nuclei from mid-epiboy to early segmentation by digital sheet light microscopy (DSLM), organize the surface of the embryo into multi-cell spherical domains, construct velocity fields from the movements of these domains and extract 3D strain rate maps. Tensile/expansive and compressive strains in the axial and equatorial directions are detected during gastrulation as anterior and posterior expansion along the anterior-posterior axis and medial-lateral compression across the dorsal-ventral axis corresponding to convergence and extension. In later stages in development are represented by localized medial expansion at the onset of segmentation and anterior expansion at the onset of neurulation. Symmetric patterns of rotation are first detected in the animal hemispheres at mid-epiboly and then the vegetal hemispheres by the end of gastrulation. By analysing the temporal sequence of large scale movements, deformations across the embryo can be attributed to a combination of epiboly and dorsal convergence-extension.SignificanceStrain is an emergent property of tissues that originates from the mechanical coupling of cell-cell and cell-substrate interactions, individual cell shape changes, and cell level forces. By imaging the positions of nuclei from mid-epiboly to early segmentation of the zebrafish embryo we are able to calculate three types of strain maps by a plate tectonics based method. The regions of expansive and compressive axial and equatorial strain correspond to areas undergoing convergence and extension, a major step in the formation of the embryonic body plan as well as the formation of somite and head structures. The most striking signatures of strain are: 1. the bilateral symmetry of linear strain across the anterior-posterior, dorsal-ventral axis during gastrulation, 2. the complementary counter-rotational strains or curl in the animal hemisphere at mid epiboly, and 3. a divergence or saddle point in the region of the dorsal organizer, head-trunk boundary. These strains represent a general method to describe large-scale tissue-level mechanics not only of embryonic development but also tissue homeostasis and disease.