bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Hidden Markov Model for Detecting Confinement in Single Particle Tracking Trajectories
Authors: Slator PJ , Burroughs NJ 
Published: March 2018

AbstractState-of-the-art single particle tracking (SPT) techniques can generate long trajectories with high temporal and spatial resolution. This offers the possibility of mechanistically interpreting particle movements and behaviour in membranes. To this end, a number of statistical techniques have been developed that partition SPT trajectories into states with distinct diffusion signatures, allowing a statistical analysis of diffusion state dynamics and switching behaviour. Here we develop a confinement model, within a hidden Markov framework, that switches between phases of free diffusion, and confinement in a harmonic potential well. By using a Markov chain Monte Carlo (MCMC) algorithm to fit this model, automated partitioning of individual SPT trajectories into these two phases is achieved, which allows us to analyse confinement events. We demonstrate the utility of this algorithm on a previously published dataset, where gold nanoparticle (AuNP) tagged GM1 lipids were tracked in model membranes. We performed a comprehensive analysis of confinement events, demonstrating that there is heterogeneity in the lifetime, shape, and size of events, with confinement size and shape being highly conserved within trajectories. Our observations suggest that heterogeneity in confinement events is caused by both individual nanoparticle characteristics and the binding site environment. The individual nanoparticle heterogeneity ultimately limits the ability of iSCAT to resolve molecular dynamics to the order of the tag size; homogeneous tags could potentially allow the resolution to be taken below this limit by deconvolution methods. In a wider context, the presented harmonic potential well confinement model has the potential to detect and characterise a wide variety of biological phenomena, such as hop diffusion, receptor clustering, and lipid rafts.
Effect of chromatin flexibility on diffusive loop extrusion via molecular slip-links
Authors: Brackley C. A. , Johnson J. , Michieletto D. , Marenduzzo D. 
Published: March 2018

AbstractWe use Brownian dynamics simulations to study the formation of chromatin loops through diffusive sliding of molecular slip links, mimicking the behaviour of cohesin-like molecules. We recently proposed that diffusive sliding is sufficient to explain the extrusion of chromatin loops of hundreds of kilo-base-pairs (kbp), which may then be stabilised by interactions between cohesin and CTCF proteins. Here we show that the elasticity of the chromatin fibre strongly affects this dynamical process, and find that diffusive loop extrusion is more efficient on stiffer chromatin regions. Efficiency is also enhanced if cohesin loading sites are close to regions where CTCF is bound. In light of the heterogeneous physical properties of eukaryotic chromatin, we suggest that our results should be relevant to the looping and organisation of interphase chromosomes in vivo.
Electromechanics and Volume Dynamics in Non-excitable Tissue Cells
Authors: Yellin F. , Li Y. , Sreenivasan V. K. A. , Farrell B. , Johny M. B. , Yue D. , Sun S. X. 
Published: March 2018

AbstractCell volume regulation is fundamentally important in phenomena such as cell growth, proliferation, tissue homeostasis and embryogenesis. How the cell size is set, maintained, and changed over a cell’s lifetime is not well understood. In this work we focus on how the volume of non-excitable tissue cells is coupled to the cell membrane electrical potential and the concentration of membrane-permeable ions in the cell environment. Specifically, we demonstrate that a sudden cell depolarization using the whole cell patch clamp results in a 30 percent increase in cell volume, while hyperpolarization results in a slight volume decrease. We find that cell volume can be partially controlled by changing the chloride or the sodium/potassium concentrations in the extracellular environment while maintaining a constant external osmotic pressure. Depletion of external chloride leads to a volume decrease in suspended HN31 cells. Introducing cells to a high potassium solution causes volume increase by up to 50%. Cell volume is also influenced by cortical tension: actin depolymerization leads to cell volume increase. We present an electrophysiology model of water dynamics driven by changes in membrane potential and in the concentration of permeable ions in the cell surrounding. The model quantitatively predicts that the cell volume is determined by the total amount of intracellular ion and protein content.
Multi-Link Analysis: Brain Network Comparison via Sparse Connectivity Analysis
Authors: Crimi Alessandro , Giancardo Luca , Sambataro Fabio , Gozzi Alessandro , Murino Vittorio , Sona Diego ,   the Alzheimer’s Disease Neuroimaging Initiative
Published: March 2018

ABSTRACTThe analysis of the brain from a connectivity perspective is unveiling novel insights into brain structure and function. Discovery is, however, hindered by the lack of prior knowledge used to make hypotheses. On the other hand, exploratory data analysis is made complex by the high dimensionality of data. Indeed, in order to assess the effect of pathological states on brain networks, neuroscientists are often required to evaluate experimental effects in case-control studies, with hundreds of thousand connections.In this paper, we propose an approach to identify the multivariate relationships in brain connections that characterise two distinct groups, hence permitting the investigators to immediately discover sub-networks that contain information about the differences between experimental groups. In particular, we are interested in data discovery related to connectomics, where the connections that characterize differences between two groups of subjects are found. Nevertheless, those connections not necessarily maximize accuracy in classification since this does not guarantee reliable interpretation of specific differences between groups. In practice, our method exploits recent machine learning techniques employing sparsity to deal with weighted networks describing the whole-brain macro connectivity. We evaluated our technique on functional and structural connectomes from human and mice brain data. In our experiments, we automatically identified disease-relevant connections in datasets with supervised and unsupervised anatomy-driven parcellation approaches, and by using high-dimensional datasets.
Labels of aberrant Clusters of Differentiation gene expression in a compendium of systemic lupus erythematosus patients
Authors: Le Trang T. , Blackwood Nigel O. , Breitenstein Matthew K. 
Published: March 2018

BackgroundThis author manuscript serves as an extended annotation of gene expression for all known clusters of differentiation (CD) within a compendium of systemic lupus erythematosus (SLE) patients. The overarching goal for this line of research is to enrich the perspective of the CD transcriptome with upstream gene expression features.
Study of the DiI method accuracy on the example of the afferent connections of the Habenula in P6 F1-C57Bl6 / CBA mice
Authors: Klepukov A , Apryshko V.P , Yakovenko S.A. 
Published: March 2018

ABSTACTDiI (1,1’-dioctadecyl-3,3,3’3’-tetramethylindocarbocyanine perchlorate) is a lipophilic carbocyanine stain diffusing in the plasma membrane and coloring the cell as a whole.The DiI injection method is an alternative to stereotaxis in the study of the neural connections of higher vertebrates. However, despite a number of studies performed to identify the neural connections of embryos and fetuses of different animals, the question of the accuracy of the DiI method remains open. The main goal of this study is to investigate the accuracy of the DiI method by examining the afferent Habenula (Hb) connections in P6 F1-C57Bl6/CBA mice. Hb is a paired structure of the intermediate brain, consisting of two nuclei - the medial (MHb) and lateral (LHb). At P6, the main Hb tracts are already formed but not yet myelinated. To estimate the accuracy of the method, two groups of cases with different types of application on different Hb nuclei were compared: bilateral applications of several DiI crystals - group 1 (26 applications); Unilateral applications of a single crystal DiI - control group 2 (7 applications). It is known that MHb is strictly innervated by Triangular septal nuclei (TS) and Septofimbrial septal nuclei (SFi); LHb is strictly innervated by the Lateral preopteic area (LPA). Any deviation from this scheme is a false positive result. When applying the marker to different Hb nuclei in group 1, the number of successful cases without deviations was -0%; in group 2 (control) - 28.57%. Unilateral applications of a single DiI crystal are more accurate. However, there are still a number of unavoidable problems, such as the fragmentation or loss of a single DiI crystal during application and the super-strong diffusion of the marker at the application site. Given this, the overall accuracy of the DiI injection method, even in the form of a single crystal, remains low.
Ancient Genomics Reveals Four Prehistoric Migration Waves into Southeast Asia
Authors: McColl Hugh , Racimo Fernando , Vinner Lasse , Demeter Fabrice , Víctor Moreno Mayar J. , Wilken Uffe Gram , Seguin-Orlando Andaine , Fuente Castro Constanza de la , Wasef Sally , Prohaska Ana , Margarayan Ashot , Barros Damgaard Peter de , Shoocongdej Rasmi , Souksavatdy Viengkeo , Sayavongkhamdy Thongsa , Saidin Mohd Mokhtar , Kaewsutthi Supannee , Lertrit Patcharee , Nguyen Huong Mai , Hung Hsiao-chun , Tran Thi Minh , Truong Huu Nghia , Shahidan Shaiful , Wiradnyana Ketut , Bacon Anne-Marie , Duringer Philippe , Ponche Jean-Luc , Shackelford Laura , Patole-Edoumba Elise , Nguyen Anh Tuan , Bellina-Pryce Bérénice , Galipaud Jean-Christophe , Kinaston Rebecca , Buckley Hallie , Pottier Christophe , Rasmussen Simon , Higham Tom , Foley Robert A. , Lahr Marta Mirazón , Orlando Ludovic , Sikora Martin , Higham Charles , Lambert David M. , Willerslev Eske 
Published: March 2018

AbstractTwo distinct population models have been put forward to explain present-day human diversity in Southeast Asia. The first model proposes long-term continuity (Regional Continuity model) while the other suggests two waves of dispersal (Two Layer model). Here, we use whole-genome capture in combination with shotgun sequencing to generate 25 ancient human genome sequences from mainland and island Southeast Asia, and directly test the two competing hypotheses. We find that early genomes from Hoabinhian hunter-gatherer contexts in Laos and Malaysia have genetic affinities with the Onge hunter-gatherers from the Andaman Islands, while Southeast Asian Neolithic farmers have a distinct East Asian genomic ancestry related to present-day Austroasiatic-speaking populations. We also identify two further migratory events, consistent with the expansion of speakers of Austronesian languages into Island Southeast Asia ca. 4 kya, and the expansion by East Asians into northern Vietnam ca. 2 kya. These findings support the Two Layer model for the early peopling of Southeast Asia and highlight the complexities of dispersal patterns from East Asia.
Loss of Peroxisomal Hydroxypyruvate Reductase Inhibits Triose Phosphate Isomerase but Stimulates Cyclic Photosynthetic Electron Flow and the Glc-6P-Phosphate Shunt
Authors: Li Jiying , Weraduwage Sarathi M. , Preiser Alyssa L. , Weise Sean E. , Strand Deserah D. , Froehlich John E. , Kramer David M. , Hu Jianping , Sharkey Thomas D. 
Published: March 2018

AbstractThe oxygenation of ribulose 1,5-bisphosphate by Rubisco is the first step in photorespiration and reduces the efficiency of photosynthesis in C3plants. Our recent data indicates that mutants in photorespiration have increased rates of photosynthetic cyclic electron flow around photosystem I. We investigated mutant lines lacking peroxisomal hydroxypyruvate reductase to determine if there are connections between 2-PG accumulation and cyclic electron flow. We found that 2-PG is a competitive inhibitor of triose phosphate isomerase (TPI), an enzyme in the Calvin-Benson cycle that converts glyceraldehyde 3-phosphate to dihydroxyacetone phosphate. This block in metabolism could be overcome if glyceraldehyde 3-phosphate is exported to the cytosol where the cytosolic triose phosphate isomerase could convert it to dihydroxyacetone phosphate. We found evidence that carbon is reimported as Glc-6P-phosphate forming a cytosolic bypass around the block of stromal TPI. However, this also stimulates a Glc-6P-phosphate shunt, which consumes ATP, which can be compensated by higher rates of cyclic electron flow.Once Sentence SummaryTriose phosphate isomerase is inhibited in plants lacking hydroxypyruvate reductase 1 and this is overcome by exporting triose phosphate to the cytosol and importing Glc-6P, which stimulates a Glc-6P-phosphate shunt and cyclic electron flow.
Inferring the shape of global epistasis
Authors: Otwinowski Jakub , McCandlish David M. , Plotkin Joshua B. 
Published: March 2018

AbstractGenotype-phenotype relationships are notoriously complicated. Idiosyncratic interactions between specific combinations of mutations occur, and are difficult to predict. Yet it is increasingly clear that many interactions can be understood in terms ofglobal epistasis. That is, mutations may act additively on some underlying, unobserved trait, and this trait is then transformed via a nonlinear function to the observed phenotype as a result of subsequent biophysical and cellular processes. Here we infer the shape of such global epistasis in three proteins, based on published high-throughput mutagenesis data. To do so, we develop a maximum-likelihood inference procedure using a flexible family of monotonic nonlinear functions spanned by an I-spline basis. Our analysis uncovers dramatic nonlinearities in all three proteins; in some proteins a model with global epistasis accounts for virtually all the measured variation, whereas in others we find substantial local epistasis as well. This method allows us to test hypotheses about the form of global epistasis and to distinguish variance components attributable to global epistasis, local epistasis, and measurement error.
The illusion of uniformity does not depend on low-level vision: evidence from sensory adaptation
Authors: Suárez-Pinilla Marta , Seth Anil K. , Roseboom Warrick 
Published: March 2018

ABSTRACTVisual experience appears richly detailed despite the poor resolution of the majority of the visual field, thanks to foveal-peripheral integration. The recently described Uniformity Illusion (UI), in which peripheral elements of a pattern seem to take on the properties of foveal elements, may shed light on this integration. We examined the basis of UI by generating adaptation to a pattern of Gabors suitable for producing UI on orientation. After removing the pattern, participants reported the tilt of a single peripheral Gabor. The tilt after-effect (TAE) followed the physical adapting orientation rather than the global orientation perceived under UI, even when the illusion had been reported for a long time. Conversely, a control experiment replacing illusory for physical uniformity for the same durations did produce an after-effect to the global orientation. Our results indicate that the UI is not associated with changes in sensory encoding, but likely depends on high-level processes.
Higher-Order Organization Principles of Pre-translational mRNPs
Authors: Metkar Mihir , Ozadam Hakan , Lajoie Bryan R. , Imakaev Maxim , Mirny Leonid A. , Dekker Job , Moore Melissa J. 
Published: March 2018

SummaryCompared to noncoding RNAs (ncRNAs) such as rRNAs and ribozymes, for which high resolution structures abound, little is known about the tertiary structures of mRNAs. In eukaryotic cells, newly made mRNAs are packaged with proteins in highly compacted mRNPs, but the manner of this mRNA compaction is unknown. Here we developed and implemented RIPPLiT (RNA ImmunoPrecipitation and Proximity Ligation in Tandem), a transcriptome-wide method for probing the 3D conformations of RNAs stably-associated with defined proteins, in this case exon junction complex (EJC) core factors. EJCs multimerize with other mRNP components to form megadalton sized complexes that protect large swaths of newly synthesized mRNAs from endonuclease digestion. Unlike ncRNAs, mRNAs behave more like flexible polymers without strong locus-specific interactions. Polymer analysis of proximity ligation data for hundreds of mRNA species demonstrates that pre-translational mammalian mRNPs fold as linear rod-like structures with no strong propensity for 5’ and 3’ end interaction.
Three-dimensional cell geometry controls excitable membrane signaling in Dictyotelium cells
Authors: Hörning Marcel , Shibata Tatsuo 
Published: March 2018

AbstractPhosphatidylinositol (3,4,5)-trisphosphate (PtdInsP3) is known to propagate as waves on the plasma membrane and is related to the membrane protrusive activities in Dictyostelium and mammalian cells. While there have been a few attempts to study the three-dimensional dynamics of these processes, most studies have focused on the dynamics extracted from single focal planes. However, the relation between the dynamics and three-dimensional cell shape remains elusive, due to the lack of signaling information about the unobserved part of the membrane. Here we show that PtdInsP3 wave dynamics are directly regulated by the three-dimensional geometry - size and shape - of the plasma membrane. By introducing an analysis method that extracts the three-dimensional spatiotemporal activities on the entire cell membrane, we show that PtdInsP3 waves self-regulate their dynamics within the confined membrane area. This leads to changes in speed, orientation and pattern evolution, following the underlying excitability of the signal transduction system. Our findings emphasize the role of the plasma membrane topology in reaction-diffusion driven biological systems and indicate its importance in other mammalian systems.
A generalization of the informational view of non-random mating: Models with variable population frequencies
Authors: Carvajal-Rodríguez A. 
Published: March 2018

AbstractMate choice may generate non-random mating patterns. It has been recently shown that the mating distribution caused by mate choice can be expressed as a gain in information with respect to random mating. In that model, the population phenotypic frequencies were assumed as constant during the breeding season. In the present work such restriction was relaxed to consider different encounter-mating processes in which the population frequencies of available individuals change over mating rounds. As with the constant case, here we describe the change in the mating phenotypes by the flow of information with respect to random mating. This information can be partitioned into sexual selection, sexual isolation and a mixed effect. Likewise, the pairwise statistics for total change, sexual selection and sexual isolation are generalized for variable population frequencies.The new tests had more power for the detection of the effects of non-random mating when the population frequencies vary during the breeding season. The differences in power were high for sexual selection but slight for sexual isolation scenarios. However, the application of the new formulas require the estimation of frequencies at each mating round. Therefore, choosing one or another type of statistics would depend on the biological scenario as well as in the availability and easiness to split the sampling in more than one mating round.
Providing rescue services in remote areas of Estonia
Authors: Puolokainen Tarmo , Jaansoo Annika , Klaos Margo 
Published: March 2018

Purpose
The purpose of this paper is to analyze the effect of delivering rescue services in remote areas, where there is little or no natural incentive to provide this service, taking the case of Estonia as an example.

Design/methodology/approach
The case study is based on secondary data obtained via analysis of legal acts, rescripts and strategic documents, as well as (applied) studies. In addition, the transcripts of ten half-structured interviews were analyzed, which were conducted with rescue services experts in December 2012. The benefits and risks pointed out in the literature are discussed against an example of providing rescue services in the remote areas of Estonia.

Findings
Outsourcing rescue services has led to cost effectiveness and thereby provides a better-quality service in densely populated areas. The main risks are yet to emerge. It is highly probable that the Estonian Rescue Board has to deal with the issues regarding the lack of control over service, which in turn is caused by the lack of skills and competence to manage the relationships and to design appropriate service-level agreements.

Research limitations/implications
Since the voluntary rescue service provision is rapidly evolving, there have not yet been many studies undertaken to describe the positive and negative aspects of its development. Therefore, the collected data have gaps and are open for discussion.

Practical implications
The introduction of an extensive network of voluntary fire and rescue service brigades is a paradigm shift in Estonia, where the rescue services have so far been provided publicly. Thus, it gives a guidance to other practitioners, on which aspects they should focus on, while planning a change in service provision/provider.

Originality/value
The novelty of this paper is to systematically analyze the benefits and risks occurred on a shift from public provision of rescue services to providing it in an extensive co-operation with voluntary rescuers.
Can we mandate partnership working? Top down meets bottom up in structural reforms in Scotland and Norway
Authors: Huby Guro Øyen , Cook Ailsa , Kirchhoff Ralf 
Published: March 2018

Purpose
Partnership working across health and social care is considered key to manage rising service demand whilst ensuring flexible and high-quality services. Evidence suggests that partnership working is a local concern and that wider structural context is important to sustain and direct local collaboration. “Top down” needs to create space for “bottom up” management of local contingency. Scotland and Norway have recently introduced “top down” structural reforms for mandatory partnerships. The purpose of this paper is to describe and compare these policies to consider the extent to which top-down approaches can facilitate effective partnerships that deliver on key goals.

Design/methodology/approach
The authors compare Scottish (2015) and Norwegian (2012) reforms against the evidence of partnership working. The authors foreground the extent to which organisation, finance and performance management create room for partnerships to work collaboratively and in new ways.

Findings
The two reforms are held in place by different health and social care organisation and governance arrangements. Room for manoeuvre at local levels has been jeopardised in both countries, but in different ways, mirroring existing structural challenges to partnership working. Known impact of the reforms hitherto suggests that the potential of partnerships to facilitate user-centred care may be compromised by an agenda of reducing pressure on hospital resources.

Originality/value
Large-scale reforms risk losing sight of user outcomes. Making room for collaboration between user and services in delivering desired outcomes at individual and local levels is an incremental way to join bottom up to top down in partnership policy, retaining the necessary flexibility and involving key constituencies along the way.